Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry

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Neuropharmacological intervention in the form of combination antiretroviral therapy (cART) does not reverse cognitive decline in pediatric and adolescent HIV. In search of options to enhance cognition in affected adolescents, we evaluated the effectiveness of attention training. Methods The training was evaluated by pairing participants’ outcomes on the Stroop Colour Word Test (SCWT), a test of attention and inhibitory control, to brain hemodynamic responses measured by functional near-infrared spectrometry (fNIRS) both prior to, and after, the training. Changes in oxygenated haemoglobin in the prefrontal cortex during the SCWT were compared in 15 HIV+ participants who received attention training with that of 13 HIV+ participants who did not receive the intervention. Results Intragroup analyses showed differences in oxygenated haemoglobin levels between congruent and incongruent conditions of the SCWT only for participants who received the attention training. Specifically, there was a significant decrease in oxygenated haemoglobin in the dorsolateral prefrontal cortex, and frontopolar brain areas in the training group. Conclusions Findings suggest that customised attention training maybe an effective complementary adjunct to cART for children and adolescents living with HIV. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1000/v1", "name": "Shining Light into Adolescent HIV Neuroplasticity: A Study of the..." } } ] } Home Browse Shining Light into Adolescent HIV Neuroplasticity: A Study of the... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Zondo S, Cockcroft K, da Silva Ferreira Barreto C and Ferreira Correia A. Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.12688/f1000research.169799.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] Sizwe Zondo https://orcid.org/0000-0002-2592-6171 1 , Kate Cockcroft 2 , Candida da Silva Ferreira Barreto 3 , Aline Ferreira Correia https://orcid.org/0000-0003-2495-3159 2 Sizwe Zondo https://orcid.org/0000-0002-2592-6171 1 , Kate Cockcroft 2 , Candida da Silva Ferreira Barreto 3 , Aline Ferreira Correia https://orcid.org/0000-0003-2495-3159 2 PUBLISHED 29 Sep 2025 Author details Author details 1 Psychology, Rhodes University Psychology Clinic, Grahamstown, Eastern Cape, South Africa 2 Psychology, University of the Witwatersrand Johannesburg School of Human and Community Development, Johannesburg, Gauteng, South Africa 3 Neuroergonomics & Neuroimaging Lab, Drexel University School of Biomedical Engineering Science and Health Systems, Philadelphia, Pennsylvania, USA Sizwe Zondo Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Kate Cockcroft Roles: Supervision, Writing – Review & Editing Candida da Silva Ferreira Barreto Roles: Writing – Review & Editing Aline Ferreira Correia Roles: Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background The human immunodeficiency virus (HIV) crosses the blood-brain barrier, compromising cortical networks and cognition. Neuropharmacological intervention in the form of combination antiretroviral therapy (cART) does not reverse cognitive decline in pediatric and adolescent HIV. In search of options to enhance cognition in affected adolescents, we evaluated the effectiveness of attention training. Methods The training was evaluated by pairing participants’ outcomes on the Stroop Colour Word Test (SCWT), a test of attention and inhibitory control, to brain hemodynamic responses measured by functional near-infrared spectrometry (fNIRS) both prior to, and after, the training. Changes in oxygenated haemoglobin in the prefrontal cortex during the SCWT were compared in 15 HIV+ participants who received attention training with that of 13 HIV+ participants who did not receive the intervention. Results Intragroup analyses showed differences in oxygenated haemoglobin levels between congruent and incongruent conditions of the SCWT only for participants who received the attention training. Specifically, there was a significant decrease in oxygenated haemoglobin in the dorsolateral prefrontal cortex, and frontopolar brain areas in the training group. Conclusions Findings suggest that customised attention training maybe an effective complementary adjunct to cART for children and adolescents living with HIV. READ ALL READ LESS Keywords adolescent HIV, attention, cART, fNIRS, prefrontal cortex Corresponding Author(s) Sizwe Zondo ( [email protected] ) Close Corresponding author: Sizwe Zondo Competing interests: No competing interests were disclosed. Grant information: This study is supported by funding from the South African National Research Foundation, Thuthuka Grant (TTK200408511634), the Rhodes University Research Grant (PGSD05/2022) and funding from the University of the Witwatersrand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Zondo S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Zondo S, Cockcroft K, da Silva Ferreira Barreto C and Ferreira Correia A. Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.12688/f1000research.169799.1 ) First published: 29 Sep 2025, 14 :1000 ( https://doi.org/10.12688/f1000research.169799.1 ) Latest published: 24 Apr 2026, 14 :1000 ( https://doi.org/10.12688/f1000research.169799.2 )  There is a newer version of this article available. Suppress this message for one day. Introduction The human immunodeficiency virus (HIV) is a significant global pandemic, with approximately 39 million people living with the virus. South Africa has the highest burden of HIV, with approximately 14% of the population affected by the virus ( UNAIDS, 2019 ). Children and adolescents living with HIV are particularly vulnerable to neurocognitive deficits which result from neuroinvasion by the virus, together with the toxicity of combination antiretroviral therapies (cARTs) ( Yuan & Kaul, 2019 ). These neurocognitive deficits typically manifest as difficulties in higher order executive functions, such as sustained attention and working memory ( Milligan & Cockcroft, 2017 ). These findings have a neuroanatomical basis since HIV preferentially affects neuronal networks associated with the fronto-striatal cortex, a key node of the central executive network (CEN), implicated with attention and executive functions ( Yu et al., 2019 ). For example, Chang et al. (2001) investigated blood oxygen level dependency (BOLD) in HIV+ (n = 11; mean age = 41 years; SD = 4.8 years) and HIV unaffected controls (n = 11; mean age = 38 years; SD = 4.8 years) using functional magnetic resonance imaging (fMRI) during the execution of simple and complex attention tasks. In the simple attention reaction task, participants pressed a button in response to a number that appeared at random intervals on a screen, while the complex attention task required participants to respond only when the displayed number was twice as high as the preceding number. The complex attention task placed a greater cognitive load 1 on participants, tapping into inhibitory control and working memory. For the simple attention task, the HIV group showed significantly greater BOLD activation in the inferior lateral prefrontal cortex, and parietal lobes compared to controls (p < 0.05). The increased neural activation in both the frontal and parietal regions for the HIV+ group during a simple attention task is proposed to reflect the brain’s compensatory response to neuroHIV. 2 Increased BOLD activation within the prefrontal cortex is indicative of greater requirement for ‘top-down’ neuronal resources necessary to manipulate and maintain working memory during cognitively demanding tasks ( Chang et al., 2001 ). Building on their earlier findings, Chang et al. (2004) examined BOLD responses in the visual attention network among HIV+ (n = 18; mean age = 38.2 years; SD = 1.7 years) and HIV-unaffected participants (n = 18; M = 38 years; SD = 2.1 years). Consistent with Chang et al. (2001) , HIV+ individuals showed significantly greater activation in the right prefrontal and parietal cortices under increasing cognitive load. This heightened neural activation was interpreted as compensatory recruitment linked to neuronal inefficiency associated with neuroHIV. These converging findings, alongside the limited cognitive benefits of cART, underscore the importance of developing non-pharmaceutical interventions to address HIV-related cognitive impairment. Cognitive rehabilitation therapy (CRT), grounded in the principle of cortical neuroplasticity, holds potential to reverse cognitive decline in individuals with neuroHIV by promoting adaptive changes in the cerebral cortex ( Crosson et al., 2017 ). Evidence supports CRT’s effectiveness in improving attention, working memory, and executive function among adolescents living with HIV ( Ikekwere et al., 2021 ; Fraser & Cockcroft, 2020 ; Boivin et al., 2019 ). However, no studies to date have combined behavioural outcomes with objective neural measures, such as fNIRS, to assess CRT efficacy in this population. The sole study (at the time of writing) to investigate brain plasticity in neuroHIV by pairing behavioural outcomes with objective brain measures is that of Chang et al. (2017) . They paired working memory training (via CogMed) with fMRI in adult participants. At one-month follow-up, participants (HIV+: n = 34, mean age = 50.3 years; SD = 1.9. years; HIV-: n = 42, mean age = 52.6 years; SD = 1.7 years), who underwent 25 sessions of working memory training showed statistically significant decrease in BOLD activation when completing working memory tasks (i.e., the n-back task) compared to their performance prior to the training. The HIV group showed statistically significantly decreased BOLD activation in the right middle prefrontal gyrus when completing the 2-back working memory task, which also correlated with improved scores on untrained tasks, namely the Digit-Span Backward and the Spatial Span Forward, suggesting near transfer of skills to other measures of working memory. Six months later, both groups showed BOLD deactivation in the right medial prefrontal gyrus and primary motor area during the 1-back task. In addition, BOLD deactivation was correlated with significant improvement on the Digit-Span Forward working memory task, compared to pretest. The decreased BOLD-fMRI activation is proposed to indicate cortical reorganization associated with improved neural efficiency when completing working tasks of increased cognitive load ( Chang et al., 2017 ). Empirical research on the efficacy of CRT in HIV+ children and adolescents, particularly studies combining behavioural and brain-based measures, remains limited ( Benki-Nugent & Boivin, 2019 ). Such interventions could be especially valuable in low- and middle-income contexts such as South Africa, where they may help alleviate the HIV associated mental health burden. This study thus (1) examined the impact of sustained attention training on behavioural performance (via the Stroop Colour Word Test) and (2) cortical hemodynamic responses (via fNIRS) in HIV+ adolescents receiving attention brain training. While prior research suggests brain training may enhance cognitive efficiency and reduce neural activation in relevant regions, no directional hypotheses were proposed for the study, due to the limited existing evidence from a single study with adult participants. Research questions Compared to controls receiving no attention training, do HIV+ participants receiving sustained attention training show significantly improved scores on the SCWT? Do improvements on cognitive measures on the SCWT correlate with decreased hemodynamic responses in the prefrontal cortex, post training? Methods This project is part of a larger longitudinal pre-and-post-quasi experimental study to examine the effect of brain training within a cohort of children and adolescents living with HIV in South Africa ( Zondo, et al., 2024b ). Details of the experimental protocol can be found in ( Zondo, et al., 2024a ). The current investigation evaluated whether attention training is associated with improved neural efficiency and increased functional connectivity in the CEN, as measured by the SCWT and its correlation with hemodynamic responses in the prefrontal cortex as measured by fNIRS (via changes in oxygenated (HbO) and deoxygenated hemoglobin (Hb) concentration). A repeated measures design enabled us to collect behavioural and neuroimaging data pre- and post-training. Participants Purposive sampling was used to recruit 26 participants from three shelters caring for children living with HIV. All participants (age M = 17.28 years, SD = 1.94) were diagnosed with HIV 3 and were on a course of cART. Exclusion criteria included (a) traumatic brain injury (b) central nervous system-related ailments (e.g., cerebral palsy, meningitis), or (c) learning difficulties. Written informed consent was obtained from the Directors of the shelters and, where possible, from guardians of the children. Assent was obtained from all participants. Ethical approval for this study was granted by Ethics Committee of the University of the Witwatersrand, South Africa [M211073]. Participants were randomly assigned to either the experimental (n = 13) or control group (n = 13) using Research Randomizer Software ( Urbaniak & Plous, 2013 ). The control group followed a treatment-as-usual approach. One participant in the control group was excluded from the behavioural analysis because they did not respond to more than 38% of the trials and repeatedly pressed the same response key for both congruent and incongruent trials on the SCWT post-assessment. Table 1 summarises the sample characteristics. Chi-squared tests revealed no significant differences between the groups, by schooling (χ 2 = 0.195, p = 0.658), there were, however, differences by sex (χ 2 = 3.86, p = 0.05) and age (χ 2 = 3.94, p = 0.05). Although all participants were on cART, significant differences were noted in terms of additional medication between the groups (χ 2 = 6.01, p = 0.01) with three participants in the experimental group on a course of cART and psychotropic medication and one on ADHD medication. Table 1. Demographics characteristics of participants and their comparisons. Sample characteristics Treatment group Control group χ 2 p value n = 13 n = 13 Sex (F/M) a 5/8 9/4 3.86 0.05 Age Range b (0-13 years/14-18 years) 3/10 8/5 3.93 0.05 Medication (Mood c /ADHD) 2/1 0/0 6.19 0.01 School (Primary/Secondary) 3/10 4/9 0.195 0.658 a Female and Male categories for sex. b Age