The long term objective of this proposal is to increase our understanding of the pathophysiology of attention- deficit/hyperactivity disorder (ADHD) by furthering our knowledge regarding how the cerebellum and corticocerebellar circuits contribute to abnormalities in ADHD. Most ADHD research has focused on ADHD youth, exploring hypotheses regarding frontal or fronto-striatal abnormalities. However, ADHD in adulthood exacts a high cost to society as it is associated with impairments in multiple domains, including interpersonal relationships, academic performance, work productivity, and personal safety. Furthermore, a growing body of structural and functional neuroimaging research implicates the cerebellum in the pathophysiology of ADHD. In addition, behavioral atypicalities such as abnormalities in timing and motor control, two problems for which the cerebellum has been shown to play a role, also point to the cerebellum and corticocerebellar circuits as being involved in ADHD. Building on our prior work, we propose a series of experiments designed to test the hypothesis that corticocerebellar network abnormalities contribute to ADHD in adults via a breakdown in the cerebellum's ability to accurately predict timing for perceptual and motor domains. In the proposed experiments we will use fMRI with timing paradigms of both perceptual and motor timing. We will also conduct a comprehensive motor assessment which includes MRI-compatible kinematic recording methods to quantify movement variability that may not be observable using clinical rating methods alone. We will use fMRI with tasks involving movements performed under varying conditions of visual guidance and visuomotor gain to examine corticocerebellar contributions to abnormal performance of these movements. This overall approach will allow us to obtain a finer behavioral assessment of movement abnormalities and also to examine the relationship between corticocerebellar function and performance on motor tasks that can be performed during neuroimaging. Finally, we will use bivariate correlation and dynamic causal modeling to specifically examine how abnormalities in functional relationships between cerebellar and cortical regions contribute to deficits in timing and motor control. These studies will contribute to our understanding of the neurobiological substrate of ADHD and serve to inform models used to develop effective treatments.

Public Health Relevance

In order to treat and ultimately prevent psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD), we must understand how the brain is related to behavioral impairments. This project seeks to further this goal by examining how brain function is related to timing and motor abnormalities in ADHD adults. An improved understanding of this brain-behavior relationship will help inform treatments for ADHD.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Freund, Lisa S
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Massachusetts General Hospital
United States
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Makris, Nikos; Liang, Lichen; Biederman, Joseph et al. (2015) Toward Defining the Neural Substrates of ADHD: A Controlled Structural MRI Study in Medication-Naïve Adults. J Atten Disord 19:944-53
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Spencer, Thomas J; Brown, Ariel; Seidman, Larry J et al. (2013) Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies. J Clin Psychiatry 74:902-17