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


Vaghi, Matilde M; Hampshire, Adam; Fineberg, Naomi A; Kaser, Muzaffer; Brühl, Annette B; Sahakian, Barbara J; Chamberlain, Samuel R; Robbins, Trevor W (2017). Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2(8):655-663.

Abstract

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 tested whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in patients with OCD and in their unaffected first-degree relatives.
Methods: In total, 21 comorbidity-free patients with OCD, 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: Patients with OCD 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.

Abstract

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 tested whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in patients with OCD and in their unaffected first-degree relatives.
Methods: In total, 21 comorbidity-free patients with OCD, 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: Patients with OCD 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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiology, Nuclear Medicine and Imaging
Life Sciences > Cognitive Neuroscience
Health Sciences > Neurology (clinical)
Life Sciences > Biological Psychiatry
Language:English
Date:2017
Deposited On:12 Mar 2019 16:42
Last Modified:12 Sep 2020 04:30
Publisher:Elsevier
ISSN:2451-9022
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.bpsc.2017.05.005
PubMed ID:29167834

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