Attention and Inhibition Deficits in Narcolepsy Type 1: Behavioral and Electrophysiological Markers

Attention and Inhibition Deficits in Narcolepsy Type 1: Behavioral and Electrophysiological Markers | 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 Attention and Inhibition Deficits in Narcolepsy Type 1: Behavioral and Electrophysiological Markers Lisan Zhang, Zongshan Li, Xiao Han, Jiahui Xu, Qinglin Xu, Xuelian Ge, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6340580/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Oct, 2025 Read the published version in Translational Psychiatry → Version 1 posted 10 You are reading this latest preprint version Abstract Cognitive impairments in narcolepsy type 1 (NT1) significantly compromise daily functioning, but their neural mechanisms remain unclear. This study employed multimodal electroencephalography (EEG) analyses to investigate electrophysiological substrates of attention and inhibition deficits in NT1 and their association with clinical characteristics, particularly orexin deficiency. High-density EEG recordings were acquired during a Go/NoGo task from 39 NT1 patients and 41 age-/sex-matched healthy controls. Behavioral analyses reveled that compared to controls, NT1 patients exhibited significantly prolonged reaction times and increased errors across both Go and NoGo conditions. Electrophysiological analyses demonstrated that NT1 patients showed: (1) delayed Go-P3 latencies, meaning impaired response preparation; (2) reduced NoGo-P3 amplitudes, reflecting deficient inhibitory control; and (3) attenuated theta-band power and inter-trial phase consistency across conditions. Notably, decreased theta-band power correlated with both lower orexin levels and slower reaction times. These findings suggest that orexin deficiency may mediate theta-band oscillation impairments in NT1, which mechanistically contribute to cognitive dysfunction. Thus, we propose theta-band oscillations as a clinically translatable biomarker for NT1-related cognitive deficits, with promising implications for objective monitoring of disease progression and developing EEG-targeted neuromodulation therapies. Health sciences/Biomarkers/Diagnostic markers Biological sciences/Psychology/Human behaviour Biological sciences/Neuroscience Health sciences/Diseases Health sciences/Pathogenesis narcolepsy cognitive function attention executive function event-related potentials inhibition response time-frequency analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Background Narcolepsy type 1 (NT1) is a chronic and disabling neurological disorder characterized by excessive daytime sleepiness (EDS), cataplexy and sleep–wake symptoms, such as hallucinations, sleep paralysis, and nocturnal sleep disturbance[ 1 ]. With a prevalence of 0.025–0.05% in Western populations, NT1 has seen a rising annual incidence across all age groups, likely due to increased disease awareness[ 2 ]. Its pathogenesis involves the immune-mediated loss of orexin-producing neurons in the lateral hypothalamus, leading to significantly reduced orexin levels in the cerebrospinal fluid (CSF; <110 pg/mL)[ 3 ]. Despite their localized origin, orexin neurons project widely to brainstem, limbic, and cortical regions to regulate multiple physiological functions[ 4 ]. Based on such anatomical characteristics, besides sleep-related symptoms, NT1 can also be combined with metabolic, autonomic, psychiatric, and cognitive impairments[ 1 , 5 ]. Among these, cognitive dysfunction is one of the most prevalent, with approximately 40–50% of patients reporting problems in attention and executive function[ 6 ]. However, subjective cognitive complaints often do not align with objective impairments, emphasizing the need for neuropsychological assessments[ 7 ]. Attention, a fundamental cognitive function, enables individuals to selectively focus on relevant stimuli while filtering out distractions[ 8 ]. People with narcolepsy often report difficulties in engaging, sustaining, and shifting attention, which significantly impair their daily functioning and quality of life[ 7 , 9 – 13 ]. Additionally, impulsivity behaviors such as unhealthy eating and substance abuse are also common in NT1, which are thought to reflect inhibitory control deficits[ 14 ]. Inhibitory control, a core component of executive function, refers to the ability to suppress inappropriate or habitual responses[ 15 ]. While attention deficits in NT1 have been relatively well-studied, research on inhibitory control remains limited and inconsistent[ 16 – 19 ]. The Sustained Attention to Response Task (SART) is a classic Go/NoGo paradigm for assessing sustained attention and inhibitory control. The task requires participants to respond rapidly to frequent Go stimuli while withholding responses to infrequent NoGo stimuli[ 20 , 21 ]. Omission errors (OEs; failures to respond to Go stimuli) and reaction times (RTs) are considered indices of sustained attention, whereas commission errors (CEs; responses to NoGo stimuli) reflect inhibitory control. A systematic review reveled that NT1 patients exhibit more OEs and slower RTs compared to controls, but no differences in CEs[ 22 ]. However, the neural mechanisms underlying these behavioral deficits remain elusive, likely contributing to the lack of broadly effective interventions for cognitive impairments. Electroencephalography (EEG) offers a powerful tool to investigate the neural dynamics of rapid cognitive processes, even in the absence of overt behavioral responses (e.g., successful response inhibition). Two event-related potentials (ERPs)—N2 and P3—are closely associated with attention and inhibitory control, reflecting different stages of cognitive processing. N2, a frontocentral negative deflection occurring 200–300 ms post-stimulus, is thought to reflect stimulus evaluation (Go-N2) or conflict monitoring (NoGo-N2)[ 23 – 26 ]. P3, a centroparietal positive deflection occurring 300–500 ms post-stimulus, is linked to response execution (Go-P3) or inhibition (NoGo-P3)[ 24 , 25 , 27 ]. Source-localization and functional MRI studies have further identified distinct neural networks activated during Go/NoGo tasks: the NoGo condition engages a frontal network, including the anterior cingulate cortex and orbitofrontal cortex, while the Go condition activates a temporal-parietal network involving primary and supplementary motor areas [ 28 , 29 ]. Notably, these regions are key projection sites for orexin neurons, suggesting that cognitive-electrophysiological assessments may provide valuable insights into the neural mechanisms underlying cognitive impairments of NT1. To complement ERP analyses, time–frequency (TF) analysis was employed to capture fine-grained neural dynamics, including event-related spectral power and inter-trial phase coherence (ITPC)[ 30 – 32 ]. Previous studies have shown that theta (3–7 Hz) and alpha (8–12 Hz) oscillations play critical roles in the cognitive processes underlying Go/NoGo tasks[ 33 – 35 ]. Specifically, alpha oscillations are involved in attentional modulation and response execution[ 36 , 37 ], while theta oscillations are more associated with top-down inhibitory control[ 38 , 39 ]. However, no studies to date have examined how NT1 affects neural oscillations during Go/NoGo tasks. As the first study to investigate the impact of NT1 on behavioral and electrophysiological indicators using the SART, our aim is twofold: (1) to determine whether attention and inhibitory control are impaired in NT1, and (2) to explore the neural mechanisms underlying these deficits through ERPs and TF analyses. We hypothesized that NT1 patients would exhibit deficits in both attention and inhibitory control, manifested as poorer behavioral performance (e.g., more OEs/CEs, longer RTs), altered N2/P3 components (e.g., reduced N2/P3 amplitudes, prolonged latencies), and reduced theta/alpha-band oscillations (e.g., lower power or ITPC) compared to healthy controls. These findings may provide novel insights into the neural basis of cognitive dysfunction in NT1 and inform the development of targeted interventions. 2. Materials and Methods 2.1 Subjects A total of 39 patients diagnosed with NT1 were recruited from the Department of Neurology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China, between October 2021 and November 2023. Forty-one healthy controls matched for age, sex, and education level, were recruited through advertisements. All participants were aged 10–50 years, right-handed, and had normal or corrected-to-normal vision. The study was approved by the local ethics committee according to the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal representatives. NT1 diagnosis was confirmed by sleep specialists based on clinical presentation, Multiple Sleep Latency Test (MSLT), nocturnal polysomnography (nPSG), and/or CSF orexin levels, following the International Classification of Sleep Disorders (ICSD)-3 criteria[ 40 ]. Exclusion criteria included other sleep disorders (e.g., obstructive sleep apnea or insomnia), mental retardation, neurological or psychiatric disorders, and a history of alcohol, drug, or substance abuse. Participants were instructed to refrain from using medications (e.g., modafinil, methylphenidate) or substances (e.g., coffee, alcohol, stimulating beverages) for at least one week before testing. All participants underwent a comprehensive neurological examination and completed a demographic survey capturing age, sex, body mass index (BMI), and education level. For NT1 patients, additional clinical data were collected, including disease duration, cataplexy frequency, self-reported symptoms, and medication history. Data from nPSG, MSLT, HLA typing, and CSF orexin levels were obtained from medical records. 2.2 Questionnaires All participants completed a series of validated questionnaires prior to the EEG examination. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), while the Epworth Sleepiness Scale (ESS) was used to measure the severity of EDS. Additional assessments included sleep quality (Pittsburgh Sleep Quality Index [PSQI]), depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), and impulsive tendencies (Barratt Impulsiveness Scale Version 11 [BIS-11]). 2.3 Sustained Attention to Response Task (SART) As shown in Fig. 1 , the SART consisted of a 4-minute 20-second session during which 225 numbers (ranging from 1 to 9) were randomly presented in varying sizes, displayed in white font on a black background[ 21 ]. Each number was displayed for 250 ms, followed by a 900 ms fixation cross (“+”) at the center of the screen. Participants were instructed to press the spacebar in response to all numbers (Go trials) except for the number 3 (NoGo trials). The task included 200 Go trials and 25 NoGo trials. Participants were instructed to prioritize both speed and accuracy equally. To accurately assess behavioral performance, we discarded anticipation responses with RTs < 150 ms and calculated the following indicators: OEs (the number of non-3-digit stimuli with no response within the allowed time); CEs (the number of 3-digit stimuli followed by a response); mean RTs (average response time for correct Go trials ); and RTs variability (RTV), quantified as the coefficient of variation (standard deviation divided by the mean RTs) for correct Go trials[ 16 , 41 ]. 2.4 Procedure The experiment was conducted in a sound-attenuated, electrically shielded room. To ensure participants remained awake during SART, they were allowed a 15-minute nap prior to the task. Participants were seated 70 cm in front of a computer screen with their chin stabilized on a support and the screen center aligned with their eye level. To minimize learning effects, a 2-min practice session was conducted before the formal task. EEG data were recorded simultaneously during the SART. Participants were instructed to remain still, focus on the screen, and respond using only their fingers to reduce electromyographic artifacts. 