Targeting replay and default mode network dynamics during rest in psychiatric disorders

Abstract

The default mode network (DMN), a hallmark of spontaneous brain activity during rest, is altered in various psychiatric disorders and linked to cognitive deficits. However, the underlying mechanisms remain unclear, and the development of targeted treatments has been challenging. Historically, resting-state research in psychiatry and task-based studies in cognitive neuroscience have progressed independently, limiting the translation of mechanistic insights into clinical practice. Recent advances in neural decoding methods, specifically those linking hippocampal replay to DMN activity during rest, have begun to bridge this gap. By probing the representations of resting brain activity in psychopathology research, we can more precisely characterise DMN-related dysfunction and uncover symptom-relevant mechanisms. These developments also lay the groundwork for targeted interventions: noninvasive neuromodulation techniques, such as transcranial focused ultrasound, can be used to test causal hypotheses and optimise therapeutic strategies. Together, these innovations offer a more integrated framework for understanding the DMN and improving psychiatric outcomes.