Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 21, Issue 1, Pages 42-58Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ijnp/pyx088
Keywords
cognitive domains; neural circuitry; treatment
Funding
- Wellcome Trust [104631/Z/14/Z]
- Pinsent-Darwin Studentship in Mental Pathology
- Cambridge Home
- European Union Scholarship Scheme studentship
- Wellcome Trust Fellowship [110049/Z/15/Z]
- Medical Research Council [G1000183B, MR/J012009/1, G1000183] Funding Source: researchfish
- National Institute for Health Research [PB-PG-0712-28044, NF-SI-0513-10051] Funding Source: researchfish
- MRC [G1000183, MR/J012009/1] Funding Source: UKRI
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Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder.
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