Comparative Effects of BCI-Based Attention Training, Methylphenidate, and Citicoline on Attention and Executive Function in School-Age Children: A Naturalistic Quasi-Experimental Study
Conditions: Attention Deficit Hyperactivity Disorder (ADHD), Brain Computer Interface
Sponsor: Uludag University

CLINICAL TRIAL PROTOCOL
Title: Comparative Effects of BCI-Based Attention Training, Methylphenidate, and Citicoline
on Attention, Executive Function, and Emotional/Behavioral Outcomes in School-Age
Children with Attentional Difficulties
Protocol Version: 1.0
Date: 16.12.2025
Principal Investigator (PI): Serkan TURAN, Assoc. Prof.
Institution: Uludağ University
Sponsor / Funding: Uludağ University Scientific Grant Project
Trial Phase: Exploratory clinical study (quasi-experimental)
Registration: Registered online
1. SYNOPSIS
Study Design:
Prospective, quasi-experimental, non-randomized, parallel-group, pre–post clinical study with
four intervention arms.
Study Arms (4 groups):
1. COGO + Methylphenidate (Mph)
2. COGO + Citicoline
3. COGO-only
4. Citicoline-only
Target Population:
School-age children (approximately 6–18 years) with clinically significant attentional
difficulties and/or ADHD symptoms, referred to child and adolescent psychiatry or pediatric
neurology clinics.
Planned Sample Size:
Total n = 170–180 (approximately 40–45 participants per group), reflecting a naturalistic
convenience sample and expected attrition.

Study Duration per Participant:
Screening period: up to 4 weeks
Intervention period: 8 weeks
Total participation: approximately 10–12 weeks
Primary Objective:
To compare within- and between-group changes in attention performance (CPT-3 indices)
following 8 weeks of COGO BCI-based attention training and/or
pharmacological/nutraceutical intervention.
Secondary Objectives:
To evaluate changes in behavioral, emotional, and executive-function outcomes
between baseline and post-treatment.
To compare the pattern of change across the four treatment modalities.
Primary Outcome:
Change from baseline to week 8 in Conners Continuous Performance Test–Third Edition
(CPT-3) T-scores, focusing on:
Omission errors
Commission errors
Hit Reaction Time (HRT)
HRT Standard Deviation (HRT SD)
Variability
HRT Block Change
HRT ISI Change

Secondary Outcomes:
Change from baseline to week 8 on:
SNAP-IV (Inattention, Hyperactivity/Impulsivity)
Sluggish Cognitive Tempo (SCT) Scale
Revised Child Anxiety and Depression Scale (RCADS)
Strengths and Difficulties Questionnaire (SDQ)
Behavior Rating Inventory of Executive Function (BRIEF: BRI, MI, GEC and
subscales)
Statistical Methods (summary):
Descriptive statistics for all variables
Within-group pre–post changes: paired t-tests
Between-group differences: ANCOVA/one-way ANOVA (adjusted for age)
Group-by-time effects: repeated-measures ANOVA
Significance threshold: p < 0.05 (two-sided)
2. BACKGROUND AND RATIONALE
Attention-deficit/hyperactivity disorder (ADHD) and attentional difficulties are prevalent in
childhood and are associated with deficits in sustained attention, inhibitory control, and
executive function, impacting academic and socio-emotional functioning. Pharmacological
treatment with stimulants such as methylphenidate is considered first-line but has important
limitations, including side effects, variable response, and concerns about long-term use.
Citicoline (CDP-choline) is a nutraceutical agent with potential cognitive-enhancing
properties via effects on phospholipid metabolism and dopaminergic/cholinergic pathways,
but evidence in pediatric ADHD is still limited and mixed. Brain–computer-interface (BCI)-

