Targeted memory reactivation during REM sleep in patients with social anxiety disorder
Authors: Borghese F. , Henckaerts P. , Guy F. , Mayo C. , Delplanque S. , Schwartz S. , Perogamvros L. 
Published: March 2022

AbstractBackgroundSocial anxiety disorder (SAD) is an anxiety disorder characterized by a significant amount of fear when confronted to social situations and can cause considerable distress in daily life. Exposure therapy, which is based on fear extinction, is a popular and effective treatment for SAD, although it does not often lead to full remission. Here, we aimed at improving exposure therapy outcome. Specifically, based on previous research showing that rapid eye movement (REM) sleep promotes the consolidation of extinction memory, we used targeted memory reactivation (TMR) during REM sleep to enhance extinction learning.Methods48 subjects (32 women and 16 men, mean age of 24.41 ± 4.91) with moderate or severe SAD according to DSM-5 participated in our study, and were randomly assigned to one of two matched groups: control or TMR group. All patients had two successive exposure therapy sessions in a virtual reality (VR) environment, where they were asked to give a public talk in front of a virtual jury. At the end of each session, and only in the TMR group (N=24), a sound was paired to the positive feedback phase of exposure therapy (i.e. approval of their performance), and which represents the extinction memory to be strengthened during REM sleep. All participants slept at home with a wearable headband device which automatically identified sleep stages online and administered the sound several times during REM sleep. Anxiety level was assessed using measures of sympathetic (electrodermal activity component : non-specific skin conductance responses, ns-SCRs) and parasympathetic (heart rate variability component : root mean square of successive differences between normal heartbeats, RMSSD) activity, and subjective measures (Subjective Units of Distress Scale, SUDS), during the preparation phase of their virtual talks before (T1) and after (T2) one full-night’s sleep with auditory stimulation and after one week of auditory stimulation at home (T3). Participants also filled in a dream diary one week prior and one week after the day of exposure therapy.ResultsSubjective anxiety was reduced during the second and third anticipatory preparation phase of exposure, compared to the first one, for both groups (p < 0.001). RMSSD levels were lower in the TMR group compared to the control group (p=.037) during the preparation phase after 8 nights of stimulation at home (T3). No significant result between groups was observed for SUDS and the ns-SCRs at T3. Importantly, the longer REM sleep and the more stimulations the TMR group (but not the control group) had at home, the less anxious (increased RMSSD) these participants were. Finally, fear in dreams correlated positively with measures of stress (ns-SCRs and SUDS) in this group.ConclusionsTMR during REM sleep did not modulate the beneficial effect of exposure therapy on anxiety-related distress (SUDS). Yet, our results support that REM sleep can contribute to extinction processes and substantiate strong links between emotional experiences in dreams and waking stress levels in these patients.