The STRENGTHEN Study

University of Wisconsin, Madison64 enrolled

Overview

This study uses two different types of interventions including electrical brain stimulation delivered during sleep, and brief, daily meditation training. The investigators are trying to figure out whether these techniques, either alone or in combination with each other, can positively impact the brain networks that support our ability to think flexibly and to regulate our emotions. 48 participants will be enrolled into each of 2 phases and can expect to be on study for up to 9 months.

The investigators will evaluate the independent and synergistic effect of Cognitive Flexibility (CF)/Emotional Regulation (ER) - targeted meditation and CF/ER-targeted Transcranial Electrical Stimulation with Temporal Interference (TES-TI) during sleep in low-risk participants (n = 48). After informed consent, all participants will undergo a set of baseline assessments, including self-report measures, behavioral tasks, functional and structural MRI, and a baseline in-laboratory sleep study. Following these assessments, participants undergo four weeks of the study intervention. The participants will be assigned into one of four groups. Each group consists of 12 participants. After completing the 4-week intervention, participants will repeat the behavioral, self-report, and imaging assessments given at baseline. Participants will also complete a 7-day ecological momentary assessment (EMA) at baseline, the week after intervention, and at 4-months following intervention. At the 4-month follow-up, participants may complete another round of self-report and behavioral measures. The Primary Objectives are to: * Evaluate the effects of the following on CF and ER networks: 1. meditation practice alone 2. meditation practice and high-dose TES-TI 3. meditation practice and low-dose TES-TI 4. TES-TI alone The Secondary Objectives are to: * Evaluate the differential synergies between Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep TES-TI intervention and the restoration of CF verses ER circuits For Phase 2, an additional 48 participants will be recruited and will eliminate TES-TI once per week. All participants will come to the sleep laboratory for 2 nights over the 4 week intervention period. Planned interim analysis of slow wave activity data from N=20 participants is adequately powered to evaluate whether TES-TI produces the anticipated modulation of deep sleep.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Cognitive Flexibility Emotional Regulation

Interventions

Healthy Minds ProgramOTHER

Participants will follow daily instructions from the Healthy Minds Program at home for four weeks, including guided meditation exercises.

Sham Meditation Didactic MaterialOTHER

Participants will listen to lessons from the Healthy Minds Program at home for four weeks, which will not include any actual meditation exercises.

Sham Stimulation in LabDEVICE

On two nights each week during the four weeks of the intervention, participants will sleep in the lab and undergo sham TES-TI stimulation for approximately 10 hours per night

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria (Phase 1 and 2): * Medically healthy * English-speaking (able to provide consent and complete questionnaires) * Citizen or legal resident Exclusion Criteria (Phase 1): * Any current or recent history (6 months) of any mental health diagnosis (Examples include major depression, hypomania, psychosis, schizophrenia, and bipolar disorder) * Any current or recent (past 6 months) history of treatment for mental illness (including anti-depressant/anti anxiety medications, therapy) * Scoring above Moderate range for Anxiety or Depression - Patient Health Questionnaire-9 (PHQ-9) greater than or equal to 15 or General Anxiety Disorder (GAD7) greater than or equal to 15 * At risk for suicide (PHQ item 9 greater than 0) * Any current or past history of neurological disorders or acquired neurological disease (e.g. stroke, traumatic brain injury), including intracranial lesions and obstructive sleep apnea * History of head trauma resulting in prolonged loss of consciousness; or a history of greater than 3 grade I concussions * Current history of poorly controlled headaches including intractable or poorly controlled migraines * Any systemic illness or unstable medical condition that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) * History of fainting spells of unknown or undetermined etiology that might constitute seizures * History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) electroencephalogram, or family history of treatment resistant epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist * Possible pregnancy or plan to become pregnant in the next 6 months. * Any metal in the brain, skull or elsewhere * Any hair braid, dreadlocks, hair pieces, or extensions which cannot be taken out before the MRI scans and/or sleep stimulation sessions * Any head coverings or headdress that participant feels uncomfortable removing for the purposes of the MRI scans and/or sleep stimulation sessions * Any medical devices or implants (i.e. cardiac pacemaker, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible physician * Dental implants containing metal (titanium or titanium alloys) surgically implanted post and core * Substance use disorder within the past six months * Any medication that may alter seizure threshold i.e., Attention-deficit/hyperactivity disorder (ADHD) stimulants (Adderall, amphetamine); Tricyclic/atypical antidepressants (amitriptyline, doxepine, imipramine, maprotiline, nortriptyline, bupropion); Antipsychotics (chlorpromazine, clozapine), Bronchodilators (theophylline, aminophylline); Antibiotics (fluoroquinolones, imipenem, penicillin, cephalosporins, metronidazole, isoniazid); Antivirals (valacyclovir, ritonavir); Over the Counter (OTC) (diphenhydramine, Benadryl) * Claustrophobia (a fear of small or closed places) * Back problems that would prevent lying flat for up to two hours * Regular night-shift work (second or third shift) * Do not have access to a smartphone or the internet * Regular meditation practice and/or prior use of the Healthy Minds Program app * Cannot visit the lab in-person for 7 consecutive weeks in the next year * Permanent retainers Additional Exclusion Criteria (Phase 2): * Any current or recent history (6 months) of bipolar disorder, psychosis, schizophrenia. A history of stable depression or anxiety is not exclusionary. * Mental health treatment (e.g, psychotherapy) is no longer exclusionary, although all the medication exclusions outlined above still apply

