0433 Suppression of the Default Mode Network Affects the Arousal and Reduces Time in Non-Restorative Sleep

Abstract Introduction We recently demonstrated that continuous theta burst stimulation (cTBS), a form of suppressive transcranial magnetic stimulation (TMS), was effective at improving total sleep time, sleep efficiency and arousal index scores in people with symptoms of insomnia (Killgore, 2023, zsad077.0332). We now present additional analyses on the effects of this stimulation on functional brain activation during a complex cognitive task (multi-source interference task; MSIT) that targets the cingulo-frontal-parietal cognitive/attention network and its correlations with overnight polysomnography (PSG). Methods Nineteen people (11 females) with moderately severe symptoms of insomnia (age=27.2 SD=6.6), underwent active or sham cTBS followed by an overnight PSG monitored sleep study on two counterbalanced occasions separated by at least a week. Immediately before and after each cTBS/sham stimulation, participants completed functional MRI scans that included the MSIT. Contrasts were created between the more difficult interference condition and the simple control condition and task activation changes were compared across time and treatment condition using paired t-tests, repeated measures ANOVA, and within-condition Pearson’s correlations. Results A paired t-test of the primary task contrast (interference>control) maps showed a significant decline from pre- to post-treatment in a region of the supplementary motor area (SMA) for the active cTBS (p< 0.001, FWE corrected), but no change for the sham condition, as evidenced by a significant time x treatment interaction (p=.004). Moreover, for the sham condition, activation of this region was correlated with more time in wake/non-restorative sleep (i.e., wake, N1, N2, awakenings, and arousal index, all p-values<.05), while for the active cTBS, changes in activation within this region were no longer associated with indices of poor sleep. Conclusion Building on our previously reported finding that cTBS reduced arousal and improved sleep time, this analysis suggests that activity within the SMA may play a role in mediating the insomnia-related symptoms with respect to arousal. Under sham conditions, increased activity of the SMA was associated with increased awakenings and arousal index. This disruptive effect appears to be eliminated by cTBS to the DMN. This result raises the possibility that insomnia symptoms may be partially mediated through the interactions between DMN and cognitive-attention networks. Support (if any) USAMRAA: W81XWH2010173