Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 8
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Healthy men and non-pregnant, non-lactating women 18-50 (inclusive) years of age, free from contraindicated diseases, medications, devices, and conditions.
- •Participants must meet the criteria for primary insomnia as determined by scores on the ISI, PSQI, and ESS. Participants must obtain two out of three of the following required scores for each questionnaire:
- •Greater than or equal to 15 for ISI (Gagnon, Belanger, Ivers, & Morin, 2013)
- •Greater than or equal to 6 for PSQI (Buysse et al 1989)
- •Greater than or equal to 11 for ESS (Johns, 2000)
排除标准
- •Presence of any metal implant or medical device which may pose a safety risk for MRI or TMS (see below for examples)
- •Cardiac pacemakers
- •Metal clips on blood vessels (also called stents)
- •Artificial heart valves
- •Artificial arms, hands, legs, etc.
- •Brain stimulator devices
- •Implanted drug pumps
- •Ear implants
- •Eye implants or known metal fragments in eyes
- •Exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others)
- •Other metallic surgical hardware in vital areas
- •Certain tattoos with metallic ink
- •Certain transdermal (skin) patches such as NicoDerm (nicotine for tobacco dependence), Transderm Scop (scopolamine for motion sickness), or Ortho Evra (birth control)
- •Past or present history of sleep or breathing-related disorders such as sleep apnea (exclusion upon obtaining a score of 3 or higher on the STOP-BANG questionnaire)
- •Travel outside the time zone within the two weeks prior to enrollment visit and at any point while active in the study
- •Self-reported major medical problems including past or present history of heart problems and/or neurological problems (to include but not limited to heart murmur, heart attack, TBI, stroke, tumor, epilepsy or another seizure disorder)
- •Self-reported past or present history of cardiovascular disease (to include but not limited to arrhythmias, valvular heart disease, congestive heart failure, history of sudden cardiac death or myocardial infarction)
- •Self-reported past or present history of neurological disorder (to include but not limited to traumatic brain injury including concussions, strokes, tumors, epilepsy or another seizure disorder, amnesia for any reason, hydrocephalus, multiple sclerosis)
- •Self-reported past or present history of any seizures or seizure disorders
- •Self-reported first-degree family history (like a mother, father, or sibling) of a seizure or seizure disorder
- •Self-reported underlying acute or chronic pulmonary disease requiring daily inhaler use
- •Self-reported history of fainting spells or syncope
- •Self-reported past (at any point in the participant's history) or present psychiatric problems not including depression and/or anxiety disorders (to include but not limited to bipolar, mania, ADHD, or psychotic disorders)
- •Self-reported history of depression and/or anxiety disorders within the past 2 years
- •Self-reported suicidal ideation as indicated by a score equal to or greater than 2 on the BDI
- •Self-reported current use of certain prescription medications including Ambien, benzodiazepines, stimulants (amphetamines, medication for narcolepsy), antidepressants (SSRIs, SNRIs), antipsychotics, blood pressure medications, thyroid medications.
