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Abstract
BackgroundA decreased ability to inhibit a speeded motor response is a well-studied deficit in Attention Deficit Hyperactivity Disorder (ADHD), and has been proposed as an endophenotype. Inhibitory control has been assessed reliably with the Stop Signal Task (SST) and is associated with prior documented differences in regional brain function using f-MRI. Here, we advance on these findings by examining their structural connectivity and white matter integrity with the goal of identifying a network underlying a core cognitive deficit in ADHD.MethodsHealthy controls (N=16) and youth diagnosed with ADHD (N=60) were recruited through the Province of Ontario Neurodevelopmental Disorders Network (POND) and the Hospital for Sick Children. An f-MRI activation difference map was co-registered with each participant’s white matter imaging data, representing the specific network nodes where ADHD youth diverged significantly from controls while performing the SST. Probabilistic tractography was applied from these nodes, and white matter integrity indices such as fractional anisotropy (FA) within the tracts of interest were contrasted between the groups and correlated with SST output measures, including the measure of inhibitory control, the stop signal reaction time (SSRT).ResultsThe tracts that connected the network nodes belonged primarily to the inferior fronto-occipital fasciculus (IFOF) and cingulum. ADHD subjects showed trend differences in FA compared to controls between right inferior frontal gyrus (IFG) and right superior temporal gyrus (P= 0.09), right IFG and right posterior cingulate (P= 0.01), right anterior cingulate to posterior cingulate (p= 0.08), and between left middle temporal gyrus (BA 39) and left posterior cingulate (P=0.02). A trend correlation was found between radial diffusivity within IFG to STG white matter (IFOF) and SSRT.ConclusionsWe identified potential white matter tracts related to deficient inhibitory control, elucidating the brain mechanisms of an important cognitive deficit in ADHD. These findings could be integrated into future endophenotypic biomarker studies, incorporating altogether brain structure, function, and behavior for future studies of ADHD and other psychiatric conditions that exhibit this deficit.
Highlights
Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset neurodevelopmental disorder with a prevalence estimate of 5% [1], characterized clinically by elevated activity levels, inattentiveness, and high impulsivity
Shifting away from symptom criteria is in line with the Research Domain Criteria-RDoc method, yielding potential insights into specific brain network changes related to important neurocognitive constructs in ADHD neurobiology [13, 14]
In a past f-MRI study with the Stop Signal Task (SST), we investigated where ADHD youth differed from healthy controls and found that activation differed mainly within the time where prospective withholding occurred [30]
Summary
Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset neurodevelopmental disorder with a prevalence estimate of 5% [1], characterized clinically by elevated activity levels, inattentiveness, and high impulsivity. Diffusion Tensor Imaging (DTI) of white matter connectivity in ADHD has shown broad white matter changes within most major tracts [8, 9]. With this extensive background of neuroimaging findings, it would be advantageous to link these with key behavioral processes, such as executive functioning in ADHD [10, 11]. These could potentially map more reliably to brain structure and function compared to clinical symptoms listed within the DSM-5 [12].
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