Cortico-Striatal Activity Characterizes Human Safety Learning via Pavlovian Conditioned Inhibition.

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviors. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (7 Tesla) fMRI to examine the neural basis of safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation (PFDR whole-brain corrected). The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular, and dorsolateral PFC compared with the standard safety signal, whereas the latter evoked greater activation of the ventromedial PFC, posterior cingulate, and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, midbrain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS-). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of "stimulus-safety" associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning.SIGNIFICANCE STATEMENT Identifying safety is critical for maintaining adaptive levels of anxiety, but the neural mechanisms of human safety learning remain unclear. Using 7 Tesla fMRI, we compared learning-related brain activity for a conditioned inhibitor, which actively predicted threat omission, and a standard safety signal (CS-), which was passively unpaired with threat. The inhibitor engaged an extended circuitry primarily featuring the dorsal striatum, along with thalamic, midbrain, and premotor/PFC regions. The CS- exclusively involved cortical safety-related regions observed in basic safety conditioning, such as the vmPFC. These findings extend current models to include learning-specific mechanisms for encoding stimulus-safety associations, which might be distinguished from expression-related cortical mechanisms. These insights may suggest novel avenues for targeting dysfunctional safety learning in psychopathology.

Prevalence and heritability of compulsive hoarding: a twin study.

OBJECTIVE: Compulsive hoarding is a serious health problem for the sufferers, their families, and the community at large. It appears to be highly prevalent and to run in families. However, this familiality could be due to genetic or environmental factors. This study examined the prevalence and heritability of compulsive hoarding in a large sample of twins. METHOD: A total of 5,022 twins completed a validated measure of compulsive hoarding. The prevalence of severe hoarding was determined using empirically derived cutoffs. Genetic and environmental influences on compulsive hoarding were estimated using liability threshold models, and maximum-likelihood univariate model-fitting analyses were employed to decompose the variance in the liability to compulsive hoarding into additive genetic and shared and nonshared environmental factors (female twins only; N=4,355). RESULTS: A total of 2.3% of twins met criteria for caseness, with significantly higher rates observed for male (4.1%) than for female (2.1%) twins. Model-fitting analyses in female twins showed that genetic factors accounted for approximately 50% of the variance in compulsive hoarding, with nonshared environmental factors and measurement error accounting for the other half. CONCLUSIONS: Compulsive hoarding is highly prevalent and heritable, at least in women, with nonshared environmental factors also likely to play an important role.