REM sleep fragmentation is associated with impaired configural threat learning.

Rapid eye movement (REM) phases of sleep are consistently disrupted after trauma and in post-traumatic stress disorder (PTSD). REM disruption impairs cued fear learning, a core element of trauma processing linked to PTSD risk and symptom persistence. Configural threat learning depends on the hippocampus and may be influenced by REM sleep, though its role in humans remains unclear. Here, 55 healthy participants were randomly assigned to REM sleep fragmentation or a control group without sleep disruption for two nights. On the final day, participants completed a configural threat learning task while electrodermal activity (EDA) and behavioral threat expectancy ratings were recorded. REM fragmentation group (REM frag group) had significantly lower threat responses as measured by EDA to the threat configuration relative to the control group. Relative to the REM frag group, the control group showed a significantly greater increase in threat discrimination from the first to the second block of learning. Polysomnography revealed that weighted REM efficiency, but not slow wave sleep or total sleep time, was significantly associated with configural threat learning. REM sleep fragmentation did not affect mnemonic pattern separation, a non-threat measure of hippocampal learning. These results provide evidence that REM sleep is a critical component of configural threat. These findings set the stage for future investigations into how REM sleep disruptions may impair the neural processes supporting threat generalization and discrimination in PTSD, with implications for targeted sleep-based interventions aimed at modulating trauma-related learning and memory.