Theta-burst stimulation of a default mode network node modulates extended-amygdala connectivity and pre-sleep rumination
Alisa Huskey, Jungwon Cha, Lindsey L Hildebrand, Samantha Jankowski, Kymberly Henderson-Arredondo, Kathryn Kennedy, David Negelspach, Salma Imran Patel, William D. S. Killgore
SLEEP Advances October 21, 2026 DOI: 10.1093/sleepadvances/zpag116 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized crossover double-blind pilot clinical trial Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Adults with self-reported insomnia symptoms (12 women; mean age 27) |
| Topics | Default mode network |
| Key findings | Greater pre-sleep rumination was associated with stronger BNST–precuneus connectivity and weaker BNST–left frontal pole connectivity. Reductions in rumination after active cTBS were accompanied by decreased BNST–precuneus connectivity and anticorrelated BNST–right frontal pole connectivity. Stronger BNST–precuneus/posterior cingulate connectivity predicted delayed sleep onset and fewer awakenings during sham but not active cTBS, suggesting that inhibitory DMN neuromodulation may attenuate these associations. |
Abstract
Abstract Dysfunction in default mode network (DMN) connectivity plays a role in the etiology and maintenance of insomnia symptoms. Negative self-referential thinking is a perpetuating factor of insomnia that has been linked with DMN connectivity. The Bed Nucleus of the Stria Terminalis (BNST), part of the extended-amygdala pathway, facilitates cognitive and physiological hyperarousal. We hypothesized that BNST functional connectivity to DMN would promote pre-sleep rumination and delayed sleep onset and that inhibition of the DMN would attenuate this effect. In a small pilot clinical trial, adults with self-reported insomnia symptoms (N = 20; 12 women; mean age = 27) were randomized into a crossover, double-blind comparison of active continuous theta-burst (cTBS), repeated transcranial magnetic stimulation targeted to a node of the DMN (i.e., inferior parietal lobule) versus sham. At baseline, greater pre-sleep rumination severity was associated with BNST–precuneus connectivity and inversely associated with BNST–left frontal pole connectivity. Participants who exhibited greater reductions in pre-sleep rumination following active cTBS also showed decreased BNST-precuneus connectivity and anticorrelated BNST-right frontal pole connectivity. Stronger BNST–precuneus/posterior cingulate gyrus connectivity predicted delayed sleep onset latency and fewer awakenings during sham, but not active cTBS. Stronger BNST–right frontal pole anticorrelations prior to sleep predicted greater total sleep time across conditions. These results suggest that BNST connectivity with DMN nodes underlies pre-sleep rumination as well as sleep onset timing and total sleep time in insomnia. Furthermore, targeted inhibitory neuromodulation of the DMN may attenuate the effect of BNST connectivity on pre-sleep rumination.
Comparable studies
Other randomized controlled trials on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Healthy volunteers | 2012 | Within-subjects, placebo-controlled, task-free fMRI study | n = 30 |
| The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers | 2014 | Placebo-controlled study | |
| Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action Healthy subjects | 2012 | Randomized, placebo-controlled, double-blind, crossover rsfMRI challenge | |
| Antidepressants Normalize the Default Mode Network in Patients With Dysthymia Subjects with dysthymic disorder and healthy control participants aged 18 to 53 years | 2013 | Randomized controlled trial | n = 41 |
| Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis Healthy volunteers | 2012 | Within-subject, placebo-controlled experimental study | n = 15 |