Effect of medication on the rostrolateral prefrontal oxygenation and thalamic volume asymmetry in youths with ADHD

Effect of medication on the rostrolateral prefrontal oxygenation and thalamic volume asymmetry in youths with ADHD | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Effect of medication on the rostrolateral prefrontal oxygenation and thalamic volume asymmetry in youths with ADHD Hyuna Kim, Da Hyun Kang, Young Hun Jang, Ja-Hye Ahn, Won Sojin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4083291/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Symptoms of attention deficit hyperactivity disorder (ADHD) are associated with impaired executive functions. Some functional magnetic resonance imaging (fMRI) studies on medication effects have provided positive evidence of neuroactivation patterns in children with ADHD; however, they should be extended to functional near-infrared spectroscopy (fNIRS)-based examination of the neuropharmacological effects of medication. We investigated the differences in brain hemodynamic activity between 23 children with ADHD taking medication and 22 children who were not taking medication. Compared with the medicated ADHD group, the unmedicated ADHD group showed significantly reduced activation in the left rostrolateral prefrontal cortex (channel 9, p = 0.01; channel 13, p = 0.02) and dorsolateral prefrontal cortex (channel 14, p = 0.01). The unmedicated ADHD group exhibited a negative correlation between oxygenated hemoglobin (HbO) and symptom scores, while the ADHD with medication group exhibited a positive correlation. Moreover, the abnormal asymmetry of the thalamic volume was reduced in children with ADHD receiving medication compared to those not receiving medication ( p = 0.02). Current findings suggest that left rostrolateral prefrontal activation and reduced thalamic asymmetry are important for inhibitory control, and that the activity of this region is restored by ADHD medication. Health sciences/Diseases/Psychiatric disorders Health sciences/Diseases/Psychiatric disorders/Adhd Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1 Introduction Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in school-age children and is characterized by age-inappropriate symptoms of inattention, hyperactivity, and impulsivity 1 . Approximately 50% of individuals with these symptoms progress to a chronic state during adulthood 2 , debilitating the quality of their social, academic, or occupational functions 3 . Furthermore, patients with ADHD show impaired response inhibition, which is associated with the suppression of executive function, causing crucial neurophysiological defect 4–6 . Functional near-infrared spectroscopy (fNIRS) has been used to measure regional oxygenation in the brain, suggesting the potential of using fNIRS for diagnosis and treatment surveillance. A study using fNIRS found discriminative signals in specific brain regions, both between children with ADHD and controls and between medication-naïve and non-naïve children with ADHD 7 . A previous meta-analysis of fNIRS studies on ADHD reported inconsistencies among study results; some studies showed hyperactivity in the dorsolateral prefrontal cortex and left superior frontal cortex 8–11 , whereas another study reported hypoactivity in the right prefrontal brain regions of patients with ADHD 12 . Additionally, reduced oxyhemoglobin signals in the inferior and middle frontal gyri during cognitive tasks are normalized by medication in children with ADHD 13 . The first-line treatment for ADHD is medication, including methylphenidate (MPH; a dopamine and norepinephrine reuptake inhibitor) and atomoxetine (ATM; a selective norepinephrine reuptake inhibitor). fNIRS can identify biomarkers of treatment effects that are more objective than conventional clinician- or questionnaire-based evaluation methods because it is a non-invasive, portable neuroimaging technique with superior spatial resolution and reduced susceptibility to motion artifacts 14–16 . A previous study has suggested that reduced prefrontal activation by fNIRS could serve as an objective biomarker for predicting the clinical course and treatment response 17 . Another study reported that children with ADHD who were taking medication showed hyperactivation in the prefrontal cortex (PFC) during a high-workload task compared to children with ADHD without medication; however, there were no significant differences in cognitive task scores 18 . However, Nagashima et al. revealed that the mode of normalization in children with ADHD receiving medication was asymmetrical in the frontoparietal attention network 9 . Brain activation was significantly higher in the right middle frontal gyrus and right inferior prefrontal gyrus after the administration of atomoxetine 13 and methylphenidate 19 . Other studies have reported opposite directionality, in which children with ADHD exhibited hyperactivity in brain activity, especially in the left PFC, when they performed the SCWT, regardless of the medication type 20 . Some studies have investigated using functional magnetic resonance imaging (fMRI) to identify the effects of medication in ADHD populations and found that hyperactivity is the primary outcome. A previous meta-analysis has explored the medication effect associated with enhanced function of right dorsolateral prefrontal cortex in children with ADHD compared to health control 21 . Another meta-analysis found that psychostimulants improve bilateral inferior frontal cortex and insular activation in children with ADHD 22 . Hemispheric differences in brain structure are thought to reflect aberrant developmental synchrony between the left and right brain in an asymmetric manner 23 , contributing to or accompanied by ADHD symptom severity. A recent meta-analysis of abnormal hemispheric asymmetry using resting-state fMRI reported that children with ADHD had both structural (in the prefrontal cortex, subcortical cortices, and cerebellum) and functional abnormalities (in the inferior frontal gyrus, temporal pole, and cerebellum) 24 . Particularly, as the symptoms of ADHD become severe, hemispheric brain asymmetry differences increase, indicating a pathoplastic role for asymmetry with a structural basis during development. Moreover, volumetric anomalies of thalamocortical regions have been demonstrated in children with ADHD, revealing the pathogenesis of various ADHD symptoms 25 . Ivanov et al. showed reduced pulvinar volumes of the thalamus in patients with ADHD without medication compared to those with medication, suggesting a medication effect on the thalamic subcircuit 26 . Subcortical changes in children with ADHD could be more evident in thalamic regions that could not be detected using fNIRS. Although fNIRS can provide information only on cortical activity, information on the thalamic volume in structural magnetic resonance imaging (sMRI) may help reveal the pathological characteristics of patients with ADHD. Past studies have focused on comparing the hemodynamic response between children with ADHD receiving medication and controls, while there has been limited research comparing children with ADHD receiving medication and those not receiving medication. Moreover, numerous studies examining the neural substrates of the effects of medication have largely focused on single neuroimaging or neurophysiological results. Simultaneous fNIRS-sMRI studies in children with ADHD with and without medication offer clinical advantages for detecting treatment responses to medication and the reliability of variable functional patterns with robust results. We explored whether there were any differences in abnormal brain activity and structural asymmetry on magnetic resonance imaging (MRI) between ADHD patients with and without medication, using fNIRS and sMRI to elucidate the neural mechanism of medication in children with ADHD. 2 Results 2.1. Demographic and clinical characteristics The demographic and clinical characteristics of the study participants are shown in Table 1 . A total of 45 children with ADHD (23 medicated and 22 unmedicated) were evaluated. The participant groups did not differ in terms of mean age, sex, FSIQ, ADHD-RS-IV inattention, or socioeconomic characteristics. The ADHD-RS-IV total score and hyperactivity-impulsivity score was significantly higher in the ADHD without medication group than ADHD with medication group (28.27 ± 9.01 vs. 23.22 ± 7.50, p = 0.05; 11.91 ± 5.08 vs 8.83 ± 4.15, p = 0.03, respectively). There were no significant differences in the ATA and SCWT parameter scores. The CGI-S score was significantly lower in the ADHD with medication group compared to the ADHD without medication group (4.22 ± 0.4 vs 4.62 ± 0.59, p = 0.01). Table 1 Demographic and clinical characteristics. factors ADHD with medication (n = 23) ADHD without medication (n = 22) p Children characteristics Age (years) 11.09 ± 1.93 10.64 ± 1.73 0.42 Male sex 20 (87%) 14 (63.6%) 0.07 FSIQ 95.30 ± 16.70 94.14 ± 12.33 0.79 ADHD-RS-IV total 23.22 ± 7.50 28.27 ± 9.01 0.05* ADHD-RS-inattention 14.39 ± 4.55 16.36 ± 4.56 0.15 ADHD-RS-hyperactivity-impulsivity 8.83 ± 4.15 11.91 ± 5.08 0.03* MPH 17 MPH dose (mg) 32.06 ± 19.78 ATM 12 ATM dose (mg) 39.67 ± 14.67 Height (cm) 153.69 ± 14.95 Weight (kg) 51.52 ± 17.71 Handedness 0.55 Left 2 (8.7%) 3 (13.6%) Right 20 (87.0%) 19 (86.4%) Mixed 1 (4.3%) 0 (0%) CGI CGI-S 4.22 ± 0.42 4.62 ± 0.59 0.01* C-GAS 60.22 ± 7.46 56.00 ± 7.81 0.07 ATA Visual Task Omission error 57.83 ± 19.08 63.73 ± 19.70 0.31 Commission error 60.83 ± 18.09 63.55 ± 19.77 0.63 RT 62.70 ± 14.47 68.36 ± 12.99 0.18 RTV 57.30 ± 19.37 67.77 ± 17.39 0.06 ATA Auditory Task Omission error 71.22 ± 23.27 67.77 ± 22.54 0.62 Commission error 69.74 ± 22.27 70.95 ± 22.90 0.86 RT 53.52 ± 8.87 53.50 ± 12.71 1.00 RTV 50.13 ± 10.76 53.50 ± 10.42 0.29 SCWT Word score 38.26 ± 10.18 39.32 ± 13.96 0.77 Color score 42.09 ± 8.86 44.14 ± 8.71 0.44 Color-word score 45.91 ± 10.89 46.45 ± 9.92 0.86 Interference score 57.26 ± 8.91 54.50 ± 10.76 0.35 Socioeconomic characteristics Economic Status 0.13 High 0 (0%) 1 (4.5%) High average 7 (30.4%) 3 (13.6%) Average 7 (30.4%) 14 (63.6%) Low Average 6 (26.1%) 2 (9.1%) Low 3 (13.0%) 2 (9.1%) Maternal education level 0.92 High school 2 (8.7%) 2 (9.5%) College or university 21 (91.3%) 19 (90.5%) Father’s education level 0.09 High school 5 (21.7%) 1 (4.5%) College or university 18 (78.3%) 21 (95.5%) Data are the mean ± SD or n (%). ADHD, attention deficit/hyperactivity disorder; FSIQ, full-scale intellectual quotation; MPH, methylphenidate; ATM, atomoxetine; CGI-S, clinical global impression scale-severity; C-GAS children’s global assessment scale; ATA, advanced test of attention; RT, response time; RTV, response time variability; SCWT, stroop color-word test. Six children were medicated with both MPH and ATM. * p < 0.05. 2.2. Comparison of hemodynamic differences between groups The HbO of channel 9 ( p = 0.01) in the 1st rest period and the HbO of channels 13 ( p = 0.02) and 14 ( p = 0.01) during task 2 (color) were significantly different after Bonferroni correction. The medicated ADHD group showed significantly lower HbO than the unmedicated ADHD group in channel 9 of 1st rest (-0.0400 ± 0.01 vs 0.0613 ± 0.01). Contrastingly, the medicated ADHD group showed significantly higher HbO than those in the unmedicated group in channel 13 and 14 during task 2 (color test) (0.0818 ± 0.10 vs 0.0057 ± 0.11, 0.0592 ± 0.10 vs -0.0188 ± 0.10, respectively). The differences in HbO levels between the two groups are shown in Table 2 and Fig. 3 and hemodynamic of deoxygenated hemoglobin (HbR) was found in Supplementary table S1 . However, there was no significant difference in hemispheric asymmetry score of HbO and HbR between groups ( Supplementary table S2 ). Table 2 Differences in mean oxyhemoglobin measurements between participants with ADHD with and without medication. section channel ADHD with medication (n = 23) ADHD without medication (n = 22) p section channel ADHD with medication (n = 23) ADHD without medication (n = 22) p 1st rest 1 0.171 ± 0.11 0.346 ± 0.08 0.56 Task1 (Word) 1 0.032 ± 0.09 -0.071 ± 0.10 0.73 2 -0.061 ± 0.14 0.174 ± 0.12 0.55 2 0.444 ± 0.11 0.671 ± 0.18 0.62 3 0.053 ± 0.10 0.021 ± 0.11 0.92 3 0.492 ± 0.11 0.144 ± 0.13 0.33 4 0.297 ± 0.12 0.194 ± 0.13 0.78 4 0.173 ± 0.11 -0.144 ± 0.12 0.37 5 0.121 ± 0.18 -0.177 ± 0.12 0.51 5 0.570 ± 0.17 0.191 ± 0.11 0.38 6 -0.117 ± 0.12 -0.186 ± 0.17 0.86 6 0.184 ± 0.13 0.063 ± 0.10 0.73 7 0.091 ± 0.11 -0.123 ± 0.10 0.49 7 0.332 ± 0.13 -0.144 ± 0.09 0.17 8 -0.066 ± 0.08 -0.083 ± 0.14 0.96 8 0.147 ± 0.14 0.122 ± 0.13 0.95 9 -0.400 ± 0.13 0.613 ± 0.11 0.01* 9 0.231 ± 0.21 -0.312 ± 0.18 0.36 10 -0.259 ± 0.11 -0.227 ± 0.09 0.92 10 0.196 ± 0.17 0.359 ± 0.05 0.67 11 0.104 ± 0.11 0.558 ± 0.17 0.30 11 0.358 ± 0.16 0.222 ± 0.16 0.78 12 0.065 ± 0.18 0.049 ± 0.13 0.36 12 0.340 ± 0.11 -0.044 ± 0.17 0.37 13 0.234 ± 0.17 0.005 ± 0.12 0.60 13 0.402 ± 0.10 -0.153 ± 0.13 0.12 14 0.504 ± 0.13 -0.183 ± 0.14 0.09 14 0.265 ± 0.11 0.447 ± 0.11 0.58 15 0.000 ± 0.12 0.146 ± 0.13 0.69 15 0.523 ± 0.19 0.316 ± 0.15 0.68 2nd rest 1 -0.112 ± 0.05 -0.051 ± 0.12 0.83 Task2 (Color) 1 0.475 ± 0.08 -0.111 ± 0.11 0.05 2 0.178 ± 0.16 -0.047 ± 0.13 0.15 2 0.462 ± 0.21 0.489 ± 0.20 0.97 3 0.127 ± 0.09 0.035 ± 0.10 0.75 3 0.393 ± 0.08 0.108 ± 0.11 0.33 4 0.070 ± 0.08 -0.317 ± 0.12 0.20 4 0.240 ± 0.08 -0.145 ± 0.10 0.18 5 0.219 ± 0.13 -0.305 ± 0.12 0.17 5 0.730 ± 0.18 0.377 ± 0.19 0.52 6 0.406 ± 0.11 -0.067 ± 0.11 0.17 6 0.547 ± 0.11 0.084 ± 0.10 0.14 7 0.300 ± 0.16 -0.244 ± 0.09 0.08 7 0.571 ± 0.10 0.415 ± 0.17 0.71 8 0.058 ± 0.06 -0.342 ± 0.09 0.08 8 0.418 ± 0.10 0.163 ± 0.15 0.51 9 -0.143 ± 0.14 -0.117 ± 0.13 0.95 9 0.865 ± 0.21 0.153 ± 0.16 0.21 10 -0.266 ± 0.15 -0.597 ± 0.11 0.40 10 0.825 ± 0.17 0.852 ± 0.24 0.97 11 0.555 ± 0.18 -0.131 ± 0.16 0.18 11 0.727 ± 0.19 -0.260 ± 0.11 0.07 12 0.003 ± 0.07 -0.013 ± 0.11 0.87 12 0.670 ± 0.10 0.194 ± 0.13 0.24 13 0.048 ± 0.11 -0.804 ± 0.18 0.06 13 0.818 ± 0.10 0.057 ± 0.11 0.02* 14 0.091 ± 0.15 -0.030 ± 0.07 0.73 14 0.592 ± 0.10 -0.188 ± 0.10 0.01* 15 0.114 ± 0.10 0.094 ± 0.14 0.95 15 0.334 ± 0.13 -0.120 ± 0.21 0.38 3rd rest 1 0.195 ± 0.07 0.426 ± 0.11 0.40 Task3 (Color-Word) 1 0.107 ± 0.12 0.129 ± 0.15 0.24 2 0.898 ± 0.25 0.403 ± 0.20 0.47 2 0.582 ± 0.11 0.360 ± 0.20 0.97 3 0.213 ± 0.11 0.206 ± 0.14 0.99 3 0.505 ± 0.10 0.447 ± 0.11 0.55 4 0.410 ± 0.10 0.114 ± 0.13 0.39 4 0.481 ± 0.08 0.022 ± 0.09 0.44 5 0.132 ± 0.16 0.385 ± 0.17 0.61 5 0.358 ± 0.08 0.200 ± 0.11 0.65 6 -0.167 ± 0.28 0.161 ± 0.12 0.61 6 0.455 ± 0.13 0.289 ± 0.10 0.41 7 -0.118 ± 0.17 0.413 ± 0.14 0.27 7 0.412 ± 0.11 -0.011 ± 0.11 0.82 8 0.162 ± 0.27 0.162 ± 0.27 0.91 8 0.386 ± 0.15 0.065 ± 0.07 0.65 9 -0.332 ± 0.33 0.195 ± 0.14 0.49 9 0.173 ± 0.30 0.184 ± 0.12 0.44 10 -0.163 ± 0.25 0.526 ± 0.13 0.25 10 0.394 ± 0.18 0.333 ± 0.11 0.97 11 -0.484 ± 0.46 0.379 ± 0.13 0.40 11 0.085 ± 0.15 0.058 ± 0.12 0.26 12 -0.122 ± 0.21 0.510 ± 0.18 0.28 12 -0.597 ± 0.21 0.439 ± 0.09 0.44 13 0.459 ± 0.21 0.469 ± 0.15 0.99 13 0.303 ± 0.10 0.265 ± 0.09 0.17 14 0.505 ± 0.14 0.505 ± 0.13 1.00 14 0.202 ± 0.11 -0.117 ± 0.11 0.15 15 0.542 ± 0.19 0.004 ± 0.18 0.37 15 0.501 ± 0.19 0.359 ± 0.11 0.57 Data are the mean ± SD (10 − 3 ). ADHD, attention deficit hyperactivity disorder; SD, standard deviation. * Significant with Bonferroni correction for multiple comparison calculated by NIRSITLiteAnalysisTool. 