{"paper_id":"14f437b7-df4f-4281-9d0d-cce8936ebd24","body_text":"Neural markers of methylphenidate response in children with attention deficit hyperactivity disorder and the impact on executive function | 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 Research Article Neural markers of methylphenidate response in children with attention deficit hyperactivity disorder and the impact on executive function Anqi Wang, Hua Yang, Yue Yang, Jie Yang, Xiaowen Yang, Qianhui Wen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4389214/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Currently, objective biomarkers of methylphenidate (MPH) for the treatment of attention deficit hyperactivity disorder (ADHD) are lacking. Many symptoms of ADHD are associated with impaired executive function. We investigated the effects of MPH on executive function based on an electroencephalogram (EEG) and looked for biomarkers of responsiveness to methylphenidate in ADHD. Methods Twenty-two children with ADHD (18 males, 4 females; mean age 8.72 ± 1.46 years). All patients were treated with oral MPH 18 mg/day in the morning for 8 weeks. Executive function assessment and event-related potential (ERP) acquisition were completed at baseline and after 8 weeks of MPH treatment. Results We found that the BRIEF2 multiple factor scores in children with ADHD were significantly reduced after treatment with MPH ( P < 0.05). The correct response time was lower than that at baseline, and the correctness rate was higher than that at baseline ( P = 0.011, P = 0.016). Nogo-P300 latency at Fz was shorter than that at baseline ( P < 0.001), and the latency at Pz was shorter than at baseline ( P < 0.001). Conclusions Normalization of the P300 components by MPH is a predictor of efficacy in children with ADHD who respond positively to this treatment. Thus, MPH can improve executive function deficits. Attention Deficit Hyperactivity Disorder Children Executive function Methylphenidate P300 Figures Figure 1 Figure 2 Background Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in which individuals exhibit inattentive, hyperactive, and impulsive behaviors that are inappropriate for their age [ 1 ]. Behavioral functions can reflect the higher neural processes of the brain that control and coordinate cognition and behavior, including cognitive abilities such as planning, goal setting, judgment, flexibility, and working memory, and behavioral abilities such as behavioral control and inhibition [ 2 , 3 ]. Exploring executive function deficits in children with ADHD not only reveals the complexity of the disorder but also provides possible avenues of assessment for the treatment of the disease. Methylphenidate (MPH) is a first-line central stimulant for the treatment of ADHD. Its mechanism of action is to block the presynaptic reuptake of dopamine and norepinephrine, thereby increasing the concentration of these two neurotransmitters in the synaptic gap [ 4 ]. MPH is effective in improving the core symptoms of ADHD as well as executive function deficits such as working memory and inhibition [ 5 ]. Patients with ADHD treated with MPH may exhibit characteristic changes in the electroencephalogram (EEG) activity [ 6 ]. Event-related potentials (ERP) are evoked potentials that show stimulus-related postsynaptic activity in brain regions, reflecting changes in brain electrical activity during specific events [ 7 ]. With the advantages of non-invasiveness, high temporal resolution, and low cost, ERP is suitable for studying specific functions of brain regions involved in cognitive tasks and is widely used in basic and translational research on sensory, cognitive, emotional, and motor processes [ 8 ]. The P300 (also called P3) is the most studied wave for assessing information processing in the brain because of its wide scalp distribution, simplicity of recording, and reliability, thus providing a basis for studying the neural mechanisms of cognitive activity [ 9 ]. Few studies have directly investigated whether ERP components predict behavioral responses to MPH. Therefore, exploring the mechanisms of MPH in the treatment of ADHD, especially its improvement in executive function and potential effects on electrical brain activity, may provide a scientific basis for personalized treatment of ADHD. Methods Participants This study enrolled 22 children with ADHD (8.72 ± 1.46 years) who attended West China Second University Hospital, Sichuan University, from October 2022 to January 2023. Physicians diagnosed children with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Inclusion criteria were: (1) draw a person with a Test score ≥ 85; (2) right-handedness;(3) Han Chinese ethnicity. The exclusion criteria were as follows: (1) neurological abnormalities or traumatic brain injury; (2) other mental disorders, mental retardation, or various physical illnesses; (3) one or more comorbid mental disorders (e.g., Tourette syndrome, intellectual disability, learning disability, or conduct disorder); and (4) the use of cortical excitatory drugs. The patients were asked not to take any medication for at least 24 h before the experiment. Written informed consent was obtained from each participant’s parents, and the study was approved by the Human Research Ethics Committee of the West China Second University Hospital, Sichuan University. The patients were enrolled and treated with oral MPH (18 mg every morning for 8 weeks). Executive function and ERP data were collected at baseline and after 8 weeks of treatment with MPH, respectively. Executive function assessment The Behavior Rating Inventory of Executive Function-Parent form, Second edition(BRIEF2) The BRIEF2 was developed by Gioia et al. [ 10 ] and assessed behavioral, affective, and cognitive abilities in executive functioning in children and adolescents aged 5–18 years. It consists of three main dimensions and nine subscales with 63 items in total. The three dimensions are as follows: (1) Behavioral Regulation Index (BRI), including inhibition and self-monitoring; (2) Emotional Regulation index (ERI), including shifting and emotional control; and (3) Cognitive regulation index (CRI), including planning/organization, organization of materials, initiation, task monitoring, and working memory. Higher scores for each factor indicated more serious behavioral problems. Digit Span Test (DST) The DST [ 11 ] is a subtest of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV), which assesses a participant’s working memory and consists of digit forward (FDS) and digit backward (BDS) tasks. The longer the string of numbers the participant recited, the higher the score. Clinical Global Impressions (CGI) The Clinical Global Impressions-Improvement Scale (CGI-I) score was used to describe participants with ADHD as methylphenidate responders or non-responders [ 12 ]. Responses were rated on a 7-point scale (1 = significant progress, 2 = progress, 3 = slight progress, 4 = no change, 5 = slightly worse, 6 = much worse, and 7 = very much worse). Patients with a CGI-I score of less than 3 had a MPH response, whereas patients with a CGI-I score greater than or equal to 3 had a MPH non-response. The Clinical Global Impressions-Severity of Illness (CGI-S) assesses the severity of a patient’s illness on a seven-point scale: 1, no illness, 2 = borderline mental illness, 3 = mild illness, 4 = moderate illness, 5 = marked illness, 6 = severe illness; and 7, most severe illness [ 13 ]. Go/Nogo task The neuropsychological experimental paradigm for studying the response inhibition function is commonly called Go/No-go. Target stimuli for the Go/Nogo task: the letter “R” as the Go stimulus and the letter “P “as the NoGo stimulus. The number of letters “R” was 144 (80%), and the number of letters “P” was 36 (20%). The task started with a cross appearing in the middle of the computer screen for 400ms as a cue, followed by the letters “R” and “P” appearing randomly in the center of the computer screen for 200ms each, with the next letter appearing after a time interval of 800 ± 200ms. Participants press the left mouse button when they see the letter “R” and do not press the button when they see the letter “P”(Fig. 1 ). Variables related to behavioral performance (correct response time and