- •Self-reported current use of supplements that may affect sleep (to include but not limited to melatonin, valerian root, kava root)
- •Self-reported caffeine use in excess of 300 mg (e.g., approximately 8 caffeinated sodas or approximately 3-4 12-oz cups of coffee) per day on average
- •Self-reported or suspected regular nicotine use (or addiction) (defined as more than 1 cigarette or equivalent per week within the last 1 year)
- •Self-reported or suspected heavy alcohol use (minimum limit to define heavy alcohol use is 14 drinks per week)
- •Self-reported or suspected use of illicit drugs (to include but not limited to benzodiazepines, amphetamines, cocaine, opioids)
- •(Females only) Positive urine pregnancy result (Urine HCG Test results)
- •(Females only) Self-reported or suspected current breast-feeding or collecting breast-milk
- •Learned English past age 3
- •Speaking English as a non-primary language
- •Less than 9th grade education
- •Unusual sleep schedules in past six months
- •Overnight shift work
- •Inability to read and sign consent
- •Failure to cooperate with requirements of the study
结局指标
主要结局
Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 8
时间窗: Once during Overnight Visit 1 post-TMS MRI scan session (day 8)
Measure neurochemistry in anterior cingulate and occipitoparietal cortex using spectroscopy during MRI scan
Sleep onset latency (SOL) following administration of active or sham cTBS TMS
时间窗: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)
Sleep period polysomnographic (PSG) measurement day 15
Total sleep time (TST) following administration of active or sham cTBS TMS - day 15-16
时间窗: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)
Sleep period polysomnographic (PSG) measurement
Percentage of time spent in each sleep stage following administration of active or sham cTBS TMS
时间窗: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)
Sleep period polysomnographic (PSG) measurement (percentage of time) day 15
Total sleep time (TST) following administration of active or sham cTBS TMS - day 8-9
时间窗: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9)
Sleep period polysomnographic (PSG) measurement
Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 15
时间窗: Once during Overnight 2 post-TMS MRI scan session (day 15)
Measure neurochemistry in anterior cingulate and occipitoparietal cortex using spectroscopy during MRI scan
Wake after sleep onset (WASO) following administration of active or sham cTBS TMS - day 15-16
时间窗: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)
Sleep period polysomnographic (PSG) measurement
Sleep onset latency (SOL) following administration of active or sham cTBS TMS - day 8
时间窗: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9)
Sleep period polysomnographic (PSG) measurement
Wake after sleep onset (WASO) following administration of active or sham cTBS TMS - day 8-9
时间窗: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9)
Sleep period polysomnographic (PSG) measurement
Sleep efficiency (SE) following administration of active or sham cTBS TMS - day 8-9
时间窗: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)
Sleep period polysomnographic (PSG) measurement
Time spent in each sleep stage following administration of active or sham cTBS TMS
时间窗: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)
Sleep period polysomnographic (PSG) measurement (time) day 15
次要结局
- Karolinska Sleepiness Scale (KSS) - day 8, admin 1(Once during cognitive testing portion of Overnight Visit 1 (day 8-9), day 8)
- Karolinska Sleepiness Scale (KSS) - day 9, admin 4(Once during cognitive testing portion of Overnight Visit 1 (day 8-9), day 9)
- Karolinska Sleepiness Scale (KSS) - day 9, admin 6(Approximately one hour after previous administration (2 hours after initial) during cognitive testing portion of Overnight Visit 1 (day 8-9), day 9)
- Karolinska Sleepiness Scale (KSS) - day 15, admin 3(Approximately one hour after previous administration (2 hours after initial) during cognitive testing portion of Overnight Visit 2 (day 15-16), day 15)
- Karolinska Sleepiness Scale (KSS) - day 8, admin 3(Approximately one hour after previous administration (2 hours after initial) during cognitive testing portion of Overnight Visit 1 (day 8-9), day 8)
- Karolinska Sleepiness Scale (KSS) - day 16, admin 6(Approximately one hour after previous administration (2 hours after initial) during cognitive testing portion of Overnight Visit 2 (day 15-16), day 16)
- Psychomotor Vigilance Tests (PVT) - day 1, admin 1 (mean RT)(Once during cognitive testing on Enrollment day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 1, admin 2 (mean RT)(Approximately one hour after previous administration during cognitive testing on Enrollment day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 1, admin 2 (Lapses)(Approximately one hour after previous administration during cognitive testing on Enrollment day (day 1))