categories were based on WHO age range suggestions for children and adolescents. c Participants were receiving either Risperidol or Citalopram at low dosages. Measures Participants completed a battery of neurocognitive tests pre- and post-training as detailed in ( Zondo, et al., 2024a ). Assessments included a demographic questionnaire, the Developmental Neuropsychological Assessment Second Edition (NEPSY-II) and the Behaviour Rating Inventory for Executive Function (BRIEF). Functional Near-Infrared Spectrometry (fNIRS) data was acquired using the NIRxSport2 (NIRx, Medical Technologies), a portable continuous wave fNIRS device, which was administered while participants completed the SCWT (described in Zondo, et al., 2024a ). Specifically, the SWCT took the form of an fNIRS block design 4 adapted from Schroeter et al. (2002) . Before completing the computerised version of the SCWT, participants completed the pencil and paper version of the test and received feedback to improve test-wiseness. Lastly, this study followed recommendations for best practices in fNIRS research ( Yücel et al., 2021 ) and the protocol used for data acquisition and montage is described in ( Zondo, et al., 2024a ). Data analysis Behavioural performance Statistical analysis was performed using SPSS Statistics Version 27. First, the normality of the behavioural data was evaluated using the Shapiro-Wilk test. Then, the reaction time (in milliseconds) and accuracy (in total correct scores) data of the SCWT were analysed within groups and between groups (experimental vs control). Cohen’s d reported effects sizes. fNIRS Using guidelines for the analysis of repeated measures in fNIRS (NIRx Medical Technologies), standardized beta coefficients were first derived using Satori. For each channel, pre-processing filters were applied, followed by convolving each stimulus (congruent, incongruent) to a hemodynamic response model. General Linear Models were then applied with the measured fNIRS (oxyHb and Hb) signals as dependent variables, and the convolved functions as independent variables. The beta values of these models were used as estimates for hemodynamic responses for the brain regions of interest. The sign and magnitude of each beta coefficient provided an indicator of the direction (positive/negative) and intensity of concentration changes in HbO (i.e., cortical activity) for each condition. Once all beta values were estimated, we then pattened our analysis following Khoe et al. (2020) . As such, beta values representing HbO response activation were recorded at pre-training, and these served as a baseline for post-training hemodynamic response comparison. Primary outcomes for HbO activation were, therefore, changes in HbO, at post-training, minus those at pre-training (ΔHbO = (Post-intervention HbO) − (Pre-intervention HbO)). Concentration changes (ΔHbO) were calculated for congruent and incongruent trials for both groups. Figure 1 provides an example of an event marker to calculate ΔHbO at pre- and post-test within Satori fNIRS. Figure 1. Event marker evaluating changes in oxygenated hemoglobin (ΔHbO), at pre- and post-test. Note. Green bars under ‘parameter weights’ indicate congruent trials. Red bars indicate incongruent trials. Within the ‘Conditions’ panel, run1 indicates pretest HbO levels; run2 , indicates post intervention HbO levels. For the above example, the congruent stimuli time course is indicated in green within the ‘Intervals’ (seconds) panel. Changes in HbO (ΔHbO) within the experimental and control group were then represented by topographical maps of regions of the prefrontal cortex. Increase in brain hemodynamic response was represented in red. Increased oxygenated hemoglobin levels correlated with increased hemodynamic activation and cognitive effort. Light or dark blue represented hemodynamic deactivation and decreased brain activity. The Shapiro-Wilk Test evaluated normality of changes in oxygenated hemoglobin (ΔHbO), pre- and post-training. Differences in pre- and post-measures within each group were calculated using paired samples t-test. Between-group differences in ΔHbO were evaluated using an independent samples t-test. The Benjamini-Yekutieli method ( Benjamini & Yekutieli, 2001 ) adjusted for multiple comparisons. Results Behavioural data Within subjects group analyses The reaction time and accuracy scores of the SCWT at pre- and post-test, for the groups are presented in Table 2 . For the experimental group, within-group analyses indicated no significant differences in reaction times when correctly identifying congruent trials ( M = -0.01; SD = 0.43, t (170) = - 0.45, p = 0.469, d = 0.43). Notably, although not significant, this group’s accuracy rates improved from 52% at pre-test to 61% post-test (p > 0.05). At pre-test, this group accurately identified 54.9% of incongruent trials, with a minimal improvement of 57% at post-test (p > 0.05). Notably, although there were increases in accuracy rates (%) at post-test, reaction times were significantly slower at post-test ( M = 1.24), compared to pre-test ( M = 1.09; p = 0.001, d = 0.6). Table 2. Reaction time and accuracy % on the SCWT. Variable Experimental Control M SD M SD Reaction Time Sec (Congruent) Pre 1.09 0.3 0.97 0.02 Post 1.03 0.2 1.17 0.07 Reaction Time Sec (Incongruent) Pre 1.24 0.4 1.03 0.2 Post 1.27 0.5 1.15 0.03 Accuracy Rate % Accuracy Rate % Accuracy % (Congruent) Pre 52 47.8 Post 61.4 39.1 Accuracy % (Incongruent) Pre 54 45.1 Post 57 43.4 Within-groups analyses for the control group indicated an accuracy rate of 48% for congruent trials at pre-test and 39% at post-test. On average, participants indicated significantly slower reaction times (millisecond) at post-test ( M = 1.37; SD = 0.81) compared to pre-test ( M = 0.97) when correctly identifying congruent trials ( M = -0.33; SD = 0.91, t (108) = -3.85, p = 0.011, d = 0.91). At pre-test, participants accurately identified 45.1% of incongruent trials and 43.4% at post-test (p > 0.05). On average, participants’ reaction time was significantly slower at post-test ( M = 1.17; SD = 0.6) when identifying incongruent trials ( M = 0.11; SD = 0.47, t (134) = -2.85, p = 0.05, d = 0.47). Between subject group analyses Between group analyses indicated no significant differences between the group’s reaction times at pre- and post-test, when correctly identifying congruent trials ( U = 1175, p = 0.76). Similarly, no significant differences were found at pre- and post-test between the groups in terms of reaction times when accurately identifying incongruent trials ( U = 1200, p = 0.065). fNIRS Neuroimaging results PFC brain activation: Pre & Post intervention: Congruent trial Differences in brain activation are indicated by contrast t-statistics maps for HbO. We compared brain activation in the prefrontal cortex at pre- and post-test in relation to congruent and incongruent trials on the SCWT. Figure 2 indicates neuronal differences in ΔHbO between the groups during the congruent task. Although the control group indicated greater differences in HbO activation (ΔHbO), there were no significant differences (p > 0.05) between the groups on any of the optodes in the regions of interest. Figure 2. Changes in PFCA (ΔHbO) between the treatment and control groups on congruent trials. Note. A . The experimental group indicated lesser hemodynamic changes at pre- and post-test (ΔHbO). B . The control group shows greater hemodynamic changes on pre- and post-test congruent trials (ΔHbO), but they were not statistically significant ( p > 0.05). Concentration of colour blue denotes less HbO, and red, greater HbO. Prefrontal cortex activation: Pre- and Post-test: Incongruent trials Figure 3 shows differences in ΔHbO between the groups. Independent t-tests revealed that completing incongruent trials resulted in significantly lower hemodynamic responses in the left and right dorsolateral prefrontal cortex (DLPF) and left frontopolar Area 5 in the experimental group compared to the control group (p < 0.05; see Table 3 ). Figure 3. Changes in PFCA (ΔHbO) between the experimental and control groups on incongruent trials. Note. A . The experimental group indicated lesser hemodynamic changes at pre- and post-test (ΔHbO). B . The control group indicated greater hemodynamic changes in pre- and post-test incongruent trials (ΔHbO). Concentration of colour blue denotes less HbO, and red, greater HbO. Table 3. Areas of significantly lower activation in the HIV treatment group in relation to completing incongruent trials. Channel Optode name MNI position BA Anatomical region x y z CH 2 S1 - D3 46 38 24 45 Right pars triangularis Broca’s Area 46 Right dorsolateral prefrontal cortex CH 7 S3 - D5 -46 39 26 45 Left pars triangularis Broca’s Area 46 Left dorsolateral prefrontal cortex CH 14 S6 - D3 48 46 5 45 Right pars triangularis Broca’s Area 46 Right dorsolateral prefrontal cortex CH 18 S7 - D7 -12 67 0 10 Left frontopolar area 11 Left Orbitofrontal area CH 19 S8 - D5 -47 46 6 45 Left pars triangularis Broca’s area 46 Left dorsolateral prefrontal cortex CH 20 S8 - D7 -23 62 23 9 Left dorsolateral prefrontal cortex 46 Left dorsolateral prefrontal cortex 10 Left frontopolar Area Discussion Disturbance in neural cytoarchitecture following HIV-infection is associated with decreased cognitive function, particularly in attention and executive functions, such as working memory ( Hammond et al., 2019 ). Significantly, cART cannot reverse cognitive decline ( Gonzalez et al., 2020 ). Functional neuroimaging studies suggest individuals living with HIV typically show lower BOLD activation in the CEN on simple undemanding tasks, but greater BOLD activation as cognitive load increases, in both the CEN and compensatory brain regions (i.e., the parietal regions) ( Chang & Shukla, 2018 ). In individuals with neuroHIV, increased BOLD activation is typically a marker of neuronal inefficiency, as the cortex overcompensates and recruits associated neural networks in response to increasing cognitive demands ( Chang et al., 2004, 2013 ). With adults, there is evidence that working memory training may result in greater cognitive proficiency in related tasks and is associated with decreased BOLD activation, symbolizing neural efficiency and task proficiency ( Chang et al., 2017 ). No empirical studies exist investigating changes in BOLD or hemodynamic responses in children or adolescents living in Sub-Saharan Africa, which continues to bear the burden of neuroHIV. Given this dearth, our study investigated whether customized attention remediation improved performance on the SCWT (a measure of attention and inhibitory control) and also whether any such cognitive outcomes were related to decreased hemodynamic response activation within the prefrontal cortex. Potential brain plasticity was investigated in our participants using optical neuroimaging in the form of fNIRS. Although no significant behavioural differences were observed on the Stroop task, HIV+ participants who received sustained attention training showed modest improvements in congruent trial accuracy, while the control group’s performance declined. Incongruent trial accuracy remained largely unaffected by training. Notably, significant between-group differences emerged in hemodynamic responses during incongruent trials, suggesting neural effects of the intervention despite limited behavioural impact. With reference to neural effects, we investigated whether improvements on the SCWT correlated with decreased hemodynamic responses in the prefrontal cortex following the attention training. While the control group showed increased hemodynamic response activation on ΔHbO compared to the experimental group on congruent trials, these changes were statistically insignificant. Concerning incongruent trials, there were significant differences in ΔHbO between the groups, with the control group showing increased hemodynamic responses, and the experimental group indicating attenuation in hemodynamic responses, suggesting greater neural efficiency in the latter group in dedicated brain areas. Defined cortical regions of hemodynamic attenuation were localised to the frontopolar/anterior prefrontal area, dorsolateral PFC, the orbitofrontal region, and the pars triangularis Broca’s Area, when completing incongruent trials of the SCWT. The SCWT interference task typically places significant cognitive load on cortical processes, resulting in hyperactivation of cortical regions, including the dorsal, orbitofrontal, medial prefrontal and ventrolateral prefrontal cortex ( Banich, 2019 ). Our findings suggest that attention training decreases hemodynamic responses in the dorsolateral prefrontal cortex, a key network node with the CEN. Since the dorsolateral prefrontal network is connected to the orbitofrontal cortex through association fibres, the concomitant decrease in hemodynamic responses in these regions may suggest that cognitive training could strengthen participants’ ability to inhibit automatic responses and enable better monitoring and adjustment of their response strategies (which improved their accuracy on incongruent trials of the SCWT) ( Spielberg et al., 2015 ). The findings from our study corroborate those of Chang et al. (2017) , who observed decreased BOLD activation in the dorsal and lateral prefrontal cortices following working memory intervention. In their study, decreased BOLD activation was accompanied by improved performance on the 2-back working memory task. Where our findings differ from those by Chang et al. (2017) , is that we did not find concomitant increased scores on the SCWT at post-test. Notwithstanding the absence of significant cognitive test score improvements following the attention training, decreased cortical activation in the frontopolar area, as observed in the experimental group, is an interesting finding. This area is implicated in maintaining alertness and subsequent retrieval of stored information ( Hogeveen et al., 2022 ). Due to projections of the frontopolar region to the anterior cingulate cortex, the latter which is implicated in neuroHIV ( Israel et al., 2019 ; Toich et al., 2017 ), decreased hemodynamic activation in Area 10 may suggests improved neural efficiency and cortical proficiency. Moreover, attenuation in hemodynamic responses may indicate reduced involvement of the ‘top-down attention network’ (CEN) during demanding cognitive tasks such as the SCWT ( Banich, 2019 ). Importantly, we found decreased hemodynamic responses in the left pars triangularis (Broca’s Area) and the orbitofrontal