correct response rate) were extracted for statistical analysis. EEG Acquisition The participants sat in a quiet, temperature-adapted room without strong lights for the EEG test. Nineteen Ag/AgCl electrodes were placed at Fp1, Fp2, Fz, F3, F4, F7, F8, Cz, C3, C4, Pz, P3, P4, T3, T4, T5, T6, O1, and O2 according to the International 10–20 system. The sampling rate was 2000 Hz, and the impedance between the electrodes and the scalp was kept less than 5 k Ω. Two reference electrodes (A1 and A2) were placed on both earlobes. This study utilized PsychToolbox software to present visual stimuli. EEG recordings while participants completed the computerized go/no-go task. EEG Preprocessing The acquired EEG data were processed in MATLAB R2021a using EEGLAB v14.1.2. This study aimed to obtain reliable EEG signal segments for each participant. The procedure included downsampling to 512 Hz, averaging reference, 0.5–35 Hz bandpass filtering, baseline correction, artifact removal by independent component analysis (ICA), and setting the threshold to ± 100 µV. Segments during responses were set with windows from − 200 ms before the event to 600 ms after. The mean amplitude and latency of the P300 component were extracted from the Fz, Cz, and Pz electrodes in a 250–500 ms time window. Statistical analysis The EEG data were analyzed using SPSS 23.0. Data were tested for normality using the Kolmogorov-Smirnov and Shapiro-Wilk methods, with measures that conformed to normality described as “mean ± standard deviation” and those that did not conform to the normal distribution described as “median ± interquartile spacing.” Paired t-tests were used for measures that conformed to a normal or approximately normal distribution, and nonparametric rank-sum tests were used for measures that did not conform to a normal distribution. The chi-squared test was used for between-group comparisons of categorical information. Results Demographics The demographic characteristics of children with ADHD are presented in Table 1 . This study enrolled 22 children with ADHD (8.72 ± 1.46 years), 18 males and 4 females. Seven ADHD-inattention types (ADHD-I), one ADHD-hyperactive-impulsive type(ADHD-HI) (4.6%), and 14 ADHD-combined types (ADHD-C) (63.8%) were included. Table 1 Demographic characteristics Characteristics ADHD N 22 Male/Female 18/4 Age, mean (SD), years 8.72 ± 1.46 Subtype, No. (%) - ADHD-I 7(31.8) ADHD-HI 1(4.6) ADHD-C 14(63.6) Executive function Changes in executive functioning scale scores after eight weeks of treatment with MPH in children with ADHD compared to baseline are shown in Table 2 . Inhibition, self-monitoring, initiation, working memory, task monitoring, material organization, BRI, CRI, and total scores were significantly lower ( P < 0.05). There were no significant differences in the FDS and BDS scores from baseline after 8 weeks of MPH treatment ( P > 0.05). Table 2 Methylphenidate treatment executive function changes in children with ADHD baseline 8weeks P BRIEF2 Inhibition 62.59 ± 10.36 56.36 ± 7.64 0.020 * Self-monitoring 65.09 ± 9.96 59.23 ± 7.41 0.048 * Shifting 57.59 ± 8.49 54.41 ± 7.31 0.098 Emotional control 56.82 ± 9.97 53.91 ± 7.24 0.197 Initiation 61.45 ± 6.88 56.41 ± 7.79 0.009 * Working memory 69.86 ± 7.88 64.45 ± 7.54 0.002 * Planning/ Organisation 64.86 ± 9.23 60.27 ± 6.11 0.057 Task monitoring 67.73 ± 9.81 63.36 ± 8.43 0.028 * Organization of Materials 60.95 ± 9.86 56.09 ± 7.22 0.012 * BRI 63.55 ± 8.91 58.05 ± 7.36 0.020 * ERI 59.59 ± 10.41 55.95 ± 9.98 0.156 CRI 67.00 ± 7.83 60.95 ± 7.05 0.001 * Total score 66.64 ± 7.62 62.50 ± 7.12 0.027 * DST FDS 7.41 ± 1.76 7.73 ± 1.24 0.231 BDS 3.77 ± 1.27 3.27 ± 1.28 0.102 BRIEF2: Behavior Rating Inventory of Executive Function-Parent form, Second edition; BRI: Behavioral Regulation Index; ERI: Emotional Regulation Index; CRI: Cognitive Regulation Index; DST: Digit Span Test; FDS: Digits Forward; BDS: Digits Backward. ** P < 0.05 by Paired t-tests CGI and behavioral characteristics The results of the correctness and response time of the behavioral data after MPH treatment are shown in Table 3 . The no-go task correct response time was lower than baseline in children with ADHD after 8 weeks of treatment with MPH compared to baseline (p = 0.011). The no-correctness rate was higher than that at baseline (p = 0.016). The CGI-GI score after eight weeks of treatment with MPH in children with ADHD was 2.59 ± 0.16. CGI-S scores decreased significantly after MPH treatment( P = 0.001). Table 3 Behavioural characteristics and CGI-I after methylphenidate treatment in children with ADHD items baseline 8weeks P correct response time(ms) 606.69 ± 80.03 579.87 ± 69.33 0.011 correctness rate(%) 43.43 ± 17.11 48.99 ± 17.64 0.016 CGI-I - 2.59 ± 0.16 - CGI-S 4.32 ± 0.72 3.23 ± 0.81 0.001 P300 component The changes in P300 composition after eight weeks of treatment with MPH in children with ADHD are shown in Table 4 . Nogo-P300 latency at Fz was shortened from baseline ( P < 0.001). The Nogo-P300 at Pz was shorter than at baseline ( P < 0.001). Nogo-P300 amplitudes at Fz, Cz, and Pz were elevated from baseline, but the differences were not statistically significant( P > 0.05) (Fig. 2 ). Table 4 Comparison of Fz, Cz, and Pz Electrode Nogo-P300 after methylphenidate treatment in Children with ADHD items baseline 8weeks P Fz latency(ms) 233.17±107.18 172.88±1.5.54 <0.001 ∗ amplitudes(µv) 3.26±2.87 3.51±1.97 0.793 Cz latency(ms) 247.34±63.40 217.93±28.82 0.058 amplitudes(µv) 1.68±2.04 1.74±1.98 0.198 Pz latency(ms) 242.37±100.85 213.17±97.50 <0.001 ∗ amplitudes(µv) 5.73±4.45 7.13±3.50 0.077 * P < 0.05 Discussion EEG signals contain information related to the dynamics of brain function, and electrophysiological studies using ERPs have established relevant features of executive dysfunction in ADHD [ 14 ]. In contrast to resting-state EEG, ERP reflects changes in the brain’s electrical activity during a specific event [ 15 ] and can be used to assess dysfunctional brain dynamics, including cognitive processes that may not be apparent at the behavioral level [ 16 ]. In this study, we investigated the acute effects of MPH on executive functioning. After 8 weeks of MPH treatment, children with ADHD showed significant improvements from baseline in executive functioning in inhibition, self-monitoring, initiation, working memory, task monitoring, and organization of materials areas. Deficits in response inhibition are thought to be central to the pathogenesis of ADHD [ 17 ]. Broyd et al. [ 18 ] found that MPH was associated with reduced errors in a go/no-go task, suggesting that MPH specifically improves inhibitory motor control in children with ADHD. Many studies have shown that older adolescents and young adults perform better and more effectively than children in response inhibition tasks and that inhibitory processes have long maturation processes [ 19 ]. Structural MRI studies have found that poorer inhibitory function in patients with ADHD is associated with a thicker caudal inferior frontal gyrus [ 20 ] and that the maturation of this region may vary in patients who perform poorly on Go/Nogo tasks. A CGI-I score of less than 3 after 8 weeks of treatment with MPH in patients with ADHD suggests a response to MPH treatment [ 12 ]. A CGI-S score of > 4 indicated moderately severe ADHD symptoms. Rosenau et al. [ 2 ] found that patients with ADHD had CGI-S scores greater than 4 before treatment with methylphenidate, similar to the results of this study, suggesting that children with ADHD improved after MPH treatment. Previous studies have not identified objective indicators for evaluating the efficacy of MPH, and recent studies have increasingly focused on identifying biomarkers to provide precise medical care for patients with ADHD. ERP amplitudes and latency of ERPs have been identified as promising biomarkers for pharmacological therapy in children with ADHD [ 21 ]. The amplitude of an early subcomponent of P300 is reduced in patients with ADHD when confronted with salient or novel stimuli [ 22 ]. Subcomponent P3a of the P300 is generated by the excitation of the frontal striatal nerve groups involved in the orientation and assessment of auditory or visual stimuli. Frontal striatal neural circuits are regulated by catecholamine