Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits

Abstract

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients' scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

Keywords: Compulsivity; DCM; Disinhibition; GD; Impulsivity; OCD.

Figure 1

Effective connectivity between regions in cortical-striatal-thalamic-cortical (CSTC) circuits covaries with individual differences in disinhibition, compulsivity, and impulsivity. Left, (A) brain regions in the left hemisphere (i.e., search volumes for subject-specific DCM ROIs) and (B) wiring diagram representing the model that was specified. Solid lines represent connectivity between regions. Arrow heads depict direction of connection. Dashed lines represent inhibitory self-connections. Right, effects of phenotypes (C, D, and E) and clinical severity (F) on effective connectivity within CSTC circuits in the left hemisphere as assessed using parametric empirical Bayes. Effective connectivity parameters are described in Hz (right panel, bold numbers), where the activity in one node influences the rate of change in the activity in another. Self-connections are (log)scaled. In both cases, the interpretaion is the same, with increasing scores on a given phenotype the effective connectivity between, or the inhibitory activity within, node connectivity decreases/increases as specified. The DCM ROIs have each been labeled according to which subregions of their respective anatomical ROI they were localized to during DCM ROI generation (see method and supplementary results for details). daCC = dorsal anterior cingulate cortex, vaCC = ventral anterior cingulate cortex, miOFC = middle orbitofrontal cortex, meOFC = medial orbitofrontal cortex, aThal = anterior thalamus, pThal = posterior thalamus, dlPFC = dorsolateral prefrontal cortex, DS = dorsal striatum, VS = ventral striatum.