2.5 EEG recording and preprocessing EEG data were recorded using an ActiveTwo system (BioSemi, Amsterdam, The Netherlands) with 64 sintered Ag/AgCl electrodes placed according to the 10/20 system, at a sampling rate of 2048 Hz[ 42 ]. EEG preprocessing was performed offline using the EEGLAB toolbox in MATLAB (The MathWorks, Inc., Natick, MA). Raw EEG data were down-sampled to 512Hz, re-referenced to the average of all electrodes, and band-pass filtered (0.5–30 Hz). Ocular and cardiac artifacts were removed using infomax Independent Component Analysis (ICA)[ 43 ]. 2.6 ERP Analysis based on RIDE Artifact-free, continuous EEG data were segmented into epochs from 250 ms pre-stimulus to 900 ms post-stimulus, with stimulus onset set at zero. Each epoch was baseline-corrected using the mean voltage during the 250 ms pre-stimulus period. Epochs with amplitudes exceeding ± 100 µV or containing artifacts were discarded, and trials with incorrect responses were excluded from further analysis[ 26 ]. Time windows and electrode clusters for ERP extraction were selected based on previous literature and topographical maps (Fig. 2 ). For Go trails, N2 was measured at electrodes Fz, FCz, FC1, FC2 and Cz between 250–350 ms, while P3 was measured at CPz, Pz, P1, P2 and POz between 300–500 ms. For NoGo trials, N2 was measured at the same electrodes and time window (250–350 ms), and P3 was measured at Fz, FCz, FC1, FC2 and Cz between 350–500 ms. ERPs data were rebuilt using the To minimize the impact of random keystroke feedback, ERPs were reconstructed using the Residue Iteration Decomposition (RIDE) method[ 44 ]. ERPs were averaged by group and trial type. Peak amplitude (defined as the average amplitude within a 50-ms window around the peak) and latency were averaged across the assigned electrode clusters for each component. Grand-averaged ERP waveforms for Go and NoGo trials at midline electrodes are presented in Fig. S1 . 2.7 TF analysis TF decomposition was applied to cleaned EEG epochs (-250–900 ms) for trials with correct responses. Each epoch was analyzed using Morlet wavelet-based transformation from 3‒40 Hz, with 40 logarithmical steps with 4 cycles per frequency. The epoch data were segmented according to ERP component time window: 0-250 ms, 250–350 ms, 350–500 ms, and 500–900 ms, respectively. For each time window, event-related power and ITPC were calculated across three frequency bands of interest—theta (3–7 Hz), slow alpha (8–10 Hz), and fast alpha (10–12 Hz)—based on previous studies on Go/NoGo tasks[ 33 , 45 , 46 ]. Power values were standardized in decibels (dB), baseline-corrected (− 250 to 0 ms), and averaged across correct trials for each condition and participant. ITPC, which quantifies the consistency of phase across trials at a given time point (ranging from 0 to 1, with higher values indicating greater consistency), was also computed. 2.8 Statistical analysis Statistical analyses were performed using IBM SPSS Statistics 22 software (IBM, Chicago, IL) and R (R Core Team, 2022). Demographic, questionnaire, and behavioral data were analyzed using independent t-tests or Mann–Whitney U tests, and chi-square tests. For ERPs data, a 2 (Group: NT1 and controls) × 2 (Condition: Go and NoGo) repeated-measures analysis of variance (ANOVA) was performed on the mean amplitude and peak latency of N2, with group as a between-subjects factor and condition as a within-subjects factor. A similar 2 (Group: NT1 vs. controls) × 2 (Condition: Go vs. NoGo) × 2 (Location: Frontal vs. Parietal) ANOVA was performed for P3. Independent t-tests were used to compare mean power and ITPC between groups across different time windows for theta, slow and fast alpha during Go and NoGo trials. To control for false positives, the false discovery rate correction was applied for multiple comparisons, with a significance threshold of P < 0.05. Post hoc tests were conducted to explore significant main effects and interactions. Pearson’s correlation analysis was used to examine relationships between behavioral, electrophysiological and clinical measures. 3. Results 3.1 Participant characteristics A total of 39 NT1 patients and 41 healthy controls participated in the study. Demographic, psychometric, and clinical characteristics of all participants are summarized in Table 1 . The two groups were matched for age and sex distribution. As expected, compared with controls, the NT1 group showed significantly poorer cognitive performance (MoCA: 26.55 ± 2.21 vs. 28.05 ± 1.52, p < 0.001), more daytime sleepiness (ESS: 16.31 ± 4.32 vs. 8.90 ± 3.81, p < 0.001), more severe depressive symptoms (PHQ-9: 7.85 ± 4.31 vs. 4.37 ± 3.17, p < 0.001), greater impulsivity (BIS-11: 81.46 ± 16.44 vs. 67.71 ± 11.27, p < 0.001), and worse sleep quality (PSQI: 7.64 ± 3.38 vs. 4.78 ± 2.43, P < 0.001). All NT1 patients were positive for HLA-DQB1*0602. CSF orexin levels, available for 21 patients (53.8%), were significantly reduced (mean: 34.51 ± 24.89 pg/mL), consistent with the diagnostic criteria for NT1. Table 1 Demographic and Clinical Characteristics NT1 ( n = 39) Controls ( n = 41) P -value Male (Female) 27(12) 24(17) 0.866 Age (y) 25.33 ± 8.77 24.51 ± 6.00 0.629 BMI (kg/m 2 ) 26.49 ± 5.26 21.59 ± 3.02 < 0.001 Educational level (y) 12.04 ± 3.24 16.18 ± 3.28 < 0.001 Disease duration (y) 8.72 ± 6.21 - - MoCA score 26.55 ± 2.21 28.05 ± 1.52 < 0.001 ESS score 16.31 ± 4.32 8.90 ± 3.81 < 0.001 PSQI score 7.64 ± 3.38 4.78 ± 2.43 < 0.001 PHQ-9 score 7.85 ± 4.31 4.37 ± 3.17 < 0.001 BIS-11 score 81.46 ± 16.44 67.71 ± 11.27 < 0.001 Data are presented as n (%) or mean ± standard deviation. P -values < 0.05 are shown in bold. BIS-11 Barratt Impulsiveness Scale Version 11, BMI body mass index, ESS Epworth Sleepiness Scale, MoCA Montreal Cognitive Assessment, NT1 narcolepsy type 1, PHQ-9 Patient Health Questionnaire-9, PSQI Pittsburgh Sleep Quality Index. 3.2 Behavioral measures Differences in SART performance between NT1 patients and healthy controls are presented in Table 2 . Independent t-tests revealed that NT1 patients exhibited significantly more OEs (6.77 ± 7.24 vs. 1.83 ± 2.74, p < 0.001), longer mean RTs (371.78 ± 72.29 vs. 321.36 ± 45.97, p < 0.001) and greater RTV (113.78 ± 61.11 vs. 66.89 ± 18.12, p < 0.001) compared to controls. However, no significant differences were observed in CEs ( p = 0.767). Table 2 Differences in SART Performance Between NT1 Patients and Healthy Controls NT1 ( n = 39) Controls ( n = 41) P -value SART accuracy measures Omission Errors 6.77 ± 7.24 1.83 ± 2.74 < 0.001 Commission Errors 9.18 ± 4.91 8.88 ± 4.08 0.767 SART RTs measures Mean RTs (ms) 371.78 ± 72.29 321.36 ± 45.97 < 0.001 RTV (ms) 113.78 ± 61.11 66.89 ± 18.12 < 0.001 Data are presented as n (%) or mean ± standard deviation. P -values < 0.05 are shown in bold. NT1 narcolepsy type 1, RTs reaction times, RTV reaction time variability, SART sustained attention to response task. Spearman’s correlation analysis was performed to evaluate the relationship between RTs and accuracy for each group, aiming to identify potential differences in speed-accuracy tradeoff strategies. Mean RTs were negatively correlated with CEs in both groups (NT1: r = -0.536; controls: r = -0.553; p < 0.001), suggesting that slower responses during Go trials were associated with better inhibitory control during NoGo trials (Fig. S2 ). A linear regression model was constructed to further examine the effect of CEs while controlling for mean RTs, revealing a significant group difference in CEs after adjustment ( p 0.05). 3.3 Electrophysiological results To ensure data quality, only participants with at least 8 artifact-free trials per condition were analyzed. Consequently, ERP analyses were conducted with data from 36 NT1 and 40 controls for the Go condition, and 31 NT1 and 35 controls for the NoGo condition. Detailed results for N2 and P3 components, including amplitudes and peak latencies, are summarized in Table 3 . Grand-average ERP waveforms at midline electrodes are shown in Fig. S1 , illustrating typical neural responses for each condition. Additionally, ERP waveforms for N2 and P3 at selected electrode clusters, along with topographic maps are presented in Fig. 2 . Table 3 Comparison of N2 and P3 Amplitudes and Latencies Between NT1 Patients and Healthy Controls Across Different Conditions. Controls NT1 P-value Go Condition N2 Amplitude( \(\:\mu\:A\) ) -1.8(2.0) -1.1(1.6) 0.122 N2 Latency(ms) 296.9(26.8) 306.7(30.5) 0.187 P3 Amplitude( \(\:\mu\:A\) ) 2.7(1.6) 3.2(1.5) 0.223 P3 Latency(ms) 346.4(52.2) 391.9(58.1) 0.004 NoGo Condition N2 Amplitude( \(\:\mu\:A\) ) -5.0(3.6) -3.3(3.3) 0.098 N2 Latency(ms) 302.1(22.5) 313.4(24.1) 0.098 P3 Amplitude( \(\:\mu\:A\) ) 8.2(4.2) 5.6(3.7) 0.033 P3 Latency(ms) 419.7(38.0) 428.2(36.5) 0.342 Data are presented as n (%) or mean ± standard deviation. P -values < 0.05 are shown in bold. NT1 narcolepsy type 1. 3.3.1 Time-domain Results N2 Component. For N2 amplitude, ANOVA revealed a significant main effect of Condition ( F [ 1 , 68 ] = 58.642, p < 0.001),with larger (more negative) amplitudes in the NoGo condition compared to the Go condition. A significant main effect of Group was also observed ( F [ 1 , 68 ] = 4.826, p = 0.032); however, post-hoc analysis indicated no significance differences between groups in either condition ( p > 0.05). For N2 latency, no significant main effects or interactions were found (Table 3 and S1). P3 Component. For P3 amplitude, ANOVA revealed a significant main effect of Condition ( F [ 1 , 68 ] = 125.444, p < 0.001) and a Condition × Location interaction (F[ 1 , 68 ] = 17.623, p < 0.001), indicating that P3 amplitudes were larger in the frontal region during the NoGo condition compared to the parietal region during the Go condition. No main effect of Group was observed ( F [ 1 , 68 ] = 2.328, p = 0.132); however, significant Group × Location ( F [ 1 , 68 ] = 11.669, p = 0.001) and Group × Location × Condition ( F [ 1 , 68 ] = 5.948, p = 0.017) interactions were identified. Post-hoc analysis demonstrated significantly reduced frontal NoGo-P3 amplitudes in NT1 compared to controls, while parietal Go-P3 amplitudes did not differ between groups (Table 3 ). For P3 latency, no main effect of Group was observed, but significant Group × Location ( F [ 1 , 68 ] = 11.669, p = 0.001) and Group × Location × Condition interactions ( F [ 1 , 68 ] = 7.247, p = 0.009) were found. Post-hoc analysis revealed longer parietal Go-P3 latencies in NT1 patients compared to controls, while frontal NoGo-P3 latencies showed no group differences (Table 3 and S2). 3.3.2 TF Results For the Go condition, significant group differences in power were primarily observed in the theta (3–7 Hz) and slow alpha (8–10 Hz) bands. Specifically, compared to controls, NT1 patients exhibited lower theta power across all post-stimulus time windows (0-250 ms, 250–350 ms, 350–500 ms, and 500–900 ms) and reduced slow alpha power in the 0-250 ms, 250–350 ms, and 500–900 ms time windows. Additionally, group differences in ITPC were observed within the first 500 ms post-stimulus across the theta (3–7 Hz), slow alpha (8–10 Hz), and fast alpha (11–13 Hz) bands, with NT1 patients showing lower ITPC (Fig. 3 A and 3 C). For the NoGo condition, significant group differences in power were primarily observed in the theta band (3–7 Hz) within the first 500 ms and in the slow alpha band (8–10 Hz) during the 250–350 ms time window. Furthermore, ITPC differences were noted in the theta band during the N2 (250–350 ms) and P3 (350–500 ms) time windows, with NT1 patients exhibiting lower ITPC (Fig. 3 B and 3 D). 3.4 Relationship between behavioral and ERP data Go-P3 latency was positively correlated with mean RTs in both groups (NT1: r = 0.56; controls: r = 0.53; p < 0.001; Fig. 4 A), indicating that delayed response execution contributes to slower overall RTs. In the NT1 group, NoGo-P3 amplitude was negatively correlated with mean RTs ( r = − 0.46, p = 0.008; Fig. 4 B), suggesting that faster responders during the Go condition required larger Nogo-P3 amplitudes to effectively inhibit motor responses during the NoGo condition. 