- Karolinska Sleepiness Scale (KSS) - day 8, admin 2(Approximately one hour after previous administration during cognitive testing portion of Overnight Visit 1 (day 8-9), day 8)
- Karolinska Sleepiness Scale (KSS) - day 15, admin 2(Approximately one hour after previous administration during cognitive testing portion of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 8, admin 3 (mean Speed)(Once during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 9 (Lapses)(Once during cognitive testing of Overnight Visit 2 (day 15))
- Psychomotor Vigilance Tests (PVT) - day 8, admin 4 (mean RT)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Karolinska Sleepiness Scale (KSS) - day 9, admin 5(Approximately one hour after previous administration during cognitive testing portion of Overnight Visit 1 (day 8-9), day 9)
- Karolinska Sleepiness Scale (KSS) - day 15, admin 1(Once during cognitive testing portion of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 1, admin 1 (Lapses)(Once during cognitive testing on Enrollment day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 8, admin 3 (Lapses)(Once during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 8, admin 4 (mean Speed)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 10 (mean RT)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 2 (day 15-16), day 15)
- Karolinska Sleepiness Scale (KSS) - day 16, admin 4(Once during cognitive testing portion of Overnight Visit 2 (day 15-16), day 16)
- Karolinska Sleepiness Scale (KSS) - day 16, admin 5(Approximately one hour after previous administration during cognitive testing portion of Overnight Visit 2 (day 15-16), day 16)
- Psychomotor Vigilance Tests (PVT) - day 1, admin 1 (mean Speed)(Once during cognitive testing on Enrollment day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 1, admin 2 (mean Speed)(Approximately one hour after previous administration during cognitive testing on Enrollment day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 8, admin 3 (mean RT)(Once during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 10 (mean Speed)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 6 (Lapses)(Once during cognitive testing during Overnight Visit 1 (day 8-9), day 9)
- Spielberger State-Trait Anxiety Inventory - State (STAI-S) - day 15(During cognitive testing portion of Overnight Visit 2 (day 15))
- Psychomotor Vigilance Tests (PVT) - day 15, admin 9 (mean RT)(Once during cognitive testing of Overnight Visit 2 (day 15))
- Psychomotor Vigilance Tests (PVT) - day 15, admin 9 (mean Speed)(Once during cognitive testing of Overnight Visit 2 (day 15))
- Psychomotor Vigilance Tests (PVT) - day 8, admin 4 (Lapses)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 8, admin 5 (Lapses)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 6 (mean RT)(Once during cognitive testing during Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 6 (mean Speed)(Once during cognitive testing during Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 16, admin 12 (Lapses)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 2 (day 15-16), day 16)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 7 (mean Speed)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 7 (mean RT)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 8 (Lapses)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 10 (Lapses)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 11 (mean Speed)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 16, admin 12 (mean RT)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 2 (day 15-16), day 16)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 8 (mean Speed)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 16, admin 13 (Lapses)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 2 (day 15-16), day 16)
- Spielberger State-Trait Anxiety Inventory - State (STAI-S) - day 1(During cognitive testing portion of Enrollment Day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 8, admin 5 (mean RT)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 8, admin 5 (mean Speed)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 1 (day 8-9), day 8)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 11 (mean RT)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 15, admin 11 (Lapses)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 2 (day 15-16), day 15)
- Psychomotor Vigilance Tests (PVT) - day 16, admin 12 (mean Speed)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 2 (day 15-16), day 16)
- Psychomotor Vigilance Tests (PVT) - day 16, admin 13 (mean RT)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 2 (day 15-16), day 16)
- Spielberger State-Trait Anxiety Inventory - State (STAI-S) - day 8(During cognitive testing portion of Overnight Visit 1 (day 8))
