scholarly journals Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

2019 ◽  
Vol 116 (9) ◽  
pp. 3799-3804 ◽  
Author(s):  
Tingting Sun ◽  
Zihua Song ◽  
Yanghua Tian ◽  
Wenbo Tian ◽  
Chunyan Zhu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Obsessive Compulsive Disorder ◽  
Medial Prefrontal Cortex ◽  
Basolateral Amygdala ◽  
Obsessive Compulsive ◽  
Neuronal Tracing ◽  
Compulsive Disorder ◽  
Glutamatergic Neurons ◽  
Fmri Study ◽  
Checking Behavior

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.

scholarly journals Role of the medial prefrontal cortex and nucleus accumbens in an operant model of checking behaviour and uncertainty

2017 ◽  
Vol 1 ◽  
pp. 239821281773340 ◽  
Author(s):  
Camilla d’Angelo ◽  
Dawn M. Eagle ◽  
Cristina-M. Coman ◽  
Trevor W. Robbins
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Obsessive Compulsive Disorder ◽  
Medial Prefrontal Cortex ◽  
Nucleus Accumbens Core ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Observing Response ◽  
Response Task ◽  
Accumbens Core

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.

scholarly journals Distinct Effects of Social Stress on Working Memory in Obsessive-Compulsive Disorder

2020 ◽  
Author(s):  
Qianqian Li ◽  
Jun Yan ◽  
Jinmin Liao ◽  
Xiao Zhang ◽  
Lijun Liu ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Obsessive Compulsive Disorder ◽  
Medial Prefrontal Cortex ◽  
Supplementary Motor Area ◽  
Motor Area ◽  
Healthy Controls ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
The Right

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.

scholarly journals Transcranial direct current stimulation (tDCS) targeting the medial prefrontal cortex (mPFC) modulates functional connectivity and enhances inhibitory safety learning in obsessive-compulsive disorder (OCD)

2021 ◽  
Author(s):  
Thomas G. Adams ◽  
Josh M. Cisler ◽  
Benjamin Kelmendi ◽  
Jamilah R. George ◽  
Stephen A. Kichuk ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Obsessive Compulsive Disorder ◽  
Medial Prefrontal Cortex ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Fear Extinction ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Direct Current Stimulation

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.

scholarly journals Deep brain stimulation for obsessive compulsive disorder: A review of results by anatomical target

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Candace Borders ◽  
Frank Hsu ◽  
Alexander J. Sweidan ◽  
Emily S. Matei ◽  
Robert G. Bota
Keyword(s):  
Deep Brain Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Basolateral Amygdala ◽  
Accurate Determination ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
First Time ◽  
Deep Brain ◽  
Time Point

Studies suggest deep brain stimulation (DBS) as a treatment modality for the refractory obsessive-compulsive disorder (OCD). It is unclear where to place the DBS. Various sites are proposed for placement with the ventral capsule/ventral striatum (VC/VS) among the most studied. Herein, we aim to summarize both quantitative Yale-Brown Obsessive-Compulsive Scale (YBOCS) data and qualitative descriptions of the participants’ symptoms when given. A literature search conducted via PubMed yielded 32 articles. We sought to apply a standard based on the utilization of YBOCS. This yielded 153 distinct patients. The outcome measure we focused on in this review is the latest YBOCS score reported for each patient/cohort in comparison to the location of the DBS. A total of 32 articles were found in the search results. In total, 153 distinct patients’ results were reported in these studies. Across this collection of papers, a total of 9 anatomic structures were targeted. The majority of studies showed a better response at the last time point as compared to the first time point. Most patients had DBS at nucleus accumbens followed by VC/VS and the least patients had DBS at the bilateral superolateral branch of the median forebrain bundle and the bilateral basolateral amygdala. The average YBOCS improvement did not seem to directly correlate with the percentile of patients responding to the intervention. Well-controlled, randomized studies with larger sample sizes with close follow up are needed to provide a more accurate determination for placement of DBS for OCD.

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