area. Broca’s area is activated during the completion of the SCWT, especially in incongruent trials ( Wallentin et al., 2015 ). To this end, the incongruent trial of the SCWT places significant cognitive load on language processes that require identifying the ink colour of the stimulus, while inhibiting any conflict that arises with the actual word name (which is also a colour). In addition to correctly identifying incongruent stimuli, participants manipulated visual data (colour/word) and employed inhibitory control, in order not to associate a colour with a word (colour name), thus engaging the orbitofrontal cortex ( Rolls et al., 1996 ). Thus, a decrease in hemodynamic activation in this region suggests decreased requirement for ‘top-down’ attention processing, which was found following the training. Although the experimental group showed cortical-level changes in hemodynamic activity, these neural effects were not accompanied by significant improvements in SCWT accuracy or reaction times compared to controls. This dissociation between neural and behavioural outcomes is consistent with prior findings, such as those reported in a systematic review by Brooks et al. (2020) , which noted that neural adaptations—including changes in BOLD activation and functional connectivity—often precede observable cognitive gains. Such delays may be influenced by factors like training duration, neural plasticity, and intervention intensity. These findings suggest that early neural changes may reflect emerging plasticity, with behavioural improvements potentially requiring extended intervention periods to manifest. Several empirical studies support this view ( Powell & Redish, 2016 ; Tremblay et al., 1998 ). Conclusions This appears to be the first study investigating hemodynamic responses related to attention training in pediatric neuroHIV. Despite promising findings—namely, reduced prefrontal hemodynamic activation post-training and improved SCWT performance on incongruent trials—several limitations must be acknowledged. Due to the nature of the sample (vulnerable children living with HIV), the study experienced high attrition, which led to a reduced sample size, limiting statistical power, and pre-test group differences in age and sex may have influenced outcomes. Additionally, important moderators such as HIV genotype, age of cART initiation, and individual neurobiological variability were not assessed ( Brew & Garber, 2018 ). Moreover, we only investigated neural changes one month after the cognitive training and further post-test follow ups would have added valuable data about whether any effects were sustained over time. The fNIRS protocol was also limited in spatial coverage ( Extended Data - Supplementary File ) and lacked short-separation channels to control for physiological noise ( Pfeifer et al., 2018 ). Nonetheless, the observed neural attenuation suggests emerging neuroplasticity, supporting the potential of attention training—alongside cART—to enhance cognitive outcomes in children and adolescents affected by neuroHIV. Data availability Underlying data All data underlying the results are available as part of the article and no additional source data are required. Extended data can be found on the below DOI. Zenodo: HIV Cognitive Rehabilitation BRIEF and NEPSY Data. https://doi.org/10.5281/zenodo.16937317 This project contains the following extended data: - Dataset - Supplementary data Acknowledgment The authors would like to thank the Directors of the children’s shelters, the children, and their guardians for participating in the study. The authors would like to acknowledge Professor Rickson Mesquita for his assistance with fNIRS data analysis. Lastly, the corresponding, acknowledges the Centre for African Studies (CAS), at Harvard University, for hosting him during his Fellowship at the University. References Banich MT: The Stroop effect occurs at multiple points along a cascade of control: Evidence from cognitive neuroscience approaches. Front. Psychol. 2019; 10 : 2164. PubMed Abstract | Publisher Full Text | Free Full Text Benjamini Y, Yekutieli D: The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 2001; 29 : 1165–1188. 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J Sens. 2024b; 2024 : 1–14. Publisher Full Text Footnotes 1 Cognitive load refers to the total amount of mental effort being utilised to solve a mental task. 2 neuroHIV refers to the neuropathological and neurocognitive sequalae associated with HIV infection ( Nolan & Gaskill, 2019 ). 3 HIV status was attained from participant medical records, and confirmed by the attending nurse, or Director of the shelter. 4 We adopted a block design procedure as opposed to an event-related design. The former shows stronger statistical power and elucidates greater hemodynamic responses ( Scholkmann et al., 2014 ). 5 Studies include the medial prefrontal cortex (MPFC) as part of Broadman Area 10, with the terms frontopolar and anterior prefrontal cortex used simultaneously ( Passingham, 2021 ). Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 29 Sep 2025 ADD YOUR COMMENT Comment Author details Author details 1 Psychology, Rhodes University Psychology Clinic, Grahamstown, Eastern Cape, South Africa 2 Psychology, University of the Witwatersrand Johannesburg School of Human and Community Development, Johannesburg, Gauteng, South Africa 3 Neuroergonomics & Neuroimaging Lab, Drexel University School of Biomedical Engineering Science and Health Systems, Philadelphia, Pennsylvania, USA Sizwe Zondo Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Kate Cockcroft Roles: Supervision, Writing – Review & Editing Candida da Silva Ferreira Barreto Roles: Writing – Review & Editing Aline Ferreira Correia Roles: Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This study is supported by funding from the South African National Research Foundation, Thuthuka Grant (TTK200408511634), the Rhodes University Research Grant (PGSD05/2022) and funding from the University of the Witwatersrand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) version 2 Revised Published: 24 Apr 2026, 14:1000 https://doi.org/10.12688/f1000research.169799.2 version 1 Published: 29 Sep 2025, 14:1000 https://doi.org/10.12688/f1000research.169799.1 Copyright © 2025 Zondo S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. 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Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 29 Sep 2025 Views 0 Cite How to cite this report: Fitzpatrick-Schmidt T. Reviewer Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r441630 ) The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-441630 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Jan 2026 Taylor Fitzpatrick-Schmidt , Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187175.r441630 This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written ... Continue reading READ ALL This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Including p-values in Table 2 (even for non-significant results) would improve transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: HIV-associated neurocognitive disorders, HIV-associated neuropathy, alcohol use disorder I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Fitzpatrick-Schmidt T. Reviewer Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r441630 ) The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-441630 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 24 Apr 2026 Sizwe Zondo , Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa 24 Apr 2026 Author Response This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy ... Continue reading This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Response: Thank you for your comment. The abstract has since been revised to explicitly report the behavioural results. Additionally, a brief interpretive statement has been added to contextualize the observed changes in oxygenated haemoglobin levels. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Response: It is acknowledged that the focus on attention is not emphasized – to rectify this anomaly the manuscript has added a section on the construct of attention and linked this construct to prefrontal lobe anatomy and the regions of interest of the study. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Response: Thank you for this comment. Unfortunately, at the time of data collection, this critical medical data was not available to the researchers. The research was executed at data sites that care for children living with HVI and not at tertiary clinical sites where the data might be easily available. The sites were unfortunately unable to provide this key biomarker data, except for medication other relevant data. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Response: We thank the reviewer for this constructive suggestion. We agree that examining associations between behavioural performance and hemodynamic responses would further clarify the functional significance of the observed neuroimaging findings. While the current study was primarily designed to evaluate group-level differences, correlational analyses examining brain–behaviour relationships are currently underway as part of an ongoing extension of the study dataset. These analyses will form the basis of a subsequent manuscript submission focusing on neurocognitive–hemodynamic coupling. The article we are currently working will investigate associations, as well as (b) efficiency index analysis, and (c) implement moderation models to investigate cognition (all attention and NEPSY measures) by group and hemodynamic responses Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Response: Thank you very much for this suggestion. This implementation is being extended to form part of the above noted article (the power analysis is weak at this stage, due to a small sample size). Including p-values in Table 2 (even for non-significant results) would improve transparency. Response: We have since revised the Table 2 with the necessary statistics for replicability and transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Response: Thank you for the suggestion, we have since created a Limitations section to the manuscript and noted the above limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Response: We have incorporated this suggestion and the importance of translational research in the Discussion section. We thank the reviewer for all the above observations which we believe have strengthened the academic integrity of this work. This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Response: Thank you for your comment. The abstract has since been revised to explicitly report the behavioural results. Additionally, a brief interpretive statement has been added to contextualize the observed changes in oxygenated haemoglobin levels. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Response: It is acknowledged that the focus on attention is not emphasized – to rectify this anomaly the manuscript has added a section on the construct of attention and linked this construct to prefrontal lobe anatomy and the regions of interest of the study. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Response: Thank you for this comment. Unfortunately, at the time of data collection, this critical medical data was not available to the researchers. The research was executed at data sites that care for children living with HVI and not at tertiary clinical sites where the data might be easily available. The sites were unfortunately unable to provide this key biomarker data, except for medication other relevant data. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Response: We thank the reviewer for this constructive suggestion. We agree that examining associations between behavioural performance and hemodynamic responses would further clarify the functional significance of the observed neuroimaging findings. While the current study was primarily designed to evaluate group-level differences, correlational analyses examining brain–behaviour relationships are currently underway as part of an ongoing extension of the study dataset. These analyses will form the basis of a subsequent manuscript submission focusing on neurocognitive–hemodynamic coupling. The article we are currently working will investigate associations, as well as (b) efficiency index analysis, and (c) implement moderation models to investigate cognition (all attention and NEPSY measures) by group and hemodynamic responses Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Response: Thank you very much for this suggestion. This implementation is being extended to form part of the above noted article (the power analysis is weak at this stage, due to a small sample size). Including p-values in Table 2 (even for non-significant results) would improve transparency. Response: We have since revised the Table 2 with the necessary statistics for replicability and transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Response: Thank you for the suggestion, we have since created a Limitations section to the manuscript and noted the above limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Response: We have incorporated this suggestion and the importance of translational research in the Discussion section. We thank the reviewer for all the above observations which we believe have strengthened the academic integrity of this work. Competing Interests: no competing interests from authors. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 24 Apr 2026 Sizwe Zondo , Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa 24 Apr 2026 Author Response This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy ... Continue reading This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Response: Thank you for your comment. The abstract has since been revised to explicitly report the behavioural results. Additionally, a brief interpretive statement has been added to contextualize the observed changes in oxygenated haemoglobin levels. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Response: It is acknowledged that the focus on attention is not emphasized – to rectify this anomaly the manuscript has added a section on the construct of attention and linked this construct to prefrontal lobe anatomy and the regions of interest of the study. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Response: Thank you for this comment. Unfortunately, at the time of data collection, this critical medical data was not available to the researchers. The research was executed at data sites that care for children living with HVI and not at tertiary clinical sites where the data might be easily available. The sites were unfortunately unable to provide this key biomarker data, except for medication other relevant data. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Response: We thank the reviewer for this constructive suggestion. We agree that examining associations between behavioural performance and hemodynamic responses would further clarify the functional significance of the observed neuroimaging findings. While the current study was primarily designed to evaluate group-level differences, correlational analyses examining brain–behaviour relationships are currently underway as part of an ongoing extension of the study dataset. These analyses will form the basis of a subsequent manuscript submission focusing on neurocognitive–hemodynamic coupling. The article we are currently working will investigate associations, as well as (b) efficiency index analysis, and (c) implement moderation models to investigate cognition (all attention and NEPSY measures) by group and hemodynamic responses Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Response: Thank you very much for this suggestion. This implementation is being extended to form part of the above noted article (the power analysis is weak at this stage, due to a small sample size). Including p-values in Table 2 (even for non-significant results) would improve transparency. Response: We have since revised the Table 2 with the necessary statistics for replicability and transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Response: Thank you for the suggestion, we have since created a Limitations section to the manuscript and noted the above limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Response: We have incorporated this suggestion and the importance of translational research in the Discussion section. We thank the reviewer for all the above observations which we believe have strengthened the academic integrity of this work. This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Response: Thank you for your comment. The abstract has since been revised to explicitly report the behavioural results. Additionally, a brief interpretive statement has been added to contextualize the observed changes in oxygenated haemoglobin levels. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Response: It is acknowledged that the focus on attention is not emphasized – to rectify this anomaly the manuscript has added a section on the construct of attention and linked this construct to prefrontal lobe anatomy and the regions of interest of the study. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Response: Thank you for this comment. Unfortunately, at the time of data collection, this critical medical data was not available to the researchers. The research was executed at data sites that care for children living with HVI and not at tertiary clinical sites where the data might be easily available. The sites were unfortunately unable to provide this key biomarker data, except for medication other relevant data. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Response: We thank the reviewer for this constructive suggestion. We agree that examining associations between behavioural performance and hemodynamic responses would further clarify the functional significance of the observed neuroimaging findings. While the current study was primarily designed to evaluate group-level differences, correlational analyses examining brain–behaviour relationships are currently underway as part of an ongoing extension of the study dataset. These analyses will form the basis of a subsequent manuscript submission focusing on neurocognitive–hemodynamic coupling. The article we are currently working will investigate associations, as well as (b) efficiency index analysis, and (c) implement moderation models to investigate cognition (all attention and NEPSY measures) by group and hemodynamic responses Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Response: Thank you very much for this suggestion. This implementation is being extended to form part of the above noted article (the power analysis is weak at this stage, due to a small sample size). Including p-values in Table 2 (even for non-significant results) would improve transparency. Response: We have since revised the Table 2 with the necessary statistics for replicability and transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Response: Thank you for the suggestion, we have since created a Limitations section to the manuscript and noted the above limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Response: We have incorporated this suggestion and the importance of translational research in the Discussion section. We thank the reviewer for all the above observations which we believe have strengthened the academic integrity of this work. Competing Interests: no competing interests from authors. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Van Wyhe K. Reviewer Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r425390 ) The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-425390 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 05 Jan 2026 Kaylee Van Wyhe , Stellenbosch University, Stellenbosch, Western Cape, South Africa Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187175.r425390 This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on ... Continue reading READ ALL This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments 1. Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pediatric and adolescent HIV neuropsychology; developmental cognitive neuroscience; neuropsychological assessment and test adaptation in African populations; longitudinal neurodevelopmental research I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Van Wyhe K. Reviewer Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r425390 ) The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-425390 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 24 Apr 2026 Sizwe Zondo , Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa 24 Apr 2026 Author Response This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an ... Continue reading This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. Response: We thank the reviewer for this positive comment. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. Response: We have since updated the epidemiological data – and included the latest reference from WHO / UNAIDS (2024). 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. Response: Thank you for this important point, we have since rephrased the section and subsequently included a note detailing reduced neurotoxicity of current cART regimens. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. Response: In addition to the above key reference, we have updated the section by including a meta-analysis reference (2024) that indicates the persistence of cognitive deficits in this group. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. Response: Thank you for this observation – we have since included a section expanding on the above, by highlighting accuracy levels as noted by the authors. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Response: This observation is welcome and has been adopted into the manuscript when speaking in general terms pertaining to individuals living with HIV. However, the term ‘HIV+’ is retained for easier reporting and consistency within the manuscript, so as not to confuse ‘adults’ and ‘adolescents’ living with HIV. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. Response: We thank the reviewer for this important point. Data for the study was collected at children’s homes – with one nurse available at one of the homes. As noted in the discussion section, while all participants were receiving combination antiretroviral therapy, concomitant viral load measurement was not available on the children’s medical records and had to be directly sourced from the provincial hospital. The absence of viral load data is noted in the Limitations and Discussion section. We further agree that viral suppression status is clinically important, and an influential factor in neurocognitive functioning. This key data variable will be collected on the Phase 2 of our study. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. Response: This point is well taken, and a limitation of the study. The authors acknowledge that recategorization of the age variable, although expedient, would mean reanalysis of imaging data. We will however seek to take this consideration in future publications emerging from the current work. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. Response: This is a much-appreciated observation. From the data collected at the HIV shelters, we could not ascertain the mean years of schooling completed; this data was either not available, or not forthcoming, as its availability could indirectly affect donor funding for certain populations of children. Nonetheless, the authors acknowledge the implication of this oversight for developmental and socio-demographic interpretability. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Response: Thank you for this observation. The relevant information has been incorporated into the manuscript. As indicated on the manuscript revisions, no data was available pertaining to viral suppression (CD4+ count), for research participants. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. Response: We thank the reviewer for this suggestion. The Discussion section has been revised to include a brief comment on the feasibility and clinical implications of implementing attention training in real-world settings such as where the study was executed. Specifically, we comment on approximate sessions, their duration, and the use of pencil paper cognitive interventions for potential rehabilitation delivery by non-specialist facilitators. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Response: We thank the reviewer for this helpful comment. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Response: We thank the reviewer for all the above comments, and other observations to strengthen the academic integrity of this work. This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. Response: We thank the reviewer for this positive comment. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. Response: We have since updated the epidemiological data – and included the latest reference from WHO / UNAIDS (2024). 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. Response: Thank you for this important point, we have since rephrased the section and subsequently included a note detailing reduced neurotoxicity of current cART regimens. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. Response: In addition to the above key reference, we have updated the section by including a meta-analysis reference (2024) that indicates the persistence of cognitive deficits in this group. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. Response: Thank you for this observation – we have since included a section expanding on the above, by highlighting accuracy levels as noted by the authors. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Response: This observation is welcome and has been adopted into the manuscript when speaking in general terms pertaining to individuals living with HIV. However, the term ‘HIV+’ is retained for easier reporting and consistency within the manuscript, so as not to confuse ‘adults’ and ‘adolescents’ living with HIV. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. Response: We thank the reviewer for this important point. Data for the study was collected at children’s homes – with one nurse available at one of the homes. As noted in the discussion section, while all participants were receiving combination antiretroviral therapy, concomitant viral load measurement was not available on the children’s medical records and had to be directly sourced from the provincial hospital. The absence of viral load data is noted in the Limitations and Discussion section. We further agree that viral suppression status is clinically important, and an influential factor in neurocognitive functioning. This key data variable will be collected on the Phase 2 of our study. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. Response: This point is well taken, and a limitation of the study. The authors acknowledge that recategorization of the age variable, although expedient, would mean reanalysis of imaging data. We will however seek to take this consideration in future publications emerging from the current work. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. Response: This is a much-appreciated observation. From the data collected at the HIV shelters, we could not ascertain the mean years of schooling completed; this data was either not available, or not forthcoming, as its availability could indirectly affect donor funding for certain populations of children. Nonetheless, the authors acknowledge the implication of this oversight for developmental and socio-demographic interpretability. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Response: Thank you for this observation. The relevant information has been incorporated into the manuscript. As indicated on the manuscript revisions, no data was available pertaining to viral suppression (CD4+ count), for research participants. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. Response: We thank the reviewer for this suggestion. The Discussion section has been revised to include a brief comment on the feasibility and clinical implications of implementing attention training in real-world settings such as where the study was executed. Specifically, we comment on approximate sessions, their duration, and the use of pencil paper cognitive interventions for potential rehabilitation delivery by non-specialist facilitators. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Response: We thank the reviewer for this helpful comment. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Response: We thank the reviewer for all the above comments, and other observations to strengthen the academic integrity of this work. Competing Interests: no competing interests from the authors. