Overnight therapy: harnessing memory replay in sleep to combat depression and PTSD

In this project, we will develop an early intervention to combat burgeoning depression and PTSD through manipulation of brain activity in sleep. Memories reactivate spontaneously during sleep, and this alters neural representations. Such reactivation can be controlled via ‘targeted memory reactivation’ (TMR), in which a sound is linked to a target memory during wake, then used to trigger reactivation in sleep. TMR of negative memories during rapid eye movement sleep (REM) leads them to be rated as less upsetting, and to elicit reduced responses in the brain’s arousal system. TMR in non-rapid eye movement sleep (NREM) reliably strengthens memories. We will therefore use negative REM TMR to disarm toxic autobiographical memories and positive NREM TMR to disrupt depressive rumination and improve mood. We will first optimise these two interventions in healthy controls, determining the ideal circadian phase for stimulation and characterising any impact it has on mood and on brain structure or function. We will then work with lived-experience experts to bring our interventions to people recently diagnosed with PTSD or depression in proof of concept and feasibility trials. To ensure these interventions will work irrespective of societal factors we will work hand in hand with colleagues in Colombia.