Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep in Individuals With Insomnia Symptoms: Protocol for a Double-Blind Randomized Controlled Trial.

BACKGROUND: Cortical hyperarousal and ruminative thinking are common aspects of insomnia that have been linked with greater connectivity in the default mode network (DMN). Therefore, disrupting network activity within the DMN may reduce cortical and cognitive hyperarousal and facilitate better sleep. OBJECTIVE: This trial aims to establish a novel, noninvasive method for treating insomnia through disruption of the DMN with repetitive transcranial magnetic stimulation, specifically with continuous theta burst stimulation (cTBS). This double-blind, pilot randomized controlled trial will assess the efficacy of repetitive transcranial magnetic stimulation as a novel, nonpharmacological approach to improve sleep through disruption of the DMN prior to sleep onset for individuals with insomnia. Primary outcome measures will include assessing changes in DMN functional connectivity before and after stimulation. METHODS: A total of 20 participants between the ages of 18 to 50 years with reported sleep disturbances will be recruited as a part of the study. Participants will then conduct an in-person screening and follow-on enrollment visit. Eligible participants then conduct at-home actigraphic collection until their first in-residence overnight study visit. In a double-blind, counterbalanced, crossover study design, participants will receive a 40-second stimulation to the left inferior parietal lobule of the DMN during 2 separate overnight in-residence visits. Participants are randomized to the order in which they receive the active stimulation and sham stimulation. Study participants will undergo a prestimulation functional magnetic resonance imaging scan and a poststimulation functional magnetic resonance imaging scan prior to sleep for each overnight study visit. Sleep outcomes will be measured using clinical polysomnography. After their first in-residence study visit, participants conduct another at-home actigraphic collection before returning for their second in-residence overnight study visit. RESULTS: Our study was funded in September 2020 by the Department of Defense (W81XWH2010173). We completed the enrollment of our target study population in the October 2022 and are currently working on neuroimaging processing and analysis. We aim to publish the results of our study by 2024. Primary neuroimaging outcome measures will be tested using independent components analysis, seed-to-voxel analyses, and region of interest to region of interest analyses. A repeated measures analysis of covariance (ANCOVA) will be used to assess the effects of active and sham stimulation on sleep variables. Additionally, we will correlate changes in functional connectivity to polysomnography-graded sleep. CONCLUSIONS: The presently proposed cTBS protocol is aimed at establishing the initial research outcomes of the effects of a single burst of cTBS on disrupting the network connectivity of the DMN to improve sleep. If effective, future work could determine the most effective stimulation sites and administration schedules to optimize this potential intervention for sleep problems. TRIAL REGISTRATION: ClinicalTrials.gov NCT04953559; https://clinicaltrials.gov/ct2/show/NCT04953559. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51212.

Functional connectivity of the default mode network predicts subsequent polysomnographically measured sleep in people with symptoms of insomnia.

Insomnia is often accompanied by excessive pre-sleep rumination. Such ruminative thinking is also associated with increased connectivity of the default mode network (DMN). It is likely that DMN connectivity and associated rumination contribute to the pathogenesis of insomnia. We hypothesized that resting state functional connectivity (rsFC) between the DMN and other brain regions prior to bedtime would predict objectively measured sleep among individuals with insomnia. Twenty participants (12 female; M age = 26.9, SD = 6.6 years) with symptoms of insomnia underwent an rsFC scan in the early evening followed by a night of polysomographically (PSG) measured sleep. Connectivity of the DMN with other brain regions was regressed against several PSG sleep metrics, including time in wake, N1, N2, N3, REM, total sleep time (TST), and sleep efficiency (SE) at a cluster corrected false discovery rate (FDR) correction P < 0.05. The connectivity between DMN and cortical regions was negatively correlated with PSG indices of poorer sleep including time in wake (right angular gyrus) and N1 (precuneus) but positively correlated with time in REM (orbitofrontal cortex), TST (insula, orbitofrontal cortex, superior frontal gyrus, paracingulate gyrus), SE (orbitofrontal cortex). Connectivity between DMN and the pons was negatively correlated with SE. Among individuals with symptoms of insomnia, better sleep was predicted by rsFC between the DMN and cortical regions involved in executive functioning, consciousness, and complex cognition. Findings raise the possibility that future interventions aimed at suppressing pre-sleep DMN activation may weaken synergy between pre-sleep ruminative worry and complex cognitions, potentially ameliorating problems falling asleep.