Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: Evidence from resting-state functional connectivity

Vaghi, Matilde M. ORCID: https://orcid.org/0000-0002-0999-9055, Vértes, Petra E., Kitzbichler, Manfred G., Apergis-Schoute, Annemieke M., van der Flier, Febe E., Fineberg, Naomi A., Sule, Akeem, Zaman, Rashid, Voon, Valerie, Kundu, Prantik, Bullmore, Edward T. and Robbins, Trevor W. (2017) Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: Evidence from resting-state functional connectivity. Biological Psychiatry, 81 (8). pp. 708-717. ISSN 0006-3223

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Background: A recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity. Methods: Multiecho resting-state acquisition, combined with micromovement correction by blood oxygen level–dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects. We measured cognitive flexibility (attentional set-shifting) and goal-directed performance (planning of sequential response sequences) by means of well-validated, standardized behavioral cognitive paradigms. Functional connectivity strength of striatal seed regions was related to cognitive flexibility and goal-directed performance. To gain insights into fundamental network alterations, graph theoretical models of brain networks were derived. Results: Reduced functional connectivity between the caudate and the ventrolateral prefrontal cortex was selectively associated with reduced cognitive flexibility. In contrast, goal-directed performance was selectively related to reduced functional connectivity between the putamen and the dorsolateral prefrontal cortex in OCD patients, as well as to symptom severity. Whole-brain data-driven graph theoretical analysis disclosed that striatal regions constitute a cohesive module of the community structure of the functional connectome in OCD patients as nodes within the basal ganglia and cerebellum were more strongly connected to one another than in healthy control subjects. Conclusions: These data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable frontostriatal circuits and those cognitive processes underlying OCD symptoms.

Item Type: Article
Additional Information: Funding information: This work was supported by a Wellcome Trust Senior Investigator Award Grant No. 104631/Z/14/Z (to TWR). Work was completed at the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom, supported by a joint award from the Medical Research Council and Wellcome Trust Grant No. G00001354. MMV is supported by a Pinsent-Darwin Studentship in Mental Pathology and a Cambridge Home and European Union Scholarship Scheme studentship. PEV is supported by the Medical Research Council Grant No. MR/K020706/1. AMA-S is supported by the Wellcome Trust Grant above. VV is a Wellcome Trust Fellow.
Faculty \ School: Faculty of Social Sciences > School of Psychology
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Depositing User: LivePure Connector
Date Deposited: 05 Oct 2022 09:30
Last Modified: 06 Mar 2024 23:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/88856
DOI: 10.1016/j.biopsych.2016.08.009


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