neurotransmitters, particularly dopamine [ 23 ]. Electroencephalographic studies of patients with PD with low dopamine levels have found a decrease in P3a amplitude [ 24 ], which increases to normal levels after the administration of stimulant medication, which is the effect of dopamine agonists [ 9 ]. In this study, we found that children with ADHD who completed the Go/No-go task after 8 weeks of treatment with MPH had elevated Nogo-P300 amplitudes and shortened latencies at Fz, Cz, and Pz. The Nogo-P300 latency was significantly shortened at Fz and Pz. We suggest that the normalization of the MPH to the P300 component may be due to improved frontal striatal cortical network integrity and increased excitatory synaptic capacity. Changes in P300 amplitude and latency are an effect of stimulant medication, suggesting that stimulant medication persistently alters ERPs in cognitive function (e.g., attention, inhibitory control, memory) tasks. The simultaneous discharge of localized networks of pyramidal cells resulted in greater ERP amplitudes in the scalp, and the increase in P300 amplitude may reflect greater coordination of cortical network activation, particularly during the action execution phase of attentional processing. Stimulant drug-associated P300 alterations suggest that cognitive and behavioral deficits in patients with ADHD are associated with reduced cortical network activation and coordinated recruitment, which can be attenuated by increasing presynaptic catecholamine availability. The P300 component is by far the most promising ERP neuromarker for precision medicine in ADHD [ 9 ], and normalization of the P300 amplitude after stimulant treatment is a predictor of a positive response to such treatment. Conclusions In this study, by examining the executive function and ERP, we found that normalization of P300 components by MPH is a predictor of efficacy in children with ADHD who respond positively to this treatment and that ERP for identifying responses to MPH treatment is a feasible and promising neuromarker. MPH improves executive function in children with ADHD, and the modulatory effects of MPH treatment on executive function provide new insights into neurophysiological mechanisms. Abbreviations MPH: Methylphenidate; ADHD: Attention deficit hyperactivity disorder; EEG: Electroencephalogram; ERP: Event-related potentials; CGI: Clinical Global Impressions; BRIEF2: The Behavior Rating Inventory of Executive Function-Parent form, Second edition; Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Department of Pediatrics, West China Second University Hospital, Sichuan University. We confirmed that all methods were performed according to relevant guidelines and regulations. Also, the Informed consent was obtained from the participants’ parents and/or legal guardians. All research findings are disseminated to the public through peer-reviewed publications, journals, and academic conferences. Consent for publication Not applicable. Availability of data and materials The data supporting the conclusions of this article are held electronically in the Department of Paediatric Neurology, West China Second University Hospital, Sichuan University, Chengdu, China. The datasets used and/or analyzed in this study are available from the corresponding author upon reasonable request. Competing interest The authors declare that they have no competing interests. Funding This research was funded by the National Key R&D Program of China (No.2021YFC1005305) and Sichuan Provincial Department of Science and Technology Project（No.2023NSFSC1492）. Authors’ contributions AW and HY wrote the manuscript, planned and designed the study, collected and interpreted the data, and coordinated the study. YY and JY supported the writing of the manuscript and collected and interpreted the data. XY and QW participated in the experimental design and discussion of results. QW and HLcollected the needed information and revised the manuscript. Professor RL participated in the experimental design, participant recruitment, discussion of the results, and manuscript revision. Acknowledgments We want to thank all those who participated in this study. References Bausela-Herreras E, Alonso-Este-ban Y, Alcantud-Marín F. Behavior Rating Inventory of Executive Function in preschool (BRIEF-P) and attention-deficit and hyperactivity disorders (ADHD): A systematic review and meta-analysis of floor and ceiling effects. Child (Basel). 2023;11:58. Rosenau PT, Openneer TJC, Matthijssen AM, van de Loo-Neus GHH, Buitelaar JK, van den Hoofdakker BJ, et al. 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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-4389214\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":304077306,\"identity\":\"dc5e9bdb-242e-4c2f-8c4d-3aa1b3fa4ec9\",\"order_by\":0,\"name\":\"Anqi Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"West China Second University Hospital of Sichuan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Anqi\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":304077307,\"identity\":\"ddfa591a-b5db-4203-8e86-d48026dda3da\",\"order_by\":1,\"name\":\"Hua 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Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"West China Second University Hospital of Sichuan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Qian\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":304077313,\"identity\":\"3d5699e6-0db6-4ec2-bb7e-49ef38fce568\",\"order_by\":7,\"name\":\"Hao Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"West China Second University Hospital of Sichuan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hao\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":304077314,\"identity\":\"946e493a-9fe6-4bb4-9c06-329287b8d995\",\"order_by\":8,\"name\":\"Rong Luo\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYBACPjBZAeFIEKWFDUyeIVkLYxtJWqSPP/zMO69O3uAA88HbPAx2eYS18OUYS/NuO2y44QBbsjUPQ3IxYS08PGzMvNsOJBgc4DGT5mE4kNhAWAv7M2beOXVALfzfiNXCYMbM28AMsoWNWC08xpJzjh02nHmYzdhyjkEyYS38POwPP7ypqZPnO9788MabCjvCWhCAGUQYEK9+FIyCUTAKRgEeAABOLy6gDouPCgAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"West China Second University Hospital of Sichuan University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Rong\",\"middleName\":\"\",\"lastName\":\"Luo\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-05-08 12:15:05\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4389214/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4389214/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":56810006,\"identity\":\"01a04eff-663c-479d-b8c5-f3e37e6ebc56\",\"added_by\":\"auto\",\"created_at\":\"2024-05-20 18:55:04\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":57831,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eGo/Nogo task design\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4389214/v1/3d2697ed7928e5596e105064.jpg\"},{\"id\":56810007,\"identity\":\"ce7af6fa-993b-404d-893f-a59d3b5bdb1a\",\"added_by\":\"auto\",\"created_at\":\"2024-05-20 18:55:04\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":66146,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChanges in P300 composition after MPH treatment in children with ADHD. The horizontal coordinate is the time (ms), and the vertical coordinate is the amplitude of the waves (mV).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4389214/v1/b9546518f85ed4f86d9d5668.jpg\"},{\"id\":61575122,\"identity\":\"3c309d91-89bb-4fda-b224-40dc1855256f\",\"added_by\":\"auto\",\"created_at\":\"2024-08-01 12:06:50\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":525601,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4389214/v1/8740b353-b5ca-41e8-8654-e0f85eaf0abd.