based attention training and EEG-based neurofeedback have emerged as non-pharmacological
modalities aiming to improve attention by modulating neurophysiological markers through
real-time feedback and gamified training tasks.
The COGO Cognitive Training Program is an EEG-based BCI attention training system using
adaptive game-based tasks, typically delivered over 8 weeks (3 sessions/week, total 24
sessions). Preliminary data suggest feasibility and potential benefit on attention and related
behavioral domains. Integrating COGO with methylphenidate or citicoline may yield additive
or synergistic effects on attention, executive functioning, and emotional regulation, but direct
comparative clinical data are scarce.
This protocol describes a quasi-experimental clinical study comparing four treatment
strategies: COGO + methylphenidate, COGO + citicoline, COGO-only, and citicoline-only,
using both neuropsychological (CPT-3) and parent-report measures (SNAP-IV, SCT, RCADS,
SDQ, BRIEF).
3. STUDY OBJECTIVES AND HYPOTHESES
3.1 Primary Objective
To assess and compare the effects of four intervention modalities on attention performance, as
measured by CPT-3 T-scores, after 8 weeks of treatment.
3.2 Secondary Objectives
1. To evaluate changes in behavioral and emotional symptoms (SNAP-IV, SCT,
RCADS, SDQ).
2. To evaluate changes in executive functioning (BRIEF indices and subscales).
3. To explore whether combined interventions (COGO + methylphenidate and COGO +
citicoline) show greater improvements than single-modality interventions (COGO-
only, citicoline-only).
3.3 Hypotheses

H1: COGO + methylphenidate will produce the largest improvements in CPT-3
omission errors and HRT-related measures compared with other groups.
H2: COGO + citicoline will yield greater improvements in commission errors and
emotional/internalizing symptoms compared with other groups.
4. STUDY DESIGN
4.1 Overview
This is a single-center (or multicenter, if applicable), prospective, quasi-experimental clinical
trial with four parallel treatment arms. Treatment allocation is based on routine clinical
decision-making rather than randomization (naturalistic design).
4.2 Study Arms
1. COGO + Methylphenidate Group
o
COGO BCI-based attention training for 8 weeks
o
Concurrent methylphenidate treatment at clinically appropriate doses
2. COGO + Citicoline Group
o
COGO training for 8 weeks
o
Concurrent citicoline at age-appropriate doses
3. COGO-only Group
o
COGO training for 8 weeks
o
No methylphenidate or citicoline
4. Citicoline-only Group
o
Citicoline at age-appropriate doses for 8 weeks
o
No COGO training and no methylphenidate
4.3 Study Visits and Timepoints
•
Visit 1 (Screening / Baseline, Week 0):
o
Eligibility assessment
o
Informed consent/assent
o
Sociodemographic and clinical data

o
Baseline CPT-3
o
Baseline parent-rated scales: SNAP-IV, SCT, RCADS, SDQ, BRIEF
•
Visits 2–[n] (Intervention Period, Weeks 1–8):
o
COGO sessions (3/week) for arms 1–3
o
Medication dispensation/monitoring for arms 1, 2, and 4
o
Adverse event (AE) assessment at each contact
•
Visit Final (Post-treatment, Week 8 ± 1 week):
o
Repeat CPT-3
o
Repeat SNAP-IV, SCT, RCADS, SDQ, BRIEF
o
AE and concomitant medication review
o
Study termination procedures
5. STUDY POPULATION
5.1 Inclusion Criteria
1. Children and adolescents aged approximately 6-18 years.
2. Referred for attentional difficulties and/or suspected/diagnosed ADHD based on
clinical evaluation.
3. Clinically significant attention problems (e.g., elevated SNAP-IV inattention scores or
comparable clinician-rated criteria).
4. Enrolled in regular school education (any grade).
5. Able to comply with study procedures and attend scheduled COGO sessions (where
applicable).
6. At least one parent/legal guardian able to give informed consent; child able to provide
assent according to local regulations.
5.2 Exclusion Criteria
1. Known intellectual disability (IQ < approx. 70) that would impede participation.
2. Severe neurological disorders (e.g., epilepsy with frequent seizures, major brain
injury) interfering with EEG-based training.
3. Severe psychiatric comorbidity requiring immediate intensive intervention (e.g.,
psychosis, acute suicidality).

