Hyperactive Error Responses and Altered Connectivity in Ventromedial and Frontoinsular Cortices in Obsessive-Compulsive Disorder

Abstract

Background Patients with obsessive compulsive disorder (OCD) show abnormal functioning in ventral frontal brain regions involved in emotional/motivational processes, including anterior insula/frontal operculum (aI/fO) and ventromedial frontal cortex (VMPFC). While OCD has been associated with an increased neural response to errors, the influence of motivational factors on this effect remains poorly understood. Methods To investigate the contribution of motivational factors to error processing in OCD, and to examine functional connectivity between regions involved in the error response, functional magnetic resonance imaging data were measured in 39 OCD patients (20 unmedicated, 19 medicated) and 38 control subjects (20 unmedicated, 18 medicated) during an error-eliciting interference task where motivational context was varied using monetary incentives (null, loss, and gain). Results Across all errors, OCD patients showed reduced deactivation of VMPFC and greater activation in left aI/fO as compared to controls. For errors specifically resulting in a loss, patients further hyperactivated VMPFC as well as right aI/fO. Independent of activity associated with task events, OCD patients showed greater functional connectivity between VMPFC and regions of bilateral aI/fO and right thalamus. Conclusions OCD patients show greater activation in neural regions associated with emotion and valuation when making errors, which could be related to altered intrinsic functional connectivity between brain networks. These results highlight the importance of emotional/motivational responses to mistakes in OCD, and point to the need for further study of network interactions in the disorder.

Structural covariance of neostriatal and limbic regions in patients with obsessive–compulsive disorder

“…Although the vmPFC has been characterized as hypoactive at rest in OCD populations, 20 perhaps owing to difficulties in fear extinction, 55 hyperactivation of this region has been reported in response to error processing, 56 uncertainty 57 and moral di lemma. 58 Such findings indicate that the vmPFC may be in volved in the regulation of transiently increased limbic activity when individuals experience anxiety symptoms, a hypothesis that seems to concur with our findings.…”

Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

“…The urge to perform an experimentally trained habit has been shown to be associated with hyperactivity in the caudate in OCD patients (33), whereas the vmPFC is thought to influence the caudate for goal selection (35,36). Therefore, an aberrant vmPFC valuation system as demonstrated across several tasks in OCD (5,17,37) is of critical relevance to the maintenance of the disorder.…”

“…As fear extinction relies on revaluation of threatening stimuli as safe, it is critical to address how the brain processes the safety of stimuli in the environment. The ventromedial prefrontal cortex (vmPFC) is known to play a multifaceted role in integrating affective evaluative processes while mediating flexible behavior and is implicated in fear learning and anxiety-related disorders (1)(2)(3)(4)(5)(6)(7). Prefrontal inflexibility in Obsessive Compulsive Disorder (OCD) suggests rigidity in threat estimation alongside a persistent urge to perform compulsive behaviors, yet only one study has examined the neural correlates of fear learning and extinction in this disorder, implicating a maladaptive vmPFC (8).…”

“…Based on the significance of the role of the vmPFC to estimate values to guide goal-directed behavior (12) and the interference of maladaptive vmPFC functioning in a variety of tasks in OCD (5,8,(13)(14)(15)(16)(17), we postulated that impaired vmPFC valuation would be central to the disorder. We sought to determine how patients with OCD perform on a task that is dependent on accurate and flexible value signaling by this prefrontal region.…”

Brain functional connectivity during induced sadness in patients with obsessive–compulsive disorder

“…23 In other contexts, the subgenual ACC and extended ventral medial frontal cortex have also been identified as hyper active in patients with OCD when making performance errors in the context of goal-directed tasks. 24,25 The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation. To do so, we used a previously validated mood induction paradigm 26,27 and functional magnetic resonance imaging (fMRI) to assess changes in subgenual ACC functional connectivity during the recollection of neutral versus sad personal emotional events.…”