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Neural markers of methylphenidate response in children with attention deficit hyperactivity disorder and the impact on executive function\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eAttention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in which individuals exhibit inattentive, hyperactive, and impulsive behaviors that are inappropriate for their age [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Behavioral functions can reflect the higher neural processes of the brain that control and coordinate cognition and behavior, including cognitive abilities such as planning, goal setting, judgment, flexibility, and working memory, and behavioral abilities such as behavioral control and inhibition [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. Exploring executive function deficits in children with ADHD not only reveals the complexity of the disorder but also provides possible avenues of assessment for the treatment of the disease. Methylphenidate (MPH) is a first-line central stimulant for the treatment of ADHD. Its mechanism of action is to block the presynaptic reuptake of dopamine and norepinephrine, thereby increasing the concentration of these two neurotransmitters in the synaptic gap [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. MPH is effective in improving the core symptoms of ADHD as well as executive function deficits such as working memory and inhibition [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Patients with ADHD treated with MPH may exhibit characteristic changes in the electroencephalogram (EEG) activity [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eEvent-related potentials (ERP) are evoked potentials that show stimulus-related postsynaptic activity in brain regions, reflecting changes in brain electrical activity during specific events [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. With the advantages of non-invasiveness, high temporal resolution, and low cost, ERP is suitable for studying specific functions of brain regions involved in cognitive tasks and is widely used in basic and translational research on sensory, cognitive, emotional, and motor processes [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. The P300 (also called P3) is the most studied wave for assessing information processing in the brain because of its wide scalp distribution, simplicity of recording, and reliability, thus providing a basis for studying the neural mechanisms of cognitive activity [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Few studies have directly investigated whether ERP components predict behavioral responses to MPH. Therefore, exploring the mechanisms of MPH in the treatment of ADHD, especially its improvement in executive function and potential effects on electrical brain activity, may provide a scientific basis for personalized treatment of ADHD.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eParticipants\\u003c/p\\u003e \\u003cp\\u003eThis study enrolled 22 children with ADHD (8.72\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.46 years) who attended West China Second University Hospital, Sichuan University, from October 2022 to January 2023. Physicians diagnosed children with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Inclusion criteria were: (1) draw a person with a Test score\\u0026thinsp;\\u0026ge;\\u0026thinsp;85; (2) right-handedness;(3) Han Chinese ethnicity. The exclusion criteria were as follows: (1) neurological abnormalities or traumatic brain injury; (2) other mental disorders, mental retardation, or various physical illnesses; (3) one or more comorbid mental disorders (e.g., Tourette syndrome, intellectual disability, learning disability, or conduct disorder); and (4) the use of cortical excitatory drugs. The patients were asked not to take any medication for at least 24 h before the experiment. Written informed consent was obtained from each participant\\u0026rsquo;s parents, and the study was approved by the Human Research Ethics Committee of the West China Second University Hospital, Sichuan University.\\u003c/p\\u003e \\u003cp\\u003eThe patients were enrolled and treated with oral MPH (18 mg every morning for 8 weeks). Executive function and ERP data were collected at baseline and after 8 weeks of treatment with MPH, respectively.\\u003c/p\\u003e \\u003cp\\u003eExecutive function assessment\\u003c/p\\u003e \\u003cp\\u003eThe Behavior Rating Inventory of Executive Function-Parent form, Second edition(BRIEF2)\\u003c/p\\u003e \\u003cp\\u003eThe BRIEF2 was developed by Gioia et al. [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e] and assessed behavioral, affective, and cognitive abilities in executive functioning in children and adolescents aged 5\\u0026ndash;18 years. It consists of three main dimensions and nine subscales with 63 items in total. The three dimensions are as follows: (1) Behavioral Regulation Index (BRI), including inhibition and self-monitoring; (2) Emotional Regulation index (ERI), including shifting and emotional control; and (3) Cognitive regulation index (CRI), including planning/organization, organization of materials, initiation, task monitoring, and working memory. Higher scores for each factor indicated more serious behavioral problems.\\u003c/p\\u003e \\u003cp\\u003eDigit Span Test (DST)\\u003c/p\\u003e \\u003cp\\u003eThe DST [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e] is a subtest of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV), which assesses a participant\\u0026rsquo;s working memory and consists of digit forward (FDS) and digit backward (BDS) tasks. The longer the string of numbers the participant recited, the higher the score.\\u003c/p\\u003e \\u003cp\\u003eClinical Global Impressions (CGI)\\u003c/p\\u003e \\u003cp\\u003eThe Clinical Global Impressions-Improvement Scale (CGI-I) score was used to describe participants with ADHD as methylphenidate responders or non-responders [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Responses were rated on a 7-point scale (1\\u0026thinsp;=\\u0026thinsp;significant progress, 2\\u0026thinsp;=\\u0026thinsp;progress, 3\\u0026thinsp;=\\u0026thinsp;slight progress, 4\\u0026thinsp;=\\u0026thinsp;no change, 5\\u0026thinsp;=\\u0026thinsp;slightly worse, 6\\u0026thinsp;=\\u0026thinsp;much worse, and 7\\u0026thinsp;=\\u0026thinsp;very much worse). Patients with a CGI-I score of less than 3 had a MPH response, whereas patients with a CGI-I score greater than or equal to 3 had a MPH non-response. The Clinical Global Impressions-Severity of Illness (CGI-S) assesses the severity of a patient\\u0026rsquo;s illness on a seven-point scale: 1, no illness, 2\\u0026thinsp;=\\u0026thinsp;borderline mental illness, 3\\u0026thinsp;=\\u0026thinsp;mild illness, 4\\u0026thinsp;=\\u0026thinsp;moderate illness, 5\\u0026thinsp;=\\u0026thinsp;marked illness, 6\\u0026thinsp;=\\u0026thinsp;severe illness; and 7, most severe illness [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eGo/Nogo task\\u003c/p\\u003e \\u003cp\\u003eThe neuropsychological experimental paradigm for studying the response inhibition function is commonly called Go/No-go. Target stimuli for the Go/Nogo task: the letter \\u0026ldquo;R\\u0026rdquo; as the Go stimulus and the letter \\u0026ldquo;P \\u0026ldquo;as the NoGo stimulus. The number of letters \\u0026ldquo;R\\u0026rdquo; was 144 (80%), and the number of letters \\u0026ldquo;P\\u0026rdquo; was 36 (20%). The task started with a cross appearing in the middle of the computer screen for 400ms as a cue, followed by the letters \\u0026ldquo;R\\u0026rdquo; and \\u0026ldquo;P\\u0026rdquo; appearing randomly in the center of the computer screen for 200ms each, with the next letter appearing after a time interval of 800\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;200ms. Participants press the left mouse button when they see the letter \\u0026ldquo;R\\u0026rdquo; and do not press the button when they see the letter \\u0026ldquo;P\\u0026rdquo;(Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Variables related to behavioral performance (correct response time and correct response rate) were extracted for statistical analysis.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eEEG Acquisition\\u003c/p\\u003e \\u003cp\\u003eThe participants sat in a quiet, temperature-adapted room without strong lights for the EEG test. Nineteen Ag/AgCl electrodes were placed at Fp1, Fp2, Fz, F3, F4, F7, F8, Cz, C3, C4, Pz, P3, P4, T3, T4, T5, T6, O1, and O2 according to the International 10\\u0026ndash;20 system. The sampling rate was 2000 Hz, and the impedance between the electrodes and the scalp was kept less than 5 k Ω. Two reference electrodes (A1 and A2) were placed on both earlobes. This study utilized PsychToolbox software to present visual stimuli. EEG recordings while participants completed the computerized go/no-go task.