2.3. Correlation between HbO and clinical scores in groups In channel 9, the HbO values during the 1st resting period showed a significant positive correlation with ATA visual task response time (RT) scores and a negative correlation with SCWT interference scores in the unmedicated ADHD group ( Supplementary table S3 ). In channel 13, the HbO values of task 2 were negatively correlated with the hyperactivity-impulsivity scores and total ARS scores in the unmedicated ADHD group ( Supplementary table S4 ). The HbO values positively correlated with the SCWT word scores in the medicated ADHD- group ( Supplementary Table S4 ). In the interaction analyses, there was a significant interaction effect between response time variability (RTV) scores of the ATA visual task and the medicated ADHD group in channel 9 of the 1st rest period ( interaction p = 0.02). In channel 9, the correlation between RTV scores and HbO during the 1st resting period showed opposite directions according to medication in the two groups; although not significant, there was a negative correlation in the medicated ADHD group and a positive correlation in the unmedicated ADHD group. There was a similar tendency in ATA visual task commission error [ interaction p = 0.09 at channel 9 during 1st rest, interaction p = 0.07 at channel 13 during task 2 (color)] and ARS inattention scores [ interaction p = 0.07 at channel 13 during task 2 (color)]. The interaction effects between the clinical scores and medication are shown in Fig. 4 . 2.4. Comparison of fNIRS network metrics between groups and correlation with clinical scores There were no significant differences in brain network metrics between the two groups. The correlations between the network metrics and SCWT scores are shown in Supplementary table 5 . 2.5. Comparison of hemispheric asymmetry of gross volume between groups There was no significant difference in the structural brain volume ( Supplementary table S6 ) between the medicated and unmedicated ADHD groups and among three groups categorized by type of medication (methylphenidate only, atomoxetine only, and both) (Supplementary table S7) . Figure 5 and Supplementary table S8 show the asymmetric patterns in the volume of the cortex, white matter, cerebellum, and subcortical regions, including the hippocampus and thalamus. There was a similar pattern of lateralization between groups, as the medicated ADHD group tended to be lateralized to the left hemisphere and the unmedicated ADHD group tended to be lateralized to the right hemisphere. There were significant differences in the (a) hippocampus, (b) centomedian, (c) paracentral, and (d) paratenial of the thalamus after adjusting sex, age, handedness, and total brain volume excluded ventricle or total thalamus volume (adjusted p = 0.03, 0.04, 0.04, and 0.03, respectively) asymmetry scores between the medicated and unmedicated ADHD groups. Children with ADHD who were not taking medication showed more rightward asymmetry in the volumes of the thalamus and hippocampus than those with ADHD who were taking medication. 3 Discussion To our knowledge, this is the first multimodal fNIRS-MRI study to compare the effect of medication during a cognitive task and the resting state, elucidating the neuropharmacological substrate based on thalamic asymmetry in children with ADHD. We observed differential brain activity, especially in the left prefrontal cortex during the SCWT, and reduced hemispheric asymmetry in thalamic volume in medicated compared to unmedicated children with ADHD. More specifically, we found reduced hemodynamic activity during the resting state, but increased HbO during the SCWT following pharmacotherapy. The difference in brain activity during the SCWT tasks according to medication was especially prominent in the left prefrontal cortex. Moreover, we found significantly reduced thalamic asymmetry in children with ADHD treated with medication, suggesting a pathoplastic role of neural substrates in the medication effect. Another review also reported inconsistent results among studies investigating the pharmacological effects of MPH and ATM 27 . Most studies revealed increased HbO activation in the prefrontal cortex following medication and a higher frequency of right lateralization. Specifically, HbO activation increases after medication intake in the right dorsolateral and ventrolateral prefrontal cortices 28 . In other studies, bilateral increases in oxygenation due to medication 29,30 and left-lateralized treatment effects have been examined due to pharmacological effects during neural assessments 20,31 . Some previous studies were limited to boys who did not receive psychotropic medication 8,11 whereas others compared children with ADHD to healthy controls 10 . Moreover, few studies have differentiated the neural substrates associated with brain activation using fNIRS in children with ADHD receiving medication compared to those not receiving medication. It is also noteworthy that the heterogeneity of the patient group, including both naïve and non-naïve children with ADHD, and the diversity of neurocognitive tasks, could be partly attributed to the inconsistent results 27 . In our study, we found that prefrontal activity in medicated children with ADHD increased during cognitive tasks. This result is in line with previous findings that brain activation increases during the SCWT after taking medication 20,27,32 indicating the restoration of brain activation with medication. As previous studies have used different tasks, different types of medication, and different statistical methods to investigate medication effects and have been small in sample size, more well-designed studies with larger sample sizes are needed. A recent systematic review 32 showed that brain regions associated with inhibitory control and working memory are widely distributed in the bilateral prefrontal cortices of healthy people. The left prefrontal region is implicated in inhibitory functions and plays an important role in modulating ADHD symptoms 33–37 . The rostrolateral prefrontal cortex has a large number of dendritic spines per cell 38 and is associated with higher-order cognitive functions 39 . Our results are consistent with those of Miao et al., in which children with ADHD exhibited consistent hypoactivity in the left rostrolateral prefrontal cortex during inhibition tasks 40 . The left rostrolateral prefrontal cortex plays a role in controlling attentional reallocation 41 , which is impaired in patients with ADHD. To investigate the function of the prefrontal cortex, we used a cognitive task, the SCWT, which is one of the best-known psychological experiments requiring high-level cognitive functions of response selection and response inhibition 42–44 Using the SCWT, we identified that activation of the left rostrolateral prefrontal cortex measured by fNIRS could serve as an objective neural biomarker for children with ADHD. The significant difference in brain activation in the left prefrontal cortex in the present fNIRS study is noteworthy, and in line with evidence related to the symptoms of the disease in children with ADHD. Notably, we found an interaction effect of brain activity in the left brain channels between the two groups, suggesting inefficient hemodynamic processing of cognitive function in unmedicated patients with ADHD. The unmedicated ADHD group showed decreased HbO during cognitive tasks according to symptom severity, whereas they exhibited increased HbO in the resting state according to symptom severity. This interesting result regarding the aberrant distribution of hemodynamic changes when entering the cognitive workload extends previous results that showed reduced activation of the prefrontal cortex at fNIRS in children with ADHD beyond resting-state brain activity 7,45 . As the difficulty of the task increases, children with ADHD and impaired cognitive function experience imbalances in effectively distributing hemodynamic energy 18 . Additionally, because children with ADHD are debilitated in their ability to switch tasks, they show a specific deficit regarding the flexible suppression of different rules according to instructions 46 . Consistent with previous findings that methylphenidate can enhance inhibitory control associated with attention switching, stimulant medication may modulate executive function in children with ADHD. Therefore, we conclude that alterations in hemodynamic maintenance reflect the effects of medication in the human brain when confronted with changing cognitive demands to achieve an optimal distribution of attention. We also found a significant difference in asymmetry in the hippocampus and several thalamic volumes between medicated and unmedicated patients with ADHD on sMRI, suggesting a possible mechanism involved in the different cortico-subcortical connectivities. A previous study suggested that the volume in the prefrontal cortex of patients with ADHD was smaller than that in TDC, while the subcortical volume in the right hemisphere was greater than that in TDC 24 . The prefrontal cortex receives inputs via the thalamus from other cortical regions and subcortical structures, such as the hippocampus and amygdala, selecting relevant information and ignoring distracting stimuli. An increasing number of studies have shown that the thalamus is a key anatomical structure underlying normal attentional and cognitive control mechanisms in ADHD 22,47 . The thalamus helps suppress inappropriate responses and maintain cognitive flexibility in important tasks. Ivanov et al. reported that patients with ADHD receiving medication had larger thalamic volumes than those who were not receiving medication, compensating for insufficient prefrontal function 25 . Particularly, the intralaminar and medial nuclei of the thalamus have been implicated in synchronizing cortical neurons for effective information transmission during cognitive processing 48 . Additionally, the hippocampus is involved in the neural network of learning and working memory, which is a key defect in patients with ADHD 49,50 . Although brain asymmetry is a unique feature of the human brain, aberrations in its asymmetric nature may represent plausible clues regarding the effect of ADHD on brain asymmetry, such as abnormal brain development and maturation processes. Recent studies using NIRS have reported functional asymmetry in hemodynamic activation with regard to hemispheric differences as potential biomarkers in children with ADHD 51 . However, they did not compare the structural asymmetry of the brain volume between medicated and unmedicated children with ADHD. Our findings show plausible evidence of abnormal hemispheric asymmetry as the neural basis of the core deficit associated with ADHD, in which unmedicated children with exhibited increased asymmetry in the brain volume of the thalamus and hippocampus compared to medicated children with ADHD. Altered hemispheric asymmetry in the hippocampus and thalamus may contribute to imbalanced attention control under disease conditions, leading to altered cortico-subcortical connectivity with disrupted projections from the subcortex to the frontal cortex. Consistent with our findings, Douglas et al. (2018) revealed morphometric asymmetry of the hippocampus and thalamus in patients with ADHD compared to TD 52 . Moreover, the degree of hemispheric asymmetry involving the prefrontal and subcortical regions is higher in children with more severe ADHD symptoms, indicating a neuroplastic role for disrupted neural mechanisms in the inhibition of cognitive interference 24 . This study had several limitations. First, because there is likely heterogeneity in the medication groups (MPH and ATM), the different effects of drug type on hemodynamic patterns should be considered in future studies. Additionally, few participants took medication in addition to MPH and ATM, such as risperidone or aripiprazole, so further studies should control the different pharmacotherapies that could affect the neural responses in patients with ADHD. Second, the number of participants was insufficient to identify the abilities of children with ADHD. Therefore ADHD, future studies must have a large sample size to confirm our conclusions. Third, we measured HbO in the prefrontal cortex using a 15-channel near-infrared machine, which is the only commercially available near-infrared machine for children in Korea but has the disadvantage that it is difficult to reflect high-density resolution. Therefore, further studies need to use multichannel measurements to investigate the relationship between functional networks and structural mechanisms of the entire hemisphere. Fourth, the ARS scores were significantly lower in the medication group compared to the non-medicated group. This may reflect medication effect, as 70% show a response to ADHD medication. The mismatch of baseline ARS scores may be source of selection bias in this study. Finally, all ADHD subtypes were included in this study because the sample size was too small to perform independent analyses according to subtype. This may have caused heterogeneity in the behavioral and neuroimaging characteristics of the participants. In summary, we examined the effect of medication on hemodynamic activity and functional network connectivity in the prefrontal area using fNIRS and on the hemispheric asymmetry of structural brain volume with MRI in children with ADHD. Our findings suggest that left rostrolateral prefrontal activation and reduced thalamic asymmetry are important for inhibitory control, and that the activity of this region is restored by ADHD medication. 