Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep

  • participants needed
  • sponsor
    University of Arizona
Updated on 2 October 2022
primary insomnia


Insomnia is generally believed to be caused by excessive arousal of the brain and body. Rather than transitioning normally and quickly from wakefulness to sleep, individuals with insomnia tend to enter into a self-perpetuating cycle of self-referential thought and arousal. Brain imaging research has shown that these same internally focused self-reflective thoughts tend to activate a core system in the brain known as the Default Mode Network (DMN). The DMN is usually active when a person is internally focused, such as during daydreaming or mind wandering, but tends to be deactivated when the brain is focused on the external environment. The investigators hypothesize that excess activation and connectivity of this brain network may perpetuate internal conversations, worry, and rumination, preventing individuals with insomnia from falling asleep quickly and remaining asleep. Therefore, the goal of the present study is to use a brain stimulation technique known as transcranial magnetic stimulation (TMS) to target the DMN and slightly reduce its activation before bed. This should result in an easier time falling asleep.

For this study, the investigators will recruit 20 healthy individuals and have them sleep in the lab on two occasions. On one occasion, they will be stimulated with a type of TMS called continuous theta burst stimulation (cTBS), which will be targeted toward their DMN. They will then try to sleep in the lab while the investigators record their brain waves using a technique known as polysomnography (PSG). On the other occasion, these same individuals will undergo the same procedure, but the TMS machine will be in a deactivated mode to present a "sham" stimulation. Participants will again try to sleep in the lab following the sham treatment while being recorded with PSG. Neither the participants nor the experimenters will know which condition the participant is receiving at the time. This will only be revealed later. Additionally, all participants will receive a brain scan just before and just after the TMS procedures so that the investigators can examine changes in brain connectivity and chemistry. The investigators expect that the participants will sleep better following the cTBS than following the sham condition and that this will be associated with measurable differences in their brain connectivity and brain chemistry.

If effective, this project would have identified an innovative and novel approach for improving sleep without using drugs.


Individuals with psychophysiological insomnia show greater waking functional connectivity within the DMN compared to healthy individuals. It has been postulated that excessive activation and connectivity of the DMN may be associated with ruminative thinking and internally generated arousal, which makes it difficult to fall asleep.

Primary Objective. The overall objective of this proposal is to temporarily alter the strength of connectivity within the DMN using cTBS before sleep and determine the effects on subsequent sleep. This project is expected to yield robust preliminary data that would allow more extensive research, including a larger follow-on clinical trial to determine the effectiveness of this approach for improving sleep difficulties in military personnel.

The objective of this project will be accomplished through the following Specific Aim:

Specific Aim 1: Determine the effects of cTBS targeted to the DMN on sleep quality, brain neurochemistry, functional connectivity, and next-day cognitive performance.

The investigators' working hypothesis is that relative to sham treatment, cTBS will suppress neural activity within the DMN, leading to improvements in polysomnographically (PSG) measured sleep parameters, and this will be associated with neurochemistry changes and functional connectivity in the DMN, and will improve next day cognitive performance.

Upon completion of this Specific Aim, the expected outcome is to have determined the effects of cTBS on sleep quality, timing, and duration, and identified the brain systems and neurochemistry profiles associated with this change. If successful, this would represent proof-of-concept of a potentially safe non-pharmacologic method to facilitate sleep, and this information could form the basis for follow-on research to refine and further validate this technique to potentially optimize sleep under a variety of militarily-relevant situations.

Insomnia is reported as the most common sleep disorder. It can range in severity, but the most common symptom is difficulty maintaining sleep. Other manifestations of insomnia include early-morning awakenings, and difficulty falling asleep. According to other research, its prevalence is 10 to 15% depending on diagnostic criteria. Roughly 50% of people reporting insomnia have more severe symptoms that meet the criteria for insomnia disorder. Insomnia is conceptualized as a disorder of nocturnal and daytime hyperarousal. This state of arousal is both a cause and a consequence of insomnia. Insomnia causes symptoms that effect people on a cognitive, emotional, and physiological level. People with insomnia often report the feeling of excessive worrying, racing thoughts, and selective attention. Physiologically, insomnia is associated with increased whole-body metabolic rate, increased cortisol levels, increased blood pressure, and elevated brain glucose consumption during both waking and sleeping states. The stressors of chronic insomnia are also associated with an increased risk of developing psychological disorders such as depression and anxiety disorders.

A large number of military personnel report significant sleep difficulties or chronic sleep restriction. In fact, about 42% of military personnel regularly obtain five hours of sleep or less per night, a level that is insufficient to sustain optimal alertness, vigilance, and decision-making. It has been reported that up to 85% of military Service members meet the criteria for a clinically relevant sleep disorder, with approximately 25% having a primary complaint of insomnia (i.e., difficulty falling or staying asleep). Pharmacologic sleep medications may be effective in some situations, but may also be contraindicated in operational environments where alertness is integral. Because sleep problems are among the top complaints of military personnel and can have profound impacts on force readiness, it is imperative that novel approaches to minimizing insomnia and sleep problems be developed.

TMS is a brain stimulation technique which poses far fewer safety risks and adverse experiences than its predecessor, electroconvulsive therapy. TMS has been Food and Drug Administration (FDA)-approved and found effective for use in cases of treatment resistant depression, but has also been utilized off-label to treat OCD and other psychiatric disorders. TMS has demonstrated superior efficacy in the treatment of primary insomnia than both typical medication or psychotherapy treatments. In addition, TMS of the right parietal lobe was shown to be effective for alleviating symptoms of comorbid anxiety and insomnia.

In lay terms, TMS works by targeting electromagnetic fields at particular brain areas from outside of the body. These electromagnetic fields create a current in the brain via the electrochemical firing of brain cells (neurons). This process can influence the function of the targeted brain areas by either facilitating or impairing functional connectivity in a particular network of interconnected brain regions, such as the network associated with daydreaming and self-referential thought (DMN).

The form of TMS to be utilized in present study, continuous theta burst (cTBS), allows for the induction of temporary inhibition of cortical activity using a much shorter length of stimulation as compared to rTMS (repetitive transcranial magnetic stimulation). This protocol was selected for its ability to inhibit, rather than stimulate, activity in the DMN. Prior research using cTBS has shown that this technique can safely and temporarily impair function and connectivity in targeted brain areas. Therefore, the investigators hypothesize that a mild disruption of DMN activation using cTBS prior to sleep will facilitate sleep onset among individuals meeting criteria for primary insomnia, and the investigators further propose that this change will be associated with measurable changes in DMN connectivity and neurochemistry. To test this hypothesis, the investigators will stimulate a node of the DMN approximately two hours before bedtime using cTBS in order to reduce activation and connectivity within the stimulated regions.

Condition Insomnia
Treatment Sham cTBS, Active cTBS
Clinical Study IdentifierNCT04953559
SponsorUniversity of Arizona
Last Modified on2 October 2022

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