\\u003c/p\\u003e \\u003cp\\u003eEEG Preprocessing\\u003c/p\\u003e \\u003cp\\u003eThe acquired EEG data were processed in MATLAB R2021a using EEGLAB v14.1.2. This study aimed to obtain reliable EEG signal segments for each participant. The procedure included downsampling to 512 Hz, averaging reference, 0.5\\u0026ndash;35 Hz bandpass filtering, baseline correction, artifact removal by independent component analysis (ICA), and setting the threshold to \\u0026plusmn;\\u0026thinsp;100 \\u0026micro;V. Segments during responses were set with windows from \\u0026minus;\\u0026thinsp;200 ms before the event to 600 ms after. The mean amplitude and latency of the P300 component were extracted from the Fz, Cz, and Pz electrodes in a 250\\u0026ndash;500 ms time window.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eThe EEG data were analyzed using SPSS 23.0. Data were tested for normality using the Kolmogorov-Smirnov and Shapiro-Wilk methods, with measures that conformed to normality described as \\u0026ldquo;mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation\\u0026rdquo; and those that did not conform to the normal distribution described as \\u0026ldquo;median\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;interquartile spacing.\\u0026rdquo; Paired t-tests were used for measures that conformed to a normal or approximately normal distribution, and nonparametric rank-sum tests were used for measures that did not conform to a normal distribution. The chi-squared test was used for between-group comparisons of categorical information.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eDemographics\\u003c/p\\u003e \\u003cp\\u003eThe demographic characteristics of children with ADHD are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. This study enrolled 22 children with ADHD (8.72\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.46 years), 18 males and 4 females. Seven ADHD-inattention types (ADHD-I), one ADHD-hyperactive-impulsive type(ADHD-HI) (4.6%), and 14 ADHD-combined types (ADHD-C) (63.8%) were included.\\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 characteristics\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"2\\\"\\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 \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCharacteristics\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eADHD\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eN\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e22\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\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\\u003e18/4\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, mean (SD), years\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8.72\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.46\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSubtype, No. (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eADHD-I\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e7(31.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eADHD-HI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1(4.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eADHD-C\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e14(63.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eExecutive function\\u003c/p\\u003e \\u003cp\\u003eChanges in executive functioning scale scores after eight weeks of treatment with MPH in children with ADHD compared to baseline are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e. Inhibition, self-monitoring, initiation, working memory, task monitoring, material organization, BRI, CRI, and total scores were significantly lower (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). There were no significant differences in the FDS and BDS scores from baseline after 8 weeks of MPH treatment (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05).\\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\\u003eMethylphenidate treatment executive function changes in children with ADHD\\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\\u003ebaseline\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8weeks\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eBRIEF2\\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\\u003eInhibition\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e62.59\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;10.36\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e56.36\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.64\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.020\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSelf-monitoring\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e65.09\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.96\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e59.23\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.41\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.048\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eShifting\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e57.59\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e54.41\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.31\\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\\u003eEmotional control\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e56.82\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.97\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e53.91\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.24\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.197\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eInitiation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e61.45\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.88\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e56.41\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.79\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.009\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eWorking memory\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e69.86\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.88\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e64.45\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.54\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.002\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePlanning/ Organisation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e64.86\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.23\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e60.27\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.11\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.057\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTask monitoring\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e67.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.81\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e63.36\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.43\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.028\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eOrganization of Materials\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e60.95\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.86\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e56.09\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.22\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.012\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBRI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e63.55\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.91\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e58.05\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.36\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.020\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eERI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e59.59\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;10.41\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e55.95\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.98\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.156\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCRI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e67.00\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.83\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e60.95\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.05\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.001\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTotal score\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e66.64\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.62\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e62.50\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.12\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.027\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDST\\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\\u003eFDS\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e7.41\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.76\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e7.