Vagally Mediated Heart Rate Variability During REM Sleep is Associated with Retention of Fear Extinction in Generalized Anxiety Disorder

Abstract

Fear extinction processes are central to the pathology and treatment of anxiety disorders. Emerging evidence implicates rapid eye movement (REM) sleep in the consolidation of extinction memory. Separately, converging theory and empirical work suggest that vagally mediated heart rate variability (VmHRV) serves as a peripheral index of cortico-subcortical regulatory capacity relevant to extinction circuitry. On this basis, we tested the hypothesis that VmHRV during REM sleep would be associated with the retention of extinction memory in individuals with generalized anxiety disorder (GAD). Participants underwent a validated two-day fear conditioning and extinction paradigm. Subjective extinction retention (sERI) was quantified during a recall test 24 hours after learning and ambulatory polysomnography was recorded on the intervening night. As hypothesized, higher REM VmHRV was significantly associated with better extinction retention. This association remained robust after controlling psychotropic medication use and REM density. In contrast, VmHRV during SWS or wakefulness, as well as other REM sleep measures, were not associated with extinction retention. These findings identify REM VmHRV as a significant predictor of extinction memory retention in GAD, extending prior findings in trauma-exposed individuals. We propose that reduced vagal tone indexes compromised prefrontal inhibitory control over amygdala and noradrenergic circuits, thereby impairing REM sleep-dependent consolidation. These results position VmHRV during REM sleep as a potential transdiagnostic biomarker of extinction memory processing and suggest that interventions enhancing vagal tone could improve treatment outcomes in anxiety disorders.