Locations (1)

Center for Healthy Minds

Madison, Wisconsin, United States

Outcomes

Primary Outcomes

Change in Patient Health Questionnaire-9 (PHQ-9) Score

The PHQ-9 is a 9-item inventory asking participants to rate from 0 (not at all) to 3 (nearly everyday) the frequency and intensity of depressive symptoms experienced by the respondent over the preceding two-week period. Scores range from 0 to 27 where higher scores indicate poorer patient health. Participants with scores greater than 15 will be excluded from study.

Time frame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)

Change in General Anxiety Disorder (GAD-7) Score

This 7-item inventory measures the severity of generalized anxiety disorder symptoms in individuals by asking participants to rate from 0 (not all at) to 3 (nearly everyday) the frequency and intensity of various anxiety-related symptoms experienced by the participant in the past two weeks. Scores range from 0-21 where higher scores indicate more anxiety. This study will exclude any participants who have a total score of 15 or above.

Change in Single-item Suicide Question

This single-item suicide question assesses participant's suicidal ideation to respond yes or no to "Since the last time we saw you, did you seriously consider attempting suicide?".

Change in Healthy Minds Index (HM Index)

The HM Index is a 17-question, 5-point scale well-being assessment that measures the four pillars of Wellbeing - Awareness, Connection, Insight, and Purpose. Means scores are from 1 to 5 with higher scores indicative of increased wellbeing.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Participants will sleep in the lab and undergo active TES-TI stimulation for approximately 10 hours per night.

MRI ScannerDEVICE

Imaging protocol will include: structural T1-weighted and T2-weighted images, resting-state functional MRI, task-based functional MRI, and multi-shell diffusion weighted MRI, total scan time will be approximately 2 hours

Change in the Perceived Stress Scale (PSS) Score

This is a 10-item inventory asking participants to rate from 0 (never) to 4 (very often) the frequency with which they have felt various kinds of stress in the last month. Scores range from 0 to 40 with higher score indicative of higher stress.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Emotional Styles Questionnaire (ESQ) Score

This is a 24-item inventory asking participants to rate from 1 (strongly disagree) to 7 (strongly agree). Scores range from 24 - 168, higher scores are indicative of less Healthy Emotionality

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Cognitive Flexibility Inventory (CFI) Score: Alternatives Subscale

The CFI is a 20-item self-report measure to monitor how often individuals engage in cognitive behavioral thought challenging interventions. Participants rate each item from 1 (strongly disagree) to 7 (strongly agree). Scores range from 13 - 91, higher scores are indicative of increased ability to perceive multiple alternative explanations.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Cognitive Flexibility Inventory (CFI) Score: Control Subscale

The CFI is a 20-item self-report measure to monitor how often individuals engage in cognitive behavioral thought challenging interventions. Participants rate each item from 1 (strongly disagree) to 7 (strongly agree). Scores range from 7 - 49, higher scores are indicative of increased ability to perceive difficult situations as controllable.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Difficulties in Emotion Regulation Scale-18 (DERS-18) Score

The DERS-18 is a 18-item self-report measure which assesses various aspects of emotion regulation, including emotional awareness, acceptance of emotional responses, impulse control, and effective goal-directed behavior during emotional experiences using a 5-point scale from 1 (almost never) to 5 (almost always). Higher scores suggest greater problems with emotion regulation.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in PROMIS Sleep Disturbance Score

This validated assessment tool asks participants to rate 8 items that measure sleep-related difficulties using a 5-point Likert scale. Scores range from 8 to 40 with higher scores indicative of more sleep disturbance.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in PTSD Checklist for DSM-5 (PCL-5)

This 20-item self-report questionnaire is a widely used self-report questionnaire which assesses symptoms of post-traumatic stress disorder (PTSD). Participants rate from 0 (not at all) to 4 (extremely) the severity of their symptoms. Scores range from 0 to 80 with higher scores indicative of more severe PTSD symptoms.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in World Health Organization-5 (WHO-5)

This 5-item scale is a global measure of Well-Being, where higher scores reflect greater overall wellbeing (range 0-25).

