Symptom Severity in Youths with Attention Deficit Hyperactivity Disorder Associated with Normalizing Effects of Treatment on fMRI Response during a Stop Signal Task

Abstract

Inhibitory control deficits represent one of many core cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD). Neuroimaging studies suggest that individuals with ADHD exhibit atypical engagement of neural systems during response inhibition, but the exact nature of this phenotype is obscured by mixed findings. We tested whether drug-free youths with ADHD (n=30, ages 7-14 years, 10 female) exhibited atypical neural correlates of response inhibition, as measured with a stop signal task and fMRI, compared to matched controls. We next investigated medication effects and whether there was a relationship between symptom severity and medication effects on the fMRI-evaluated signal. Finally, we tested for a significant difference between effects of monotherapy and combined pharmacological treatment. Patients showed significantly slower stop signal response time and lower percent inhibition, but no significant differences in the neural correlates of response inhibition relative to controls. However, patients showed significantly elevated signal in frontostriatal regions during responses. Prefrontal signal in patients was positively associated with reaction time variability in patients, and change (medicated - drug free) in the prefrontal signal was significantly associated with symptom scores, such that patients with elevated symptoms had greater BOLD signal reduction following treatment. Medication significantly improved go response time median and variability as well as stop signal reaction time, but there were no significant effects of medication or treatment type on BOLD signal. These findings challenge the notion of frontostriatal hypoactivation during response inhibition as a biomarker for ADHD and suggest that symptom severity may be associated with response to medication.