3.5 Relationship between behavioral and TF data In the NT1 group, Go-theta power was negatively correlated with mean RTs during the N2 (250–350 ms; r = − 0.61, p < 0.001) time window (Fig. 4 C). Go-theta ITPC showed a negative correlation with RTV during the P3 time windows (350–500 ms; r = − 0.57, p < 0.001; Fig. 4 D). These correlations were absent in the control group, suggesting that NT1 patients rely more heavily on theta-band activity to sustain attention, particularly during Go trails requiring rapid responses. 3.6 Relationship between EEG and clinical data For NT1 patients, Go-theta power during the N2 (250–350 ms; r = 0.54, p < 0.05) and P3 (350–500 ms; r = 0.61, p < 0.05) time windows was positively correlated with CSF orexin levels (Fig. 4 E and 4 F). This finding suggests that lower orexin levels may lead to reduced theta-band activity, potentially impairing performance in the Go condition. 4. Discussion Cognitive impairments in NT1, particularly in attention and inhibitory control, are clinically significant yet mechanistically unclear. Here, by integrating behavioral measures with multimodal EEG analyses (ERPs and TF analysis), we reveal that NT1 patients exhibit: (1) significant behavioral impairments (slower RTs and more OEs/CEs); (2) characteristic electrophysiological abnormalities (reduced NoGo-P3 amplitudes, delayed Go-P3 latencies, and attenuated theta-band power and ITPC). Crucially, we establish for the first time a direct association between reduced theta oscillations, behavioral impairments, and diminished CSF orexin levels, suggesting that orexin deficiency may impair cognitive function through disruption of thalamocortical theta oscillations. These findings provide both pathophysiological explanations for NT1-related cognitive dysfunction and quantifiable electrophysiological biomarkers with translational potential for disease monitoring and neuromodulation therapies. 4.1 Behavioral performances OEs in continuous performance tasks reflect deficits in sustained attention, whereas CEs reveal impaired inhibitory control. Consistent with previous studies, our findings demonstrate that NT1 patients exhibit more OEs, longer RTs, and greater RTV than healthy controls, highlighting pronounced attentional deficits[ 47 – 50 ]. Regarding inhibitory control, we initially observed no group differences in CEs. However, a significant difference emerged after controlling for mean RTs as a covariate, suggesting a speed-accuracy tradeoff: participants may slow down during Go trials to achieve higher accuracy in NoGo trials[ 51 ]. NT1 patients appear to rely more heavily on this strategy than controls, enabling them to temporarily maintain inhibitory performance. Nevertheless, when accounting for the speed-accuracy tradeoff, NT1 patients showed significantly impaired inhibitory control. 4.2 ERP characteristics The centro-parietal Go-P3 resembles the P3b component observed in oddball paradigms, reflecting involuntary relocation of attention to target stimuli, response preparation and execution[ 52 , 53 ]. Prolonged Go-P3 latency in NT1 patients indicates delayed response execution, which aligns with our finding of a positive correlation between Go-P3 latency and mean RTs. This suggests that slower response execution significantly contributes to behavioral performance during Go trials. The absence of group differences in Go-N2 latency, coupled with significant differences in Go-P3 latency, implies that attention impairments in NT1 are primarily related to delayed response execution rather than deficits in stimulus perception or early evaluation. Our study revealed a significant main effect of Condition, with both groups showing higher N2 and P3 amplitudes in the NoGo condition compared to the Go condition, consistent with prior Go/NoGo studies[ 23 , 54 – 56 ]. This pattern reflects the increased cognitive demand required for inhibitory control. While both components are critical for successful inhibition, they represent different processes. NoGo-N2 is thought to reflect bottom-up conflict monitoring, arising from competition between frequent Go stimuli and infrequent NoGo stimuli[ 57 ], whereas NoGo-P3 is thought to reflect top-down conflict resolution and the actual inhibition of the motor response [ 53 ]. Our results showed group differences in NoGo-P3 amplitudes but not in NoGo-N2 amplitudes, suggesting that behavioral inhibition deficits in NT1 are primarily driven by impaired response inhibition rather than early conflict monitoring. Furthermore, NT1 patients with faster responses in the Go condition exhibited higher NoGo-P3 amplitudes, indicating that faster responders require more cognitive resources to achieve effective inhibition. This finding not only highlights the compensatory strategies employed by NT1 patients to maintain attention but also points to potential imbalances between attention and inhibitory control networks in this population. 4.3 TF characteristics While ERPs provide initial insights into neurophysiological changes related to cognitive function, TF analysis disentangles power and phase effects across different frequencies, providing valuable insights into neural oscillations underlying ERP responses[ 32 , 45 ]. Alpha-band oscillations (8–13 Hz), the brain’s dominant rhythm, are closely linked to arousal and attention. Higher alpha power is associated with increased arousal levels[ 58 , 59 ]. Specifically, slow alpha (8–10 Hz) facilitates attentional deployment by filtering out irrelevant information[ 60 – 62 ]. In our study, NT1 patients exhibited reduced slow alpha power across multiple time windows, indicating lower levels of arousal and an impaired ability to suppress internal or external distractions. Theta-band oscillations (3–7 Hz) are critical for a range of cognitive processes, including arousal, selective attention, motor preparation, execution, and top-down inhibitory control[ 38 , 39 , 63 ]. In cognitively normal individuals, higher frontal midline theta power during NoGo trials compared to Go trials highlights the role of theta modulation in recruiting cognitive control processes necessary for response inhibition[ 38 , 64 ]. Our findings of reduced NoGo-theta power and ITPC in NT1 support the presence of impaired inhibitory control, potentially explaining their impulsive behaviors. Furthermore, the attenuation of Go-theta power and ITPC, along with their association with poorer performance on Go trials, suggests that deficits in theta-band activity also contribute to inattention. Specifically, reduced Go-theta power was correlated with slower RTs, while reduced Go-theta ITPC was linked to greater RTV, particularly within time windows aligned with the N2 and P3 components. This implies that response speed and stability rely on separate but complementary neural processes: impaired Go-theta power affects the efficiency of response execution, while impaired ITPC impacts the consistency of responses over time. For the first time, we identified a positive correlation between EEG measures (e.g., Go-theta power) and CSF orexin levels in NT1, suggesting that orexin deficiency may underlie impaired theta-band oscillations and subsequent attentional deficits. Orexin neurons, through their widespread projections to key brain regions including the prefrontal cortex, thalamus, and locus coeruleus, play a pivotal role in maintaining cortical arousal and attentional networks[ 65 , 66 ]. The observed modulation of theta oscillations by orexin is particularly noteworthy, as these neural rhythms are fundamental for attention allocation and cognitive control[ 46 , 67 – 69 ]. Thus, we propose a mechanistic hypothesis: orexin deficiency disrupts thalamocortical network dynamics by attenuating theta-band oscillations, thereby impairing the functional integrity of brain networks essential for sustained attention. Future studies should investigate whether therapeutic restoration of orexin signaling can normalize theta oscillations and improve attentional performance in NT1, potentially offering a targeted treatment approach for cognitive impairments in this population[ 70 , 71 ]. 4.4 limitations This study had several limitations. First, although our sample size was larger than that of previous cognitive studies on NT1, it remains relatively modest, warranting further research with larger populations to validate our findings. Second, the potential influence of medication on behavioral and electrophysiological outcomes could not be fully disentangled from the effects of the illness itself. Future research should investigate the impact of medication on cognitive function and neural dynamics. Third, the SART paradigm used in this study was relatively brief and simple, and other potential cognitive impairments may only emerge during more complex or prolonged tasks. 5. Conclusion This study is the first to systematically evaluate attention and executive function in NT1 using combined time-domain and time-frequency EEG analyses. By integrating behavioral and electrophysiological data, our multimodal approach reveals distinct neurophysiological signatures of cognitive deficits: (1) attention impairments are characterized by delayed response preparation and execution, as evidenced by prolonged Go-P3 latency, while (2) inhibitory control deficits are associated with impaired response inhibition and reduced attentional resource allocation, reflected by reduced NoGo-P3 amplitude. Crucially, TF analyses further reveal that attenuated theta-band oscillations underlie these cognitive impairments, likely mediated by orexin deficiency. These findings not only advance our understanding of the neural mechanisms of NT1-related cognitive dysfunction but also identify clinically translatable EEG biomarkers, such as P3 components and theta oscillations, for clinical monitoring and future therapeutic development. Declarations ACKNOWLEDGEMENTS We thank the individuals who participated in this trial, their families, and the clinical and research teams in the neurology department and school of physics of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China. COMPETING INTERESTS The authors declare no Competing interests. FUNDING This work was funded by the Shanghai Science and Technology Program/Natural Science Foundation of Shanghai (22ZR1449800), National Natural Science Foundation of China (81401038), the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission under award number (2020383055/2020KY164), and Special Fund for Clinical Research of Zhejiang Medical Association (2022ZYC-A133). AUTHOR CONTRIBUTIONS Zongshan Li : Conceptualization, Methodology, Data collection, Writing-original draft, Writing review & editing. Xiao Han : Conceptualization, Methodology, Statistical analysis, Data visualization, Writing review & editing. Jiahui Xu : Methodology, Assisted in the completion of revised manuscript. Qinglin Xu : Methodology, Assisted in the completion of revised manuscript. Xuelian Ge : Assisted with data analysis. Yi Yang : Data collection. Jiaqin Yu : Data collection. Guodong Lou : Data collection. Yaxing Gui : Methodology, Assisted in the completion of revised manuscript. Feiyan Chen : Conceptualization, Methodology, Assisted in the completion of revised manuscript. Lisan Zhang : Conceptualization, Methodology, Assisted in the completion of revised manuscript. All authors have approved for the publication of this study. ADDITIONAL INFORMATION Supplementary information The online version contains supplementary material available at Translational Psychiatry . References Bassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, et al. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15(9):519-539. doi:10.1038/s41582-019-0226-9. Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, et al. Narcolepsy. Nat Rev Dis Primers. 2017;3:16100. doi:10.1038/nrdp.2016.100. Barateau L, Liblau R, Peyron C, Dauvilliers Y. Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment. 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ERP responses are shown for NT1 patients (blue lines) and healthy controls (red lines) across midline electrode sites (Fpz, Fz, FCz, Cz, CPz, Pz, POz, Oz) during Go (solid lines) and NoGo (dashed lines) conditions. SupplementaryFigS2.tif Fig. S2. Correlation between Mean RT and Commission Error. 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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-6340580","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":438146126,"identity":"0118df6d-a404-4bd5-b2dd-851a02c8ad9e","order_by":0,"name":"Lisan Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDACdgaGAx8qGJhBbAnitDAzMD6ccYZELczGvG0QNnFa5JvZn0nzzqtjNzjAfPA2D4NdHkEtjM08ZpJzt7ExGxxgS7bmYUguJuwuZh42ibfbeIBaeMykeRgOJDYQ0sLGzP5MgneOBFAL/zfitPAwMxgb8jYYgGxhI06LBDOP4cMZxxKYJQ+zGVvOMUgmrEW+vf3BgQ81dcl8x5sf3nhTYUdYCwwkQyLTgFj1QGBHgtpRMApGwSgYaQAAWQIwpxtjI8cAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3774-9926","institution":"Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou 310016, China","correspondingAuthor":true,"prefix":"","firstName":"Lisan","middleName":"","lastName":"Zhang","suffix":""},{"id":438146127,"identity":"34f173da-4d46-4367-ac15-1e04ebfb9edc","order_by":1,"name":"Zongshan Li","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Zongshan","middleName":"","lastName":"Li","suffix":""},{"id":438146128,"identity":"267d72be-bd0d-4c49-a0ef-1b56ef896ba8","order_by":2,"name":"Xiao Han","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Han","suffix":""},{"id":438146129,"identity":"59f2dd1e-78f9-4f97-960b-1821d9146177","order_by":3,"name":"Jiahui Xu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jiahui","middleName":"","lastName":"Xu","suffix":""},{"id":438146130,"identity":"f632f7c4-3bd8-4a77-9d0d-4b8638603151","order_by":4,"name":"Qinglin Xu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Qinglin","middleName":"","lastName":"Xu","suffix":""},{"id":438146131,"identity":"6702f23f-5915-48b8-96be-bf46a4a35930","order_by":5,"name":"Xuelian Ge","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Xuelian","middleName":"","lastName":"Ge","suffix":""},{"id":438146132,"identity":"db2a06cd-730b-4acd-a482-67c3571f1e5e","order_by":6,"name":"Yi Yang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Yang","suffix":""},{"id":438146133,"identity":"b3e3ffe7-3f46-4fef-bc15-fbd23df94488","order_by":7,"name":"Jiaqin Yu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jiaqin","middleName":"","lastName":"Yu","suffix":""},{"id":438146134,"identity":"5a4b88b3-c923-4a0f-b6d7-c345bbcd213c","order_by":8,"name":"Guodong Lou","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Guodong","middleName":"","lastName":"Lou","suffix":""},{"id":438146135,"identity":"646a9f65-06fd-4561-9e3b-afc3b6c17bf4","order_by":9,"name":"Yaxing Gui","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Yaxing","middleName":"","lastName":"Gui","suffix":""},{"id":438146136,"identity":"e495a947-9b49-42f5-ba27-2c78e061ff7a","order_by":10,"name":"Feiyan Chen","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Feiyan","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-03-31 00:50:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6340580/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6340580/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41398-025-03684-x","type":"published","date":"2025-10-31T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81934276,"identity":"73bfc9ca-56ff-4391-8baf-79872e32b751","added_by":"auto","created_at":"2025-05-05 05:44:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":129590,"visible":true,"origin":"","legend":"\u003cp\u003eSustained Attention to Response Task (SART) paradigm. The 4-min 20-s SART consists of presentation of the numbers 1–9 of various sizes 225 times randomly in white font on a black computer screen. Each number is presented for 250 ms, followed by a 900 ms duration mask composed of a cross (“+”) presented in the middle of the screen. Participants are instructed to respond to the appearance of each number by pressing the spacebar (Go condition), except when presented with the number 3 (NoGo condition).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/83078f1e90fc54d535b049b5.png"},{"id":81936154,"identity":"a3472a9b-cc10-4e15-8c6c-4c25dff2c4cd","added_by":"auto","created_at":"2025-05-05 06:04:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2027783,"visible":true,"origin":"","legend":"\u003cp\u003eN2 and P3 waveforms at selected electrode clusters and topographic maps across groups during Go/NoGo conditions. (A) Grand-average ERP waveforms at frontal electrode clusters (Fz, FCz, FC1, FC2, and Cz) illustrating Go-N2, NoGo-N2 and NoGo-P3 components in NT1 patients (red lines) and healthy controls (blue lines), with Go (solid lines) and NoGo (dashed lines) conditions differentiated. (B) Grand-average ERP waveforms at parietal electrode clusters (CPz, Pz, P1, P2, and POz) showing the Go-P3 component. (C) Topographic maps of N2 and P3 components, corresponding to the average activity within time windows around the local peaks marked by the dashed boxes. Dashed boxes denote temporal boundaries for component extraction. (250–350 ms for Go-N2 and NoGo-N2, 300–500 ms for Go-P3, 350–500 ms for NoGo-P3). Abbreviations: NT1, narcolepsy type 1.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/60b06a56eb378de3cce8b764.png"},{"id":81936020,"identity":"d298f30f-0f7c-4c9a-9ad3-15d74997b8da","added_by":"auto","created_at":"2025-05-05 06:01:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":831625,"visible":true,"origin":"","legend":"\u003cp\u003eGroup differences in spectral EEG power and ITPC between NT1 patients and healthy controls during Go/NoGo conditions. TF representations show group differences across frequency bands and time windows, with dashed lines (NT1 patients) and solid lines (healthy controls). Statistical significance: *** p \u0026lt; 0.001, ** p \u0026lt; 0.01, * p \u0026lt; 0.05. Abbreviations: ITPC inter-trial phase coherence, NT1 narcolepsy type 1, TF Time-frequency.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/9a4f702e72a754cf56d74f0c.png"},{"id":81936121,"identity":"15b05469-b393-4649-a1b5-b87710b9c9a4","added_by":"auto","created_at":"2025-05-05 06:03:56","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":757192,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelations between behavioral, electrophysiological and clinical measures. (A) Correlation between Mean RT and Go-P3 latency. (B) Correlation between Mean RT and NoGo-P3 amplitude. (C) Correlation between Mean RT and Go-theta power. (D) Correlation between RT variability and Go-theta ITPC. (E) Correlation between CSF orexin levels and theta-band (3-7 Hz) power within the 250-350 ms time window. (F) Correlation between CSF orexin levels and theta-band power within the 350-500 ms time window. Abbreviations: CSF cerebrospinal fluid, ITPC inter-trial phase coherence, RT response time.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/393980f3f06d9756f1868d6c.png"},{"id":94904504,"identity":"fb44979e-37cf-49c2-92e3-9a77b9a8dc1f","added_by":"auto","created_at":"2025-11-01 07:11:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4727802,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/3dfac629-4a16-411a-9330-6a862665387f.pdf"},{"id":81934279,"identity":"1366b16a-f6fe-41cb-8a9c-27042e0e0a0f","added_by":"auto","created_at":"2025-05-05 05:44:01","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14942,"visible":true,"origin":"","legend":"Supplementary_Table_S1","description":"","filename":"SupplementaryTableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/d4addb244df47df6a0f6b4bf.docx"},{"id":81936133,"identity":"6d983ed8-755b-4e38-a777-b620affc7654","added_by":"auto","created_at":"2025-05-05 06:04:13","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15417,"visible":true,"origin":"","legend":"Supplementary_Table_S2","description":"","filename":"SupplementaryTableS2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/e540dc5b2a291325daf76f9e.docx"},{"id":81934282,"identity":"33afc220-8383-4f03-ac9d-ec99670dcd7b","added_by":"auto","created_at":"2025-05-05 05:44:01","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":495318,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig. S1. \u003c/strong\u003eGrand-averaged event-related potential (ERP) waveforms at midline electrodes. ERP responses are shown for NT1 patients (blue lines) and healthy controls (red lines) across midline electrode sites (Fpz, Fz, FCz, Cz, CPz, Pz, POz, Oz) during Go (solid lines) and NoGo (dashed lines) conditions.\u003c/p\u003e","description":"","filename":"SupplementaryFigS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/bf4a2ccdab4e13a1d19e7cda.tif"},{"id":81936164,"identity":"aeb71fdb-663e-4e73-a130-ff902fc04d50","added_by":"auto","created_at":"2025-05-05 06:04:57","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":177770,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig. S2. \u003c/strong\u003eCorrelation between Mean RT and Commission Error.\u003c/p\u003e","description":"","filename":"SupplementaryFigS2.tif","url":"https://assets-eu.researchsquare.com/files/rs-6340580/v1/7b059600744f6a3efd7bd199.tif"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"\u003cp\u003eAttention and Inhibition Deficits in Narcolepsy Type 1: Behavioral and Electrophysiological Markers\u003c/p\u003e","fulltext":[{"header":"1. Background","content":"\u003cp\u003eNarcolepsy type 1 (NT1) is a chronic and disabling neurological disorder characterized by excessive daytime sleepiness (EDS), cataplexy and sleep\u0026ndash;wake symptoms, such as hallucinations, sleep paralysis, and nocturnal sleep disturbance[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. With a prevalence of 0.025\u0026ndash;0.05% in Western populations, NT1 has seen a rising annual incidence across all age groups, likely due to increased disease awareness[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Its pathogenesis involves the immune-mediated loss of orexin-producing neurons in the lateral hypothalamus, leading to significantly reduced orexin levels in the cerebrospinal fluid (CSF; \u0026lt;110 pg/mL)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Despite their localized origin, orexin neurons project widely to brainstem, limbic, and cortical regions to regulate multiple physiological functions[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Based on such anatomical characteristics, besides sleep-related symptoms, NT1 can also be combined with metabolic, autonomic, psychiatric, and cognitive impairments[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Among these, cognitive dysfunction is one of the most prevalent, with approximately 40\u0026ndash;50% of patients reporting problems in attention and executive function[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, subjective cognitive complaints often do not align with objective impairments, emphasizing the need for neuropsychological assessments[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAttention, a fundamental cognitive function, enables individuals to selectively focus on relevant stimuli while filtering out distractions[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. People with narcolepsy often report difficulties in engaging, sustaining, and shifting attention, which significantly impair their daily functioning and quality of life[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, impulsivity behaviors such as unhealthy eating and substance abuse are also common in NT1, which are thought to reflect inhibitory control deficits[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Inhibitory control, a core component of executive function, refers to the ability to suppress inappropriate or habitual responses[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. While attention deficits in NT1 have been relatively well-studied, research on inhibitory control remains limited and inconsistent[\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Sustained Attention to Response Task (SART) is a classic Go/NoGo paradigm for assessing sustained attention and inhibitory control. The task requires participants to respond rapidly to frequent Go stimuli while withholding responses to infrequent NoGo stimuli[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Omission errors (OEs; failures to respond to Go stimuli) and reaction times (RTs) are considered indices of sustained attention, whereas commission errors (CEs; responses to NoGo stimuli) reflect inhibitory control. A systematic review reveled that NT1 patients exhibit more OEs and slower RTs compared to controls, but no differences in CEs[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, the neural mechanisms underlying these behavioral deficits remain elusive, likely contributing to the lack of broadly effective interventions for cognitive impairments.