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 24 Apr 2026 Sizwe Zondo , Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa 24 Apr 2026 Author Response This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an ... Continue reading This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. Response: We thank the reviewer for this positive comment. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. Response: We have since updated the epidemiological data – and included the latest reference from WHO / UNAIDS (2024). 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. Response: Thank you for this important point, we have since rephrased the section and subsequently included a note detailing reduced neurotoxicity of current cART regimens. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. Response: In addition to the above key reference, we have updated the section by including a meta-analysis reference (2024) that indicates the persistence of cognitive deficits in this group. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. Response: Thank you for this observation – we have since included a section expanding on the above, by highlighting accuracy levels as noted by the authors. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Response: This observation is welcome and has been adopted into the manuscript when speaking in general terms pertaining to individuals living with HIV. However, the term ‘HIV+’ is retained for easier reporting and consistency within the manuscript, so as not to confuse ‘adults’ and ‘adolescents’ living with HIV. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. Response: We thank the reviewer for this important point. Data for the study was collected at children’s homes – with one nurse available at one of the homes. As noted in the discussion section, while all participants were receiving combination antiretroviral therapy, concomitant viral load measurement was not available on the children’s medical records and had to be directly sourced from the provincial hospital. The absence of viral load data is noted in the Limitations and Discussion section. We further agree that viral suppression status is clinically important, and an influential factor in neurocognitive functioning. This key data variable will be collected on the Phase 2 of our study. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. Response: This point is well taken, and a limitation of the study. The authors acknowledge that recategorization of the age variable, although expedient, would mean reanalysis of imaging data. We will however seek to take this consideration in future publications emerging from the current work. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. Response: This is a much-appreciated observation. From the data collected at the HIV shelters, we could not ascertain the mean years of schooling completed; this data was either not available, or not forthcoming, as its availability could indirectly affect donor funding for certain populations of children. Nonetheless, the authors acknowledge the implication of this oversight for developmental and socio-demographic interpretability. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Response: Thank you for this observation. The relevant information has been incorporated into the manuscript. As indicated on the manuscript revisions, no data was available pertaining to viral suppression (CD4+ count), for research participants. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. Response: We thank the reviewer for this suggestion. The Discussion section has been revised to include a brief comment on the feasibility and clinical implications of implementing attention training in real-world settings such as where the study was executed. Specifically, we comment on approximate sessions, their duration, and the use of pencil paper cognitive interventions for potential rehabilitation delivery by non-specialist facilitators. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Response: We thank the reviewer for this helpful comment. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Response: We thank the reviewer for all the above comments, and other observations to strengthen the academic integrity of this work. This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. Response: We thank the reviewer for this positive comment. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. Response: We have since updated the epidemiological data – and included the latest reference from WHO / UNAIDS (2024). 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. Response: Thank you for this important point, we have since rephrased the section and subsequently included a note detailing reduced neurotoxicity of current cART regimens. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. Response: In addition to the above key reference, we have updated the section by including a meta-analysis reference (2024) that indicates the persistence of cognitive deficits in this group. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. Response: Thank you for this observation – we have since included a section expanding on the above, by highlighting accuracy levels as noted by the authors. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Response: This observation is welcome and has been adopted into the manuscript when speaking in general terms pertaining to individuals living with HIV. However, the term ‘HIV+’ is retained for easier reporting and consistency within the manuscript, so as not to confuse ‘adults’ and ‘adolescents’ living with HIV. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. Response: We thank the reviewer for this important point. Data for the study was collected at children’s homes – with one nurse available at one of the homes. As noted in the discussion section, while all participants were receiving combination antiretroviral therapy, concomitant viral load measurement was not available on the children’s medical records and had to be directly sourced from the provincial hospital. The absence of viral load data is noted in the Limitations and Discussion section. We further agree that viral suppression status is clinically important, and an influential factor in neurocognitive functioning. This key data variable will be collected on the Phase 2 of our study. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. Response: This point is well taken, and a limitation of the study. The authors acknowledge that recategorization of the age variable, although expedient, would mean reanalysis of imaging data. We will however seek to take this consideration in future publications emerging from the current work. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. Response: This is a much-appreciated observation. From the data collected at the HIV shelters, we could not ascertain the mean years of schooling completed; this data was either not available, or not forthcoming, as its availability could indirectly affect donor funding for certain populations of children. Nonetheless, the authors acknowledge the implication of this oversight for developmental and socio-demographic interpretability. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Response: Thank you for this observation. The relevant information has been incorporated into the manuscript. As indicated on the manuscript revisions, no data was available pertaining to viral suppression (CD4+ count), for research participants. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. Response: We thank the reviewer for this suggestion. The Discussion section has been revised to include a brief comment on the feasibility and clinical implications of implementing attention training in real-world settings such as where the study was executed. Specifically, we comment on approximate sessions, their duration, and the use of pencil paper cognitive interventions for potential rehabilitation delivery by non-specialist facilitators. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Response: We thank the reviewer for this helpful comment. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Response: We thank the reviewer for all the above comments, and other observations to strengthen the academic integrity of this work. Competing Interests: no competing interests from the authors. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Ramstrand N. Reviewer Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r425396 ) The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-425396 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 05 Nov 2025 Nerrolyn Ramstrand , Jönköping University, Jönköping, Sweden Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187175.r425396 Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in ... Continue reading READ ALL Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Were congruent and incongruent blocks randomized? How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: fNIRS, cognitive load, prosthetics and orthotics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Ramstrand N. Reviewer Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r425396 ) The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-425396 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 24 Apr 2026 Sizwe Zondo , Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa 24 Apr 2026 Author Response Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This ... Continue reading Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Response: We thank the reviewer for this positive point. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Response: We thank the reviewer for raising this important point. The primary inclusion criterion for the study was children and adolescents living with HIV. ADHD was not a target condition but was present as a comorbid diagnosis in one participant, reflecting clinical heterogeneity often observed in paediatric and adolescent HIV populations. While we acknowledge that ADHD and stimulant medication may influence prefrontal hemodynamic responses, only one participant in the sample had a reported ADHD diagnosis and was receiving pharmacological treatment. Given the small proportion of the sample represented by this case, it is unlikely that this individual meaningfully influenced the overall pattern of results. Nevertheless, we have clarified this in the Methods section and acknowledged the potential confounding influence in the Limitations section. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Response: The validity of the SCTW, NEPSY, and BRIEF for South African, and African adolescent populations has since been included in the Methods section. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Response: The information was reported in the cited publication but has since been included in the revised manuscript under the Methods section. Were congruent and incongruent blocks randomized? Response: Yes, there was randomization of blocks as per Schroeter et al., 2002. This information has been included in the revised manuscript. How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. Response: We thank the reviewer for this point. Briefly, task timestamps were generated within PsychoPy and transmitted in real time to the Aurora Acquisition Software (NIRx) via Lab Streaming Layer (LSL). Specifically, digital event markers corresponding to the onset of each congruent and incongruent block were relayed to LSL stream at block initiation. These markers were embedded as time-locked trigger channels within the fNIRS recording. Markers were time-locked with each 10-second task block accompanied by an intervening 15-second rest period, allowing for block-averaging analysis in Satori fNIRS. We have clarified this procedure in the Methods section to improve transparency regarding the block-averaging process. As noted in the initial publication, our SCWT was adapted from Schroeter et al., 2002. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Response: The signal preprocessing steps are detailed in our previous Methods publication (Zondo et al. 2024). Due to journal space limitations, we could not expand on all signal pre-processing steps, and how we handled missing data for the current submission. We have however, revised the Methods section and included reference to the fNIRS pre-processing steps, and handling missing data. With reference to reporting, we collected both oxygenated (HbO) and deoxygenated haemoglobin (HbR) signals but chose to focus on HbO for methodological and interpretative reasons. HbO has been shown to demonstrate a higher signal-to-noise ratio and greater sensitivity to task-evoked cortical activation in block-design paradigms, particularly in paediatric and adolescent samples. Similarly, we patterned our study on Khoe et al. 2020, who reported and analyzed HbO signal for easy replicability. Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Response: Thank you. The montage consisted of 8 sources and 7 detectors arranged over the prefrontal cortex, (as detailed in Table 1 of the referenced protocol (Zondo et al.2024). No parietal regions were covered. Optode coverage extended across dorsolateral prefrontal, frontopolar, orbitofrontal, and adjacent premotor regions. Regions of interest (ROIs) were anatomically grouped into three predefined clusters: dorsolateral prefrontal cortex (DLPFC), frontopolar cortex (FPC), and orbitofrontal cortex (OFC), based on MNI coordinates and fOLD specificity mapping. All 22 channels were initially included in the analysis; however, channels were excluded if they failed scalp coupling index thresholds or signal quality criteria during preprocessing (using Satori). Data blocks were segmented using time-locked event markers and averaged per condition (congruent, incongruent) across each 10-second task block. Mean HbO amplitude within each block window was computed and aggregated at the ROI level (individual and group) for analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Response : We have since revised the table to include significance, test statistic, and effect sizes. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further tools inbuilt on Satori fNIRS. We do recognize this limitation, we are however confident, as determined by the fOLD data, (specificity indices) that optode placements were accurately confirmed. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further inbuilt tools on Satori fNIRS. The configuration cap used in the study was further confirmed by NIRX technology for specificity. