| Summary: | Background: The functional significance of the impairment shown by patients with ADHD on response inhibition tasks is unclear. Dysfunctional behavioral and BOLD responses to rare no-go cues might reflect disruption of response inhibition (mediating withholding the response) or selective attention (identifying the rare cue). However, a factorial go/no-go design (involving high and low frequency go and no-go stimuli) can disentangle these possibilities. Methods: Eighty youths [22 female, mean age = 13.70 (SD = 2.21), mean IQ = 104.65 (SD = 13.00); 49 with diagnosed ADHD] completed the factorial go/no-go task while undergoing fMRI. Results: There was a significant response type-by-ADHD symptom severity interaction within the left anterior insula cortex; increasing ADHD symptom severity was associated with decreased recruitment of this region to no-go cues irrespective of cue frequency. There was also a significant frequency-by-ADHD symptom severity interaction within the left superior frontal gyrus. ADHD symptom severity showed a quadratic relationship with responsiveness to low frequency cues (irrespective of whether these cues were go or no-go); within this region, at lower levels of symptom severity, increasing severity was associated with increased BOLD responses but at higher levels of symptom severity, decreasing BOLD responses. Conclusion: The current study reveals two separable forms of dysfunction that together probably contribute to the impairments shown by patients with ADHD on go/no-go tasks. Keywords: Attention-Deficit/Hyperactivity Disorder, Go/no-go test, Anterior insula cortex, Superior frontal cortex
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