\u003c/p\u003e \u003cp\u003eElectroencephalography (EEG) offers a powerful tool to investigate the neural dynamics of rapid cognitive processes, even in the absence of overt behavioral responses (e.g., successful response inhibition). Two event-related potentials (ERPs)\u0026mdash;N2 and P3\u0026mdash;are closely associated with attention and inhibitory control, reflecting different stages of cognitive processing. N2, a frontocentral negative deflection occurring 200\u0026ndash;300 ms post-stimulus, is thought to reflect stimulus evaluation (Go-N2) or conflict monitoring (NoGo-N2)[\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. P3, a centroparietal positive deflection occurring 300\u0026ndash;500 ms post-stimulus, is linked to response execution (Go-P3) or inhibition (NoGo-P3)[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Source-localization and functional MRI studies have further identified distinct neural networks activated during Go/NoGo tasks: the NoGo condition engages a frontal network, including the anterior cingulate cortex and orbitofrontal cortex, while the Go condition activates a temporal-parietal network involving primary and supplementary motor areas [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Notably, these regions are key projection sites for orexin neurons, suggesting that cognitive-electrophysiological assessments may provide valuable insights into the neural mechanisms underlying cognitive impairments of NT1.\u003c/p\u003e \u003cp\u003eTo complement ERP analyses, time\u0026ndash;frequency (TF) analysis was employed to capture fine-grained neural dynamics, including event-related spectral power and inter-trial phase coherence (ITPC)[\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Previous studies have shown that theta (3\u0026ndash;7 Hz) and alpha (8\u0026ndash;12 Hz) oscillations play critical roles in the cognitive processes underlying Go/NoGo tasks[\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Specifically, alpha oscillations are involved in attentional modulation and response execution[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], while theta oscillations are more associated with top-down inhibitory control[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. However, no studies to date have examined how NT1 affects neural oscillations during Go/NoGo tasks.\u003c/p\u003e \u003cp\u003eAs the first study to investigate the impact of NT1 on behavioral and electrophysiological indicators using the SART, our aim is twofold: (1) to determine whether attention and inhibitory control are impaired in NT1, and (2) to explore the neural mechanisms underlying these deficits through ERPs and TF analyses. We hypothesized that NT1 patients would exhibit deficits in both attention and inhibitory control, manifested as poorer behavioral performance (e.g., more OEs/CEs, longer RTs), altered N2/P3 components (e.g., reduced N2/P3 amplitudes, prolonged latencies), and reduced theta/alpha-band oscillations (e.g., lower power or ITPC) compared to healthy controls. These findings may provide novel insights into the neural basis of cognitive dysfunction in NT1 and inform the development of targeted interventions.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Subjects\u003c/h2\u003e \u003cp\u003eA total of 39 patients diagnosed with NT1 were recruited from the Department of Neurology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China, between October 2021 and November 2023. Forty-one healthy controls matched for age, sex, and education level, were recruited through advertisements. All participants were aged 10\u0026ndash;50 years, right-handed, and had normal or corrected-to-normal vision. The study was approved by the local ethics committee according to the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal representatives.\u003c/p\u003e \u003cp\u003eNT1 diagnosis was confirmed by sleep specialists based on clinical presentation, Multiple Sleep Latency Test (MSLT), nocturnal polysomnography (nPSG), and/or CSF orexin levels, following the International Classification of Sleep Disorders (ICSD)-3 criteria[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Exclusion criteria included other sleep disorders (e.g., obstructive sleep apnea or insomnia), mental retardation, neurological or psychiatric disorders, and a history of alcohol, drug, or substance abuse. Participants were instructed to refrain from using medications (e.g., modafinil, methylphenidate) or substances (e.g., coffee, alcohol, stimulating beverages) for at least one week before testing.\u003c/p\u003e \u003cp\u003eAll participants underwent a comprehensive neurological examination and completed a demographic survey capturing age, sex, body mass index (BMI), and education level. For NT1 patients, additional clinical data were collected, including disease duration, cataplexy frequency, self-reported symptoms, and medication history. Data from nPSG, MSLT, HLA typing, and CSF orexin levels were obtained from medical records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Questionnaires\u003c/h2\u003e \u003cp\u003eAll participants completed a series of validated questionnaires prior to the EEG examination. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), while the Epworth Sleepiness Scale (ESS) was used to measure the severity of EDS. Additional assessments included sleep quality (Pittsburgh Sleep Quality Index [PSQI]), depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), and impulsive tendencies (Barratt Impulsiveness Scale Version 11 [BIS-11]).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Sustained Attention to Response Task (SART)\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the SART consisted of a 4-minute 20-second session during which 225 numbers (ranging from 1 to 9) were randomly presented in varying sizes, displayed in white font on a black background[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Each number was displayed for 250 ms, followed by a 900 ms fixation cross (\u0026ldquo;+\u0026rdquo;) at the center of the screen. Participants were instructed to press the spacebar in response to all numbers (Go trials) except for the number 3 (NoGo trials). The task included 200 Go trials and 25 NoGo trials. Participants were instructed to prioritize both speed and accuracy equally.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo accurately assess behavioral performance, we discarded anticipation responses with RTs\u0026thinsp;\u0026lt;\u0026thinsp;150 ms and calculated the following indicators: OEs (the number of non-3-digit stimuli with no response within the allowed time); CEs (the number of 3-digit stimuli followed by a response); mean RTs (average response time for correct Go trials ); and RTs variability (RTV), quantified as the coefficient of variation (standard deviation divided by the mean RTs) for correct Go trials[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Procedure\u003c/h2\u003e \u003cp\u003eThe experiment was conducted in a sound-attenuated, electrically shielded room. To ensure participants remained awake during SART, they were allowed a 15-minute nap prior to the task. Participants were seated 70 cm in front of a computer screen with their chin stabilized on a support and the screen center aligned with their eye level. To minimize learning effects, a 2-min practice session was conducted before the formal task. EEG data were recorded simultaneously during the SART. Participants were instructed to remain still, focus on the screen, and respond using only their fingers to reduce electromyographic artifacts.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 EEG recording and preprocessing\u003c/h2\u003e \u003cp\u003eEEG data were recorded using an ActiveTwo system (BioSemi, Amsterdam, The Netherlands) with 64 sintered Ag/AgCl electrodes placed according to the 10/20 system, at a sampling rate of 2048 Hz[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. EEG preprocessing was performed offline using the EEGLAB toolbox in MATLAB (The MathWorks, Inc., Natick, MA). Raw EEG data were down-sampled to 512Hz, re-referenced to the average of all electrodes, and band-pass filtered (0.5\u0026ndash;30 Hz). Ocular and cardiac artifacts were removed using infomax Independent Component Analysis (ICA)[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 ERP Analysis based on RIDE\u003c/h2\u003e \u003cp\u003eArtifact-free, continuous EEG data were segmented into epochs from 250 ms pre-stimulus to 900 ms post-stimulus, with stimulus onset set at zero. Each epoch was baseline-corrected using the mean voltage during the 250 ms pre-stimulus period. Epochs with amplitudes exceeding\u0026thinsp;\u0026plusmn;\u0026thinsp;100 \u0026micro;V or containing artifacts were discarded, and trials with incorrect responses were excluded from further analysis[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTime windows and electrode clusters for ERP extraction were selected based on previous literature and topographical maps (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For Go trails, N2 was measured at electrodes Fz, FCz, FC1, FC2 and Cz between 250\u0026ndash;350 ms, while P3 was measured at CPz, Pz, P1, P2 and POz between 300\u0026ndash;500 ms. For NoGo trials, N2 was measured at the same electrodes and time window (250\u0026ndash;350 ms), and P3 was measured at Fz, FCz, FC1, FC2 and Cz between 350\u0026ndash;500 ms. ERPs data were rebuilt using the To minimize the impact of random keystroke feedback, ERPs were reconstructed using the Residue Iteration Decomposition (RIDE) method[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. ERPs were averaged by group and trial type. Peak amplitude (defined as the average amplitude within a 50-ms window around the peak) and latency were averaged across the assigned electrode clusters for each component. Grand-averaged ERP waveforms for Go and NoGo trials at midline electrodes are presented in Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7 TF analysis\u003c/h2\u003e \u003cp\u003eTF decomposition was applied to cleaned EEG epochs (-250\u0026ndash;900 ms) for trials with correct responses. Each epoch was analyzed using Morlet wavelet-based transformation from 3‒40 Hz, with 40 logarithmical steps with 4 cycles per frequency. The epoch data were segmented according to ERP component time window: 0-250 ms, 250\u0026ndash;350 ms, 350\u0026ndash;500 ms, and 500\u0026ndash;900 ms, respectively. For each time window, event-related power and ITPC were calculated across three frequency bands of interest\u0026mdash;theta (3\u0026ndash;7 Hz), slow alpha (8\u0026ndash;10 Hz), and fast alpha (10\u0026ndash;12 Hz)\u0026mdash;based on previous studies on Go/NoGo tasks[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Power values were standardized in decibels (dB), baseline-corrected (\u0026minus;\u0026thinsp;250 to 0 ms), and averaged across correct trials for each condition and participant. ITPC, which quantifies the consistency of phase across trials at a given time point (ranging from 0 to 1, with higher values indicating greater consistency), was also computed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics 22 software (IBM, Chicago, IL) and R (R Core Team, 2022). Demographic, questionnaire, and behavioral data were analyzed using independent t-tests or Mann\u0026ndash;Whitney U tests, and chi-square tests.