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Response: Thank you for the comment. As detailed in our MethodsX paper, the study was affected by bad channels, and poor scalp index coupling, primarily due to the population under study (skin pigmentation). We have however added this information to the methods section. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Response: We thank the reviewer for this comment. Within the Discussion section, we have sought to highlight the emergence of neural efficiency, concomitant with brain plasticity. Due to the small sample size, the clinical implications (at this stage), of significant hemodynamic differences on incongruent trials, is largely discussed in the context of emergent brain plasticity and neural efficiency. Our group is currently collecting Phase 2 data, to investigate the implications of the above findings at a clinical scale. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Response: We have since revised the manuscript and created a section detailing ‘Limitations’. Resulting from this revision, the ‘conclusion’, section is succinct, incorporating further suggestions from the other reviewers. Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Response: We thank the reviewer for this positive point. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Response: We thank the reviewer for raising this important point. The primary inclusion criterion for the study was children and adolescents living with HIV. ADHD was not a target condition but was present as a comorbid diagnosis in one participant, reflecting clinical heterogeneity often observed in paediatric and adolescent HIV populations. While we acknowledge that ADHD and stimulant medication may influence prefrontal hemodynamic responses, only one participant in the sample had a reported ADHD diagnosis and was receiving pharmacological treatment. Given the small proportion of the sample represented by this case, it is unlikely that this individual meaningfully influenced the overall pattern of results. Nevertheless, we have clarified this in the Methods section and acknowledged the potential confounding influence in the Limitations section. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Response: The validity of the SCTW, NEPSY, and BRIEF for South African, and African adolescent populations has since been included in the Methods section. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Response: The information was reported in the cited publication but has since been included in the revised manuscript under the Methods section. Were congruent and incongruent blocks randomized? Response: Yes, there was randomization of blocks as per Schroeter et al., 2002. This information has been included in the revised manuscript. How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. Response: We thank the reviewer for this point. Briefly, task timestamps were generated within PsychoPy and transmitted in real time to the Aurora Acquisition Software (NIRx) via Lab Streaming Layer (LSL). Specifically, digital event markers corresponding to the onset of each congruent and incongruent block were relayed to LSL stream at block initiation. These markers were embedded as time-locked trigger channels within the fNIRS recording. Markers were time-locked with each 10-second task block accompanied by an intervening 15-second rest period, allowing for block-averaging analysis in Satori fNIRS. We have clarified this procedure in the Methods section to improve transparency regarding the block-averaging process. As noted in the initial publication, our SCWT was adapted from Schroeter et al., 2002. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Response: The signal preprocessing steps are detailed in our previous Methods publication (Zondo et al. 2024). Due to journal space limitations, we could not expand on all signal pre-processing steps, and how we handled missing data for the current submission. We have however, revised the Methods section and included reference to the fNIRS pre-processing steps, and handling missing data. With reference to reporting, we collected both oxygenated (HbO) and deoxygenated haemoglobin (HbR) signals but chose to focus on HbO for methodological and interpretative reasons. HbO has been shown to demonstrate a higher signal-to-noise ratio and greater sensitivity to task-evoked cortical activation in block-design paradigms, particularly in paediatric and adolescent samples. Similarly, we patterned our study on Khoe et al. 2020, who reported and analyzed HbO signal for easy replicability. Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Response: Thank you. The montage consisted of 8 sources and 7 detectors arranged over the prefrontal cortex, (as detailed in Table 1 of the referenced protocol (Zondo et al.2024). No parietal regions were covered. Optode coverage extended across dorsolateral prefrontal, frontopolar, orbitofrontal, and adjacent premotor regions. Regions of interest (ROIs) were anatomically grouped into three predefined clusters: dorsolateral prefrontal cortex (DLPFC), frontopolar cortex (FPC), and orbitofrontal cortex (OFC), based on MNI coordinates and fOLD specificity mapping. All 22 channels were initially included in the analysis; however, channels were excluded if they failed scalp coupling index thresholds or signal quality criteria during preprocessing (using Satori). Data blocks were segmented using time-locked event markers and averaged per condition (congruent, incongruent) across each 10-second task block. Mean HbO amplitude within each block window was computed and aggregated at the ROI level (individual and group) for analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Response : We have since revised the table to include significance, test statistic, and effect sizes. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further tools inbuilt on Satori fNIRS. We do recognize this limitation, we are however confident, as determined by the fOLD data, (specificity indices) that optode placements were accurately confirmed. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further inbuilt tools on Satori fNIRS. The configuration cap used in the study was further confirmed by NIRX technology for specificity. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Response: Thank you for the comment. As detailed in our MethodsX paper, the study was affected by bad channels, and poor scalp index coupling, primarily due to the population under study (skin pigmentation). We have however added this information to the methods section. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Response: We thank the reviewer for this comment. Within the Discussion section, we have sought to highlight the emergence of neural efficiency, concomitant with brain plasticity. Due to the small sample size, the clinical implications (at this stage), of significant hemodynamic differences on incongruent trials, is largely discussed in the context of emergent brain plasticity and neural efficiency. Our group is currently collecting Phase 2 data, to investigate the implications of the above findings at a clinical scale. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Response: We have since revised the manuscript and created a section detailing ‘Limitations’. Resulting from this revision, the ‘conclusion’, section is succinct, incorporating further suggestions from the other reviewers. Competing Interests: no competing interests from the authors. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 24 Apr 2026 Sizwe Zondo , Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa 24 Apr 2026 Author Response Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This ... Continue reading Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Response: We thank the reviewer for this positive point. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Response: We thank the reviewer for raising this important point. The primary inclusion criterion for the study was children and adolescents living with HIV. ADHD was not a target condition but was present as a comorbid diagnosis in one participant, reflecting clinical heterogeneity often observed in paediatric and adolescent HIV populations. While we acknowledge that ADHD and stimulant medication may influence prefrontal hemodynamic responses, only one participant in the sample had a reported ADHD diagnosis and was receiving pharmacological treatment. Given the small proportion of the sample represented by this case, it is unlikely that this individual meaningfully influenced the overall pattern of results. Nevertheless, we have clarified this in the Methods section and acknowledged the potential confounding influence in the Limitations section. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Response: The validity of the SCTW, NEPSY, and BRIEF for South African, and African adolescent populations has since been included in the Methods section. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Response: The information was reported in the cited publication but has since been included in the revised manuscript under the Methods section. Were congruent and incongruent blocks randomized? Response: Yes, there was randomization of blocks as per Schroeter et al., 2002. This information has been included in the revised manuscript. How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. Response: We thank the reviewer for this point. Briefly, task timestamps were generated within PsychoPy and transmitted in real time to the Aurora Acquisition Software (NIRx) via Lab Streaming Layer (LSL). Specifically, digital event markers corresponding to the onset of each congruent and incongruent block were relayed to LSL stream at block initiation. These markers were embedded as time-locked trigger channels within the fNIRS recording. Markers were time-locked with each 10-second task block accompanied by an intervening 15-second rest period, allowing for block-averaging analysis in Satori fNIRS. We have clarified this procedure in the Methods section to improve transparency regarding the block-averaging process. As noted in the initial publication, our SCWT was adapted from Schroeter et al., 2002. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Response: The signal preprocessing steps are detailed in our previous Methods publication (Zondo et al. 2024). Due to journal space limitations, we could not expand on all signal pre-processing steps, and how we handled missing data for the current submission. We have however, revised the Methods section and included reference to the fNIRS pre-processing steps, and handling missing data. With reference to reporting, we collected both oxygenated (HbO) and deoxygenated haemoglobin (HbR) signals but chose to focus on HbO for methodological and interpretative reasons. HbO has been shown to demonstrate a higher signal-to-noise ratio and greater sensitivity to task-evoked cortical activation in block-design paradigms, particularly in paediatric and adolescent samples. Similarly, we patterned our study on Khoe et al. 2020, who reported and analyzed HbO signal for easy replicability. Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Response: Thank you. The montage consisted of 8 sources and 7 detectors arranged over the prefrontal cortex, (as detailed in Table 1 of the referenced protocol (Zondo et al.2024). No parietal regions were covered. Optode coverage extended across dorsolateral prefrontal, frontopolar, orbitofrontal, and adjacent premotor regions. Regions of interest (ROIs) were anatomically grouped into three predefined clusters: dorsolateral prefrontal cortex (DLPFC), frontopolar cortex (FPC), and orbitofrontal cortex (OFC), based on MNI coordinates and fOLD specificity mapping. All 22 channels were initially included in the analysis; however, channels were excluded if they failed scalp coupling index thresholds or signal quality criteria during preprocessing (using Satori). Data blocks were segmented using time-locked event markers and averaged per condition (congruent, incongruent) across each 10-second task block. Mean HbO amplitude within each block window was computed and aggregated at the ROI level (individual and group) for analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Response : We have since revised the table to include significance, test statistic, and effect sizes. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further tools inbuilt on Satori fNIRS. We do recognize this limitation, we are however confident, as determined by the fOLD data, (specificity indices) that optode placements were accurately confirmed. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further inbuilt tools on Satori fNIRS. The configuration cap used in the study was further confirmed by NIRX technology for specificity. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Response: Thank you for the comment. As detailed in our MethodsX paper, the study was affected by bad channels, and poor scalp index coupling, primarily due to the population under study (skin pigmentation). We have however added this information to the methods section. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Response: We thank the reviewer for this comment. Within the Discussion section, we have sought to highlight the emergence of neural efficiency, concomitant with brain plasticity. Due to the small sample size, the clinical implications (at this stage), of significant hemodynamic differences on incongruent trials, is largely discussed in the context of emergent brain plasticity and neural efficiency. Our group is currently collecting Phase 2 data, to investigate the implications of the above findings at a clinical scale. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Response: We have since revised the manuscript and created a section detailing ‘Limitations’. Resulting from this revision, the ‘conclusion’, section is succinct, incorporating further suggestions from the other reviewers. Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Response: We thank the reviewer for this positive point. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Response: We thank the reviewer for raising this important point. The primary inclusion criterion for the study was children and adolescents living with HIV. ADHD was not a target condition but was present as a comorbid diagnosis in one participant, reflecting clinical heterogeneity often observed in paediatric and adolescent HIV populations. While we acknowledge that ADHD and stimulant medication may influence prefrontal hemodynamic responses, only one participant in the sample had a reported ADHD diagnosis and was receiving pharmacological treatment. Given the small proportion of the sample represented by this case, it is unlikely that this individual meaningfully influenced the overall pattern of results. Nevertheless, we have clarified this in the Methods section and acknowledged the potential confounding influence in the Limitations section. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Response: The validity of the SCTW, NEPSY, and BRIEF for South African, and African adolescent populations has since been included in the Methods section. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Response: The information was reported in the cited publication but has since been included in the revised manuscript under the Methods section. Were congruent and incongruent blocks randomized? Response: Yes, there was randomization of blocks as per Schroeter et al., 2002. This information has been included in the revised manuscript. How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. Response: We thank the reviewer for this point. Briefly, task timestamps were generated within PsychoPy and transmitted in real time to the Aurora Acquisition Software (NIRx) via Lab Streaming Layer (LSL). Specifically, digital event markers corresponding to the onset of each congruent and incongruent block were relayed to LSL stream at block initiation. These markers were embedded as time-locked trigger channels within the fNIRS recording. Markers were time-locked with each 10-second task block accompanied by an intervening 15-second rest period, allowing for block-averaging analysis in Satori fNIRS. We have clarified this procedure in the Methods section to improve transparency regarding the block-averaging process. As noted in the initial publication, our SCWT was adapted from Schroeter et al., 2002. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Response: The signal preprocessing steps are detailed in our previous Methods publication (Zondo et al. 2024). Due to journal space limitations, we could not expand on all signal pre-processing steps, and how we handled missing data for the current submission. We have however, revised the Methods section and included reference to the fNIRS pre-processing steps, and handling missing data. With reference to reporting, we collected both oxygenated (HbO) and deoxygenated haemoglobin (HbR) signals but chose to focus on HbO for methodological and interpretative reasons. HbO has been shown to demonstrate a higher signal-to-noise ratio and greater sensitivity to task-evoked cortical activation in block-design paradigms, particularly in paediatric and adolescent samples. Similarly, we patterned our study on Khoe et al. 2020, who reported and analyzed HbO signal for easy replicability. Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Response: Thank you. The montage consisted of 8 sources and 7 detectors arranged over the prefrontal cortex, (as detailed in Table 1 of the referenced protocol (Zondo et al.2024). No parietal regions were covered. Optode coverage extended across dorsolateral prefrontal, frontopolar, orbitofrontal, and adjacent premotor regions. Regions of interest (ROIs) were anatomically grouped into three predefined clusters: dorsolateral prefrontal cortex (DLPFC), frontopolar cortex (FPC), and orbitofrontal cortex (OFC), based on MNI coordinates and fOLD specificity mapping. All 22 channels were initially included in the analysis; however, channels were excluded if they failed scalp coupling index thresholds or signal quality criteria during preprocessing (using Satori). Data blocks were segmented using time-locked event markers and averaged per condition (congruent, incongruent) across each 10-second task block. Mean HbO amplitude within each block window was computed and aggregated at the ROI level (individual and group) for analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Response : We have since revised the table to include significance, test statistic, and effect sizes. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further tools inbuilt on Satori fNIRS. We do recognize this limitation, we are however confident, as determined by the fOLD data, (specificity indices) that optode placements were accurately confirmed. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further inbuilt tools on Satori fNIRS. The configuration cap used in the study was further confirmed by NIRX technology for specificity. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Response: Thank you for the comment. As detailed in our MethodsX paper, the study was affected by bad channels, and poor scalp index coupling, primarily due to the population under study (skin pigmentation). We have however added this information to the methods section. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Response: We thank the reviewer for this comment. Within the Discussion section, we have sought to highlight the emergence of neural efficiency, concomitant with brain plasticity. Due to the small sample size, the clinical implications (at this stage), of significant hemodynamic differences on incongruent trials, is largely discussed in the context of emergent brain plasticity and neural efficiency. Our group is currently collecting Phase 2 data, to investigate the implications of the above findings at a clinical scale. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Response: We have since revised the manuscript and created a section detailing ‘Limitations’. Resulting from this revision, the ‘conclusion’, section is succinct, incorporating further suggestions from the other reviewers. Competing Interests: no competing interests from the authors. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 29 Sep 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 24 Apr 26 read Version 1 29 Sep 25 read read read Nerrolyn Ramstrand , Jönköping University, Jönköping, Sweden Kaylee Van Wyhe , Stellenbosch University, Stellenbosch, South Africa Taylor Fitzpatrick-Schmidt , Louisiana State University Health Sciences Center, New Orleans, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Ramstrand N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 May 2026 | for Version 2 Nerrolyn Ramstrand , Jönköping University, Jönköping, Sweden 0 Views copyright © 2026 Ramstrand N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Many thanks to the authors for addressing my initial comments in relation to this manuscript. I have no additional comments to make and wish the author team all the best. Competing Interests No competing interests were disclosed. Reviewer Expertise fNIRS, cognitive load, prosthetics and orthotics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Ramstrand N. Peer Review Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.197457.r478731) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1000/v2#referee-response-478731 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Fitzpatrick-Schmidt T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Jan 2026 | for Version 1 Taylor Fitzpatrick-Schmidt , Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA 0 Views copyright © 2026 Fitzpatrick-Schmidt T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Including p-values in Table 2 (even for non-significant results) would improve transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise HIV-associated neurocognitive disorders, HIV-associated neuropathy, alcohol use disorder I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 24 Apr 2026 Sizwe Zondo, Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article. Abstract Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. Response: Thank you for your comment. The abstract has since been revised to explicitly report the behavioural results. Additionally, a brief interpretive statement has been added to contextualize the observed changes in oxygenated haemoglobin levels. Introduction The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. Response: It is acknowledged that the focus on attention is not emphasized – to rectify this anomaly the manuscript has added a section on the construct of attention and linked this construct to prefrontal lobe anatomy and the regions of interest of the study. Methods and Results The Methods and Results sections are generally well-organized. The following points may further strengthen these sections: If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. Response: Thank you for this comment. Unfortunately, at the time of data collection, this critical medical data was not available to the researchers. The research was executed at data sites that care for children living with HVI and not at tertiary clinical sites where the data might be easily available. The sites were unfortunately unable to provide this key biomarker data, except for medication other relevant data. Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results. Response: We thank the reviewer for this constructive suggestion. We agree that examining associations between behavioural performance and hemodynamic responses would further clarify the functional significance of the observed neuroimaging findings. While the current study was primarily designed to evaluate group-level differences, correlational analyses examining brain–behaviour relationships are currently underway as part of an ongoing extension of the study dataset. These analyses will form the basis of a subsequent manuscript submission focusing on neurocognitive–hemodynamic coupling. The article we are currently working will investigate associations, as well as (b) efficiency index analysis, and (c) implement moderation models to investigate cognition (all attention and NEPSY measures) by group and hemodynamic responses Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits. Response: Thank you very much for this suggestion. This implementation is being extended to form part of the above noted article (the power analysis is weak at this stage, due to a small sample size). Including p-values in Table 2 (even for non-significant results) would improve transparency. Response: We have since revised the Table 2 with the necessary statistics for replicability and transparency. Discussion Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider: Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation. Response: Thank you for the suggestion, we have since created a Limitations section to the manuscript and noted the above limitation. Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section. Response: We have incorporated this suggestion and the importance of translational research in the Discussion section. We thank the reviewer for all the above observations which we believe have strengthened the academic integrity of this work. View more View less Competing Interests no competing interests from authors. reply Respond Report a concern Fitzpatrick-Schmidt T. Peer Review Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r441630) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-441630 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Van Wyhe K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 05 Jan 2026 | for Version 1 Kaylee Van Wyhe , Stellenbosch University, Stellenbosch, Western Cape, South Africa 0 Views copyright © 2026 Van Wyhe K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments 1. Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Pediatric and adolescent HIV neuropsychology; developmental cognitive neuroscience; neuropsychological assessment and test adaptation in African populations; longitudinal neurodevelopmental research I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 24 Apr 2026 Sizwe Zondo, Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour–Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency. Major Comments Title and overall framing The title is engaging, well constructed, and suitably reflects the study’s scope. I note that its clarity and precision support the paper’s impact and readability. Response: We thank the reviewer for this positive comment. 2. Appropriateness of fNIRS The authors’ decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale. Introduction 3. Update epidemiological statistics The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. Response: We have since updated the epidemiological data – and included the latest reference from WHO / UNAIDS (2024). 4. ART toxicity statement needs clarification The introduction states that combination ART is “toxic,” referencing Yuan & Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. Response: Thank you for this important point, we have since rephrased the section and subsequently included a note detailing reduced neurotoxicity of current cART regimens. 5. Outdated literature on cognitive deficits The paper relies on Milligan & Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. Response: In addition to the above key reference, we have updated the section by including a meta-analysis reference (2024) that indicates the persistence of cognitive deficits in this group. 6. Missing behavioural interpretation from Chang et al. (2001) The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. Response: Thank you for this observation – we have since included a section expanding on the above, by highlighting accuracy levels as noted by the authors. 7. Language and terminology regarding HIV The manuscript frequently uses “HIV+.” It is recommended to adopt people-first, non-stigmatizing terminology, such as “adolescents living with HIV (ALWH).” Applying consistent, person-first language will align the manuscript with current global guidelines. Response: This observation is welcome and has been adopted into the manuscript when speaking in general terms pertaining to individuals living with HIV. However, the term ‘HIV+’ is retained for easier reporting and consistency within the manuscript, so as not to confuse ‘adults’ and ‘adolescents’ living with HIV. Methods 8. Participant viral suppression status The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. Response: We thank the reviewer for this important point. Data for the study was collected at children’s homes – with one nurse available at one of the homes. As noted in the discussion section, while all participants were receiving combination antiretroviral therapy, concomitant viral load measurement was not available on the children’s medical records and had to be directly sourced from the provincial hospital. The absence of viral load data is noted in the Limitations and Discussion section. We further agree that viral suppression status is clinically important, and an influential factor in neurocognitive functioning. This key data variable will be collected on the Phase 2 of our study. 