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.24\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.231\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBDS\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3.77\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.27\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.27\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.28\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.102\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eBRIEF2: Behavior Rating Inventory of Executive Function-Parent form, Second edition; BRI: Behavioral Regulation Index; ERI: Emotional Regulation Index; CRI: Cognitive Regulation Index; DST: Digit Span Test; FDS: Digits Forward; BDS: Digits Backward.\\u003c/p\\u003e \\u003cp\\u003e**\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 by Paired t-tests\\u003c/p\\u003e \\u003cp\\u003eCGI and behavioral characteristics\\u003c/p\\u003e \\u003cp\\u003eThe results of the correctness and response time of the behavioral data after MPH treatment are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e. The no-go task correct response time was lower than baseline in children with ADHD after 8 weeks of treatment with MPH compared to baseline (p\\u0026thinsp;=\\u0026thinsp;0.011). The no-correctness rate was higher than that at baseline (p\\u0026thinsp;=\\u0026thinsp;0.016). The CGI-GI score after eight weeks of treatment with MPH in children with ADHD was 2.59\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.16. CGI-S scores decreased significantly after MPH treatment(\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.001).\\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\\u003eBehavioural characteristics and CGI-I after methylphenidate treatment in children with ADHD\\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=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" 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 \\u003cp\\u003eitems\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ebaseline\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8weeks\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ecorrect response time(ms)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e606.69\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;80.03\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e579.87\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;69.33\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.011\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ecorrectness rate(%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e43.43\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;17.11\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e48.99\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;17.64\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.016\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCGI-I\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.59\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.16\\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\\u003eCGI-S\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4.32\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.72\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.23\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.81\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.001\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eP300 component\\u003c/p\\u003e \\u003cp\\u003eThe changes in P300 composition after eight weeks of treatment with MPH in children with ADHD are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e. Nogo-P300 latency at Fz was shortened from baseline (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). The Nogo-P300 at Pz was shorter than at baseline (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). Nogo-P300 amplitudes at Fz, Cz, and Pz were elevated from baseline, but the differences were not statistically significant(\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eComparison of Fz, Cz, and Pz Electrode Nogo-P300 after methylphenidate treatment in Children with ADHD\\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 \\u003cp\\u003eitems\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ebaseline\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8weeks\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eFz\\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\\u003elatency(ms)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e233.17\\u0026plusmn;107.18\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e172.88\\u0026plusmn;1.5.54\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;0.001\\u003csup\\u003e\\u0026lowast;\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eamplitudes(\\u0026micro;v)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3.26\\u0026plusmn;2.87\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.51\\u0026plusmn;1.97\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.793\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eCz\\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\\u003elatency(ms)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e247.34\\u0026plusmn;63.40\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e217.93\\u0026plusmn;28.82\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.058\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eamplitudes(\\u0026micro;v)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.68\\u0026plusmn;2.04\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.74\\u0026plusmn;1.98\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.198\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePz\\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\\u003elatency(ms)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e242.37\\u0026plusmn;100.85\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e213.17\\u0026plusmn;97.50\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;0.001\\u003csup\\u003e\\u0026lowast;\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eamplitudes(\\u0026micro;v)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5.73\\u0026plusmn;4.45\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e7.13\\u0026plusmn;3.50\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.077\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003e*\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eEEG signals contain information related to the dynamics of brain function, and electrophysiological studies using ERPs have established relevant features of executive dysfunction in ADHD [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. In contrast to resting-state EEG, ERP reflects changes in the brain\\u0026rsquo;s electrical activity during a specific event [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e] and can be used to assess dysfunctional brain dynamics, including cognitive processes that may not be apparent at the behavioral level [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. In this study, we investigated the acute effects of MPH on executive functioning. After 8 weeks of MPH treatment, children with ADHD showed significant improvements from baseline in executive functioning in inhibition, self-monitoring, initiation, working memory, task monitoring, and organization of materials areas. Deficits in response inhibition are thought to be central to the pathogenesis