4 Methods 4.1. Participants Participants were enrolled from a psychiatric outpatient clinic at Hanyang University Medical Center, and advertisements were made through internet posts. Among the screened participants, 47 with ADHD were recruited for the study. Two participants were later excluded owing to channel rejection during the fNIRS measurement, and 45 participants were finally included in the analysis, of which 23 were included in the medicated group and 22 in the unmedicated group. The inclusion and exclusion criteria were identical for the medicated and unmedicated groups, except for medication status. Potential participants were included if they 1) were between 8 and 15 years of age; 2) fulfilled the ADHD diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia – Present and Lifetime version (K-SADS-PL) 53 , and 3) their intelligence quotients (IQ) were above 70. Exclusion criteria included: 1) congenital hereditary problems; 2) brain injury such as cerebral palsy; 3) spasmodic disorder, other neurological disorders, or untreated dysesthesia (sensory disturbance); 4) past or current schizophrenia and childhood psychosis; 5) IQ scores under 70; and 6) comorbidity with obsessive-compulsive, depressive, or bipolar disorder. The unmedicated ADHD group consisted of participants who had never received MPH or ATM treatment or had not taken medication within four weeks prior to participating in the study. The medicated group consisted of patients with ADHD whose dosages of methylphenidate or atomoxetine had not changed over the past month. The Clinical Global Impression Scale-Severity (CGI-S) score for both the drug-naïve and drug-medicated groups was > 4, indicating that their underlying symptoms were moderate to severe, and there was no remission. Among the medicated ADHD group, 17 participants took methylphenidate (mean dosage; 32.06 ± 19.78 mg), and 12 participants took atomoxetine (mean dosage 39.67 ± 14.67 mg). Among these participants, seven were prescribed methylphenidate and atomoxetine. The CGI scores for each group and drug information for the medication group are listed in Table 1 . The diagnosis of psychiatric disorders was confirmed using the K-SADS-PL, which was conducted by a single board-certified psychiatrist. IQ scores were determined using the Korean version of the Wechsler Intelligence Scale for Children (WISC), Fourth or Fifth Edition 54 . All participants and their parents provided written informed consent to participate in the study after receiving sufficient explanation of the study. All experimental protocols were approved by the Institutional Review Board of the Hanyang University Medical Center (IRB Approval no.2020-02-025) and performed in compliance with the principles of the Declaration of Helsinki. 4.2. Clinical assessment tools 4.2.1. ADHD Rating Scale (ARS) The ARS is the most widely used scale to screen children with ADHD by their parents and teachers and was developed by Du Paul based on the diagnostic criteria of ADHD illustrated in the DSM-IV 55 . The scale consists of 18 items rated from 0 to 3, with parents or teachers scoring each item based on the frequency of the children’s problematic behaviors. The total scores of the odd-numbered questions measures inattention and the total number of even-numbered items measures impulsivity and hyperactivity. Higher scores indicate more severe attention-deficit and hyperactivity symptoms, and the cutoff score for the ADHD criteria is a total score of 19. In this study, the parents completed the Korean version of the ADHD Rating Scale-IV (K-ARS-Ⅳ) to measure the ADHD symptoms of the participants during the past three months. The K-ARS has been shown to have high reliability and validity to discriminate and identify children with ADHD 56,57 . 4.2.2. The Advanced Test of Attention (ATA) The ATA is a computerized continuous performance test used to assess attention and inhibitory control 58 . The test consists of visual and auditory subtests, each lasting 15 min. The participants were instructed to press the button (response) for the target stimuli as fast as possible and ignore the non-target stimuli (inhibit). Three nonverbal stimuli were presented for each subtest, all of which were non-target stimuli except for one target stimulus 58 . In the visual test, an image with a triangle inside a square was the target stimulus, and the non-target stimuli were circles and squares drawn within a square. The target stimulus of an auditory test to which the participant should respond was three consecutive beep sounds; if two or four consecutive beeps were presented, the participants were not required to press the button. Each subtest was implemented after the practice trial according to the researcher’s instructions. The test yielded four main indicators:1) omission error to measure the symptoms of inattention; 2) commission error to measure impulsivity and disinhibition; 3) mean response time for correct responses to measure the speed at which target stimuli were processed; and 4) standard deviation of reaction time (response time variability) to measure the consistency of attention. All scores were translated into T-scores, adjusted based on normative distribution according to age and sex, with an average score of 50 and a standard deviation of 15. 4.2.3. Stroop Color-Word Test (SCWT) The participants underwent fNIRS assessment during SCWT administration. The SCWT is a frequently used neuropsychological test for evaluating cognitive control and entails multiple cognitive processes, including selective attention, response inhibition, interference control, and speeded response 59 . The test consisted of three subtests (word, color, and color words), and with each subtest lasting 45s. First, during the word subtest, participants were instructed to look at black-printed words and read the letters of the words as quickly as possible within the time limit. During the color test, the participants were instructed to read three types of color patches as quickly as possible. Finally, in the color-word subtest, the letters and colors of the words were presented incongruently, and the participants were instructed to say colors instead of letters. When the target (color) and obstruction (letter) stimuli were presented simultaneously, the ability to sustain attention was measured by inhibiting the interference of the obstruction stimuli and selecting only the target stimuli. In this study, the Korean version of the standardized SCWT was implemented using E-Prime 3.0 software (Psychology Software Tools, Pittsburgh, PA, USA). For each subtest condition, after being guided by each test instructions and 30s of resting state, the participants proceeded to perform the task while watching the stimuli on the screen. The stimuli were presented in five rows with 20 words in each row. The raw score was calculated by counting the total number of correct answers for each test, and the interference score was calculated as the difference between the color and color-word scores. All scores were converted to T-scores based on the normative distribution according to age and sex. The protocol for SCWT administration during fNIRS assessment is shown in Fig. 1 . 4.3. fNIRS data acquisition and pre-processing To quantify the amount of oxygen in the blood, we used a NIRSIT Lite Kids machine (OBELAB, Seoul, Republic of Korea), which is an fNIRS instrument with five dual-wavelength (780/850 nm) light-emitting diode light sources and 7 detectors spaced 2.5 cm apart, comprising 15 regular (2.5 cm) channels covering the prefrontal cortex. The 15 channels are spaced 2.5 cm apart from each other, with 8 channels on the right side of the orbitofrontal cortex (channel 1), the dorsolateral prefrontal cortex (channels 2, 3), and the rostrolateral prefrontal cortex (channels 4, 5, 6, 7, 8), respectively, and 7 channels on the left side of the orbitofrontal cortex (channel 15), the dorsolateral prefrontal cortex (channels 12, 14), and the rostrolateral prefrontal cortex (channels 8, 9, 10, 11, 13). Channel 8 was excluded from the analysis because it belongs to both sides of the left and right rostrolateral prefrontal cortices. The alignment of the 15 channels is shown in Fig. 2 . If more than three of the 15 channels were disconnected, the subjects were excluded from the analysis. The optical-signal variation in each channel was sampled at a frequency of 8.138 Hz. The threshold of the signal-to-noise ratio criterion for determining poor quality, such as the slow drift of physiological noise and environmental noise, was 30 dB, which was used to qualify the noise of the detected channels after bandpass filtering from 0.005 to 0.1 Hz. The obtained optical intensity signals were converted into an oxygenated hemoglobin (HbO) concentration change time series using the modified Beer-Lambert law (MBLL). The average signal for each channel during the last 10 s of rest and 30 s of each task was used in the analysis to compare regional neural activity between the groups. We focused on HbO rather than HbR because HbR is 1–2 seconds slower than changes in HbO and may not reflect an accurate signal 60 . 4.4. fNIRS: calculation of network parameters Network-weighted edges were defined to obtain a functional network of the fNIRS data 51 . Group-averaged connectivity data were obtained by averaging the time series of each resting and task block and then transforming the average of each participant’s Fisher-transformed value back to the Pearson’s correlation matrix. We conducted one-sample t -tests to compare the correlation values of each channel pair with a 0. The 15 network nodes had the same anatomical locations as the 15 channels and encompassed the orbitofrontal and rostrolateral prefrontal cortices. Global and local network metrics were analyzed using GRETNA software ( http://www.nitrc.org/projects/gretna/ ) 61 . The evaluated metrics included: ( 1 ) Global efficiency (Ge), which indicates the global efficiency of the parallel transfer of information in the network 62 . Ge reflects network integration 63 ; ( 2 ) the nodal clustering coefficient (NC p ), which indicates whether each node is interconnected with its neighbors 64 . The NC p reflects network segregation 63,65,66 ; and ( 3 ) the weighted degree centrality (DC w ), which is the sum of all weighted connections to a given node 67 . 4.5. MRI acquisition and analysis Individuals with ADHD were scanned using a 3T MRI (Philips, Achieva, 16-channel phase-array head coil, Best, Netherlands). In the T1-weighted images, the single-shot three-dimensional echo-planar images were obtained using these parameters: slice thickness = 1 mm, voxel sizes = 0.9 mm 2 , field of view = 224 mm 2 , repetition time = 8.3 ms, echo time = 4.6 ms, inverse time = 1 ms, and flip angle = 8°. The slice orientation was axially parallel to the anterior-posterior commissure line. A total of 150 slices contained the entire hemisphere and brainstem. Automated reconstruction and segmentation of individual high resolution T1 weighted MRI volumes were performed using FreeSurfer version 7.1.1 ( https://surfer.nmr.mgh.harvard.edu/ ). The processing pipeline comprises motion correction, automated Talairach transformation, signal intensity normalization, removal of nonbrain tissue, automated correction for topological defects, subcortical segmentation, and cortical parcellation 68–72 . The imaging process has been described in detail in previous studies 72,73 . Regions based on the Desikan-Killiany atlas were segmented for volumetric analysis, with 34 left- and 34 right-hemispheric regions. To adjust for individual differences in the skull size, we corrected the absolute volume to the relative volume. The relative volume index was calculated as follows: $$\text{R}\text{e}\text{l}\text{a}\text{t}\text{i}\text{v}\text{e} \text{v}\text{o}\text{l}\text{u}\text{m}\text{e} \left(\text{%}\right)=\frac{\text{R}\text{e}\text{g}\text{i}\text{o}\text{n} \text{o}\text{f} \text{i}\text{n}\text{t}\text{e}\text{r}\text{e}\text{s}\text{t}}{\text{I}\text{n}\text{t}\text{r}\text{a}\text{c}\text{r}\text{a}\text{n}\text{i}\text{a}\text{l} \text{v}\text{o}\text{l}\text{u}\text{m}\text{e}} \times 100$$ Thalamus segmentation was performed by using a sequence-adaptive Bayesian algorithm based on a probabilistic atlas 74 . The segmented thalamus exhibited a volume of 25 regions in both the right and left thalami. These brain regional volumes were extracted with ‘asegstats2table’ command. The segmentation outputs were visually inspected by two independent researchers (H. A. and Y. H.). Higher-order thalamic lesions can synchronize the activity of neural networks underlying various cognitive functions, including arousal, memory processing, attention, and reward-based behaviors 48,75 . To evaluate the regions of interest of the thalamus related to the projection pathway to the frontal lobe, we selected the medial group (mediodorsal lateral parvocellular, mediodorsal medial magnocellular, reuniens, and paratenial) and the intralaminar group (central medial, centromedian, center-lateral, paracentral, and parafascicular). The difference between the left and right hemispheres of each gross and subsegmentation of the thalamic region is represented by the asymmetry index. The asymmetry index was calculated using the following formula: $$\text{A}\text{s}\text{y}\text{m}\text{m}\text{e}\text{t}\text{r}\text{y} \text{i}\text{n}\text{d}\text{e}\text{x}=\frac{\text{L}-\text{R}}{(\text{L}+\text{R})}$$ Where L and R denote the values of the left and right sides of the hemisphere, respectively. 4.6. Statistical analysis For pre-processing of fNIRS data and comparison of HbO values between the two groups, we used the NIRSITLiteAnalysis Tool (OBELAB, Seoul, Republic of Korea). All statistical analyses were performed using the SPSS 28 software (SPSS, Inc., Chicago, IL, USA). GraphPad Prism 9 (GraphPad Software, Inc., San Diego, CA, USA) was used to visualize the differences in HbO levels between the groups. Group differences in demographic and clinical characteristics, and HbO levels between the ADHD with and without medication groups were calculated using two-sample t -tests. The Bonferroni-corrected p-value was calculated using the NIRSIT Lite Analysis Tool. To examine the association between the clinical scores and mean HbO levels, we conducted correlation analyses using Pearson’s method. Based on the channels showing significant mean group differences in HbO, we performed a two-way analysis of covariance (ANCOVA), adjusting for age and sex, to evaluate group differences in the fNIRS network metrics (Ge, C p , NC p , and DC w ). The interaction effects between clinical scores (ARS, ATA, and SCWT) and medication groups were evaluated using two-way ANOVA. To identify hemispheric lateralization patterns, independent t -tests were performed between the two groups using the asymmetry score. The statistical threshold was set at two-tailed p < 0.05. List Of Abbreviations ADHD, attention deficit hyperactivity MRI, magnetic resonance imaging NIRS, near-infrared spectroscopy HbO, oxygenated hemoglobin HbR, deoxygenated hemoglobin MPH, methylphenidate ATM, atomoxetine SCWT, stroop color-word test RT, response time RTV, response time variability IQ, intellectual quotients ARS, ADHD rating scale ATA, advanced test of attention MBLL, modified Beer-Lambert law NCp, nodal clustering coefficient DCw, weighted degree centrality Declarations Author Contributions KH and DHK: writing-original draft, resources, investigation, and data curation. KH and YHJ: visualization and methodology. J-HA and WS: resource and investigation. HJL and JIK: conceptualization, supervision, and data curation. JIK: funding. Acknowledgments This study was supported by the Korea Health Technology R&D Project through the Korean Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare [grant no. HI19C0844]. 