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Restorative Sleep Questionnaire (RSQ) Score

This validated assessment measuring subjective perceptions of the restorative or inadequate properties of sleep will be given the morning after every sleep lab visit. The questionnaire includes 9 items rated on a 5 point scale given at the time of awakening. Scores range from 0 to100, where higher scores are indicative of better restorative sleep.

Time frame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4)

Change in Sleep Depth Question (SDQ) Score

Participants will be asked to rate the depth of their prior night's sleep using 5-point Likert-type scale. How deep was your sleep? from 1 (light) to 5 (deep) after every sleep laboratory visit.

Time frame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4)

Change in Pittsburgh Sleep Quality Index (PSQI) Score

This validated questionnaire evaluates subjective sleep quality. Each of the questionnaire's 19 self-reported items belongs to one of seven subcategories: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Five additional questions rated by the respondent's roommate or bed partner are included for clinical purposes and are not scored. Each component is scored 0 (no difficulty) to 3 (severe difficulty), scores ranging from 0 to 21. Higher scores are indicative of worse sleep quality.

Time frame: baseline, post-intervention (week 5)

Change in Suicide Risk Survey

This battery assesses known suicide risk factors. The 13 items ask participants about their sociodemographic characteristics; past experiences with mental health symptoms; thoughts of self-harm, and self-harming actions; psychological traits. Scores range from \< 0.39408955691660219 to \>= 0.67215170692043313 with higher scores indicative of increased suicidality.

Time frame: baseline, post-intervention (week 5)

Change in Brief Suicide Cognitions Scale (B-SCS) Score

This self-report measure assesses the suicide belief system. Using a 5-point likert scale, participants rate 6 items measuring their enduring or identity-based hopelessness rooted in their beliefs about being undesirable, their emotional state as intolerable, and life challenges as insurmountable. Scores range from 6 to 30 where higher scores are indicative of increased suicidality.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Passive and Active Suicidal Ideation Scale (PASIS) Score

This 17-item validated tool assesses participants' passive and active suicidal ideation in the past seven days using a six-point Likert scale, from 0 (Not in the past 7 days) to 5 (several times every day). Higher score reflects greater suicidal ideation.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in NIH Toolbox Loneliness Score

The NIH Toolbox Loneliness consists of 5 self-report items assessing participants' feelings of loneliness and social isolation on a 5-point Likert scale ranging from 1-5 where higher scores indicate increased loneliness.

Change in Five Facet Mindfulness Questionnaire (FFMQ) Score

The FFMQ is a widely used self-report inventory that assesses mindfulness across five facets: observing, describing, acting with awareness, non-judging of inner experience, and non-reactivity to inner experience. Participants rate their agreement level with 39 items using a 5-point Likert scale. Scores range from 39 to 195 with higher scores indicative of increased mindfulness.

Change in Drexel Defusion Scale (DDS) Score

This self-report measure evaluates the ability to create a mental separation or distance from one's internal experiences by asking participants to rate 10 items assessing defusion across a spectrum of internal thoughts and emotions on a 6-point scale, ranging from 0-5. Total scores range from 0 to 50 with higher scores indicative of increased defusion.

Change in PROMIS Meaning and Purpose Score

This is a 37-item inventory asks participants to rate their sense of life with purpose and perceived reasons for living using a 5-point Likert scale. The current study will administer the computer adaptive test (CAT) version of the instrument, in which subsequent item choice of the system will be based on participants' previous responses. Scores range from 37 to 185 with higher scores indicative of higher feelings of meaning and purpose.

Change in Digital Working Alliance Inventory (D-WAI) Score

The inventory consists of 6 items which measures the quality of the therapeutic alliance between a user and a digital mental health intervention, which is the HMP in this study. Participants rate their experience using the HMP on a 7-point scale, ranging from 1 (strongly disagree) to 7 (strongly agree). Scores range from 6 to 42 where higher scores indicate better user experience with the app.