\u003c/p\u003e \u003cp\u003eFor ERPs data, a 2 (Group: NT1 and controls) \u0026times; 2 (Condition: Go and NoGo) repeated-measures analysis of variance (ANOVA) was performed on the mean amplitude and peak latency of N2, with group as a between-subjects factor and condition as a within-subjects factor. A similar 2 (Group: NT1 vs. controls) \u0026times; 2 (Condition: Go vs. NoGo) \u0026times; 2 (Location: Frontal vs. Parietal) ANOVA was performed for P3. Independent t-tests were used to compare mean power and ITPC between groups across different time windows for theta, slow and fast alpha during Go and NoGo trials. To control for false positives, the false discovery rate correction was applied for multiple comparisons, with a significance threshold of \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. \u003cem\u003ePost hoc\u003c/em\u003e tests were conducted to explore significant main effects and interactions. Pearson\u0026rsquo;s correlation analysis was used to examine relationships between behavioral, electrophysiological and clinical measures.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Participant characteristics\u003c/h2\u003e \u003cp\u003eA total of 39 NT1 patients and 41 healthy controls participated in the study. Demographic, psychometric, and clinical characteristics of all participants are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups were matched for age and sex distribution. As expected, compared with controls, the NT1 group showed significantly poorer cognitive performance (MoCA: 26.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21 vs. 28.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), more daytime sleepiness (ESS: 16.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.32 vs. 8.90\u0026thinsp;\u0026plusmn;\u0026thinsp;3.81, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), more severe depressive symptoms (PHQ-9: 7.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.31 vs. 4.37\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), greater impulsivity (BIS-11: 81.46\u0026thinsp;\u0026plusmn;\u0026thinsp;16.44 vs. 67.71\u0026thinsp;\u0026plusmn;\u0026thinsp;11.27, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and worse sleep quality (PSQI: 7.64\u0026thinsp;\u0026plusmn;\u0026thinsp;3.38 vs. 4.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). All NT1 patients were positive for HLA-DQB1*0602. CSF orexin levels, available for 21 patients (53.8%), were significantly reduced (mean: 34.51\u0026thinsp;\u0026plusmn;\u0026thinsp;24.89 pg/mL), consistent with the diagnostic criteria for NT1.\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNT1 (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControls (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.33\u0026thinsp;\u0026plusmn;\u0026thinsp;8.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.51\u0026thinsp;\u0026plusmn;\u0026thinsp;6.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.629\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.49\u0026thinsp;\u0026plusmn;\u0026thinsp;5.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.59\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducational level (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.04\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.18\u0026thinsp;\u0026plusmn;\u0026thinsp;3.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease duration (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.72\u0026thinsp;\u0026plusmn;\u0026thinsp;6.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMoCA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.90\u0026thinsp;\u0026plusmn;\u0026thinsp;3.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSQI score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.64\u0026thinsp;\u0026plusmn;\u0026thinsp;3.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePHQ-9 score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.37\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBIS-11 score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.46\u0026thinsp;\u0026plusmn;\u0026thinsp;16.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.71\u0026thinsp;\u0026plusmn;\u0026thinsp;11.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as \u003cem\u003en\u003c/em\u003e (%) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 are shown in bold.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBIS-11 Barratt Impulsiveness Scale Version 11, BMI body mass index, ESS Epworth Sleepiness Scale, MoCA Montreal Cognitive Assessment, NT1 narcolepsy type 1, PHQ-9 Patient Health Questionnaire-9, PSQI Pittsburgh Sleep Quality Index.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Behavioral measures\u003c/h2\u003e \u003cp\u003eDifferences in SART performance between NT1 patients and healthy controls are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Independent t-tests revealed that NT1 patients exhibited significantly more OEs (6.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.24 vs. 1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.74, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), longer mean RTs (371.78\u0026thinsp;\u0026plusmn;\u0026thinsp;72.29 vs. 321.36\u0026thinsp;\u0026plusmn;\u0026thinsp;45.97, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and greater RTV (113.78\u0026thinsp;\u0026plusmn;\u0026thinsp;61.11 vs. 66.89\u0026thinsp;\u0026plusmn;\u0026thinsp;18.12, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to controls. However, no significant differences were observed in CEs (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.767).\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 SART Performance Between NT1 Patients and Healthy Controls\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=\"char\" char=\"\u0026plusmn;\" 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=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNT1 (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControls (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSART accuracy measures\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 Errors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommission Errors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.18\u0026thinsp;\u0026plusmn;\u0026thinsp;4.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.767\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSART RTs measures\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\u003eMean RTs (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e371.78\u0026thinsp;\u0026plusmn;\u0026thinsp;72.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e321.36\u0026thinsp;\u0026plusmn;\u0026thinsp;45.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRTV (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e113.78\u0026thinsp;\u0026plusmn;\u0026thinsp;61.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e66.89\u0026thinsp;\u0026plusmn;\u0026thinsp;18.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as \u003cem\u003en\u003c/em\u003e (%) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 are shown in bold.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNT1 narcolepsy type 1, RTs reaction times, RTV reaction time variability, SART sustained attention to response task.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSpearman\u0026rsquo;s correlation analysis was performed to evaluate the relationship between RTs and accuracy for each group, aiming to identify potential differences in speed-accuracy tradeoff strategies. Mean RTs were negatively correlated with CEs in both groups (NT1: r = -0.536; controls: r = -0.553; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suggesting that slower responses during Go trials were associated with better inhibitory control during NoGo trials (Fig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). A linear regression model was constructed to further examine the effect of CEs while controlling for mean RTs, revealing a significant group difference in CEs after adjustment (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, no significant correlations were observed between SART performance measures and clinical indicators in the NT1 group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Electrophysiological results\u003c/h2\u003e \u003cp\u003eTo ensure data quality, only participants with at least 8 artifact-free trials per condition were analyzed. Consequently, ERP analyses were conducted with data from 36 NT1 and 40 controls for the Go condition, and 31 NT1 and 35 controls for the NoGo condition. Detailed results for N2 and P3 components, including amplitudes and peak latencies, are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Grand-average ERP waveforms at midline electrodes are shown in Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e, illustrating typical neural responses for each condition. Additionally, ERP waveforms for N2 and P3 at selected electrode clusters, along with topographic maps are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of N2 and P3 Amplitudes and Latencies Between NT1 Patients and Healthy Controls Across Different Conditions.\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNT1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGo Condition\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\u003eN2 Amplitude(\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\mu\\:A\\)\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.8(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-1.1(1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2 Latency(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e296.9(26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e306.7(30.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3 Amplitude(\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\mu\\:A\\)\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.7(1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.2(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3 Latency(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e346.4(52.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e391.9(58.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNoGo Condition\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\u003eN2 Amplitude(\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\mu\\:A\\)\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-5.0(3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-3.3(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2 Latency(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e302.1(22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e313.4(24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3 Amplitude(\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\mu\\:A\\)\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.2(4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.6(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3 Latency(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e419.7(38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e428.2(36.