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Additional Declarations No competing interests reported. Supplementary Files fNIRSsupplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4083291","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":284058534,"identity":"961d2f77-a239-4912-bcf7-5199acd025ce","order_by":0,"name":"Hyuna Kim","email":"","orcid":"","institution":"Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, Republic of Korea","correspondingAuthor":false,"prefix":"","firstName":"Hyuna","middleName":"","lastName":"Kim","suffix":""},{"id":284058535,"identity":"6cd69989-dfb2-465b-a549-426f93d71624","order_by":1,"name":"Da Hyun Kang","email":"","orcid":"","institution":"Institute of Mental Health, Hanyang University, Seoul, Republic of Korea","correspondingAuthor":false,"prefix":"","firstName":"Da","middleName":"Hyun","lastName":"Kang","suffix":""},{"id":284058536,"identity":"3f628e9a-2fda-465c-bae8-daf18f9513d8","order_by":2,"name":"Young Hun Jang","email":"","orcid":"","institution":"Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, Republic of Korea","correspondingAuthor":false,"prefix":"","firstName":"Young","middleName":"Hun","lastName":"Jang","suffix":""},{"id":284058537,"identity":"20593947-a408-4ab6-8d57-aa0cf5854b2b","order_by":3,"name":"Ja-Hye Ahn","email":"","orcid":"","institution":"Department of Pediatrics, Hanyang University Hospital, Hanyang University College of Medicine, Seoul","correspondingAuthor":false,"prefix":"","firstName":"Ja-Hye","middleName":"","lastName":"Ahn","suffix":""},{"id":284058538,"identity":"7639dd5e-c324-43c6-b72a-3d54af5875e6","order_by":4,"name":"Won Sojin","email":"","orcid":"","institution":"Hanyang Inclusive Clinic for Developmental Disorders, Seoul, Republic of Korea","correspondingAuthor":false,"prefix":"","firstName":"Won","middleName":"","lastName":"Sojin","suffix":""},{"id":284058539,"identity":"25968eb1-0778-4c78-b576-51618be84619","order_by":5,"name":"Hyun Ju Lee","email":"","orcid":"","institution":"Department of Pediatrics, Hanyang University Hospital, Hanyang University College of Medicine, Seoul","correspondingAuthor":false,"prefix":"","firstName":"Hyun","middleName":"Ju","lastName":"Lee","suffix":""},{"id":284058540,"identity":"8b171a36-0e54-4213-817c-a224ab7fb101","order_by":6,"name":"Johanna Inhyang Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYBACNhBibAAxmY9BRNiJ18KWBhFhBpEJBHRBtPCYQfiEtPCxn0578HPH4cR+iZxvQMY2eT5mBrYHH3/gsYInd7th75nDiTN7zoIYtw3bmBnYDWfgsYWNIXebBG/bYWOD470gxm1GoBY2aR58WvjfbpP8C9JymOcZkHHbHqzlDz4tErnbpIG2yBkc72EDMm4ngrXg8z6bxNvtxrJn0uUke46ZScu23U5uY2Zsk+xJw61Fvj9328O3O6x5+CWSn0m+bbttO7+9+ZjEDxvcWqCgGZkDiSZCoI4YRaNgFIyCUTBSAQBg3Uz7Mex72AAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Psychiatry, Hanyang University Medical Center, Seoul, Republic of Korea","correspondingAuthor":true,"prefix":"","firstName":"Johanna","middleName":"Inhyang","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2024-03-12 11:32:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4083291/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4083291/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53581482,"identity":"cf6f9e7a-c50c-45e1-9e7b-f38d255addd9","added_by":"auto","created_at":"2024-03-27 17:35:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":476345,"visible":true,"origin":"","legend":"\u003cp\u003eAn illustration of the protocol and task arrangement. SWCT, Stroop Word Color Test; ADHD, attention deficit hyperactivity disorder; NIRS, near-infrared spectroscopy.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/1a1e8c61fcc72397a39d32cd.png"},{"id":53581488,"identity":"178a7bf3-d456-4389-97e1-d36c81a47b9e","added_by":"auto","created_at":"2024-03-27 17:35:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":907176,"visible":true,"origin":"","legend":"\u003cp\u003eTopographical distribution of the 15 fNIRS recording channels within the prefrontal cortex. fNIRS, functional near-infrared spectroscopy.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/1b9684c0f8c3a43fe48d9041.png"},{"id":53581481,"identity":"8a82f96b-e429-47f2-8525-cd47fc992c1f","added_by":"auto","created_at":"2024-03-27 17:35:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":834243,"visible":true,"origin":"","legend":"\u003cp\u003eDifferences of HbO between participants with ADHD with and without. ADHD, attention deficit hyperactivity disorder; HbO, hemoglobin oxygen.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/cb27b6064c521f9dca4e24a3.png"},{"id":53582649,"identity":"7f169ff3-f0fa-4823-b67c-f548aefcb745","added_by":"auto","created_at":"2024-03-27 17:43:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":303426,"visible":true,"origin":"","legend":"\u003cp\u003eInteraction effect between psychological test and group using two-way ANOVA. ATA, advanced test of attention; HbO, hemoglobin oxygen; SD, standard deviation; RT, response time; ARS, ADHD rating scale; ADHD, attention deficit hyperactivity disorder; ANOVA, Analysis of variance. *\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/3b6d78518f63113d208b39a3.png"},{"id":53581480,"identity":"9b75b680-0831-4d9e-b331-4fd89611bbdb","added_by":"auto","created_at":"2024-03-27 17:35:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":268012,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic representation of lateralization on brain. The four-areas bar graph on the right shows where there were significantly differences between groups in asymmetry scores calculated based on the absolute volumes adjusted for sex, age, handedness, and total volume excluded ventricles. *\u003cem\u003eadjusted p\u003c/em\u003e\u0026lt;0.05.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/0778718d6a123dff34c3ccb4.png"},{"id":77095157,"identity":"3267ecf2-bf3b-4678-8ed6-755c0ccf52ab","added_by":"auto","created_at":"2025-02-25 06:11:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4703532,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/26ee88cc-1bde-40ab-b4cd-9835718c2c11.pdf"},{"id":53581487,"identity":"aef26b2d-ac09-4971-a019-c4980b177fa7","added_by":"auto","created_at":"2024-03-27 17:35:17","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":83970,"visible":true,"origin":"","legend":"","description":"","filename":"fNIRSsupplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4083291/v1/f6ba4b73f84674dd31313bb3.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of medication on the rostrolateral prefrontal oxygenation and thalamic volume asymmetry in youths with ADHD","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eAttention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in school-age children and is characterized by age-inappropriate symptoms of inattention, hyperactivity, and impulsivity \u003csup\u003e1\u003c/sup\u003e. Approximately 50% of individuals with these symptoms progress to a chronic state during adulthood \u003csup\u003e2\u003c/sup\u003e, debilitating the quality of their social, academic, or occupational functions \u003csup\u003e3\u003c/sup\u003e. Furthermore, patients with ADHD show impaired response inhibition, which is associated with the suppression of executive function, causing crucial neurophysiological defect \u003csup\u003e4\u0026ndash;6\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFunctional near-infrared spectroscopy (fNIRS) has been used to measure regional oxygenation in the brain, suggesting the potential of using fNIRS for diagnosis and treatment surveillance. A study using fNIRS found discriminative signals in specific brain regions, both between children with ADHD and controls and between medication-na\u0026iuml;ve and non-na\u0026iuml;ve children with ADHD \u003csup\u003e7\u003c/sup\u003e. A previous meta-analysis of fNIRS studies on ADHD reported inconsistencies among study results; some studies showed hyperactivity in the dorsolateral prefrontal cortex and left superior frontal cortex \u003csup\u003e8\u0026ndash;11\u003c/sup\u003e, whereas another study reported hypoactivity in the right prefrontal brain regions of patients with ADHD \u003csup\u003e12\u003c/sup\u003e. Additionally, reduced oxyhemoglobin signals in the inferior and middle frontal gyri during cognitive tasks are normalized by medication in children with ADHD \u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe first-line treatment for ADHD is medication, including methylphenidate (MPH; a dopamine and norepinephrine reuptake inhibitor) and atomoxetine (ATM; a selective norepinephrine reuptake inhibitor). fNIRS can identify biomarkers of treatment effects that are more objective than conventional clinician- or questionnaire-based evaluation methods because it is a non-invasive, portable neuroimaging technique with superior spatial resolution and reduced susceptibility to motion artifacts \u003csup\u003e14\u0026ndash;16\u003c/sup\u003e. A previous study has suggested that reduced prefrontal activation by fNIRS could serve as an objective biomarker for predicting the clinical course and treatment response \u003csup\u003e17\u003c/sup\u003e. Another study reported that children with ADHD who were taking medication showed hyperactivation in the prefrontal cortex (PFC) during a high-workload task compared to children with ADHD without medication; however, there were no significant differences in cognitive task scores \u003csup\u003e18\u003c/sup\u003e. However, Nagashima et al. revealed that the mode of normalization in children with ADHD receiving medication was asymmetrical in the frontoparietal attention network \u003csup\u003e9\u003c/sup\u003e. Brain activation was significantly higher in the right middle frontal gyrus and right inferior prefrontal gyrus after the administration of atomoxetine \u003csup\u003e13\u003c/sup\u003e and methylphenidate \u003csup\u003e19\u003c/sup\u003e. Other studies have reported opposite directionality, in which children with ADHD exhibited hyperactivity in brain activity, especially in the left PFC, when they performed the SCWT, regardless of the medication type \u003csup\u003e20\u003c/sup\u003e. Some studies have investigated using functional magnetic resonance imaging (fMRI) to identify the effects of medication in ADHD populations and found that hyperactivity is the primary outcome. A previous meta-analysis has explored the medication effect associated with enhanced function of right dorsolateral prefrontal cortex in children with ADHD compared to health control \u003csup\u003e21\u003c/sup\u003e. Another meta-analysis found that psychostimulants improve bilateral inferior frontal cortex and insular activation in children with ADHD \u003csup\u003e22\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHemispheric differences in brain structure are thought to reflect aberrant developmental synchrony between the left and right brain in an asymmetric manner \u003csup\u003e23\u003c/sup\u003e, contributing to or accompanied by ADHD symptom severity. A recent meta-analysis of abnormal hemispheric asymmetry using resting-state fMRI reported that children with ADHD had both structural (in the prefrontal cortex, subcortical cortices, and cerebellum) and functional abnormalities (in the inferior frontal gyrus, temporal pole, and cerebellum) \u003csup\u003e24\u003c/sup\u003e. Particularly, as the symptoms of ADHD become severe, hemispheric brain asymmetry differences increase, indicating a pathoplastic role for asymmetry with a structural basis during development. Moreover, volumetric anomalies of thalamocortical regions have been demonstrated in children with ADHD, revealing the pathogenesis of various ADHD symptoms \u003csup\u003e25\u003c/sup\u003e. Ivanov et al. showed reduced pulvinar volumes of the thalamus in patients with ADHD without medication compared to those with medication, suggesting a medication effect on the thalamic subcircuit \u003csup\u003e26\u003c/sup\u003e. Subcortical changes in children with ADHD could be more evident in thalamic regions that could not be detected using fNIRS. Although fNIRS can provide information only on cortical activity, information on the thalamic volume in structural magnetic resonance imaging (sMRI) may help reveal the pathological characteristics of patients with ADHD.\u003c/p\u003e \u003cp\u003ePast studies have focused on comparing the hemodynamic response between children with ADHD receiving medication and controls, while there has been limited research comparing children with ADHD receiving medication and those not receiving medication. Moreover, numerous studies examining the neural substrates of the effects of medication have largely focused on single neuroimaging or neurophysiological results. Simultaneous fNIRS-sMRI studies in children with ADHD with and without medication offer clinical advantages for detecting treatment responses to medication and the reliability of variable functional patterns with robust results. We explored whether there were any differences in abnormal brain activity and structural asymmetry on magnetic resonance imaging (MRI) between ADHD patients with and without medication, using fNIRS and sMRI to elucidate the neural mechanism of medication in children with ADHD.\u003c/p\u003e"},{"header":"2 Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Demographic and clinical characteristics\u003c/h2\u003e \u003cp\u003eThe demographic and clinical characteristics of the study participants are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 45 children with ADHD (23 medicated and 22 unmedicated) were evaluated. The participant groups did not differ in terms of mean age, sex, FSIQ, ADHD-RS-IV inattention, or socioeconomic characteristics. The ADHD-RS-IV total score and hyperactivity-impulsivity score was significantly higher in the ADHD without medication group than ADHD with medication group (28.27\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01 vs. 23.