期刊
BIOLOGICAL PSYCHIATRY
卷 81, 期 8, 页码 708-717出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2016.08.009
关键词
Cognitive flexibility; Frontostriatal circuits; Functional connectivity; Goal-directed planning; Obsessive-compulsive disorder; Resting state
资金
- Wellcome Trust Senior Investigator Award [104631/Z/14/Z]
- Medical Research Council
- Wellcome Trust [G00001354]
- Pinsent-Darwin Studentship in Mental Pathology
- Cambridge Home
- European Union Scholarship Scheme studentship
- Medical Research Council [MR/K020706/1]
- Lundbeck
- GSK
- European College of Neuropsychopharmacology (ECNP)
- Servier
- Cephalon
- AstraZeneca
- Medical Research Council (UK)
- National Institute for Health Research
- Wellcome Foundation
- Oxford University Press
- Taylor and Francis
- MRC [MR/K020706/1, MR/J012084/1, G1000183] Funding Source: UKRI
- Medical Research Council [MR/J012084/1, MR/K020706/1, G1000183B, G1000183, G0001354] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10051] Funding Source: researchfish
- Wellcome Trust [104631/Z/14/Z] Funding Source: researchfish
BACKGROUND: A recent hypothesis has suggested that core deficits in goal-directed behavior in obsessivecompulsive 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 restingstate functional connectivity. METHODS: Multiecho resting-state acquisition, combined with micromovement correction by blood oxygen leveldependent 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.
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