Altered activation in fronto-striatal circuits during sequential processing of conflict in unmedicated adults with obsessive-compulsive disorder

Abstract

Background: The aim of this study was to examine the functioning of fronto-striatal brain circuits that support self-regulatory capacities including conflict resolution and sequential processing in unmedicated adults with obsessive-compulsive disorder (OCD).

Methods: We compared functional magnetic resonance imaging blood oxygen level-dependent response in 22 adults with OCD with 22 healthy, age-matched control subjects during performance of a Simon Spatial Incompatibility task. We used general linear modeling to compare groups in their patterns of brain activation during correct responses to conflict-laden stimuli and explore the effects of trial sequence on group differences.

Results: Behavioral performance on the Simon task did not differ between groups. In response to conflict-laden stimuli, OCD participants activated fronto-striatal regions significantly more than control subjects, specifically a right hemisphere cluster encompassing the putamen, insula, and inferior frontal gyrus. Their activation of this cluster was driven not by conflict on a current trial but by their response to the alternation of stimulus congruence (incongruent or congruent) across trial sequences (i.e., current and preceding trials) and was most accentuated in participants with more severe symptoms in the doubt/checking dimension. Functional connectivity from the putamen to other fronto-striatal regions was also greater in the OCD compared with control participants.

Conclusions: When engaging the self-regulatory control necessary to resolve conflict and process alternating stimuli, OCD participants displayed excessive activation in a fronto-striatal circuit that differs from the orbitofrontal cortex-anterior cingulate cortex-caudate circuit typically implicated in OCD. Dysfunction in this circuit was associated with processing changes in the stimulus context. We speculate that this dysfunction might be related to the cognitive inflexibility typical of persons with OCD.

Keywords: Cognitive conflict; Simon task; fMRI; fronto-striatal systems; obsessive-compulsive disorder; self-regulation.

Figure 1. Group Average Brain Activations Associated with Post-Congruent Conflict

(a) Group differences in brain activations associated with the processing and resolution of cognitive conflict preceded by congruent trials (post-congruent conflict, cI-cC) were detected in fronto-striatal (red) and default mode network (blue) regions. Group average brain activations are shown for the OCD (b) and healthy (c) participants. Increases in signal during correct responses to cI relative to cC trials are shown in red, and decreases are shown in blue. For display purposes, these maps (generated with MRIcroN) are thresholded at P = 0.025, uncorrected, with a cluster filter of 25. The within-group effects did not survive our a priori significance threshold (P = 0.005, cluster filter of 61). The between-group effects remained after controlling for age of onset in the OCD group. OCD, Obsessive-Compulsive Disorder; HC, healthy control; IFG, inferior frontal gyrus; Put, putamen; Cd, caudate; PCC, posterior cingulate cortex.

Figure 2. Functional Connectivity

Group differences in seed connectivity from the putamen. This map is thresholded at P = 0.025, uncorrected, with a cluster filter of 25. Also shown are the cluster- and peak-level statistics corresponding to these group differences in connectivity. OCD, Obsessive-Compulsive Disorder; HC, healthy control; Put, putamen; Cd, caudate; Thal, thalamus; SFG, superior frontal gyrus; CG, cingulate gyrus; Pcu, precuneus; IPL, inferior parietal lobule.

Figure 3. Main Effects of Symptom Severity in the OCD Participants

A scatterplot of the association of sequence-related neural activity in the right fronto-striatal cluster with scores on the doubt/checking symptom dimension of the Y-BOCS.