Specific fronto-striatal circuits for impaired cognitive flexibility and goal-directed planning in Obsessive-Compulsive Disorder: Evidence from resting-state functional connectivity
van, der Flier Febe E
Fineberg, Naomi A
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Vaghi, M., Vertes, P., Kitzbichler, M., Apergis-Schoute, A., van, d. F. F. E., Fineberg, N. A., Sule, A., et al. (2016). Specific fronto-striatal circuits for impaired cognitive flexibility and goal-directed planning in Obsessive-Compulsive Disorder: Evidence from resting-state functional connectivity. Biological Psychiatry https://doi.org/10.1016/j.biopsych.2016.08.009
Background: A recent hypothesis has suggested that core deficits in goal-directed behavior in Obsessive-Compulsive Disorder (OCD) are caused by impaired fronto-striatal function. We tested this hypothesis in OCD patients and controls, by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity. Methods: Multi-echo resting-state acquisition, combined with micro-movement correction by BOLD-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 controls. Conclusions: These data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable fronto-striatal circuits and those cognitive processes underlying OCD symptoms.
obsessive-compulsive disorder, resting-state, fronto-striatal circuits, functional connectivity, cognitive flexibility, goal-directed planning
This research was funded by a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) awarded to T.W. Robbins. Work was completed at the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK, supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). M.M. Vaghi is supported by a Pinsent Darwin Scholarship in Mental Pathology and a Cambridge Home and EU Scholarship Scheme (CHESS) studentship. P.E. Vértes is supported by the Medical Research Council (grant no. MR/K020706/1). A.M. Apergis-Schoute is supported by the Wellcome Trust above. V. Voon is a Wellcome Trust Fellow.
WELLCOME TRUST (104631/Z/14/Z)
Wellcome Trust (093875/Z/10/Z)
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External DOI: https://doi.org/10.1016/j.biopsych.2016.08.009
This record's URL: https://www.repository.cam.ac.uk/handle/1810/260598
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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