Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy Comparison Subjects by Neural Activation Patterns During Response Inhibition

• DOI: 10.1176/appi.ajp.2014.13121635
• Publication Date: 2015-01-23T09:54:56Z
• Authors: Daan van Rooij; Pieter J. Hoekstra; Maarten Mennes; Daniel von Rhein; Andrieke J.A.M. T...; Dirk Heslenfeld; Marcel P. Zwiers; Stephen V. Faraone; Jaap Oosterlaan; Barbara Franke; Nanda Rommelse; Jan K. Buitelaar; Catharina A. Hartman
• Keywords: Male; TRANSCRANIAL MAGNETIC STIMULATION; Adolescent; DEFICIT HYPERACTIVITY DISORDER; ERROR-DETECTION; PREFRONTAL CORTEX; Neuropsychological Tests; Executive Function; 03 medical and health sciences; 0302 clinical medicine; MEDICATION; SDG 3 - Good Health and Well-being; Reference Values; Reaction Time; BRAIN ACTIVATION; Humans; Attention; Cerebral Cortex; Brain Mapping; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; REACTION-TIME VARIABILITY; 16. Peace & justice; Magnetic Resonance Imaging; MOTOR AREA; 3. Good health; Inhibition, Psychological; Attention Deficit Disorder with Hyperactivity; Impulsive Behavior; Female; INFERIOR FRONTAL GYRUS; Psychomotor Performance; Follow-Up Studies

Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates.Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124).Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity.Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.