Circuit-informed modulation of traumatic memory in PTSD: integrating extinction, suppression, and reconsolidation.

Post-traumatic stress disorder persists when stress biases memory systems, broadening threat engrams and weakening context-appropriate inhibition. Integrating preclinical and human evidence, the authors argue that extinction can be stabilized by engaging hippocampal-prefrontal-amygdala pathways and their thalamic coordinators. Targeted training and sleep-based reactivation strengthen top-down control over intrusions and sharpen safety-threat discrimination. Brief, prediction-error-rich retrieval opens a reconsolidation window through which maladaptive content can be updated; pairing this with state-aligned neuromodulation or psychedelic pharmacology biases plasticity toward safety. Integrating extinction reinforcement with voluntary memory control and reconsolidation editing offers a coherent route to more durable relief from traumatic memories in PTSD.

Study at a glance

Abstract

Post-traumatic stress disorder (PTSD) persists when stress biases memory systems-broadening threat engrams, weakening context-appropriate inhibition, and rendering extinction fragile. Integrating preclinical and human evidence, we argue that these liabilities are tractable within a circuit-informed framework that aligns behavioral procedures with the biology of fear memory. Extinction can be stabilized by preferentially engaging hippocampal-prefrontal-amygdala pathways and their thalamic coordinators; targeted training and sleep-based reactivation strengthen top-down control over intrusions and sharpen discrimination between safety and threat. Brief, prediction-error-rich retrieval opens a reconsolidation window through which maladaptive content can be updated; pairing this window with state-aligned neuromodulation or phase-specific psychedelic pharmacology biases plasticity toward safety without relying on nonspecific anxiolysis. Framed this way, integrating extinction reinforcement with voluntary memory control and reconsolidation editing offers a coherent route to more durable relief from traumatic memories in PTSD.