# Identifying the effects of methylphenidate on brain network dynamics of cognitive control and motivation in pediatric ADHD

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $45,055

## Abstract

Project Summary/Abstract
Pediatric ADHD is diagnosed in ~9% of youths in the United States and has long-term debilitating mental
health, social, and educational effects. ADHD is primarily characterized by inattentive and
hyperactive/impulsive behaviors, and methylphenidate is a first line of treatment to alleviate symptoms. While
generally effective, 20-30% of youth with ADHD do not respond to methylphenidate. It is currently unknown
why methylphenidate does not successfully treat a subset of youth with ADHD, nor is it known who will
respond before treatment is initiated. The proposed work aims to fill this knowledge gap by testing the effects
of methylphenidate on two neurobiological systems thought to be disrupted in ADHD, with a goal of identifying
biomarkers of methylphenidate response. The dual pathway model of ADHD proposes that dysfunction in
neurobiological pathways underlying cognitive control and motivational processing gives rise to ADHD
symptoms, providing two candidate pathways that methylphenidate may act upon. We propose to examine this
framework at the whole brain level by employing functional connectivity and graph theoretical tools to test the
effects of methylphenidate on brain organization during tasks that tax cognitive control and reward responsivity
in medication naïve children with ADHD. This work will use cutting edge methods that model whole brain
functional connectivity on the order of seconds to investigate dynamic changes in brain organization of the
hypothesized pathways across the cognitive tasks. Using dynamic functional connectivity approaches we can
measure flexibility of connections between brain regions, indexed by how often functional connectivity patterns
change across the course of a task. We predict that during a cognitive control task, regions belonging to
cognitive control networks (fronto-parietal, cingulo-opercular, default mode) will become less hyperconnected
and more flexible on methylphenidate (Specific Aim 1). We further predict that when reward is introduced to a
cognitive control task, networks supporting motivational processing (reward, salience, default mode) will
reconfigure and become more flexible; we further predict that this reconfiguration will be more pronounced on
methylphenidate (Specific Aim 2). Lastly, we predict that flexibility of brain regions from these hypothesized
pathways will be powerful predictors of response to methylphenidate (operationalized by performance
improvement on control demanding cognitive tasks) above and beyond baseline behavioral measures of
ADHD symptomology (Exploratory Aim 3). This work combines new tools (dynamic functional connectivity) with
new approaches (modeling brain organization across cognitive task states) to form a comprehensive model of
the effects of methylphenidate in pediatric ADHD. By identifying features of brain network organization that
change on methylphenidate and testing how these features predict behavioral change, we stand to identif...

## Key facts

- **NIH application ID:** 10536398
- **Project number:** 1F32MH127877-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Tehila Nugiel
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $45,055
- **Award type:** 1
- **Project period:** 2022-12-28 → 2023-08-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536398

## Citation

> US National Institutes of Health, RePORTER application 10536398, Identifying the effects of methylphenidate on brain network dynamics of cognitive control and motivation in pediatric ADHD (1F32MH127877-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10536398. Licensed CC0.

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