| Summary: | Background: Impaired response inhibition is one of the most consistent findings in attention deficit hyperactivity disorder (ADHD). However, the underlying brain mechanisms are not clear. This study aimed to underpin atypical inhibition-related brain activation and connectivity patterns in ADHD using a novel Go/No-go task design, and to determine its association with clinical symptoms of the disorder. Methods: Forty-eight adults with ADHD performed a Go/No-go task in which target frequency was manipulated during functional MRI. Specific inhibition-related brain activation was correlated with ADHD symptom severity, to assess the relationship of individual differences in engagement of inhibition-related brain circuits with the magnitude of every-day functioning impairments. Finally, generalized psychophysical interaction analyses were carried out to examine whether not only engagement but also functional connectivity between regions implicated in response inhibition is related to symptom severity. Results: We found no evidence for the expected parietal modulation by increased demand for inhibition at the group-level results. However, this lack of modulation was mediated by individual differences in ADHD symptom severity – increased engagement of the intraparietal sulcus (IPS) in inhibition-demanding events was evident in individuals with less severe symptoms but dissipated with increase in symptomatology. Similarly, functional connectivity between the IPS and the right inferior frontal gyrus (rIFG) was elevated under high inhibitory demand conditions, but this effect diminished with increased symptom severity. Conclusions: The results highlight the importance of IPS engagement in response inhibition and suggest that IPS modulation may be driven by top-down control from the IFG. Moreover, the current findings force the point of treating ADHD as a continuum whereby brain correlates are scaled with severity of the disorder, and point to the potential use of individual differences in the modulation of IPS activation and connectivity as a neuromarker of ADHD. Keywords: ADHD, Adults, FMRI, Response inhibition, Connectivity, Parietal cortex
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