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as \u003cem\u003en\u003c/em\u003e (%) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 are shown in bold.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNT1 narcolepsy type 1.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1 Time-domain Results\u003c/h2\u003e \u003cp\u003e \u003cb\u003eN2 Component.\u003c/b\u003e For N2 amplitude, ANOVA revealed a significant main effect of Condition (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;58.642, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001),with larger (more negative) amplitudes in the NoGo condition compared to the Go condition. A significant main effect of Group was also observed (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;4.826, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032); however, post-hoc analysis indicated no significance differences between groups in either condition (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). For N2 latency, no significant main effects or interactions were found (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and S1).\u003c/p\u003e \u003cp\u003e \u003cb\u003eP3 Component.\u003c/b\u003e For P3 amplitude, ANOVA revealed a significant main effect of Condition (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;125.444, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a Condition \u0026times; Location interaction (F[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;17.623, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating that P3 amplitudes were larger in the frontal region during the NoGo condition compared to the parietal region during the Go condition. No main effect of Group was observed (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;2.328, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.132); however, significant Group \u0026times; Location (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;11.669, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and Group \u0026times; Location \u0026times; Condition (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;5.948, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017) interactions were identified. Post-hoc analysis demonstrated significantly reduced frontal NoGo-P3 amplitudes in NT1 compared to controls, while parietal Go-P3 amplitudes did not differ between groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). For P3 latency, no main effect of Group was observed, but significant Group \u0026times; Location (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;11.669, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and Group \u0026times; Location \u0026times; Condition interactions (\u003cem\u003eF\u003c/em\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u0026thinsp;=\u0026thinsp;7.247, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) were found. Post-hoc analysis revealed longer parietal Go-P3 latencies in NT1 patients compared to controls, while frontal NoGo-P3 latencies showed no group differences (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and S2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 TF Results\u003c/h2\u003e \u003cp\u003eFor the Go condition, significant group differences in power were primarily observed in the theta (3\u0026ndash;7 Hz) and slow alpha (8\u0026ndash;10 Hz) bands. Specifically, compared to controls, NT1 patients exhibited lower theta power across all post-stimulus time windows (0-250 ms, 250\u0026ndash;350 ms, 350\u0026ndash;500 ms, and 500\u0026ndash;900 ms) and reduced slow alpha power in the 0-250 ms, 250\u0026ndash;350 ms, and 500\u0026ndash;900 ms time windows. Additionally, group differences in ITPC were observed within the first 500 ms post-stimulus across the theta (3\u0026ndash;7 Hz), slow alpha (8\u0026ndash;10 Hz), and fast alpha (11\u0026ndash;13 Hz) bands, with NT1 patients showing lower ITPC (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the NoGo condition, significant group differences in power were primarily observed in the theta band (3\u0026ndash;7 Hz) within the first 500 ms and in the slow alpha band (8\u0026ndash;10 Hz) during the 250\u0026ndash;350 ms time window. Furthermore, ITPC differences were noted in the theta band during the N2 (250\u0026ndash;350 ms) and P3 (350\u0026ndash;500 ms) time windows, with NT1 patients exhibiting lower ITPC (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eB and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Relationship between behavioral and ERP data\u003c/h2\u003e \u003cp\u003eGo-P3 latency was positively correlated with mean RTs in both groups (NT1: r\u0026thinsp;=\u0026thinsp;0.56; controls: r\u0026thinsp;=\u0026thinsp;0.53; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003eA), indicating that delayed response execution contributes to slower overall RTs. In the NT1 group, NoGo-P3 amplitude was negatively correlated with mean RTs (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.46, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003eB), suggesting that faster responders during the Go condition required larger Nogo-P3 amplitudes to effectively inhibit motor responses during the NoGo condition.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Relationship between behavioral and TF data\u003c/h2\u003e \u003cp\u003eIn the NT1 group, Go-theta power was negatively correlated with mean RTs during the N2 (250\u0026ndash;350 ms; \u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.61, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) time window (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). Go-theta ITPC showed a negative correlation with RTV during the P3 time windows (350\u0026ndash;500 ms; \u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.57, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003eD). These correlations were absent in the control group, suggesting that NT1 patients rely more heavily on theta-band activity to sustain attention, particularly during Go trails requiring rapid responses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Relationship between EEG and clinical data\u003c/h2\u003e \u003cp\u003eFor NT1 patients, Go-theta power during the N2 (250\u0026ndash;350 ms; \u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.54, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and P3 (350\u0026ndash;500 ms; \u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.61, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) time windows was positively correlated with CSF orexin levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003eE and \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003eF). This finding suggests that lower orexin levels may lead to reduced theta-band activity, potentially impairing performance in the Go condition.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eCognitive impairments in NT1, particularly in attention and inhibitory control, are clinically significant yet mechanistically unclear. Here, by integrating behavioral measures with multimodal EEG analyses (ERPs and TF analysis), we reveal that NT1 patients exhibit: (1) significant behavioral impairments (slower RTs and more OEs/CEs); (2) characteristic electrophysiological abnormalities (reduced NoGo-P3 amplitudes, delayed Go-P3 latencies, and attenuated theta-band power and ITPC). Crucially, we establish for the first time a direct association between reduced theta oscillations, behavioral impairments, and diminished CSF orexin levels, suggesting that orexin deficiency may impair cognitive function through disruption of thalamocortical theta oscillations. These findings provide both pathophysiological explanations for NT1-related cognitive dysfunction and quantifiable electrophysiological biomarkers with translational potential for disease monitoring and neuromodulation therapies.\u003c/p\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Behavioral performances\u003c/h2\u003e \u003cp\u003eOEs in continuous performance tasks reflect deficits in sustained attention, whereas CEs reveal impaired inhibitory control. Consistent with previous studies, our findings demonstrate that NT1 patients exhibit more OEs, longer RTs, and greater RTV than healthy controls, highlighting pronounced attentional deficits[\u003cspan additionalcitationids=\"CR48 CR49\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Regarding inhibitory control, we initially observed no group differences in CEs. However, a significant difference emerged after controlling for mean RTs as a covariate, suggesting a speed-accuracy tradeoff: participants may slow down during Go trials to achieve higher accuracy in NoGo trials[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. NT1 patients appear to rely more heavily on this strategy than controls, enabling them to temporarily maintain inhibitory performance. Nevertheless, when accounting for the speed-accuracy tradeoff, NT1 patients showed significantly impaired inhibitory control.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e4.2 ERP characteristics\u003c/h2\u003e \u003cp\u003eThe centro-parietal Go-P3 resembles the P3b component observed in oddball paradigms, reflecting involuntary relocation of attention to target stimuli, response preparation and execution[\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Prolonged Go-P3 latency in NT1 patients indicates delayed response execution, which aligns with our finding of a positive correlation between Go-P3 latency and mean RTs. This suggests that slower response execution significantly contributes to behavioral performance during Go trials. The absence of group differences in Go-N2 latency, coupled with significant differences in Go-P3 latency, implies that attention impairments in NT1 are primarily related to delayed response execution rather than deficits in stimulus perception or early evaluation.\u003c/p\u003e \u003cp\u003eOur study revealed a significant main effect of Condition, with both groups showing higher N2 and P3 amplitudes in the NoGo condition compared to the Go condition, consistent with prior Go/NoGo studies[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR55\" citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. This pattern reflects the increased cognitive demand required for inhibitory control. While both components are critical for successful inhibition, they represent different processes. NoGo-N2 is thought to reflect bottom-up conflict monitoring, arising from competition between frequent Go stimuli and infrequent NoGo stimuli[\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e], whereas NoGo-P3 is thought to reflect top-down conflict resolution and the actual inhibition of the motor response [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Our results showed group differences in NoGo-P3 amplitudes but not in NoGo-N2 amplitudes, suggesting that behavioral inhibition deficits in NT1 are primarily driven by impaired response inhibition rather than early conflict monitoring. Furthermore, NT1 patients with faster responses in the Go condition exhibited higher NoGo-P3 amplitudes, indicating that faster responders require more cognitive resources to achieve effective inhibition. This finding not only highlights the compensatory strategies employed by NT1 patients to maintain attention but also points to potential imbalances between attention and inhibitory control networks in this population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003e4.3 TF characteristics\u003c/h2\u003e \u003cp\u003eWhile ERPs provide initial insights into neurophysiological changes related to cognitive function, TF analysis disentangles power and phase effects across different frequencies, providing valuable insights into neural oscillations underlying ERP responses[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Alpha-band oscillations (8\u0026ndash;13 Hz), the brain\u0026rsquo;s dominant rhythm, are closely linked to arousal and attention. Higher alpha power is associated with increased arousal levels[\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Specifically, slow alpha (8\u0026ndash;10 Hz) facilitates attentional deployment by filtering out irrelevant information[\u003cspan additionalcitationids=\"CR61\" citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. In our study, NT1 patients exhibited reduced slow alpha power across multiple time windows, indicating lower levels of arousal and an impaired ability to suppress internal or external distractions.