Dataset Information

Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity.

ABSTRACT:

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.

SUBMITTER: Vaghi MM

PROVIDER: S-EPMC6020061 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceDimensional definitions of transdiagnostic mental health problems have been suggested as an alternative to categorical diagnoses, having the advantage of capturing heterogeneity within diagnostic categories and similarity across them and bridging more naturally psychological and neural substrates.ObjectiveTo examine whether a self-reported compulsivity dimension has a stronger association with goal-directed and related higher-order cognitive deficits compared with a diagnosis of obsessive-compulsive disorder (OCD).Design, setting, and participantsIn this cross-sectional study, patients with OCD and/or generalized anxiety disorder (GAD) from across the United States completed a telephone-based diagnostic interview by a trained rater, internet-based cognitive testing, and self-reported clinical assessments from October 8, 2015, to October 1, 2017. Follow-up data were collected to test for replicability.Main outcomes and measuresPerformance was measured on a test of goal-directed planning and cognitive flexibility (Wisconsin Card Sorting Test [WCST]) and a test of abstract reasoning. Clinical variables included DSM-5 diagnosis of OCD and GAD and 3 psychiatric symptom dimensions (general distress, compulsivity, and obsessionality) derived from a factor analysis.ResultsOf 285 individuals in the analysis (mean [SD] age, 32 [12] years; age range, 18-77 years; 219 [76.8%] female), 111 had OCD; 82, GAD; and 92, OCD and GAD. A diagnosis of OCD was not associated with goal-directed performance compared with GAD at baseline (? [SE], -0.02 [0.02]; P?=?.18). In contrast, a compulsivity dimension was negatively associated with goal-directed performance (? [SE], -0.05 [0.02]; P?=?.003). Results for abstract reasoning task and WCST mirrored this pattern; the compulsivity dimension was associated with abstract reasoning (? [SE], 2.99 [0.63]; P?<?.001) and several indicators of WCST performance (eg, categories completed: ? [SE], -0.57 [0.09]; P?<?.001), whereas OCD diagnosis was not (abstract reasoning: ? [SE], 0.39 [0.66]; P?=?.56; categories completed: ? [SE], -0.09 [0.10]; P?=?.38). Other symptom dimensions relevant to OCD, obsessionality, and general distress had no reliable association with goal-directed performance, WCST, or abstract reasoning. Obsessionality had a positive association with requiring more trials to reach the first category on the WCST at baseline (? [SE], 2.92 [1.39]; P?=?.04), and general distress was associated with impaired goal-directed performance at baseline (? [SE],-0.04 [0.02]; P?=?.01). However, unlike the key results of this study, neither survived correction for multiple comparisons or was replicated at follow-up testing.Conclusions and relevanceDeficits in goal-directed planning in OCD may be more strongly associated with a compulsivity dimension than with OCD diagnosis. This result may have implications for research assessing the association between brain mechanisms and clinical manifestations and for understanding the structure of mental illness.