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

Abstract

Objective Impaired response inhibition is a key executive function deficit of attention-deficit/hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate individuals with ADHD from unaffected individuals. We therefore investigated the neural correlates of response inhibition as well as the familial nature of these neural correlates. Methods fMRI measurements of neural activation during the stop-signal task along with behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy controls (N=124). Results Stop-signal reaction times were longer in participants with ADHD, but not in their unaffected siblings, while reaction time variability and error rates were higher in both groups than in controls. Neural hypoactivation was observed in frontal-striatal and frontal-parietal networks of participants with ADHD and unaffected siblings compared to controls, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between that of participants with ADHD and controls. 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. Conclusions 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 support the familial nature of the underlying neural process. Hypoactivation in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.

Inferior frontal cortex activity is modulated by reward sensitivity and performance variability

“…RT variability can be regarded as a measure of performance consistency, and might reflect fluctuations in attention during executive control tasks (Stuss, Murphy, Binns, & Alexander, 2003). Although this result is modest, it is consistent with previous findings that have linked both increased reward sensitivity and RT variability to ADHD (Adams et al, 2011;Carmona et al, 2012;Mitchell & Nelson-Gray, 2006), and indirectly supports the proposal of wider RT variability as an endophenotype for ADHD (Castellanos et al, 2005;van Rooij et al, 2015), which predisposes individuals to poor impulse control and other deficits. The association that links RT variability, omission errors and reward sensitivity suggests that high-SR individuals display less consistent performance, which might be detrimental in some executive tasks.…”

“…However, the behavioral pattern of ADHD patients in response inhibition tasks is not only characterized by long stopping latencies, but also by poorer performance in the main (go) task, manifested as longer reaction times (RTs), more errors and increased RT variability (Bellgrove et al, 2005;Braet et al, 2011;Carmona et al, 2012;Karalunas et al, 2012;Sebastian et al, 2012;van Rooij et al, 2015;Vaurio et al, 2009). Wide RT variability is one of the most robust findings for the performance of ADHD patients during response inhibition tasks (Alderson et al, 2007), and has been proposed as an endophenotype for this disorder (Castellanos et al, 2005;van Rooij et al, 2015).…”

“…Wide RT variability is one of the most robust findings for the performance of ADHD patients during response inhibition tasks (Alderson et al, 2007), and has been proposed as an endophenotype for this disorder (Castellanos et al, 2005;van Rooij et al, 2015). Recently, van Rooij et al (2015) showed that unaffected siblings of ADHD patients displayed wider RT variability during a stop-signal task, but not the other behavioral characteristics of ADHD.…”

“…Given the relevance of RT variability in predicting vulnerability to poor impulse control (van Rooij et al, 2015), and its link with middle and inferior frontal activity (Bellgrove et al, 2004;Esterman et al, 2014;Simmonds et al, 2007), we aim to study the relationship between IFG activity and RT variability in the Go/No-go task with correlation analyses, and the potential role of reward sensitivity in this relationship.…”

Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition

“…Our approach to first-level analysis is identical to that of Van Rooij and colleagues. 40 We constructed general linear models for each participant, containing regressors for fMRI blood-oxygen level-dependent (BOLD) responses to successful stop, failed stop and successful go trials. Failed go trials, signal from cerebral spinal fluid and white matter, and 24 realignment parameters were included as covariates.…”