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.50, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05; 11.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.08 vs 8.83\u0026thinsp;\u0026plusmn;\u0026thinsp;4.15, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03, respectively). There were no significant differences in the ATA and SCWT parameter scores. The CGI-S score was significantly lower in the ADHD with medication group compared to the ADHD without medication group (4.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 vs 4.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003efactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADHD\u003c/p\u003e \u003cp\u003ewith medication\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eADHD\u003c/p\u003e \u003cp\u003ewithout medication\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChildren characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSIQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.30\u0026thinsp;\u0026plusmn;\u0026thinsp;16.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94.14\u0026thinsp;\u0026plusmn;\u0026thinsp;12.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADHD-RS-IV total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.27\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.05*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADHD-RS-inattention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.39\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.36\u0026thinsp;\u0026plusmn;\u0026thinsp;4.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADHD-RS-hyperactivity-impulsivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.83\u0026thinsp;\u0026plusmn;\u0026thinsp;4.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.03*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPH dose (mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.06\u0026thinsp;\u0026plusmn;\u0026thinsp;19.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eATM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eATM dose (mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.67\u0026thinsp;\u0026plusmn;\u0026thinsp;14.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153.69\u0026thinsp;\u0026plusmn;\u0026thinsp;14.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.52\u0026thinsp;\u0026plusmn;\u0026thinsp;17.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHandedness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (87.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (86.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCGI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCGI-S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eC-GAS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.00\u0026thinsp;\u0026plusmn;\u0026thinsp;7.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eATA Visual Task\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOmission error\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.83\u0026thinsp;\u0026plusmn;\u0026thinsp;19.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.73\u0026thinsp;\u0026plusmn;\u0026thinsp;19.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommission error\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.83\u0026thinsp;\u0026plusmn;\u0026thinsp;18.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.55\u0026thinsp;\u0026plusmn;\u0026thinsp;19.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.70\u0026thinsp;\u0026plusmn;\u0026thinsp;14.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.36\u0026thinsp;\u0026plusmn;\u0026thinsp;12.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRTV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.30\u0026thinsp;\u0026plusmn;\u0026thinsp;19.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.77\u0026thinsp;\u0026plusmn;\u0026thinsp;17.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eATA Auditory Task\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOmission error\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.22\u0026thinsp;\u0026plusmn;\u0026thinsp;23.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.77\u0026thinsp;\u0026plusmn;\u0026thinsp;22.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommission error\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.74\u0026thinsp;\u0026plusmn;\u0026thinsp;22.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.95\u0026thinsp;\u0026plusmn;\u0026thinsp;22.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.52\u0026thinsp;\u0026plusmn;\u0026thinsp;8.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.50\u0026thinsp;\u0026plusmn;\u0026thinsp;12.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRTV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.13\u0026thinsp;\u0026plusmn;\u0026thinsp;10.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.50\u0026thinsp;\u0026plusmn;\u0026thinsp;10.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSCWT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWord score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.26\u0026thinsp;\u0026plusmn;\u0026thinsp;10.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.32\u0026thinsp;\u0026plusmn;\u0026thinsp;13.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColor score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.09\u0026thinsp;\u0026plusmn;\u0026thinsp;8.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.14\u0026thinsp;\u0026plusmn;\u0026thinsp;8.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColor-word score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.91\u0026thinsp;\u0026plusmn;\u0026thinsp;10.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.45\u0026thinsp;\u0026plusmn;\u0026thinsp;9.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterference score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.26\u0026thinsp;\u0026plusmn;\u0026thinsp;8.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.50\u0026thinsp;\u0026plusmn;\u0026thinsp;10.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSocioeconomic characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEconomic Status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh average\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow Average\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (26.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal education level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege or university\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (91.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (90.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFather\u0026rsquo;s education level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege or university\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (78.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (95.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or \u003cem\u003en\u003c/em\u003e (%). ADHD, attention deficit/hyperactivity disorder; FSIQ, full-scale intellectual quotation; MPH, methylphenidate; ATM, atomoxetine; CGI-S, clinical global impression scale-severity; C-GAS children\u0026rsquo;s global assessment scale; ATA, advanced test of attention; RT, response time; RTV, response time variability; SCWT, stroop color-word test. Six children were medicated with both MPH and ATM. *\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Comparison of hemodynamic differences between groups\u003c/h2\u003e \u003cp\u003eThe HbO of channel 9 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) in the 1st rest period and the HbO of channels 13 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) and 14 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) during task 2 (color) were significantly different after Bonferroni correction. The medicated ADHD group showed significantly lower HbO than the unmedicated ADHD group in channel 9 of 1st rest (-0.0400\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 vs 0.0613\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01). Contrastingly, the medicated ADHD group showed significantly higher HbO than those in the unmedicated group in channel 13 and 14 during task 2 (color test) (0.0818\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 vs 0.0057\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11, 0.0592\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 vs -0.0188\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10, respectively). The differences in HbO levels between the two groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e and hemodynamic of deoxygenated hemoglobin (HbR) was found in \u003cb\u003eSupplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e. However, there was no significant difference in hemispheric asymmetry score of HbO and HbR between groups (\u003cb\u003eSupplementary table S2\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifferences in mean oxyhemoglobin measurements between participants with ADHD with and without medication.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003esection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003echannel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eADHD with medication\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eADHD without medication\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003esection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003echannel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eADHD with medication\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eADHD without medication\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003e1st\u003c/p\u003e \u003cp\u003erest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.171\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.346\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003eTask1\u003c/p\u003e \u003cp\u003e(Word)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.032\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.071\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.174\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.444\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.671\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.053\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.021\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.492\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.144\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.297\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.194\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.173\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.144\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.121\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.177\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.570\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.191\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.117\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.186\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.184\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.063\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.091\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.123\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.332\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.144\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.066\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.083\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.147\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.122\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.400\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.613\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.231\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.312\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.259\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.227\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.196\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.359\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.104\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.558\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.358\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.222\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.065\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.049\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.340\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.044\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.234\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.005\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.402\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.153\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.504\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.183\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.265\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.447\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.000\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.146\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.523\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.316\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003e2nd rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.112\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.051\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003eTask2\u003c/p\u003e \u003cp\u003e(Color)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.475\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.111\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.178\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.047\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.462\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.489\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.127\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.035\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.393\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.108\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.070\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.317\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.240\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.145\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.219\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.305\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.730\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.377\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.406\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.067\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.547\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.084\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.300\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.244\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.571\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.415\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.058\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.342\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.418\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.163\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.143\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.117\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.865\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.153\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.266\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.597\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.825\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.852\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.555\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.131\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.727\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.260\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.003\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.013\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.670\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.194\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.048\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.804\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.818\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.057\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.02*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.091\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.030\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.592\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.188\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.114\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.094\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.334\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.120\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003e3rd\u003c/p\u003e \u003cp\u003erest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.195\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.426\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003eTask3\u003c/p\u003e \u003cp\u003e(Color-Word)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.107\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.129\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.898\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.403\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.582\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.360\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.213\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.206\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.505\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.447\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.410\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.114\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.481\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.022\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.132\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.385\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.358\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.200\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.167\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.161\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.455\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.289\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.118\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.413\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.412\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.011\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.162\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.162\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.386\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.065\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.332\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.195\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.173\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.184\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.163\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.526\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.394\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.333\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.484\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.379\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.085\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.058\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.122\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.510\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-0.597\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.439\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.459\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.469\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.303\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.265\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.505\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.505\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.202\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.117\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.542\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.004\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.501\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e0.359\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eData are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e). ADHD, attention deficit hyperactivity disorder; SD, standard deviation. * Significant with Bonferroni correction for multiple comparison calculated by NIRSITLiteAnalysisTool.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Correlation between HbO and clinical scores in groups\u003c/h2\u003e \u003cp\u003eIn channel 9, the HbO values during the 1st resting period showed a significant positive correlation with ATA visual task response time (RT) scores and a negative correlation with SCWT interference scores in the unmedicated ADHD group (\u003cb\u003eSupplementary table S3\u003c/b\u003e). In channel 13, the HbO values of task 2 were negatively correlated with the hyperactivity-impulsivity scores and total ARS scores in the unmedicated ADHD group (\u003cb\u003eSupplementary table S4\u003c/b\u003e). The HbO values positively correlated with the SCWT word scores in the medicated ADHD- group (\u003cb\u003eSupplementary Table S4\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eIn the interaction analyses, there was a significant interaction effect between response time variability (RTV) scores of the ATA visual task and the medicated ADHD group in channel 9 of the 1st rest period (\u003cem\u003einteraction p\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). In channel 9, the correlation between RTV scores and HbO during the 1st resting period showed opposite directions according to medication in the two groups; although not significant, there was a negative correlation in the medicated ADHD group and a positive correlation in the unmedicated ADHD group. There was a similar tendency in ATA visual task commission error [\u003cem\u003einteraction p\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.09 at channel 9 during 1st rest, \u003cem\u003einteraction p\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07 at channel 13 during task 2 (color)] and ARS inattention scores [\u003cem\u003einteraction p\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07 at channel 13 during task 2 (color)]. The interaction effects between the clinical scores and medication are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Comparison of fNIRS network metrics between groups and correlation with clinical scores\u003c/h2\u003e \u003cp\u003eThere were no significant differences in brain network metrics between the two groups. The correlations between the network metrics and SCWT scores are shown in \u003cb\u003eSupplementary table 5\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Comparison of hemispheric asymmetry of gross volume between groups\u003c/h2\u003e \u003cp\u003eThere was no significant difference in the structural brain volume (\u003cb\u003eSupplementary table S6\u003c/b\u003e) between the medicated and unmedicated ADHD groups and among three groups categorized by type of medication (methylphenidate only, atomoxetine only, and both) \u003cb\u003e(Supplementary table S7)\u003c/b\u003e. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e5\u003c/span\u003e \u003cb\u003eand Supplementary table S8\u003c/b\u003e show the asymmetric patterns in the volume of the cortex, white matter, cerebellum, and subcortical regions, including the hippocampus and thalamus. There was a similar pattern of lateralization between groups, as the medicated ADHD group tended to be lateralized to the left hemisphere and the unmedicated ADHD group tended to be lateralized to the right hemisphere. There were significant differences in the (a) hippocampus, (b) centomedian, (c) paracentral, and (d) paratenial of the thalamus after adjusting sex, age, handedness, and total brain volume excluded ventricle or total thalamus volume (adjusted \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03, 0.04, 0.04, and 0.03, respectively) asymmetry scores between the medicated and unmedicated ADHD groups. Children with ADHD who were not taking medication showed more rightward asymmetry in the volumes of the thalamus and hippocampus than those with ADHD who were taking medication.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3 Discussion","content":"\u003cp\u003eTo our knowledge, this is the first multimodal fNIRS-MRI study to compare the effect of medication during a cognitive task and the resting state, elucidating the neuropharmacological substrate based on thalamic asymmetry in children with ADHD. We observed differential brain activity, especially in the left prefrontal cortex during the SCWT, and reduced hemispheric asymmetry in thalamic volume in medicated compared to unmedicated children with ADHD. More specifically, we found reduced hemodynamic activity during the resting state, but increased HbO during the SCWT following pharmacotherapy. The difference in brain activity during the SCWT tasks according to medication was especially prominent in the left prefrontal cortex. Moreover, we found significantly reduced thalamic asymmetry in children with ADHD treated with medication, suggesting a pathoplastic role of neural substrates in the medication effect.\u003c/p\u003e \u003cp\u003eAnother review also reported inconsistent results among studies investigating the pharmacological effects of MPH and ATM \u003csup\u003e27\u003c/sup\u003e. Most studies revealed increased HbO activation in the prefrontal cortex following medication and a higher frequency of right lateralization. Specifically, HbO activation increases after medication intake in the right dorsolateral and ventrolateral prefrontal cortices \u003csup\u003e28\u003c/sup\u003e. In other studies, bilateral increases in oxygenation due to medication \u003csup\u003e29,30\u003c/sup\u003e and left-lateralized treatment effects have been examined due to pharmacological effects during neural assessments \u003csup\u003e20,31\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSome previous studies were limited to boys who did not receive psychotropic medication \u003csup\u003e8,11\u003c/sup\u003e whereas others compared children with ADHD to healthy controls \u003csup\u003e10\u003c/sup\u003e. Moreover, few studies have differentiated the neural substrates associated with brain activation using fNIRS in children with ADHD receiving medication compared to those not receiving medication. It is also noteworthy that the heterogeneity of the patient group, including both na\u0026iuml;ve and non-na\u0026iuml;ve children with ADHD, and the diversity of neurocognitive tasks, could be partly attributed to the inconsistent results \u003csup\u003e27\u003c/sup\u003e. In our study, we found that prefrontal activity in medicated children with ADHD increased during cognitive tasks. This result is in line with previous findings that brain activation increases during the SCWT after taking medication \u003csup\u003e20,27,32\u003c/sup\u003e indicating the restoration of brain activation with medication. As previous studies have used different tasks, different types of medication, and different statistical methods to investigate medication effects and have been small in sample size, more well-designed studies with larger sample sizes are needed.\u003c/p\u003e \u003cp\u003eA recent systematic review \u003csup\u003e32\u003c/sup\u003e showed that brain regions associated with inhibitory control and working memory are widely distributed in the bilateral prefrontal cortices of healthy people. The left prefrontal region is implicated in inhibitory functions and plays an important role in modulating ADHD symptoms \u003csup\u003e33\u0026ndash;37\u003c/sup\u003e. The rostrolateral prefrontal cortex has a large number of dendritic spines per cell \u003csup\u003e38\u003c/sup\u003e and is associated with higher-order cognitive functions \u003csup\u003e39\u003c/sup\u003e. Our results are consistent with those of Miao et al., in which children with ADHD exhibited consistent hypoactivity in the left rostrolateral prefrontal cortex during inhibition tasks \u003csup\u003e40\u003c/sup\u003e. The left rostrolateral prefrontal cortex plays a role in controlling attentional reallocation \u003csup\u003e41\u003c/sup\u003e, which is impaired in patients with ADHD. To investigate the function of the prefrontal cortex, we used a cognitive task, the SCWT, which is one of the best-known psychological experiments requiring high-level cognitive functions of response selection and response inhibition \u003csup\u003e42\u0026ndash;44\u003c/sup\u003e Using the SCWT, we identified that activation of the left rostrolateral prefrontal cortex measured by fNIRS could serve as an objective neural biomarker for children with ADHD.