Pathophysiology of refractory obsessive-compulsive disorder: A study of visual search combined with overactive performance monitoring

Abstract

Based on both functional and structural studies of excessive activity, fronto-striatal-thalamic-cortical and cortico-striatal circuits have been hypothesized to underlie the pathophysiology of obsessive-compulsive disorder (OCD). However, the neurobiological underpinnings of OCD refractory to medication and therapy remain controversial. This study aimed to evaluate neuroanatomical abnormalities of the whole brain and to evaluate visual processing in patients with refractory OCD.This study was comprised of 2 experiments. The neuroanatomical abnormalities of the whole brain were evaluated using a visual search in combination with overactive performance monitoring (Experiment I), and visual processing was evaluated using event-related potentials recorded from subjects during performance of a visual search task. We also examined the amplitudes and latency of the error-related negativity (ERN) using a modified flanker task (Experiment II). Standard low-resolution electromagnetic tomography analysis was applied to determine the special areas.Patients with refractory OCD had a significantly greater number of saccades and prolonged latencies relative to the healthy controls. Scalp map topography confirmed that visual cognitive and executive dysfunction was localized to the fusiform gyrus. Furthermore, we found that during a modified flanker task, ERNs had a greater amplitude and a prolonged latency relative to those of the healthy controls. Further data analysis suggested that cognitive dysfunction and compulsive behavior in OCD patients were linked to abnormalities within the dorsolateral prefrontal cortex (DLPFC).We identified abnormal activities within the fusiform gyrus and DLPFC that likely play important roles in the pathophysiology of OCD.

Figure 1

Experimental design of the visual search task (Experiment I).

Figure 2

Experimental design of the modified flanker task (Experiment II). Subjects were instructed to respond by clicking the right or left mouse button to indicate the target arrow direction. Subsequently, the subjects rated their previous response as correct, incorrect, or unsure. The letters R and F refer to correct (“right”) and incorrect (“false”), respectively.

Figure 3

The latency (ms) of component 1 at electrodes C3 (A) and C4 (B) in healthy controls, responding OCD patients, and refractory OCD patients (Experiment I). OCD = obsessive-compulsive disorder.

Figure 4

Averaged event-related potential waveforms of component 2 at electrode CP5 of the OCD patient subgroups and the healthy controls (Experiment I). OCD = obsessive-compulsive disorder.

Figure 5

sLORETA images focusing on the largest difference observed between the healthy controls and the OCD patients in the visual search (Experiment I). Yellow-Red indicates the activated areas between the two groups and presents the voxel with the most significant sLORETA values. (A) Inferior frontal gyrus (x, y, z = 35, 20, −10; BA = 47). (B) Occipital lobe (x, y, z = 0, −75, 10; BA = 18). (C) Anterior cingulate (x, y, z = 0, 0, −5; BA = 25). P < 0.05. OCD = obsessive-compulsive disorder, sLORETA = standard low-resolution electromagnetic tomography.

Figure 6

Averaged event-related potential waveforms at electrode Fz of the OCD patient subgroups and the healthy controls (Experiment II). Significantly decreased ERN amplitudes were observed in the refractory OCD patients compared to the healthy controls (P < 0.005 by latency analysis). ERN = error-related negativity, OCD = obsessive-compulsive disorder.

Figure 7

sLORETA images focusing on the largest difference observed between the healthy controls and the OCD patients in the flanker task (Experiment II). Yellow-red indicates the activated areas between the 2 groups, and blue indicates a significant decrease of sLORETA values: (A). Superior temporal gyrus (x, y, z = 65, −30, 5; BA = 42); (B). Middle temporal gyrus (x, y, z = −60, −30, 0; BA = 21); (C). Posterior cingulate (x, y, z = 0, −65, 15; BA = 23); (D). Inferior frontal gyrus (x, y, z = −50, 20, 10; BA = 45). P < 0.05. OCD = obsessive-compulsive disorder, sLORETA = standard low-resolution electromagnetic tomography.