Abnormal spontaneous neural activity in the medial prefrontal cortex and right superior temporal gyrus correlates with anhedonia severity in obsessive-compulsive disorder

2019 ◽  
Vol 259 ◽  
pp. 47-55 ◽  
Author(s):  
Jie Xia ◽  
Jie Fan ◽  
Hongyu Du ◽  
Wanting Liu ◽  
Sihui Li ◽  
...  
2019 ◽  
Vol 116 (9) ◽  
pp. 3799-3804 ◽  
Author(s):  
Tingting Sun ◽  
Zihua Song ◽  
Yanghua Tian ◽  
Wenbo Tian ◽  
Chunyan Zhu ◽  
...  

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.


2017 ◽  
Vol 1 ◽  
pp. 239821281773340 ◽  
Author(s):  
Camilla d’Angelo ◽  
Dawn M. Eagle ◽  
Cristina-M. Coman ◽  
Trevor W. Robbins

Background: Excessive checking is a common, debilitating symptom of obsessive–compulsive disorder. To further examine cognitive processes underpinning checking behaviour, and clarify how and why checking develops, we designed a novel operant paradigm for rats, the observing response task. The present study used the observing response task to investigate checking behaviour following excitotoxic lesions of the medial prefrontal cortex, nucleus accumbens core and dorsal striatum, brain regions considered to be of relevance to obsessive–compulsive disorder. Methods: In the observing response task, rats pressed an ‘observing’ lever for information (provided by light onset) about the location of an ‘active’ lever that provided food reinforcement. Following training, rats received excitotoxic lesions of the regions described above and performance was evaluated post-operatively before histological processing. Results: Medial prefrontal cortex lesions selectively increased functional checking with a less-prominent effect on non-functional checking and reduced discrimination accuracy during light information periods. Rats with nucleus accumbens core lesions made significantly more checking responses than sham-lesioned rats, including both functional and non-functional checking. Dorsal striatum lesions had no direct effect on checking per se, but reduced both active and inactive lever presses, and therefore changed the relative balance between checking responses and instrumental responses. Conclusions: These results suggest that the medial prefrontal cortex and nucleus accumbens core are important in the control of checking, perhaps via their role in processing uncertainty of reinforcement, and that dysfunction of these regions may therefore promote excessive checking behaviour, possibly relevant to obsessive-compulsive disorder.


Author(s):  
Qianqian Li ◽  
Jun Yan ◽  
Jinmin Liao ◽  
Xiao Zhang ◽  
Lijun Liu ◽  
...  

Abstract Stress might exaggerate the compulsion and impair the working memory of patients with obsessive-compulsive disorder (OCD). This study evaluated the effect of stress on the cognitive neural processing of working memory in OCD and its clinical significance using a “number calculation working memory” task. Thirty-eight patients and 55 gender- and education-matched healthy controls were examined. Stress impaired the performance of the manipulation task in patients. Healthy controls showed less engagement of the medial prefrontal cortex and striatum during the task under stress versus less stress, which was absent in the patients with OCD. The diagnosis × stress interaction effect was significant in the right fusiform, supplementary motor area, precentral cortex and caudate. The failure of suppression of the medial prefrontal cortex and striatum and stress-related hyperactivation in the right fusiform, supplementary motor area, precentral cortex, and caudate might be an OCD-related psychopathological and neural response to stress.


2021 ◽  
Author(s):  
Thomas G. Adams ◽  
Josh M. Cisler ◽  
Benjamin Kelmendi ◽  
Jamilah R. George ◽  
Stephen A. Kichuk ◽  
...  

AbstractBackgroundPsychotherapy based on fear extinction is a mainstay of treatment for obsessive-compulsive disorder (OCD). The default mode network (DMN) is important to safety signal processing, fear extinction, and exposure-based therapies. The medial prefrontal cortex (mPFC) is an anchor of the DMN. Neuromodulation targeting the mPFC might augment therapeutic learning and thereby enhance response to exposure-based therapies.MethodsTo characterize the effects of mPFC neuromodulation, 17 community volunteers completed resting-state fMRI scans before and after receiving 20 minutes of frontopolar multifocal transcranial direct current stimulation (tDCS). To examine the effects of tDCS on therapeutic learning, 24 patients with OCD were randomly assigned (double-blind, 50:50) to receive active or sham tDCS immediately before completing a two-day exposure and response prevention (ERP) challenge.ResultsAfter tDCS, frontal pole functional connectivity with regions in the anterior insula and basal ganglia decreased, while connectivity in the middle and superior frontal gyri increased (ps<.001, corrected). Functional connectivity between DMN and salience network (SN) increased after tDCS (ps<.001). OCD patients who received active tDCS exhibited more rapid within- and between-trial therapeutic extinction learning (ps<.05) during the ERP challenge compared to those who received sham tDCS.ConclusiontDCS targeting the mPFC may modulate SN and DMN functional connectivity and can accelerate therapeutic learning. Though limited by small samples, these promising findings motivate further exploration of the effects of tDCS on neural and behavioral targets associated with exposure-based treatments for OCD and for other anxiety and related disorders.


2019 ◽  
Vol 29 (11) ◽  
pp. 4753-4762 ◽  
Author(s):  
Jesus Pujol ◽  
Laura Blanco-Hinojo ◽  
Dídac Maciá ◽  
Pino Alonso ◽  
Ben J Harrison ◽  
...  

AbstractWe mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive–compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.


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