The paraventricular nucleus of the thalamus differentiates threat and safety cues during delayed recall in humans.

Abstract

The neural mechanisms supporting delayed threat memory recall in humans remain poorly understood. Animal studies indicate that the paraventricular nucleus of the thalamus (PVT) contributes to threat-memory retrieval after longer retention intervals, but whether the human PVT shows cue-related discriminability during delayed recall remains unclear. Human neuroimaging studies of threat learning have largely focused on memory assessed within 24-48 h, limiting insight into neural responses when previously threatening cues are re-encountered after longer delays. Here, adult participants completed threat acquisition on Day 1 and returned 7-10 days later (n = 28) for a delayed threat-memory recall task while undergoing fMRI. We examined activity in the dorsal midline thalamus centered on a histology-informed PVT region of interest. During Day 1 acquisition, the PVT did not discriminate between CS+ and CS-, despite differential electrodermal activity (EDA) and unconditioned stimulus expectancy ratings. In contrast, during early Day 7 recall, the PVT showed greater activation to previously reinforced CS+ than CS-. In an independent sample (n = 56), PVT activity similarly did not discriminate between CS+ and CS- during acquisition or immediate extinction, but overall PVT activation was greater during acquisition than extinction, regardless of CS type. These findings provide preliminary evidence that a human PVT-centered dorsal midline thalamic region is sensitive to prior threat reinforcement during delayed recall, while also showing engagement during acute threat-learning contexts. More broadly, they support future investigation of PVT-centered thalamic circuitry in the persistence, retrieval, and updating of threat memories, as well as in salience-related processes.