9. Age categorisation using WHO groupings Participants are divided into 0–13 and 14–18 age groups using WHO categories. While I understand the rationale, this results in a wide “0–13” group containing 11 participants across a period of rapid neurodevelopment (childhood → early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. Response: This point is well taken, and a limitation of the study. The authors acknowledge that recategorization of the age variable, although expedient, would mean reanalysis of imaging data. We will however seek to take this consideration in future publications emerging from the current work. 10. Education levels Rather than reporting “primary vs secondary schooling,” providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. Response: This is a much-appreciated observation. From the data collected at the HIV shelters, we could not ascertain the mean years of schooling completed; this data was either not available, or not forthcoming, as its availability could indirectly affect donor funding for certain populations of children. Nonetheless, the authors acknowledge the implication of this oversight for developmental and socio-demographic interpretability. 11. Outlier participant One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report: the participant’s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. Response: Thank you for this observation. The relevant information has been incorporated into the manuscript. As indicated on the manuscript revisions, no data was available pertaining to viral suppression (CD4+ count), for research participants. Discussion and Conclusion 12. Real-world implications and applicability The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example: approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists Even a brief, context-aware comment would enhance translational value. Response: We thank the reviewer for this suggestion. The Discussion section has been revised to include a brief comment on the feasibility and clinical implications of implementing attention training in real-world settings such as where the study was executed. Specifically, we comment on approximate sessions, their duration, and the use of pencil paper cognitive interventions for potential rehabilitation delivery by non-specialist facilitators. 13. Excellent summary of limitations The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. Response: We thank the reviewer for this helpful comment. Concluding Remarks This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript’s impact. I am supportive of publication following these revisions. Response: We thank the reviewer for all the above comments, and other observations to strengthen the academic integrity of this work. View more View less Competing Interests no competing interests from the authors. reply Respond Report a concern Van Wyhe K. Peer Review Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r425390) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-425390 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Ramstrand N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 05 Nov 2025 | for Version 1 Nerrolyn Ramstrand , Jönköping University, Jönköping, Sweden 0 Views copyright © 2025 Ramstrand N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Were congruent and incongruent blocks randomized? How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise fNIRS, cognitive load, prosthetics and orthotics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 24 Apr 2026 Sizwe Zondo, Psychology, Rhodes University Psychology Clinic, Grahamstown, South Africa Thank you for the opportunity to review this before-and-after study investigating the effects of an attention training intervention on Stroop Colour Word Test (SCWT) performance and cognitive load (fNIRS). This research addresses a highly relevant and timely topic, particularly in paediatric populations living with HIV, who are at increased risk for neurocognitive deficits. The manuscript is well written, and the study design is appropriate for the stated aims. To support replication and enhance transparency, I recommend clarifying several issues in the methods section. My comments on these and other elements of the manuscript are outlined below. Introduction The introduction provides a clear and compelling overview of the challenges faced by children and adolescents living with HIV, particularly regarding neurocognitive functioning. The authors are to be commended for effectively motivating the need for rehabilitation interventions targeting cognitive decline in this vulnerable population. Response: We thank the reviewer for this positive point. Methods While the methods section is generally well structured, additional detail and clarification would strengthen the manuscript: Participant Inclusion Criteria - The inclusion of a participant with ADHD warrants further justification. One child was reportedly on ADHD medication, which may influence neural activity. Prior research has shown that children with ADHD exhibit distinct patterns of brain activation compared to neurotypical peers (e.g., Cui et al., 2024), and that pharmacological treatment can increase HbO concentrations in the prefrontal cortex (e.g., Poliakova et al., 2023). The potential confounding effects of this should be addressed. Response: We thank the reviewer for raising this important point. The primary inclusion criterion for the study was children and adolescents living with HIV. ADHD was not a target condition but was present as a comorbid diagnosis in one participant, reflecting clinical heterogeneity often observed in paediatric and adolescent HIV populations. While we acknowledge that ADHD and stimulant medication may influence prefrontal hemodynamic responses, only one participant in the sample had a reported ADHD diagnosis and was receiving pharmacological treatment. Given the small proportion of the sample represented by this case, it is unlikely that this individual meaningfully influenced the overall pattern of results. Nevertheless, we have clarified this in the Methods section and acknowledged the potential confounding influence in the Limitations section. Measurement Instruments - Although the measures are outlined in the published study protocol, readers would benefit from additional detail in the manuscript itself. Specifically: Please include information on the reliability and validity of the instruments used. Response: The validity of the SCTW, NEPSY, and BRIEF for South African, and African adolescent populations has since been included in the Methods section. Clarify the administration of the SCWT. According to the protocol, 10 blocks of 10 seconds were completed—this should be explicitly stated. Response: The information was reported in the cited publication but has since been included in the revised manuscript under the Methods section. Were congruent and incongruent blocks randomized? Response: Yes, there was randomization of blocks as per Schroeter et al., 2002. This information has been included in the revised manuscript. How were timestamps used to mark the start and end of each block? This is critical for understanding the block averaging process in the fNIRS analysis. Response: We thank the reviewer for this point. Briefly, task timestamps were generated within PsychoPy and transmitted in real time to the Aurora Acquisition Software (NIRx) via Lab Streaming Layer (LSL). Specifically, digital event markers corresponding to the onset of each congruent and incongruent block were relayed to LSL stream at block initiation. These markers were embedded as time-locked trigger channels within the fNIRS recording. Markers were time-locked with each 10-second task block accompanied by an intervening 15-second rest period, allowing for block-averaging analysis in Satori fNIRS. We have clarified this procedure in the Methods section to improve transparency regarding the block-averaging process. As noted in the initial publication, our SCWT was adapted from Schroeter et al., 2002. fNIRS Data Processing and reporting - The methods mention that deoxygenated hemoglobin (HbR) was captured, yet only oxygenated hemoglobin (HbO) results are reported. Please clarify the rationale for this choice. Additionally, the data analysis section should describe: Signal preprocessing steps Handling of missing or noisy channel data, if applicable Response: The signal preprocessing steps are detailed in our previous Methods publication (Zondo et al. 2024). Due to journal space limitations, we could not expand on all signal pre-processing steps, and how we handled missing data for the current submission. We have however, revised the Methods section and included reference to the fNIRS pre-processing steps, and handling missing data. With reference to reporting, we collected both oxygenated (HbO) and deoxygenated haemoglobin (HbR) signals but chose to focus on HbO for methodological and interpretative reasons. HbO has been shown to demonstrate a higher signal-to-noise ratio and greater sensitivity to task-evoked cortical activation in block-design paradigms, particularly in paediatric and adolescent samples. Similarly, we patterned our study on Khoe et al. 2020, who reported and analyzed HbO signal for easy replicability. Optode Placement and Channel Analysis - The description of fNIRS optode placement is vague. Based on the figures, it appears that 15 optodes (8 sources and 7 detectors) were positioned over: Prefrontal and premotor areas (e.g., S1- S4, D1–D4) Parietal regions (e.g., S5–S8, D6-D7) Interhemispheric regions (e.g., D4, D6) Please clarify which channels were analyzed and whether regions of interest (ROIs) were defined. Also, describe how data blocks were averaged for statistical analysis. Response: Thank you. The montage consisted of 8 sources and 7 detectors arranged over the prefrontal cortex, (as detailed in Table 1 of the referenced protocol (Zondo et al.2024). No parietal regions were covered. Optode coverage extended across dorsolateral prefrontal, frontopolar, orbitofrontal, and adjacent premotor regions. Regions of interest (ROIs) were anatomically grouped into three predefined clusters: dorsolateral prefrontal cortex (DLPFC), frontopolar cortex (FPC), and orbitofrontal cortex (OFC), based on MNI coordinates and fOLD specificity mapping. All 22 channels were initially included in the analysis; however, channels were excluded if they failed scalp coupling index thresholds or signal quality criteria during preprocessing (using Satori). Data blocks were segmented using time-locked event markers and averaged per condition (congruent, incongruent) across each 10-second task block. Mean HbO amplitude within each block window was computed and aggregated at the ROI level (individual and group) for analysis. Results The results section is generally well presented. However, the following improvements are suggested: Include significance values and effect sizes in Table 2 to enhance interpretability. Response : We have since revised the table to include significance, test statistic, and effect sizes. Figures 2 and 3 do not clearly depict optode placement relative to the brain surface. Consider revising these to more accurately reflect spatial positioning. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further tools inbuilt on Satori fNIRS. We do recognize this limitation, we are however confident, as determined by the fOLD data, (specificity indices) that optode placements were accurately confirmed. Table 3 raises questions about the anatomical labeling of optodes. For example: Optodes S1–D3 and S6–D3 are used to represent the right dorsolateral prefrontal cortex (dlPFC), appearing anteriorly on the right side. Optodes S8–D5 and S8–D7 are used for the left dlPFC but appear posteriorly on the left side. This discrepancy should be clarified. Response: We did not use brain surface maps – all regions of interest configurations were determined using the fOLD software, and further inbuilt tools on Satori fNIRS. The configuration cap used in the study was further confirmed by NIRX technology for specificity. The manuscript does not mention any bad channels. Please confirm whether any channels were excluded due to poor signal quality. Response: Thank you for the comment. As detailed in our MethodsX paper, the study was affected by bad channels, and poor scalp index coupling, primarily due to the population under study (skin pigmentation). We have however added this information to the methods section. Discussion The discussion is well articulated, but I encourage the authors to elaborate on the clinical implications of their findings. For instance, the emergence of significant between-group differences in hemodynamic responses during incongruent trials—despite limited behavioral effects is noteworthy and merits further exploration. Response: We thank the reviewer for this comment. Within the Discussion section, we have sought to highlight the emergence of neural efficiency, concomitant with brain plasticity. Due to the small sample size, the clinical implications (at this stage), of significant hemodynamic differences on incongruent trials, is largely discussed in the context of emergent brain plasticity and neural efficiency. Our group is currently collecting Phase 2 data, to investigate the implications of the above findings at a clinical scale. Additionally, the manuscript lacks a dedicated limitations section. Currently, limitations are briefly mentioned in the conclusion. I recommend restructuring the discussion to include a clear and comprehensive limitations section, followed by a conclusion that synthesizes key findings without introducing new concerns. Response: We have since revised the manuscript and created a section detailing ‘Limitations’. Resulting from this revision, the ‘conclusion’, section is succinct, incorporating further suggestions from the other reviewers. View more View less Competing Interests no competing interests from the authors. reply Respond Report a concern Ramstrand N. Peer Review Report For: Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :1000 ( https://doi.org/10.5256/f1000research.187175.r425396) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1000/v1#referee-response-425396 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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