4. Current or recent (within 4 weeks) use of psychotropic medications other than
methylphenidate or citicoline, unless on a stable non-interacting medication regimen
approved by the investigator.
5. Known allergy or contraindication to methylphenidate or citicoline (for relevant
groups).
6. Sensory or motor impairments preventing the use of the COGO system.
7. Participation in another interventional clinical trial within the last 3 months.
6. INTERVENTIONS
6.1 COGO Cognitive Training Program
Modality: EEG-based BCI attention training using game-based tasks.
Schedule: 3 sessions per week, over 8 consecutive weeks (total of 24 sessions).
COGO study
Session Duration: Approximately [20–40] minutes per session (to be specified by site
standard).
Setting: Outpatient clinic (or supervised home-based where applicable).
Content: Adaptive attention, working memory, and inhibitory-control tasks that
integrate real-time EEG markers into game mechanics.
Compliance: Attendance will be recorded; adherence thresholds (e.g., ≥75% of
sessions completed) will be predefined for per-protocol analyses.
6.2 Pharmacological Interventions
6.2.1 Methylphenidate (Mph)
Indication: ADHD/attentional problems, according to national guidelines.
Formulation: Immediate-release or extended-release as per routine clinical practice.

Dosing: Initiated and titrated by treating child psychiatrist or pediatrician according to
body weight, symptom severity, and tolerability.
Duration: Continuous over the 8-week intervention period.
6.2.2 Citicoline
Formulation: Oral solution, capsules, or tablets, according to age and local
availability.
Dosing: Age-appropriate total daily dose as per product labeling or current clinical
practice (e.g., mg/kg/day or fixed pediatric dose), divided in 1–2 administrations.
Duration: Continuous over the 8-week intervention period.
6.3 Concomitant Medications
Stable doses of non-psychotropic medications (e.g., for asthma, allergies) are
permitted.
Initiation of new psychotropic medications during the trial is discouraged and should
be documented and evaluated case by case.
Any change in methylphenidate or citicoline dose will be documented.
7. OUTCOME MEASURES AND ASSESSMENTS
7.1 Primary Outcome Measure
Conners Continuous Performance Test–Third Edition (CPT-3)
Outcome Measure 1 Name: Conners Continuous Performance Test–Third Edition (CPT-3) –
Omission Errors Description: Number of omission errors reflecting inattention, reported as T-
scores derived from CPT-3 normative data. Unit of Measure: T-score
Outcome Measure 2 Name: Conners Continuous Performance Test–Third Edition (CPT-3) –
Commission Errors Description: Number of commission errors reflecting impulsivity, reported
as T-scores derived from CPT-3 normative data. Unit of Measure: T-score
Outcome Measure 3 Name: Conners Continuous Performance Test–Third Edition (CPT-3) –
Perseverations Description: Number of perseverative responses reflecting response control
difficulties, reported as T-scores derived from CPT-3 normative data. Unit of Measure: T-score
Outcome Measure 4 Name: Conners Continuous Performance Test–Third Edition (CPT-3) –
Hit Reaction Time (HRT) Description: Mean reaction time for correct responses, reported as T-