- Glasgow Content of Thoughts Inventory (GCTI) - day 1(During cognitive testing portion of Enrollment Day (day 1))
- Psychomotor Vigilance Tests (PVT) - day 9, admin 7 (Lapses)(Approximately one hour after previous administration during cognitive testing of Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 9, admin 8 (mean RT)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 1 (day 8-9), day 9)
- Psychomotor Vigilance Tests (PVT) - day 16, admin 13 (mean Speed)(Approximately one hour after previous administration (2 hours after initial) during cognitive testing of Overnight Visit 2 (day 15-16), day 16)
- Glasgow Content of Thoughts Inventory (GCTI) - day 8(During cognitive testing portion of Overnight Visit 1 (day 8))
- California Verbal Learning Test Third Edition (CVLT-3) - day 15-16(Learn the list and recall the list once during Overnight Visit 2 (day 15-16))
- Repeatable Battery for Neuropsychological Status (RBANS) - Attention Digit Span - day 9, admin 2(During the morning cognitive testing on Overnight Visit 1 (day 9))
- Visual Analog Mood Scale (VAMS) - day 8, admin 1(During evening of Overnight Visit 1 (day 8))
- Repeatable Battery for Neuropsychological Status (RBANS) - Attention Digit Span - day 15, admin 1(During the evening cognitive testing on Overnight Visit 2 (day 15))
- Repeatable Battery for Neuropsychological Status (RBANS) - Delayed Memory Story Recall - day 9, admin 2(During the morning cognitive testing on Overnight Visit 1 (day 9))
- Actigraphy(Throughout the entire study, except during MRI and TMS administration - up to 14 days)
- Glasgow Content of Thoughts Inventory (GCTI) - day 15(During cognitive testing portion of Overnight Visit 2 (day 15))
- Repeatable Battery for Neuropsychological Status (RBANS) - Attention Digit Span - day 16, admin 2(During the morning cognitive testing on Overnight Visit 2 (day 16))
- Repeatable Battery for Neuropsychological Status (RBANS) - Story Memory Recall - day 15(During the evening cognitive testing on Overnight Visit 2 (day 15))
- Repeatable Battery for Neuropsychological Status (RBANS) - Symbol-Digit Test - day 8, admin 1(During the evening cognitive testing on Overnight Visit 1 (day 8))
- Visual Attention Task (VAT) - day 8, admin 2(Once during post-TMS MRI scan on evening of Overnight Visit 1 (day 8))
- Visual Attention Task (VAT) - day 15, admin 2(Once during post-TMS MRI scan on evening of Overnight Visit 2 (day 15))
- Visual Analog Mood Scale (VAMS) - day 9, admin 2(During morning of Overnight Visit 1 (day 9))
- Visual Analog Mood Scale (VAMS) - day 16, admin 2(During morning of Overnight Visit 2 (day 16))
- California Verbal Learning Test Third Edition (CVLT-3) - day 8-9(Learn the list and recall the list once during Overnight Visit 1 (day 8-9))
- Repeatable Battery for Neuropsychological Status (RBANS) - Delayed Memory Story Recall - day 8, admin 1(During the evening cognitive testing on Overnight Visit 1 (day 8))
- Repeatable Battery for Neuropsychological Status (RBANS) - Story Memory Recall - day 8(During the evening cognitive testing on Overnight Visit 1 (day 8))
- Repeatable Battery for Neuropsychological Status (RBANS) - Delayed Memory Story Recall - day 16, admin 2(During the morning cognitive testing on Overnight Visit 2 (day 16))
- Repeatable Battery for Neuropsychological Status (RBANS) - Symbol-Digit Test - day 15, admin 1(During the evening cognitive testing on Overnight Visit 2 (day 15))
- Repeatable Battery for Neuropsychological Status (RBANS) - Symbol-Digit Test - day 9, admin 2(During the morning cognitive testing on Overnight Visit 1 (day 9))
- Repeatable Battery for Neuropsychological Status (RBANS) - Symbol-Digit Test - day 16, admin 2(During the morning cognitive testing on Overnight Visit 2 (day 16))
- Visual Attention Task (VAT) - day 15, admin 1(Once during pre-TMS MRI scan on evening of Overnight Visit 2 (day 15))
- Visual Analog Mood Scale (VAMS) - day 15, admin 1(During evening of Overnight Visit 2 (day 15))
- Repeatable Battery for Neuropsychological Status (RBANS) - Attention Digit Span - day 8, admin 1(During the evening cognitive testing on Overnight Visit 1 (day 8))
- Repeatable Battery for Neuropsychological Status (RBANS) - Delayed Memory Story Recall - day 15, admin 1(During the evening cognitive testing on Overnight Visit 2 (day 15))
- Visual Attention Task (VAT) - day 8, admin 1(Once during pre-TMS MRI scan on evening of Overnight Visit 1 (day 8))
- Multi-Source Interference Task (MSIT) - day 8, admin 1(Once during pre-TMS scan on evening of Overnight Visit 1 (day 8))
- Multi-Source Interference Task (MSIT) - day 15, admin 2(Once during post-TMS scan on evening of Overnight Visit 2 (day 15))
- Multi-Source Interference Task (MSIT) - day 15, admin 1(Once during pre-TMS scan on evening of Overnight Visit 2 (day 15))
- Multi-Source Interference Task (MSIT) - day 8, admin 2(Once during post-TMS scan on evening of Overnight Visit 1 (day 8))