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Hypoactivation and dysconnectivity of a frontostriatal circuit during goal-directed planning as an endophenotype for obsessive-compulsive disorder

Hypoactivation and dysconnectivity of a frontostriatal circuit during goal-directed planning as an endophenotype for obsessive-compulsive disorder
Hypoactivation and dysconnectivity of a frontostriatal circuit during goal-directed planning as an endophenotype for obsessive-compulsive disorder

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.

Connectivity, Endophenotype, Frontostriatal circuits, Goal-directed, Obsessive-compulsive disorder, Planning
2451-9022
655-663
Vaghi, Matilde M.
593cdd05-c7e8-40ab-880d-11293b8ef067
Hampshire, Adam
08af1acb-f59f-4f42-a1ca-99fd2fb66da2
Fineberg, Naomi A.
157dcac1-9fb2-4197-81f3-0167e1224f05
Kaser, Muzaffer
778cfb2c-da5f-4fc4-ab36-9b3745a29e12
Brühl, Annette B.
c21eca07-9e3a-4a07-baa3-36dc294b9db0
Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7
Vaghi, Matilde M.
593cdd05-c7e8-40ab-880d-11293b8ef067
Hampshire, Adam
08af1acb-f59f-4f42-a1ca-99fd2fb66da2
Fineberg, Naomi A.
157dcac1-9fb2-4197-81f3-0167e1224f05
Kaser, Muzaffer
778cfb2c-da5f-4fc4-ab36-9b3745a29e12
Brühl, Annette B.
c21eca07-9e3a-4a07-baa3-36dc294b9db0
Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7

Vaghi, Matilde M., Hampshire, Adam, Fineberg, Naomi A., Kaser, Muzaffer, Brühl, Annette B., Sahakian, Barbara J., Chamberlain, Samuel R. and 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. (doi:10.1016/j.bpsc.2017.05.005).

Record type: Article

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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More information

Published date: 1 November 2017
Additional Information: Publisher Copyright: © 2017 Society of Biological Psychiatry
Keywords: Connectivity, Endophenotype, Frontostriatal circuits, Goal-directed, Obsessive-compulsive disorder, Planning

Identifiers

Local EPrints ID: 492580
URI: http://eprints.soton.ac.uk/id/eprint/492580
ISSN: 2451-9022
PURE UUID: 0eafb89d-fc61-493a-acb1-116a2825f346
ORCID for Samuel R. Chamberlain: ORCID iD orcid.org/0000-0001-7014-8121

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Date deposited: 06 Aug 2024 16:47
Last modified: 07 Aug 2024 01:59

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Contributors

Author: Matilde M. Vaghi
Author: Adam Hampshire
Author: Naomi A. Fineberg
Author: Muzaffer Kaser
Author: Annette B. Brühl
Author: Barbara J. Sahakian
Author: Samuel R. Chamberlain ORCID iD
Author: Trevor W. Robbins

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