scores derived from CPT-3 normative data. Unit of Measure: T-score
Outcome Measure 5 Name: Conners Continuous Performance Test–Third Edition (CPT-3) –
Hit Reaction Time Standard Deviation (HRT SD) Description: Variability of reaction time
across correct responses, reported as T-scores derived from CPT-3 normative data. Unit of
Measure: T-score.
o
Assessed at baseline and at week 8.
7.2. Secondary Outcome Measures
Outcome Measure
7. 2. 1. Swanson, Nolan, and Pelham Rating Scale–Fourth Edition (SNAP-IV)
Description: Description: The Swanson, Nolan, and Pelham Rating Scale–Fourth Edition
(SNAP-IV)
is
a
parent-
or
teacher-rated
scale
assessing
symptoms
of
inattention,
hyperactivity/impulsivity, and oppositional defiant behavior. Items are rated on a 4-point Likert
scale (0–3), with higher scores indicating greater symptom severity. Score Range: Item scores
range from 0 to 3; subscale scores are calculated as mean scores ranging from 0 to 3. Direction
of Outcome: Higher scores indicate worse outcomes (greater symptom severity). Outcome
Measure: Change in SNAP-IV total score from baseline to post-intervention.Time Frame: 8
weeks
Outcome Measure
7. 2. 2. Barkley Sluggish Cognitive Tempo Scale
Description: Description: The Barkley Sluggish Cognitive Tempo Scale is a parent- or teacher-
rated questionnaire assessing sluggish cognitive tempo symptoms, including excessive
daydreaming, mental confusion, lethargy, and slowed behavior. Minimum–Maximum Score
Range: Items are rated on a 4-point Likert scale ranging from 0 (never or rarely) to 3 (very often).
Total and mean scores range from 0 to 3. Direction of Outcome: Higher scores indicate greater
symptom severity and therefore worse outcomes. Outcome Measure: Change in Barkley SCT
total score from baseline to post-intervention.Time Frame: 8 weeks
Outcome Measure
7. 2. 3. Revised Child Anxiety and Depression Scale (RCADS), Parent Version
Description: Description: The Revised Child Anxiety and Depression Scale (RCADS) – Parent
Form is a parent-rated questionnaire consisting of 47 items, assessing symptoms of anxiety and
depression in children and adolescents across multiple DSM-based subscales (separation anxiety,
social phobia, generalized anxiety, panic disorder, obsessive–compulsive disorder, and major
depressive disorder). Minimum–Maximum Score Range: Items are rated on a 4-point Likert
scale ranging from 0 (never) to 3 (always). Subscale and total raw scores range from 0 to 141.
Raw scores may be converted to age- and sex-adjusted T-scores. Direction of Outcome: Higher
scores indicate greater anxiety and depressive symptom severity and therefore worse outcomes.
Outcome Measure: Change in RCADS total score from baseline to post-intervention.Time
Frame: 8 weeks
Outcome Measure
7. 2. 4. Strengths and Difficulties Questionnaire (SDQ)
Description: Description: The Strengths and Difficulties Questionnaire (SDQ) is a parent-rated
behavioral screening questionnaire consisting of 25 items, assessing emotional symptoms,
conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior
in children and adolescents. Minimum–Maximum Score Range: Items are rated on a 3-point
Likert scale ranging from 0 (not true) to 2 (certainly true). The Total Difficulties Score (sum of
four difficulty subscales) ranges from 0 to 40. The Prosocial Behavior subscale ranges from 0 to

10. Direction of Outcome: For the Total Difficulties Score, higher scores indicate greater
behavioral and emotional difficulties (worse outcomes). For the Prosocial Behavior subscale,
higher scores indicate better outcomes. Outcome Measure: Change in SDQ Total Difficulties
score from baseline to post-intervention.Time Frame: 8 weeks
Outcome Measure
7. 2. 5. Behavior Rating Inventory of Executive Function (BRIEF)
Description: Description: The Behavior Rating Inventory of Executive Function (BRIEF) is a
parent-rated questionnaire consisting of 86 items, designed to assess executive functioning in
everyday settings in children and adolescents. It yields index scores including the Behavioral
Regulation Index (BRI), Metacognition Index (MI), and a Global Executive Composite (GEC).
Minimum–Maximum Score Range: Items are rated on a 3-point Likert scale. Raw scores are
converted to age- and sex-adjusted T-scores, which typically range from 30 to 100. Direction of
Outcome: Higher T-scores indicate greater executive function difficulties and therefore worse
outcomes. Outcome Measure: Change in BRIEF Global Executive Composite T-score from
baseline to post-intervention.Time Frame: 8 weeks
All questionnaires will be completed by parents or primary caregivers at baseline and at week
8.
8. SAMPLE SIZE AND POWER
This is primarily an exploratory, naturalistic clinical study. In the manuscript, no a priori
sample size calculation was performed, and group sizes of approximately 42–44 participants
per arm were obtained.

