Gaba and Inhibitory Physiology in Dominant Motor Cortex: Altered Moderation of Response Inhibition in Children with ADHD

In children with Attention Deficit/Hyperactivity Disorder (ADHD), a core domain of impaired cognitive control is response inhibition. We hypothesized that measures in dominant motor cortex might moderate efficiency of response inhibition. In 61 right-handed, 8-to-12-year-old children (ADHD n=28; typically developing controls (TDC) n=33), we evaluated 1) response inhibition, using an anticipated-response stop signal reaction time (SSRT) task; 2) left M1 inhibitory physiology, using Transcranial Magnetic Stimulation (TMS) to measure cortical silent period (CSP) duration; and 3) left M1 inhibitory neurochemistry, using Magnetic Resonance Spectroscopy (MRS) to measure gamma-amino butyric acid (GABA+) levels. Diagnostic groups were compared and relationships between SSRT and putative inhibitory moderators were modeled with regression and assessed with bivariate correlations. There were no significant diagnostic-group differences in SSRT, GABA+, or CSP; however, regression modeling showed a robust interaction of diagnosis and GABA+. Within the TDC group (only), better response inhibition (faster SSRT) is associated with both higher GABA+ levels and longer CSP duration in dominant motor cortex. This multi-modal study suggests response inhibition may be reflected by measures of inhibitory physiology and neurochemistry in motor cortex and, further, that these relationships may be disrupted in children with ADHD.