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

Abstract

BackgroundA 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.MethodsMultiecho 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.ResultsReduced 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.ConclusionsThese 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.

Abnormalities of hippocampal shape and subfield volumes in medication‐free patients with obsessive–compulsive disorder

“…Exploratory analysis of left hippocampus revealed reduced volume of presubiculum, and there was no significant group by hemisphere interaction, indicating that alterations in this specific subfield may not be fully restricted to the right hemisphere. Hence, dysfunction of subiculum and presubiculum may reduce the efficiency and precision of communication between hippocampus and striatum, leading to impairment in flexible goal-directed behaviors (Gillan et al, 2011;Vaghi et al, 2016) that represent a core neurocognitive feature of OCD (Gottlich, Kramer, Kordon, Hohagen, & Zurowski, 2014). Interactions between hippocampus and striatum are believed to generate motivational, outcome-predicting, and outcome-responsive signals that invigorate flexible contextuallyrelevant goal-directed behaviors (Pennartz et al, 2011).…”

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

“…Even outside of active task engagement, nodes of the SN are abnormally hyperactive: increased resting state functional activity of the ACC, MDN (Rauch et al, 2006a; Bourne et al, 2012), dlPFC (Figee et al, 2014) and caudate nucleus (Graybiel and Rauch, 2000) has been noted in individuals with OCD. Frontostriatal functional connectivity stemming from the dlPFC (Vaghi et al, 2016), and altered striatal connectivity to the insula (Bernstein et al, 2016) has been linked to OCD severity.…”

Prefrontal tDCS and sertraline in obsessive compulsive disorder: a case report and review of the literature

“…Furthermore, interhemispheric imbalance by disturbed thalamic filter function has been proposed to be a pathophysiological correlate (Gonçalves et al, 2011;Mataix-Cols et al, 1997). Recent functional connectivity imaging data suggest an impact of frontalstriatal connectivity on cognitive flexibility and goal-directed planning (Vaghi et al, 2017). Considering the high overlap with comorbid depression and anxiety disorders with the DLPFC as a hub region, alternative electrode montages primarily involving prefrontal brain regions could modulate OC symptoms and eventually concomitant affective disorders by restoring cognitive control, and executive functions in remote areas.…”