For this protocol, a target total sample size of approximately 160–180 participants (≈40–45
per group) is set, which is expected to provide adequate power (around 0.80) to detect
medium within-group effect sizes (Cohen’s d ≈0.5) and small-to-medium group-by-time
interactions in repeated-measures analyses, assuming alpha = 0.05 and modest attrition.
9. STATISTICAL ANALYSIS PLAN
9.1 Analysis Populations
Full Analysis Set (FAS): All enrolled participants with baseline and at least one post-
baseline primary outcome assessment.
Per-Protocol Set (PPS): Participants with high adherence (e.g., ≥75% of planned
COGO sessions where applicable, and continuous medication use without major
protocol deviations).
9.2 Descriptive Analyses
Continuous variables: mean, standard deviation, median, interquartile range.
Categorical variables: counts and percentages.
9.3 Primary Analysis
Within each group, pre–post changes in CPT-3 T-scores will be analyzed using paired-
samples t-tests.
Between-group comparisons of change scores will be conducted using ANCOVA or
one-way ANOVA, adjusting for baseline age (and grade if appropriate).
COGO study
9.4 Secondary Analyses
Pre–post changes in SNAP-IV, SCT, RCADS, SDQ, and BRIEF scores will be
examined using paired t-tests within groups.

Group-by-time interactions will be assessed using repeated-measures ANOVA (time ×
group) for each outcome.
COGO study
Effect sizes will be reported as Cohen’s d for paired comparisons and partial η² for
ANOVA models.
9.5 Handling Missing Data
Missing baseline data will preclude inclusion in FAS for that outcome.
For missing post-treatment data, analyses will primarily use available cases; sensitivity
analyses may consider simple imputation (e.g., last observation carried forward) if
appropriate.
Reasons for missing data will be documented.
9.6 Significance Level
Two-sided tests with alpha = 0.05.
No formal multiplicity correction is planned, as the study is exploratory; interpretation
will remain cautious.
10. SAFETY MONITORING
10.1 Adverse Events (AEs)
All AEs reported by participants or observed by investigators will be recorded from
the time of consent until the final visit.
10.2 Serious Adverse Events (SAEs)
SAEs (death, life-threatening events, hospitalization, disability) will be reported to the
ethics committee and relevant regulatory bodies per local regulations and within
mandated timelines.

Causality (related, possibly related, unrelated) will be assessed by the PI.
10.3 Early Withdrawal Criteria
Participants may be withdrawn in case of:
Serious or intolerable AEs.
Non-compliance with study procedures (e.g., missing most COGO sessions).
Withdrawal of consent by parent/guardian or assent by the child.
Investigator’s judgment that continued participation is not in the child’s best interest.
If appropriate, a Data and Safety Monitoring Plan (DSMP) or Data Monitoring Committee
(DMC) may be established, depending on institutional requirements.
11. ETHICAL CONSIDERATIONS
The study will be conducted in accordance with the Declaration of Helsinki, Good
Clinical Practice (GCP) guidelines, and applicable local regulations.
The study protocol, informed consent/assent forms, and recruitment materials will be
approved by the institutional ethics committee before initiation.
Written informed consent will be obtained from parents/legal guardians; age-
appropriate assent will be obtained from children.
Participants may withdraw from the study at any time without consequences for their
routine clinical care.
The quasi-experimental design reflects standard clinical decision-making, minimizing
additional risks.
12. DATA MANAGEMENT AND CONFIDENTIALITY

Each participant will be assigned a unique study ID; identifiable information will be
stored separately from research data.
Paper questionnaires and CPT-3 printouts will be stored in locked cabinets; electronic
data will be kept on password-protected computers/servers with restricted access.
Data quality checks (range checks, missing data review) will be performed regularly.
Data will be retained for at least the minimum period required by national regulations
and institutional policy.
13. STUDY TIMELINE
Protocol approval and registration: 10.10.2023
Participant recruitment: February 2025-November 2025
Data analysis and manuscript preparation: November 2025
14. PUBLICATION PLAN
Results will be analyzed and submitted for publication in peer-reviewed journals and
presented at scientific meetings. Authorship will follow standard international authorship
criteria. Participant confidentiality will be strictly maintained in all publications.