Time frame: post-intervention (week 5), follow-up (week 20)

Change in Perseverative Thinking Questionnaire (PTQ) Score

The PTQ is a self-report instrument assessing repetitive and uncontrolled thinking by asking participants to rate 15 items about the frequency, duration, and perceived uncontrollability of repetitive thoughts on a scale of 0-4. Scores range from 0 to 60. The higher the score, the higher the level of perseverative thinking or repetitive thoughts experienced by the individual.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Experiences Questionnaire's Decentering subscale (EQ-D) Score

This subscale is an 11-item scale of decentering originally developed to assess mechanisms of Mindfulness Based Cognitive Therapy (e.g., "I can separate myself from my thoughts and feelings."). The EQ-D is originally scored on a 5-point Likert scale (1 = never to 5 = all the time) where higher scores indicate increased decentering.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Experience Sampling / Ecological Momentary Assessment

The experience sampling method assesses present moment experience using a short series of questions administered on a smart phone 6 times a day for 7 days. Questions measure current emotional and cognitive state. Score range from 1-5 where higher scores indicate increased emotional state

Time frame: 6 times per day for 7 days

Change in Death Implicit Association Test Score

This task involves participants viewing words on a screen. Words are either related to self (e.g., "I"), others (e.g., "They"), life (e.g., "survive") or death (e.g., "die"). Like other Implicit Association Tests, participants are asked to indicate which category each word belongs to. Across the trials, self and other are paired with either life or death. The measure can be scored as an implicit marker of how easily participants associated death with themselves. Scores are greater than 2 or less than 2, with more positive values indicating a stronger association between self and death.

Time frame: baseline, post intervention (5 weeks)

Change in Reversal Learning Task Score

This task involves participants viewing and choosing between two abstract visual stimuli (i.e., geometric shapes). After each choice they receive feedback that is either positive (+10) or negative (-10) feedback devoid of monetary value. Stimulus-outcome pairings are reversed over the course of the experiment.

Time frame: baseline, post intervention (5 weeks)

Change in Multi-Source Interference Task Score

This task involves viewing a series of numbers and letters. Participants are asked to indicate using a button press which number was different from the other numbers. Scores are reported as percentage correct.

Time frame: baseline, post intervention (5 weeks)

Change in Emotional Stroop Score: Reaction Time

This task involves viewing a series of faces and words. Participants are asked to identify the emotional expression of the faces. Percent change in reaction time is reported.

Time frame: baseline, post intervention (5 weeks)

Change in Emotional Stroop Score: Percent Correct

This task involves viewing a series of faces and words. Participants are asked to identify the emotional expression of the faces. Percent correct is reported.

Time frame: baseline, post intervention (5 weeks)

Change in Meteor Mission Score: Mean Reaction Time

This is a mobile measure of attention, based on the Sustained Attention to Response Task (SART), a validated, standardized laboratory task. This task lasts five minutes and measures attention regulation and sustained attention, as assessed based on reaction time, reaction time variability, and accuracy.

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Meteor Mission Score: Coefficient of Variation

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Meteor Mission Score: Percent Correct

Time frame: baseline, post-intervention (week 5), follow-up (week 20)

Change in Emotional Persistence Task Score

This task involves viewing pictures categorized as neutral, positive, or negative. Participants may be asked to press a button indicating the valence category of the picture. Positive and negative affect ratings will be made on a continuous sliding scale ranging from 0 to 6.

Time frame: baseline, post intervention (5 weeks)

Change in Change Your Mind Task Score: Mean Change

This task involves viewing a series of letters and numbers. Participants are asked to determine whether a target letter was a certain letter (e.g., "T"). Participants receive feedback on their choices. The feedback is not always accurate and participants are informed of this. Change range is from 0 to 1.

Time frame: baseline, post intervention (5 weeks)

Change in Change Your Mind Task Score: Accuracy

Time frame: baseline, post intervention (5 weeks)

Change in Change Your Mind Task Score: Response Time

Time frame: baseline, post intervention (5 weeks)

Psychomotor Vigilance Task (Phase 2 only)

Psychomotor vigilance performance will be measured with the visual psychomotor vigilance task (PVT) a portable, easily usable reaction-time test with a that can yield rapid and reliable assessments of psychomotor vigilance impairment. Participants will take a 3 minute version of the PVT on a tablet or laptop every morning after an in-laboratory sleep visit to assess alertness. Reaction time is reported.

Time frame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4)

Secondary Outcomes

Change in Spectral Power Density During Stimulation-Free Sleep

Change in individual participant spectral power density during stimulation free sleep will be measured and reported separately for NREM sleep (in the 1-4 Hz frequency range) and REM sleep (in the approximately 50hz frequency range) at circadian time-matched periods of baseline sleep and time-matched, stimulation free periods on each of the intervention nights.

Time frame: baseline and up to 8 nights (4 nights for the low frequency group) over the 4 week intervention period following the baseline assessment

Resting-state fMRI Connectivity Z-Scores

Resting-state fMRI connectivity will be assessed based on the Fisher-Z transformed (FZT) correlation of each seed region with all other voxels in the brain. In order to test for intervention effects, difference maps will be computed and a voxelwise analysis of the difference maps across the whole brain will be used to identify regions that might differ in connectivity between groups over time. A z-score is the number of standard deviations away from the mean.

Time frame: baseline, post intervention (5 weeks)