Error Processing and Inhibitory Control in Obsessive-Compulsive Disorder: A Meta-analysis Using Statistical Parametric Maps

Abstract

Background: Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies.

Methods: A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male).

Results: Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001).

Conclusions: A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.

Keywords: Error processing; Inhibitory control; Meta-analysis; OCD; Performance monitoring; fMRI.

Figure 1.. Findings from a meta-analysis of differences in brain activation during error-processing in patients with OCD and HC.

(a) Error-processing in HC. Red indicates regions showing activation. Blue indicates regions showing deactivation. (b) Error-processing in OCD. Red indicates regions showing activation. Blue indicates regions showing deactivation. (c) Group differences during error processing. Red indicates regions OCD>HC. Blue indicates regions HC>OCD. Thresholded at p<0.005, SDM z-value >2, >80 voxels.

Figure 2.. Findings from a meta-analysis of differences in brain activation during inhibitory control in patients with OCD and HC.

(a) Inhibitory control in HC. Red indicates regions showing activation. Blue indicates regions showing deactivation. (b) Inhibitory control in OCD. Red indicates regions showing activation. Blue indicates regions showing deactivation. (c) Group differences during error processing. Red indicates regions OCD>HC. Blue indicates regions HC>OCD. Thresholded at p<0.005, SDM z-value >2, >80 voxels.

Figure 3:. Error-processing and inhibitory control in OCD.

(a) During errors on inhibitory control tasks, error responses in the cingulo-opercular network signal a need for behavioral correction. In patients with OCD, this error signal does not efficiently increase activation within underactive brain networks responsible for inhibitory control. Due to continued under recruitment of these brain networks, error-processing signals are increased as a compensatory attempt at correction. Heightened and repeated error signaling increases anxiety in the disorder, which further interferes with top-down behavioral control, biases behavior towards bottom-up stimulus driven responses (errors), and feeds back to further increase error signaling. (b) During obsessions and compulsions, error responses are generated to signal the need to stop goal-incongruent or goal-irrelevant behaviors. This error signal does not appropriately recruit activation in brain networks responsible for behavioral control in OCD. This means that patients with OCD continue to experience obsessive and compulsive symptoms, with these generating repeated error signals, and these signals are increased in the disorder as a compensatory attempt at generating behavioral control. Heightened, repeated and aversive error signaling increases anxiety, which further interferes with top-down behavioral control in the disorder and biases behavior towards bottom-up stimulus driven responses (compulsions). Anxiety caused by continued performance and poor perceived control over of interfering OCD compulsions also further increases cingulo-opercular activation, and creates a feeling of cognitive dissonance that is resolved through rationalization of compulsive behaviors (e.g., through reinforcement of obsessions).