Disruption of effective connectivity from the dorsolateral prefrontal cortex to the orbitofrontal cortex by negative emotional distraction in obsessive–compulsive disorder

Abstract

BackgroundObsessive–compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive–affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.MethodA total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.ResultsDuring the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected).ConclusionsExaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.

Effects of Bergen 4-Day Treatment on Resting-State Graph Features in Obsessive-Compulsive Disorder

“…Previous studies using such techniques have shown links from the vmPFC to the amygdala and dorsal striatum during symptom provocation and from the OFC to the nucleus accumbens at rest (Abe et al, 2015). In comparison, connections from the dlPFC to the OFC and IFG to amygdala have been found during emotional working memory and stop signal tasks, respectively (Han et al, 2016;. This suggests that the direction of connectivity is modulated by task demands.…”

Neural primacy of the dorsolateral prefrontal cortex in patients with obsessive-compulsive disorder

“…Meanwhile, the FC between the DLPFC and OFC was positively associated with obsession scores, suggesting a trend in which increasing severity of obsession reflects enhancement of negative functional connection between the DLPFC and OFC in OCD patients. Both the DLPFC and OFC are located in the PFC, which is involved in executive function, cognitive behavior, and regulation of self-control ( Han et al, 2016 , Kwon et al, 2009 , Savage et al, 1999 ). Notably, a previous task-induced EC study that administered a working memory task under emotional distraction revealed that hyperactivation of the DLPFC may lead to reduced top-down input to the OFC in OCD patients ( Han et al, 2016 ).…”

“…Both the DLPFC and OFC are located in the PFC, which is involved in executive function, cognitive behavior, and regulation of self-control ( Han et al, 2016 , Kwon et al, 2009 , Savage et al, 1999 ). Notably, a previous task-induced EC study that administered a working memory task under emotional distraction revealed that hyperactivation of the DLPFC may lead to reduced top-down input to the OFC in OCD patients ( Han et al, 2016 ). In light of that report combined with our own findings, which demonstrated that the OFC had an inhibitory effect on the right DLPFC in the resting state, we postulate that the OFC is a major inhibitor of the self-control function of the DLPFC in OCD patients in the resting state, while the DLPFC engages top-down control input to the OFC when emotional task stimulation is applied.…”

“…Previous studies on OCD revealed abnormal EC between the frontal region and the amygdala ( Curcic-Blake et al, 2012 ) as well as the cingulate cortex ( Schlosser et al, 2010 ) using task fMRI. In particular, hyperactivation of the DLPFC may lead to reduced top-down input to the OFC in OCD patients ( Han et al, 2016 ); however, no study has explored the EC with a focus on the DLPFC using resting-state fMRI. Therefore, in the current study, we aimed to investigate whether the DLPFC produces aberrant neural information flow in adult OCD patients.…”

Altered reward-related effective connectivity in obsessive-compulsive disorder: an fMRI study

“…Despite the fact that -from a functional perspectivethere are reasonable grounds to assume that alterations in activation may be associated with altered network connectivity, surprisingly little is known about potential alterations in connectivity between these regions in the context of reward processing, although altered connectivity in OCD has been reported in association with other processes 14,15 or during the resting state. 16 To our knowledge, only 2 studies have investigated connectivity in association with the processing of reward in OCD.…”