\u003c/p\u003e \u003cp\u003eThe significant difference in brain activation in the left prefrontal cortex in the present fNIRS study is noteworthy, and in line with evidence related to the symptoms of the disease in children with ADHD. Notably, we found an interaction effect of brain activity in the left brain channels between the two groups, suggesting inefficient hemodynamic processing of cognitive function in unmedicated patients with ADHD. The unmedicated ADHD group showed decreased HbO during cognitive tasks according to symptom severity, whereas they exhibited increased HbO in the resting state according to symptom severity. This interesting result regarding the aberrant distribution of hemodynamic changes when entering the cognitive workload extends previous results that showed reduced activation of the prefrontal cortex at fNIRS in children with ADHD beyond resting-state brain activity \u003csup\u003e7,45\u003c/sup\u003e. As the difficulty of the task increases, children with ADHD and impaired cognitive function experience imbalances in effectively distributing hemodynamic energy \u003csup\u003e18\u003c/sup\u003e. Additionally, because children with ADHD are debilitated in their ability to switch tasks, they show a specific deficit regarding the flexible suppression of different rules according to instructions \u003csup\u003e46\u003c/sup\u003e. Consistent with previous findings that methylphenidate can enhance inhibitory control associated with attention switching, stimulant medication may modulate executive function in children with ADHD. Therefore, we conclude that alterations in hemodynamic maintenance reflect the effects of medication in the human brain when confronted with changing cognitive demands to achieve an optimal distribution of attention.\u003c/p\u003e \u003cp\u003eWe also found a significant difference in asymmetry in the hippocampus and several thalamic volumes between medicated and unmedicated patients with ADHD on sMRI, suggesting a possible mechanism involved in the different cortico-subcortical connectivities. A previous study suggested that the volume in the prefrontal cortex of patients with ADHD was smaller than that in TDC, while the subcortical volume in the right hemisphere was greater than that in TDC \u003csup\u003e24\u003c/sup\u003e. The prefrontal cortex receives inputs via the thalamus from other cortical regions and subcortical structures, such as the hippocampus and amygdala, selecting relevant information and ignoring distracting stimuli. An increasing number of studies have shown that the thalamus is a key anatomical structure underlying normal attentional and cognitive control mechanisms in ADHD \u003csup\u003e22,47\u003c/sup\u003e. The thalamus helps suppress inappropriate responses and maintain cognitive flexibility in important tasks. Ivanov et al. reported that patients with ADHD receiving medication had larger thalamic volumes than those who were not receiving medication, compensating for insufficient prefrontal function \u003csup\u003e25\u003c/sup\u003e. Particularly, the intralaminar and medial nuclei of the thalamus have been implicated in synchronizing cortical neurons for effective information transmission during cognitive processing \u003csup\u003e48\u003c/sup\u003e. Additionally, the hippocampus is involved in the neural network of learning and working memory, which is a key defect in patients with ADHD \u003csup\u003e49,50\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough brain asymmetry is a unique feature of the human brain, aberrations in its asymmetric nature may represent plausible clues regarding the effect of ADHD on brain asymmetry, such as abnormal brain development and maturation processes. Recent studies using NIRS have reported functional asymmetry in hemodynamic activation with regard to hemispheric differences as potential biomarkers in children with ADHD \u003csup\u003e51\u003c/sup\u003e. However, they did not compare the structural asymmetry of the brain volume between medicated and unmedicated children with ADHD. Our findings show plausible evidence of abnormal hemispheric asymmetry as the neural basis of the core deficit associated with ADHD, in which unmedicated children with exhibited increased asymmetry in the brain volume of the thalamus and hippocampus compared to medicated children with ADHD. Altered hemispheric asymmetry in the hippocampus and thalamus may contribute to imbalanced attention control under disease conditions, leading to altered cortico-subcortical connectivity with disrupted projections from the subcortex to the frontal cortex. Consistent with our findings, Douglas et al. (2018) revealed morphometric asymmetry of the hippocampus and thalamus in patients with ADHD compared to TD \u003csup\u003e52\u003c/sup\u003e. Moreover, the degree of hemispheric asymmetry involving the prefrontal and subcortical regions is higher in children with more severe ADHD symptoms, indicating a neuroplastic role for disrupted neural mechanisms in the inhibition of cognitive interference \u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, because there is likely heterogeneity in the medication groups (MPH and ATM), the different effects of drug type on hemodynamic patterns should be considered in future studies. Additionally, few participants took medication in addition to MPH and ATM, such as risperidone or aripiprazole, so further studies should control the different pharmacotherapies that could affect the neural responses in patients with ADHD. Second, the number of participants was insufficient to identify the abilities of children with ADHD. Therefore ADHD, future studies must have a large sample size to confirm our conclusions. Third, we measured HbO in the prefrontal cortex using a 15-channel near-infrared machine, which is the only commercially available near-infrared machine for children in Korea but has the disadvantage that it is difficult to reflect high-density resolution. Therefore, further studies need to use multichannel measurements to investigate the relationship between functional networks and structural mechanisms of the entire hemisphere. Fourth, the ARS scores were significantly lower in the medication group compared to the non-medicated group. This may reflect medication effect, as 70% show a response to ADHD medication. The mismatch of baseline ARS scores may be source of selection bias in this study. Finally, all ADHD subtypes were included in this study because the sample size was too small to perform independent analyses according to subtype. This may have caused heterogeneity in the behavioral and neuroimaging characteristics of the participants.\u003c/p\u003e \u003cp\u003eIn summary, we examined the effect of medication on hemodynamic activity and functional network connectivity in the prefrontal area using fNIRS and on the hemispheric asymmetry of structural brain volume with MRI in children with ADHD. Our findings suggest that left rostrolateral prefrontal activation and reduced thalamic asymmetry are important for inhibitory control, and that the activity of this region is restored by ADHD medication.\u003c/p\u003e"},{"header":"4 Methods","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e4.1. Participants\u003c/h2\u003e \u003cp\u003eParticipants were enrolled from a psychiatric outpatient clinic at Hanyang University Medical Center, and advertisements were made through internet posts. Among the screened participants, 47 with ADHD were recruited for the study. Two participants were later excluded owing to channel rejection during the fNIRS measurement, and 45 participants were finally included in the analysis, of which 23 were included in the medicated group and 22 in the unmedicated group.\u003c/p\u003e \u003cp\u003eThe inclusion and exclusion criteria were identical for the medicated and unmedicated groups, except for medication status. Potential participants were included if they 1) were between 8 and 15 years of age; 2) fulfilled the ADHD diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia \u0026ndash; Present and Lifetime version (K-SADS-PL) \u003csup\u003e53\u003c/sup\u003e, and 3) their intelligence quotients (IQ) were above 70. Exclusion criteria included: 1) congenital hereditary problems; 2) brain injury such as cerebral palsy; 3) spasmodic disorder, other neurological disorders, or untreated dysesthesia (sensory disturbance); 4) past or current schizophrenia and childhood psychosis; 5) IQ scores under 70; and 6) comorbidity with obsessive-compulsive, depressive, or bipolar disorder.\u003c/p\u003e \u003cp\u003eThe unmedicated ADHD group consisted of participants who had never received MPH or ATM treatment or had not taken medication within four weeks prior to participating in the study. The medicated group consisted of patients with ADHD whose dosages of methylphenidate or atomoxetine had not changed over the past month. The Clinical Global Impression Scale-Severity (CGI-S) score for both the drug-na\u0026iuml;ve and drug-medicated groups was \u0026gt;\u0026thinsp;4, indicating that their underlying symptoms were moderate to severe, and there was no remission.\u003c/p\u003e \u003cp\u003eAmong the medicated ADHD group, 17 participants took methylphenidate (mean dosage; 32.06\u0026thinsp;\u0026plusmn;\u0026thinsp;19.78 mg), and 12 participants took atomoxetine (mean dosage 39.67\u0026thinsp;\u0026plusmn;\u0026thinsp;14.67 mg). Among these participants, seven were prescribed methylphenidate and atomoxetine. The CGI scores for each group and drug information for the medication group are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe diagnosis of psychiatric disorders was confirmed using the K-SADS-PL, which was conducted by a single board-certified psychiatrist. IQ scores were determined using the Korean version of the Wechsler Intelligence Scale for Children (WISC), Fourth or Fifth Edition \u003csup\u003e54\u003c/sup\u003e. All participants and their parents provided written informed consent to participate in the study after receiving sufficient explanation of the study. All experimental protocols were approved by the Institutional Review Board of the Hanyang University Medical Center (IRB Approval no.2020-02-025) and performed in compliance with the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e4.2. Clinical assessment tools\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e4.2.1. ADHD Rating Scale (ARS)\u003c/h2\u003e \u003cp\u003eThe ARS is the most widely used scale to screen children with ADHD by their parents and teachers and was developed by Du Paul based on the diagnostic criteria of ADHD illustrated in the DSM-IV \u003csup\u003e55\u003c/sup\u003e. The scale consists of 18 items rated from 0 to 3, with parents or teachers scoring each item based on the frequency of the children\u0026rsquo;s problematic behaviors. The total scores of the odd-numbered questions measures inattention and the total number of even-numbered items measures impulsivity and hyperactivity. Higher scores indicate more severe attention-deficit and hyperactivity symptoms, and the cutoff score for the ADHD criteria is a total score of 19.\u003c/p\u003e \u003cp\u003eIn this study, the parents completed the Korean version of the ADHD Rating Scale-IV (K-ARS-Ⅳ) to measure the ADHD symptoms of the participants during the past three months. The K-ARS has been shown to have high reliability and validity to discriminate and identify children with ADHD \u003csup\u003e56,57\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e4.2.2. The Advanced Test of Attention (ATA)\u003c/h2\u003e \u003cp\u003eThe ATA is a computerized continuous performance test used to assess attention and inhibitory control \u003csup\u003e58\u003c/sup\u003e. The test consists of visual and auditory subtests, each lasting 15 min. The participants were instructed to press the button (response) for the target stimuli as fast as possible and ignore the non-target stimuli (inhibit).\u003c/p\u003e \u003cp\u003eThree nonverbal stimuli were presented for each subtest, all of which were non-target stimuli except for one target stimulus \u003csup\u003e58\u003c/sup\u003e. In the visual test, an image with a triangle inside a square was the target stimulus, and the non-target stimuli were circles and squares drawn within a square. The target stimulus of an auditory test to which the participant should respond was three consecutive beep sounds; if two or four consecutive beeps were presented, the participants were not required to press the button. Each subtest was implemented after the practice trial according to the researcher\u0026rsquo;s instructions.\u003c/p\u003e \u003cp\u003eThe test yielded four main indicators:1) omission error to measure the symptoms of inattention; 2) commission error to measure impulsivity and disinhibition; 3) mean response time for correct responses to measure the speed at which target stimuli were processed; and 4) standard deviation of reaction time (response time variability) to measure the consistency of attention. All scores were translated into T-scores, adjusted based on normative distribution according to age and sex, with an average score of 50 and a standard deviation of 15.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e4.2.3. Stroop Color-Word Test (SCWT)\u003c/h2\u003e \u003cp\u003eThe participants underwent fNIRS assessment during SCWT administration. The SCWT is a frequently used neuropsychological test for evaluating cognitive control and entails multiple cognitive processes, including selective attention, response inhibition, interference control, and speeded response \u003csup\u003e59\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe test consisted of three subtests (word, color, and color words), and with each subtest lasting 45s. First, during the word subtest, participants were instructed to look at black-printed words and read the letters of the words as quickly as possible within the time limit. During the color test, the participants were instructed to read three types of color patches as quickly as possible. Finally, in the color-word subtest, the letters and colors of the words were presented incongruently, and the participants were instructed to say colors instead of letters. When the target (color) and obstruction (letter) stimuli were presented simultaneously, the ability to sustain attention was measured by inhibiting the interference of the obstruction stimuli and selecting only the target stimuli.