Action monitoring in boys with attention-deficit/hyperactivity disorder, their nonaffected siblings, and normal control subjects: evidence for an endophenotype

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a very common and highly heritable child psychiatric disorder associated with dysfunctions in fronto-striatal networks that control attention and response organization. The aim of this study was to investigate whether features of action monitoring related to dopaminergic functions represent endophenotypes that are brain functions on the pathway from genes and environmental risk factors to behavior.

Methods: Action monitoring and error processing as indicated by behavioral and electrophysiological parameters during a flanker task were examined in boys with ADHD combined type according to DSM-IV (n = 68), their nonaffected siblings (n = 18), and healthy control subjects with no known family history of ADHD (n = 22).

Results: Boys with ADHD displayed slower and more variable reaction-times. Error negativity (Ne) was smaller in boys with ADHD compared with healthy control subjects, whereas nonaffected siblings displayed intermediate amplitudes following a linear model predicted by genetic concordance. The three groups did not differ on error positivity (Pe). The N2 amplitude enhancement due to conflict (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also displayed intermediate N2 enhancement.

Conclusions: Converging evidence from behavioral and event-related potential findings suggests that action monitoring and initial error processing, both related to dopaminergically modulated functions of anterior cingulate cortex, might be an endophenotype related to ADHD.

Figure 1. Task description

Flanker arrowheads (red) preceded the presentation of the central target and flanker arrowheads (green) by 100ms. Conditions were congruent or incongruent and responses were required either to the left or right.

Figure 2. Stimulus-locked curves

For both congruent and incongruent correct responded trials a N2 is apparent at a latency of 330ms after the onset of the target. N2 amplitude is enhanced in incongruent trials.

Figure 3. Response-locked curves to correct responses and errors in incongruent trials

Response-locked grand average waves of controls (black), nonaffected siblings (red) and boys with ADHD (green). The Ne peaked for all groups at around 60–80ms after the erroneous response (red curve) and was followed by an adjacent more posterior located error positivity (Pe). Both deflections were not present in curves evoked by correct responses.

Figure 4. Stimulus-locked N2 to congruent and incongruent correct responded trials

Response-locked grand average waves of controls (black), nonaffected siblings (red) and ADHD boys (green) with spline-interpolated maps of N2 evoked by correct congruent (left) and incongruent (right) trials at the respective group mean latency.

Figure 5. Response-locked error-related components

Response-locked grand average waves of controls (black), nonaffected siblings (red) and ADHD boys (green) with spline-interpolated maps of Ne at the respective group mean latency (left side) and Pe mean activity 200–500ms post error response (right side). The response-locked Ne has its maximum at FCz (even more prominent when measured peak-to-peak), while Pe was maximal at centro-parietal electrodes.