Specific patterns of endogenous functional connectivity are associated with harm avoidance in OCD

Abstract

BackgroundIndividuals with OCD show persistent-avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomic studies of persistent-avoidance in rodents and non-human primates, our goal was to test whether connections within a hypothesized persistent-avoidance related network predicted OCD-related harm-avoidance (HA), a trait measure of persistent-avoidance. We hypothesized that 1)HA, not OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2)HA-specific findings would be robust to comorbid symptoms; and 3)reliable findings would replicate in an holdout testing subsample. MethodsUsing resting-state fcMRI, cross-validated elastic-net for feature selection and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample(n=73;71.8% Female;nHC=36,nOCD=37); robustness to comorbidities; and replicability in a testing subsample(n=30;56.7% Female;nHC=15,nOCD=15). ResultsStronger inverse connectivity between right dorsal anterior cingulate and right basolateral-amygdala (R_dACC—R_BLA) and stronger positive connectivity between right ventral anterior insula and left ventral-striatum (R_vaIns—L_VS) were associated with greater HA across groups. Network connections did not discriminate OCD diagnosis or predict HA-correlated traits, suggesting sensitivity to trait HA. The dACC—BLA relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. ConclusionStronger inverse dACC—BLA connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent-avoidance-related network to OCD, with implications for precision-based approaches and treatment.