Aberrant error processing in relation to symptom severity in obsessive-compulsive disorder: A multimodal neuroimaging study

Abstract

Background: Obsessive-compulsive disorder (OCD) is characterized by maladaptive repetitive behaviors that persist despite feedback. Using multimodal neuroimaging, we tested the hypothesis that this behavioral rigidity reflects impaired use of behavioral outcomes (here, errors) to adaptively adjust responses. We measured both neural responses to errors and adjustments in the subsequent trial to determine whether abnormalities correlate with symptom severity. Since error processing depends on communication between the anterior and the posterior cingulate cortex, we also examined the integrity of the cingulum bundle with diffusion tensor imaging.

Methods: Participants performed the same antisaccade task during functional MRI and electroencephalography sessions. We measured error-related activation of the anterior cingulate cortex (ACC) and the error-related negativity (ERN). We also examined post-error adjustments, indexed by changes in activation of the default network in trials surrounding errors.

Results: OCD patients showed intact error-related ACC activation and ERN, but abnormal adjustments in the post- vs. pre-error trial. Relative to controls, who responded to errors by deactivating the default network, OCD patients showed increased default network activation including in the rostral ACC (rACC). Greater rACC activation in the post-error trial correlated with more severe compulsions. Patients also showed increased fractional anisotropy (FA) in the white matter underlying rACC.

Conclusions: Impaired use of behavioral outcomes to adaptively adjust neural responses may contribute to symptoms in OCD. The rACC locus of abnormal adjustment and relations with symptoms suggests difficulty suppressing emotional responses to aversive, unexpected events (e.g., errors). Increased structural connectivity of this paralimbic default network region may contribute to this impairment.

Keywords: Anterior cingulate; Default network; ERN; Error processing; Multimodal neuroimaging; OCD.

Fig. 1

Antisaccade paradigm. Schematic and timeline of the three conditions: easy, hard, and fake-hard. Each trial lasted 4 s and began with an instructional cue (300 ms), either a blue or yellow “X” that indicated whether the trial was hard or easy. The mapping of cue color to trial type was counterbalanced across participants. The cue was horizontally flanked by two white squares of 0.4° width that marked the potential locations of stimulus appearance, 10° left and right of center. The squares remained visible for the duration of each run. At 300 ms, the instructional cue was replaced by a white fixation ring of 1.3° diameter at the center of the screen. At 1800 ms, the fixation ring disappeared (200 ms gap). At 2000 ms, the fixation ring reappeared at one of the two stimulus locations, right or left with equal probability. This was the imperative stimulus to which the participant responded by making a saccade in the opposite direction. The ring remained in the peripheral location for 1000 ms and then returned to the center, where participants were instructed to return their gaze for 1000 ms before the start of the next trial. Fixation epochs were simply a continuation of this fixation display. Hard trials were distinguished by a 3 dB increase in luminance of the peripheral squares starting during the gap. Except for the hard cue, fake-hard trials were identical to easy trials.

Fig. 2

Neural responses to error commission. A. Pseudocolor statistical maps of error-related fMRI activation at 6 s in the error vs. correct contrast are displayed on inflated medial cortical surfaces. The rACC and dACC ROIs are outlined in black. Gray masks cover subcortical regions in which activation is displaced in surface-based analyses. In the first two rows, warm colors indicate greater activation on error than correct trials. The third row shows the group comparison of error-related activation. The middle columns show hemodynamic response functions for each condition (correct: black; error: red) and for the error-correct difference for each group (Control: solid line; OCD: dashed line) for the left and right dACC ROIs. B. Plots in the first two rows show grand average EEG waveforms, with standard error lines, for correct (black) and error (red) trials, time-locked to the onset of the saccade (0 s), for control (first row) and OCD (second row) participants. The first peak after saccadic onset is eye movement artifact, which subtracts out of the difference waveform for error and correct trials, shown in the third row for each group. The arrow denotes the approximate time of peak ERN, which did not differ significantly by group.

Fig. 3

Preparatory fMRI activation of the default network and its relation to symptom severity. Pseudocolor statistical maps of activation at 4 s are displayed on inflated medial cortical surfaces. The default network ROI is outlined in black. Gray masks cover subcortical regions in which activation is displaced in surface-based analyses. A: Preparatory fMRI activation in the group comparison of the post-error vs. pre-error contrast at 4 s. Blue indicates regions showing greater activation for OCD than controls in the post- vs. pre-error trial. The left graph shows the differences in hemodynamic responses for post-error minus pre-error trials for each group at the vertex with the maximum group difference in the post- vs. pre-error contrast. The right graph shows the means and standard errors for preparatory activation at this same vertex in the pre-error trial, error trial, and post-error trial. B: Relations between activation on post-error trials and Y-BOCS total, obsession, and compulsion scores. The scatter plots correspond to the maximum vertices in the correlation. In accord with recent practice in fMRI research, r-values from the maximum vertices are not reported since these are based on the present data and may therefore inflate the true correlation by adding the effect of random variability (e.g., Kriegeskorte et al., 2009; Vul and Pashler, 2012; Vul et al., 2009). The correlation with obsessions did not meet the cluster-wise probability threshold for significance.

Fig. 4

DTI results. Pseudocolor statistical map of group differences in fractional anisotropy (FA) displayed on the MNI152 template brain. Red indicates higher FA in controls and blue indicates higher FA in OCD. Crosshairs denote the voxel of maximal significance.