\u003c/p\u003e \u003cp\u003eIn this study, the Korean version of the standardized SCWT was implemented using E-Prime 3.0 software (Psychology Software Tools, Pittsburgh, PA, USA). For each subtest condition, after being guided by each test instructions and 30s of resting state, the participants proceeded to perform the task while watching the stimuli on the screen. The stimuli were presented in five rows with 20 words in each row. The raw score was calculated by counting the total number of correct answers for each test, and the interference score was calculated as the difference between the color and color-word scores. All scores were converted to T-scores based on the normative distribution according to age and sex. The protocol for SCWT administration during fNIRS assessment is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.3. fNIRS data acquisition and pre-processing\u003c/h2\u003e \u003cp\u003eTo quantify the amount of oxygen in the blood, we used a NIRSIT Lite Kids machine (OBELAB, Seoul, Republic of Korea), which is an fNIRS instrument with five dual-wavelength (780/850 nm) light-emitting diode light sources and 7 detectors spaced 2.5 cm apart, comprising 15 regular (2.5 cm) channels covering the prefrontal cortex. The 15 channels are spaced 2.5 cm apart from each other, with 8 channels on the right side of the orbitofrontal cortex (channel 1), the dorsolateral prefrontal cortex (channels 2, 3), and the rostrolateral prefrontal cortex (channels 4, 5, 6, 7, 8), respectively, and 7 channels on the left side of the orbitofrontal cortex (channel 15), the dorsolateral prefrontal cortex (channels 12, 14), and the rostrolateral prefrontal cortex (channels 8, 9, 10, 11, 13). Channel 8 was excluded from the analysis because it belongs to both sides of the left and right rostrolateral prefrontal cortices. The alignment of the 15 channels is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003e. If more than three of the 15 channels were disconnected, the subjects were excluded from the analysis. The optical-signal variation in each channel was sampled at a frequency of 8.138 Hz. The threshold of the signal-to-noise ratio criterion for determining poor quality, such as the slow drift of physiological noise and environmental noise, was 30 dB, which was used to qualify the noise of the detected channels after bandpass filtering from 0.005 to 0.1 Hz. The obtained optical intensity signals were converted into an oxygenated hemoglobin (HbO) concentration change time series using the modified Beer-Lambert law (MBLL). The average signal for each channel during the last 10 s of rest and 30 s of each task was used in the analysis to compare regional neural activity between the groups. We focused on HbO rather than HbR because HbR is 1\u0026ndash;2 seconds slower than changes in HbO and may not reflect an accurate signal \u003csup\u003e60\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.4. fNIRS: calculation of network parameters\u003c/h2\u003e \u003cp\u003eNetwork-weighted edges were defined to obtain a functional network of the fNIRS data \u003csup\u003e51\u003c/sup\u003e. Group-averaged connectivity data were obtained by averaging the time series of each resting and task block and then transforming the average of each participant\u0026rsquo;s Fisher-transformed value back to the Pearson\u0026rsquo;s correlation matrix. We conducted one-sample \u003cem\u003et\u003c/em\u003e-tests to compare the correlation values of each channel pair with a 0. The 15 network nodes had the same anatomical locations as the 15 channels and encompassed the orbitofrontal and rostrolateral prefrontal cortices.\u003c/p\u003e \u003cp\u003eGlobal and local network metrics were analyzed using GRETNA software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.nitrc.org/projects/gretna/\u003c/span\u003e\u003cspan address=\"http://www.nitrc.org/projects/gretna/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) \u003csup\u003e61\u003c/sup\u003e. The evaluated metrics included: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Global efficiency (Ge), which indicates the global efficiency of the parallel transfer of information in the network \u003csup\u003e62\u003c/sup\u003e. Ge reflects network integration \u003csup\u003e63\u003c/sup\u003e; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) the nodal clustering coefficient (NC\u003csub\u003ep\u003c/sub\u003e), which indicates whether each node is interconnected with its neighbors \u003csup\u003e64\u003c/sup\u003e. The NC\u003csub\u003ep\u003c/sub\u003e reflects network segregation \u003csup\u003e63,65,66\u003c/sup\u003e; and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) the weighted degree centrality (DC\u003csub\u003ew\u003c/sub\u003e), which is the sum of all weighted connections to a given node \u003csup\u003e67\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e4.5. MRI acquisition and analysis\u003c/h2\u003e \u003cp\u003eIndividuals with ADHD were scanned using a 3T MRI (Philips, Achieva, 16-channel phase-array head coil, Best, Netherlands). In the T1-weighted images, the single-shot three-dimensional echo-planar images were obtained using these parameters: slice thickness\u0026thinsp;=\u0026thinsp;1 mm, voxel sizes\u0026thinsp;=\u0026thinsp;0.9 mm\u003csup\u003e2\u003c/sup\u003e, field of view\u0026thinsp;=\u0026thinsp;224 mm\u003csup\u003e2\u003c/sup\u003e, repetition time\u0026thinsp;=\u0026thinsp;8.3 ms, echo time\u0026thinsp;=\u0026thinsp;4.6 ms, inverse time\u0026thinsp;=\u0026thinsp;1 ms, and flip angle\u0026thinsp;=\u0026thinsp;8\u0026deg;. The slice orientation was axially parallel to the anterior-posterior commissure line. A total of 150 slices contained the entire hemisphere and brainstem.\u003c/p\u003e \u003cp\u003eAutomated reconstruction and segmentation of individual high resolution T1 weighted MRI volumes were performed using FreeSurfer version 7.1.1 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://surfer.nmr.mgh.harvard.edu/\u003c/span\u003e\u003cspan address=\"https://surfer.nmr.mgh.harvard.edu/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The processing pipeline comprises motion correction, automated Talairach transformation, signal intensity normalization, removal of nonbrain tissue, automated correction for topological defects, subcortical segmentation, and cortical parcellation \u003csup\u003e68\u0026ndash;72\u003c/sup\u003e. The imaging process has been described in detail in previous studies \u003csup\u003e72,73\u003c/sup\u003e. Regions based on the Desikan-Killiany atlas were segmented for volumetric analysis, with 34 left- and 34 right-hemispheric regions. To adjust for individual differences in the skull size, we corrected the absolute volume to the relative volume. The relative volume index was calculated as follows:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\text{R}\\text{e}\\text{l}\\text{a}\\text{t}\\text{i}\\text{v}\\text{e} \\text{v}\\text{o}\\text{l}\\text{u}\\text{m}\\text{e} \\left(\\text{%}\\right)=\\frac{\\text{R}\\text{e}\\text{g}\\text{i}\\text{o}\\text{n} \\text{o}\\text{f} \\text{i}\\text{n}\\text{t}\\text{e}\\text{r}\\text{e}\\text{s}\\text{t}}{\\text{I}\\text{n}\\text{t}\\text{r}\\text{a}\\text{c}\\text{r}\\text{a}\\text{n}\\text{i}\\text{a}\\text{l} \\text{v}\\text{o}\\text{l}\\text{u}\\text{m}\\text{e}} \\times 100$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eThalamus segmentation was performed by using a sequence-adaptive Bayesian algorithm based on a probabilistic atlas \u003csup\u003e74\u003c/sup\u003e. The segmented thalamus exhibited a volume of 25 regions in both the right and left thalami. These brain regional volumes were extracted with \u0026lsquo;asegstats2table\u0026rsquo; command. The segmentation outputs were visually inspected by two independent researchers (H. A. and Y. H.). Higher-order thalamic lesions can synchronize the activity of neural networks underlying various cognitive functions, including arousal, memory processing, attention, and reward-based behaviors \u003csup\u003e48,75\u003c/sup\u003e. To evaluate the regions of interest of the thalamus related to the projection pathway to the frontal lobe, we selected the medial group (mediodorsal lateral parvocellular, mediodorsal medial magnocellular, reuniens, and paratenial) and the intralaminar group (central medial, centromedian, center-lateral, paracentral, and parafascicular).\u003c/p\u003e \u003cp\u003eThe difference between the left and right hemispheres of each gross and subsegmentation of the thalamic region is represented by the asymmetry index. The asymmetry index was calculated using the following formula:\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\text{A}\\text{s}\\text{y}\\text{m}\\text{m}\\text{e}\\text{t}\\text{r}\\text{y} \\text{i}\\text{n}\\text{d}\\text{e}\\text{x}=\\frac{\\text{L}-\\text{R}}{(\\text{L}+\\text{R})}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eWhere L and R denote the values of the left and right sides of the hemisphere, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.6. Statistical analysis\u003c/h2\u003e \u003cp\u003eFor pre-processing of fNIRS data and comparison of HbO values between the two groups, we used the NIRSITLiteAnalysis Tool (OBELAB, Seoul, Republic of Korea). All statistical analyses were performed using the SPSS 28 software (SPSS, Inc., Chicago, IL, USA). GraphPad Prism 9 (GraphPad Software, Inc., San Diego, CA, USA) was used to visualize the differences in HbO levels between the groups.\u003c/p\u003e \u003cp\u003eGroup differences in demographic and clinical characteristics, and HbO levels between the ADHD with and without medication groups were calculated using two-sample \u003cem\u003et\u003c/em\u003e-tests. The Bonferroni-corrected \u003cem\u003ep-value\u003c/em\u003e was calculated using the NIRSIT Lite Analysis Tool. To examine the association between the clinical scores and mean HbO levels, we conducted correlation analyses using Pearson\u0026rsquo;s method. Based on the channels showing significant mean group differences in HbO, we performed a two-way analysis of covariance (ANCOVA), adjusting for age and sex, to evaluate group differences in the fNIRS network metrics (Ge, C\u003csub\u003ep\u003c/sub\u003e, NC\u003csub\u003ep\u003c/sub\u003e, and DC\u003csub\u003ew\u003c/sub\u003e). The interaction effects between clinical scores (ARS, ATA, and SCWT) and medication groups were evaluated using two-way ANOVA. To identify hemispheric lateralization patterns, independent \u003cem\u003et\u003c/em\u003e-tests were performed between the two groups using the asymmetry score. The statistical threshold was set at two-tailed \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eADHD, attention deficit hyperactivity\u003c/p\u003e\u003cp\u003eMRI, magnetic resonance imaging\u003c/p\u003e\u003cp\u003eNIRS, near-infrared spectroscopy\u003c/p\u003e\u003cp\u003eHbO, oxygenated hemoglobin\u003c/p\u003e\u003cp\u003eHbR, deoxygenated hemoglobin\u003c/p\u003e\u003cp\u003eMPH, methylphenidate\u003c/p\u003e\u003cp\u003eATM, atomoxetine\u003c/p\u003e\u003cp\u003eSCWT, stroop color-word test\u003c/p\u003e\u003cp\u003eRT, response time\u003c/p\u003e\u003cp\u003eRTV, response time variability\u003c/p\u003e\u003cp\u003eIQ, intellectual quotients\u003c/p\u003e\u003cp\u003eARS, ADHD rating scale\u003c/p\u003e\u003cp\u003eATA, advanced test of attention\u003c/p\u003e\u003cp\u003eMBLL, modified Beer-Lambert law\u003c/p\u003e\u003cp\u003eNCp, nodal clustering coefficient\u003c/p\u003e\u003cp\u003eDCw, weighted degree centrality\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKH and DHK: writing-original draft, resources, investigation, and data curation. KH and YHJ: visualization and methodology. J-HA and WS: resource and investigation. HJL and JIK: conceptualization, supervision, and data curation. JIK: funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Korea Health Technology R\u0026amp;D Project through the Korean Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare [grant no. HI19C0844].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original datasets presented in this study are available upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Statement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccess to data can be obtained through the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest. \u0026nbsp;\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e\u003cem\u003eDiagnostic and statistical manual of mental disorders: DSM-5\u0026trade;\u003c/em\u003e. 5th edition. edn, (American Psychiatric Publishing, a division of American Psychiatric Association, 2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrechsler, R., Brandeis, D., Foldenyi, M., Imhof, K. \u0026amp; Steinhausen, H. 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Some functional magnetic resonance imaging (fMRI) studies on medication effects have provided positive evidence of neuroactivation patterns in children with ADHD; however, they should be extended to functional near-infrared spectroscopy (fNIRS)-based examination of the neuropharmacological effects of medication. We investigated the differences in brain hemodynamic activity between 23 children with ADHD taking medication and 22 children who were not taking medication. Compared with the medicated ADHD group, the unmedicated ADHD group showed significantly reduced activation in the left rostrolateral prefrontal cortex (channel 9, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01; channel 13, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) and dorsolateral prefrontal cortex (channel 14, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). The unmedicated ADHD group exhibited a negative correlation between oxygenated hemoglobin (HbO) and symptom scores, while the ADHD with medication group exhibited a positive correlation. Moreover, the abnormal asymmetry of the thalamic volume was reduced in children with ADHD receiving medication compared to those not receiving medication (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). Current findings suggest that left rostrolateral prefrontal activation and reduced thalamic asymmetry are important for inhibitory control, and that the activity of this region is restored by ADHD medication.\u003c/p\u003e","manuscriptTitle":"Effect of medication on the rostrolateral prefrontal oxygenation and thalamic volume asymmetry in youths with ADHD","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-27 17:35:10","doi":"10.21203/rs.3.rs-4083291/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2ab1c4c2-3cd0-4ad1-8c09-ce8d1505b2b1","owner":[],"postedDate":"March 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29902126,"name":"Health sciences/Diseases/Psychiatric disorders"},{"id":29902127,"name":"Health sciences/Diseases/Psychiatric disorders/Adhd"}],"tags":[],"updatedAt":"2025-02-25T05:39:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-27 17:35:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4083291","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4083291","identity":"rs-4083291","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}