of ADHD [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. Broyd et al. [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e] found that MPH was associated with reduced errors in a go/no-go task, suggesting that MPH specifically improves inhibitory motor control in children with ADHD. Many studies have shown that older adolescents and young adults perform better and more effectively than children in response inhibition tasks and that inhibitory processes have long maturation processes [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. Structural MRI studies have found that poorer inhibitory function in patients with ADHD is associated with a thicker caudal inferior frontal gyrus [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e] and that the maturation of this region may vary in patients who perform poorly on Go/Nogo tasks. A CGI-I score of less than 3 after 8 weeks of treatment with MPH in patients with ADHD suggests a response to MPH treatment [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. A CGI-S score of \\u0026gt;\\u0026thinsp;4 indicated moderately severe ADHD symptoms. Rosenau et al. [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e] found that patients with ADHD had CGI-S scores greater than 4 before treatment with methylphenidate, similar to the results of this study, suggesting that children with ADHD improved after MPH treatment.\\u003c/p\\u003e \\u003cp\\u003ePrevious studies have not identified objective indicators for evaluating the efficacy of MPH, and recent studies have increasingly focused on identifying biomarkers to provide precise medical care for patients with ADHD. ERP amplitudes and latency of ERPs have been identified as promising biomarkers for pharmacological therapy in children with ADHD [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. The amplitude of an early subcomponent of P300 is reduced in patients with ADHD when confronted with salient or novel stimuli [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Subcomponent P3a of the P300 is generated by the excitation of the frontal striatal nerve groups involved in the orientation and assessment of auditory or visual stimuli. Frontal striatal neural circuits are regulated by catecholamine neurotransmitters, particularly dopamine [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Electroencephalographic studies of patients with PD with low dopamine levels have found a decrease in P3a amplitude [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e], which increases to normal levels after the administration of stimulant medication, which is the effect of dopamine agonists [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. In this study, we found that children with ADHD who completed the Go/No-go task after 8 weeks of treatment with MPH had elevated Nogo-P300 amplitudes and shortened latencies at Fz, Cz, and Pz. The Nogo-P300 latency was significantly shortened at Fz and Pz. We suggest that the normalization of the MPH to the P300 component may be due to improved frontal striatal cortical network integrity and increased excitatory synaptic capacity. Changes in P300 amplitude and latency are an effect of stimulant medication, suggesting that stimulant medication persistently alters ERPs in cognitive function (e.g., attention, inhibitory control, memory) tasks. The simultaneous discharge of localized networks of pyramidal cells resulted in greater ERP amplitudes in the scalp, and the increase in P300 amplitude may reflect greater coordination of cortical network activation, particularly during the action execution phase of attentional processing. Stimulant drug-associated P300 alterations suggest that cognitive and behavioral deficits in patients with ADHD are associated with reduced cortical network activation and coordinated recruitment, which can be attenuated by increasing presynaptic catecholamine availability. The P300 component is by far the most promising ERP neuromarker for precision medicine in ADHD [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e], and normalization of the P300 amplitude after stimulant treatment is a predictor of a positive response to such treatment.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eIn this study, by examining the executive function and ERP, we found that normalization of P300 components by MPH is a predictor of efficacy in children with ADHD who respond positively to this treatment and that ERP for identifying responses to MPH treatment is a feasible and promising neuromarker. MPH improves executive function in children with ADHD, and the modulatory effects of MPH treatment on executive function provide new insights into neurophysiological mechanisms.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eMPH: Methylphenidate; ADHD: Attention deficit hyperactivity disorder; EEG: Electroencephalogram; ERP: Event-related potentials; CGI: Clinical Global Impressions; BRIEF2: The Behavior Rating Inventory of Executive Function-Parent form, Second edition;\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003eEthics approval and consent to participate\\u003c/p\\u003e\\n\\u003cp\\u003eThis study was approved by the Ethics Committee of the Department of Pediatrics, West China Second University Hospital, Sichuan University. We confirmed that all methods were performed according to relevant guidelines and regulations. Also, the Informed consent was obtained from the participants\\u0026rsquo; parents and/or legal guardians. All research findings are disseminated to the public through peer-reviewed publications, journals, and academic conferences.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eConsent for publication\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eAvailability of data and materials\\u003c/p\\u003e\\n\\u003cp\\u003eThe data supporting the conclusions of this article are held electronically in the Department of Paediatric Neurology, West China Second University Hospital, Sichuan University, Chengdu, China.\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets used and/or analyzed in this study are available from the corresponding author upon reasonable request.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eCompeting interest\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eFunding\\u003c/p\\u003e\\n\\u003cp\\u003eThis research was funded by the National Key R\\u0026amp;D Program of China (No.2021YFC1005305) and Sichuan Provincial Department of Science and Technology Project（No.2023NSFSC1492）.\\u003c/p\\u003e\\n\\u003cp\\u003eAuthors\\u0026rsquo; contributions\\u003c/p\\u003e\\n\\u003cp\\u003eAW and HY wrote the manuscript, planned and designed the study, collected and interpreted the data, and coordinated the study. YY and JY supported the writing of the manuscript and collected and interpreted the data. XY and QW participated in the experimental design and discussion of results. QW and HLcollected the needed information and revised the manuscript. Professor RL participated in the experimental design, participant recruitment, discussion of the results, and manuscript revision.\\u003c/p\\u003e\\n\\u003cp\\u003eAcknowledgments\\u003c/p\\u003e\\n\\u003cp\\u003eWe want to thank all those who participated in this study.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eBausela-Herreras E, Alonso-Este-ban Y, Alcantud-Mar\\u0026iacute;n F. Behavior Rating Inventory of Executive Function in preschool (BRIEF-P) and attention-deficit and hyperactivity disorders (ADHD): A systematic review and meta-analysis of floor and ceiling effects. Child (Basel). 2023;11:58.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRosenau PT, Openneer TJC, Matthijssen AM, van de Loo-Neus GHH, Buitelaar JK, van den Hoofdakker BJ, et al. Effects of methylphenidate on executive functioning in children and adolescents with ADHD after long-term use: A randomized, placebo-controlled discontinuation study. J Child Psychol Psychiatry. 2021;62:1444\\u0026ndash;52.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHarkness K, Bray S, Durber CM, Dewey D, Murias K. Assessing the contribution of measures of attention and executive function to diagnosis of ADHD or autism. J Autism Dev Disord. 2024. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s10803-024-06275-9\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s10803-024-06275-9\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBorycz J, Pereira MF, Melani A, Rodrigues RJ, K\\u0026ouml;falvi A, Panlilio L, et al. Differential glutamate-dependent and glutamate-independent adenosine A1 receptor-mediated modulation of dopamine release in different striatal compartments. J Neurochem. 2007;101:355\\u0026ndash;63.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRubia K, Alegria AA, Cubillo AI, Smith AB, Brammer MJ, Radua J. Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Biol Psychiatry. 2014;76:616\\u0026ndash;28.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePaul-Jordanov I, Bechtold M, Gawrilow C. Methylphenidate and if-then plans are comparable in modulating the P300 and increasing response inhibition in children with ADHD. Atten Defic Hyperact Disord. 2010;2:115\\u0026ndash;26.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEpp T, Skrenes A, Chao T, Krigolson OE, Sch\\u0026uuml;tz CG. Associations of the P300 event-related potentials and self-reported craving in substance use disorders: A systematic review. Eur Addict Res. 2023;29:406\\u0026ndash;16.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLopez-Calderon J, Luck SJ. ERPLAB: An open-source toolbox for the analysis of event-related potentials. Front Hum Neurosci. 2014;8:213.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePeisch V, Rutter T, Wilkinson CL, Arnett AB. Sensory processing and P300 event-related potential correlates of stimulant response in children with attention-deficit/hyperactivity disorder: A critical review. Clin Neurophysiol. 2021;132:953\\u0026ndash;66.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGioia GA, Isquith PK, Guy SC, Kenworthy L. BRIEF-2: Behavior Rating Inventory of Executive Function: Professional Manual. Psychological Assessment Resources; 2015.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBaron IS. Test review: Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). Child Neuropsychol. 2005;11:471\\u0026ndash;5.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eArnett AB, Rutter TM, Stein MA. Neural markers of methylphenidate response in children with attention deficit hyperactivity disorder. Front Behav Neurosci. 2022;16:887622.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMatthijssen AM, Dietrich A, Bierens M, Kleine Deters R, van de Loo-Neus GHH, van den Hoofdakker BJ, et al. Continued benefits of methylphenidate in ADHD after 2 years in clinical practice: A randomized placebo-controlled discontinuation study. Am J Psychiatry. 2019;176:754\\u0026ndash;62.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLenartowicz A, Loo SK. Use of EEG to diagnose ADHD. Curr Psychiatry Rep. 2014;16:498.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFabiani M, Gratton G, Federmeier KD. Event-related brain potentials: Methods, theory, and applications. In: Cacioppo JT, Tassinary LG, Berntson GG, editors. Handbook of psychophysiology. 3rd ed. Cambridge University Press; 2007. pp. 85\\u0026ndash;119.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSanei S, Chambers JA. EEG Signal Processing. The Fernow Watershed Acidification Study. Netherlands: Springer; 2013.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eUsai MC. Inhibitory abilities in girls and boys: More similarities or differences? J Neurosci Res. 2023;101:689\\u0026ndash;703.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBroyd SJ, Johnstone SJ, Barry RJ, Clarke AR, McCarthy R, Selikowitz M, et al. The effect of methylphenidate on response inhibition and the event-related potential of children with attention deficit/hyperactivity disorder. Int J Psychophysiol. 2005;58:47\\u0026ndash;58.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJohnstone SJ, Dimoska A, Smith JL, Barry RJ, Pleffer CB, Chiswick D, et al. The development of stop-signal and Go/Nogo response inhibition in children aged 7\\u0026ndash;12 years: Performance and event-related potential indices. Int J Psychophysiol. 2007;63:25\\u0026ndash;38.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZhan C, Liu Y, Wu K, Gao Y, Li X. Structural and functional abnormalities in children with attention-deficit/hyperactivity disorder: A focus on subgenual anterior cingulate cortex. Brain Connect. 2017;7:106\\u0026ndash;14.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKonopka LM, Zimmerman EM. Neurofeedback and psychopharmacology: Designing effective treatment based on cognitive and EEG effects of medications. Clin Neurother. 2014:55\\u0026ndash;84.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBarry RJ, Johnstone SJ, Clarke AR. A review of electrophysiology in attention-deficit/hyperactivity disorder: II. Event-related potentials. Clin Neurophysiol. 2003;114:184\\u0026ndash;98.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChu CL, Lee IH, Chi MH, Chen KC, Chen PS, Yao WJ, et al. Availability of dopamine transporters and auditory P300 abnormalities in adults with attention-deficit hyperactivity disorder: Preliminary results. CNS Spectr. 2018;23:264\\u0026ndash;70.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSol\\u0026iacute;s-Vivanco R, Rodr\\u0026iacute;guez-Violante M, Rodr\\u0026iacute;guez-Agudelo Y, Schilmann A, Rodr\\u0026iacute;guez-Ortiz U, Ricardo-Garcell J. The P3a wave: A reliable neurophysiological measure of Parkinson\\u0026rsquo;s disease duration and severity. Clin Neurophysiol. 2015;126:2142\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Attention Deficit Hyperactivity Disorder, Children, Executive function, Methylphenidate, P300\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4389214/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4389214/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eCurrently, objective biomarkers of methylphenidate (MPH) for the treatment of attention deficit hyperactivity disorder (ADHD) are lacking. Many symptoms of ADHD are associated with impaired executive function. We investigated the effects of MPH on executive function based on an electroencephalogram (EEG) and looked for biomarkers of responsiveness to methylphenidate in ADHD.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eTwenty-two children with ADHD (18 males, 4 females; mean age 8.72\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.46 years). All patients were treated with oral MPH 18 mg/day in the morning for 8 weeks. Executive function assessment and event-related potential (ERP) acquisition were completed at baseline and after 8 weeks of MPH treatment.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eWe found that the BRIEF2 multiple factor scores in children with ADHD were significantly reduced after treatment with MPH (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). The correct response time was lower than that at baseline, and the correctness rate was higher than that at baseline (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.011, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.016). Nogo-P300 latency at Fz was shorter than that at baseline (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001), and the latency at Pz was shorter than at baseline (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001).\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eNormalization of the P300 components by MPH is a predictor of efficacy in children with ADHD who respond positively to this treatment. Thus, MPH can improve executive function deficits.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Neural markers of methylphenidate response in children with attention deficit hyperactivity disorder and the impact on executive function\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-05-20 18:55:00\",\"doi\":\"10.21203/rs.3.rs-4389214/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"77be58bf-849e-4fb2-9a9b-bebeda54199a\",\"owner\":[],\"postedDate\":\"May 20th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-08-01T12:06:41+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-05-20 18:55:00\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4389214\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4389214\",\"identity\":\"rs-4389214\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}