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Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder

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Vaghi, MMS 
Hampshire, A 
Fineberg, NA 
Bruhl, AB 


Background: The symptoms of Obsessive-Compulsive Disorder (OCD) have been postulated to result from impaired executive functioning and excessive habit formation at the expense of goal-directed control and have been objectively demonstrated using neuropsychological tests in such patients. This study tests whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in OCD patients and in their unaffected first-degree relatives. Methods: Twenty-one comorbidity free OCD patients, 19 clinically asymptomatic first-degree relatives of these patients, and 20 control participants were tested on a functional magnetic resonance optimized version of the Tower of London task. Group differences in brain activation during goal-directed planning were measured together with associated frontostriatal functional connectivity. Results: OCD patients and their clinically asymptomatic relatives manifested hypoactivation of the right dorsolateral prefrontal cortex during goal-directed planning, coupled with reduced functional connectivity between this cortical region and the basal ganglia (putamen). Conclusions: Hypoactivation of cortical regions associated with goal-directed planning, and associated frontostriatal dysconnectivity, represent a candidate endophenotype for OCD. These findings accord with abnormalities in neural networks supporting the balance between goal-directed and habitual behavior, with implications for recent neuropsychological theories of OCD and the major neurobiological model for this disorder.



connectivity, endophenotype, frontostriatal circuits, goal-directed, obsessive-compulsive disorder, planning

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Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Wellcome Trust (104631/Z/14/Z)
Wellcome Trust (110049/Z/15/Z)
Medical Research Council (G0001354)
Medical Research Council (G1000183)
This work was supported by a Wellcome Trust Senior Investigator Award (No. 104631/Z/14/Z) to TWR. Work was completed at the Behavioural and Clinical Neuroscience Institute, University of Cambridge, supported by a joint award from the Medical Research Council and Wellcome Trust (No. G00001354). MMV is supported by a Pinsent Darwin Scholarship in Mental Pathology and Angharad Dodds John Bursary in Mental Health and Neuropsychiatry. SRC’s involvement in this work was funded by a Wellcome Trust Clinical Fellowship (No. 110049/Z/15/Z).