Theta-burst stimulation of a default mode network node modulates extended-amygdala connectivity and pre-sleep rumination

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ID: 333225
2026
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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.
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Authors Alisa Huskey, Jungwon Cha, Lindsey L. Hildebrand, Samantha E. Jankowski, Kymberly Henderson-Arredondo, Kathryn E. R. Kennedy, David Negelspach, Salma Imran Patel, William D. S. Killgore
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Journal SLEEP Advances
Year 2026
DOI
10.1093/sleepadvances/zpag116
URL
https://doi.org/10.1093/sleepadvances/zpag116
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