\u003c/p\u003e \u003cp\u003eTheta-band oscillations (3\u0026ndash;7 Hz) are critical for a range of cognitive processes, including arousal, selective attention, motor preparation, execution, and top-down inhibitory control[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. In cognitively normal individuals, higher frontal midline theta power during NoGo trials compared to Go trials highlights the role of theta modulation in recruiting cognitive control processes necessary for response inhibition[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. Our findings of reduced NoGo-theta power and ITPC in NT1 support the presence of impaired inhibitory control, potentially explaining their impulsive behaviors. Furthermore, the attenuation of Go-theta power and ITPC, along with their association with poorer performance on Go trials, suggests that deficits in theta-band activity also contribute to inattention. Specifically, reduced Go-theta power was correlated with slower RTs, while reduced Go-theta ITPC was linked to greater RTV, particularly within time windows aligned with the N2 and P3 components. This implies that response speed and stability rely on separate but complementary neural processes: impaired Go-theta power affects the efficiency of response execution, while impaired ITPC impacts the consistency of responses over time.\u003c/p\u003e \u003cp\u003eFor the first time, we identified a positive correlation between EEG measures (e.g., Go-theta power) and CSF orexin levels in NT1, suggesting that orexin deficiency may underlie impaired theta-band oscillations and subsequent attentional deficits. Orexin neurons, through their widespread projections to key brain regions including the prefrontal cortex, thalamus, and locus coeruleus, play a pivotal role in maintaining cortical arousal and attentional networks[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. The observed modulation of theta oscillations by orexin is particularly noteworthy, as these neural rhythms are fundamental for attention allocation and cognitive control[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan additionalcitationids=\"CR68\" citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]. Thus, we propose a mechanistic hypothesis: orexin deficiency disrupts thalamocortical network dynamics by attenuating theta-band oscillations, thereby impairing the functional integrity of brain networks essential for sustained attention. Future studies should investigate whether therapeutic restoration of orexin signaling can normalize theta oscillations and improve attentional performance in NT1, potentially offering a targeted treatment approach for cognitive impairments in this population[\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e, \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003e4.4 limitations\u003c/h2\u003e \u003cp\u003eThis study had several limitations. First, although our sample size was larger than that of previous cognitive studies on NT1, it remains relatively modest, warranting further research with larger populations to validate our findings. Second, the potential influence of medication on behavioral and electrophysiological outcomes could not be fully disentangled from the effects of the illness itself. Future research should investigate the impact of medication on cognitive function and neural dynamics. Third, the SART paradigm used in this study was relatively brief and simple, and other potential cognitive impairments may only emerge during more complex or prolonged tasks.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis study is the first to systematically evaluate attention and executive function in NT1 using combined time-domain and time-frequency EEG analyses. By integrating behavioral and electrophysiological data, our multimodal approach reveals distinct neurophysiological signatures of cognitive deficits: (1) attention impairments are characterized by delayed response preparation and execution, as evidenced by prolonged Go-P3 latency, while (2) inhibitory control deficits are associated with impaired response inhibition and reduced attentional resource allocation, reflected by reduced NoGo-P3 amplitude. Crucially, TF analyses further reveal that attenuated theta-band oscillations underlie these cognitive impairments, likely mediated by orexin deficiency. These findings not only advance our understanding of the neural mechanisms of NT1-related cognitive dysfunction but also identify clinically translatable EEG biomarkers, such as P3 components and theta oscillations, for clinical monitoring and future therapeutic development.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the individuals who participated in this trial, their families, and the clinical and research teams in the neurology department and school of physics of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.\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\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the Shanghai Science and Technology Program/Natural Science Foundation of Shanghai (22ZR1449800), National Natural Science Foundation of China (81401038), the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission under award number (2020383055/2020KY164), and Special Fund for Clinical Research of Zhejiang Medical Association (2022ZYC-A133).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZongshan Li\u003c/strong\u003e: Conceptualization, Methodology, Data collection, Writing-original draft, Writing review \u0026amp; editing. \u003cstrong\u003eXiao Han\u003c/strong\u003e: Conceptualization, Methodology, Statistical analysis, Data visualization, Writing review \u0026amp; editing. \u003cstrong\u003eJiahui Xu\u003c/strong\u003e: Methodology, Assisted in the completion of revised manuscript. \u003cstrong\u003eQinglin Xu\u003c/strong\u003e: Methodology, Assisted in the completion of revised manuscript. \u003cstrong\u003eXuelian Ge\u003c/strong\u003e: Assisted with data analysis. \u003cstrong\u003eYi Yang\u003c/strong\u003e: Data collection. \u003cstrong\u003eJiaqin Yu\u003c/strong\u003e: Data collection. \u003cstrong\u003eGuodong Lou\u003c/strong\u003e: Data collection. \u003cstrong\u003eYaxing Gui\u003c/strong\u003e: Methodology, Assisted in the completion of revised manuscript. \u003cstrong\u003eFeiyan Chen\u003c/strong\u003e: Conceptualization, Methodology, Assisted in the completion of revised manuscript. \u003cstrong\u003eLisan Zhang\u003c/strong\u003e: Conceptualization, Methodology, Assisted in the completion of revised manuscript. All authors have approved for the publication of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eADDITIONAL INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary information\u003c/strong\u003e The online version contains supplementary material available at \u003cstrong\u003e\u003cem\u003eTranslational Psychiatry\u003c/em\u003e\u003c/strong\u003e.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, et al. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15(9):519-539. doi:10.1038/s41582-019-0226-9.\u003c/li\u003e\n\u003cli\u003eKornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, et al. Narcolepsy. Nat Rev Dis Primers. 2017;3:16100. doi:10.1038/nrdp.2016.100.\u003c/li\u003e\n\u003cli\u003eBarateau L, Liblau R, Peyron C, Dauvilliers Y. 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Proc Natl Acad Sci U S A. 2015;112(30):9448-9453. doi:10.1073/pnas.1504196112.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"narcolepsy, cognitive function, attention, executive function, event-related potentials, inhibition response, time-frequency analysis","lastPublishedDoi":"10.21203/rs.3.rs-6340580/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6340580/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCognitive impairments in narcolepsy type 1 (NT1) significantly compromise daily functioning, but their neural mechanisms remain unclear. This study employed multimodal electroencephalography (EEG) analyses to investigate electrophysiological substrates of attention and inhibition deficits in NT1 and their association with clinical characteristics, particularly orexin deficiency. High-density EEG recordings were acquired during a Go/NoGo task from 39 NT1 patients and 41 age-/sex-matched healthy controls. Behavioral analyses reveled that compared to controls, NT1 patients exhibited significantly prolonged reaction times and increased errors across both Go and NoGo conditions. Electrophysiological analyses demonstrated that NT1 patients showed: (1) delayed Go-P3 latencies, meaning impaired response preparation; (2) reduced NoGo-P3 amplitudes, reflecting deficient inhibitory control; and (3) attenuated theta-band power and inter-trial phase consistency across conditions. Notably, decreased theta-band power correlated with both lower orexin levels and slower reaction times. These findings suggest that orexin deficiency may mediate theta-band oscillation impairments in NT1, which mechanistically contribute to cognitive dysfunction. Thus, we propose theta-band oscillations as a clinically translatable biomarker for NT1-related cognitive deficits, with promising implications for objective monitoring of disease progression and developing EEG-targeted neuromodulation therapies.\u003c/p\u003e","manuscriptTitle":"Attention and Inhibition Deficits in Narcolepsy Type 1: Behavioral and Electrophysiological Markers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-05 05:43:56","doi":"10.21203/rs.3.rs-6340580/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-07-14T10:11:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-30T23:09:40+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-06-13T18:55:31+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-05-12T03:31:34+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-04-26T23:18:01+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-04-03T21:01:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-02T13:33:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-02T13:33:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Translational Psychiatry","date":"2025-04-02T02:55:31+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2025-03-31T12:57:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc476efd-508d-4284-a018-ce7097c89785","owner":[],"postedDate":"May 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":47638492,"name":"Health sciences/Biomarkers/Diagnostic markers"},{"id":47638493,"name":"Biological sciences/Psychology/Human behaviour"},{"id":47638494,"name":"Biological sciences/Neuroscience"},{"id":47638495,"name":"Health sciences/Diseases"},{"id":47638496,"name":"Health sciences/Pathogenesis"}],"tags":[],"updatedAt":"2025-11-01T07:11:39+00:00","versionOfRecord":{"articleIdentity":"rs-6340580","link":"https://doi.org/10.1038/s41398-025-03684-x","journal":{"identity":"translational-psychiatry","isVorOnly":false,"title":"Translational Psychiatry"},"publishedOn":"2025-10-31 04:00:00","publishedOnDateReadable":"October 31st, 2025"},"versionCreatedAt":"2025-05-05 05:43:56","video":"","vorDoi":"10.1038/s41398-025-03684-x","vorDoiUrl":"https://doi.org/10.1038/s41398-025-03684-x","workflowStages":[]},"version":"v1","identity":"rs-6340580","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6340580","identity":"rs-6340580","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}