Anxiety, PTSD
Conditions
Keywords
Temporal Interference
Brief summary
This study aims to understand the neural, behavioral and clinical effects of temporal interference (TI), a type of neuromodulation method, in healthy populations and in individuals with anxiety and stress-related conditions.
Detailed description
In this study, the investigators aim to understand the neural, behavioral and clinical effects of temporal interference (TI), a type of neuromodulation method. This method involves placement of electrodes on the scalp that deliver a low voltage electrical field at different alternating high frequency fields to modulate the function of brain areas. The study will use magnetic resonance imaging (MRI) and electroencephalography (EEG) to assess the effects of TI on brain response. The study team will also assess mood (measured via clinical assessments and self-report ratings), physiology (measured via electrocardiography, galvanic skin response, respiration) behavior and cognition (performance on various cognitive and other behavioral tasks). To do so, the team will stimulate and inhibit brain regions that are relevant to anxiety, mood, and cognition, areas of the brain hypothesized to be selectively engaged with cognition of a given category, or cost-benefit decision-making (depending on the behavioral tasks used). In an optional study, the investigators will use Ecological Momentary Assessment (EMA) to examine a behavioral translation of the neural mechanisms tested using TI by inquiring about individuals' mood and behavior in daily life. This study will recruit healthy controls and patients with psychiatric symptoms to investigate these effects. Psychiatric symptoms will be assessed based on self-report questionnaires. Such an aim will not only provide a deeper understanding of how TI may be used to target different processes of relevance to psychiatric disorders but also the duration of effects. Temporal Interference (TI) stimulation is an emerging, non-invasive neuromodulation method which allows focal electrical stimulation of deep brain structures without affecting overlying cortical regions. Preclinical studies and early human applications suggest that TI may modulate emotion-related brain activity with the potential to improve symptoms in psychiatric conditions. This study aims to evaluate the preliminary efficacy of TI stimulation in healthy populations and in individuals with anxiety and stress-related conditions (Aim 1) as well as feasibility, safety, and effects of different frequencies and doses of TI (Aim 2). Outcomes will be evaluated using a battery of neural (MRI, EEG), physiological, behavioral (affective tasks), cognitive, and mood assessments. In addition, the study team aim to explore the longitudinal mental-health outcomes of TI using daily assessments (Aim 3). Participants will be invited to electronically respond to questionnaires and compose a diary over a 4-week period, and these data will be compared with neural recordings. This component will assess the validity and feasibility of remote tracking of anxiety symptoms in real-world settings - and perhaps detect nuanced improvements of symptoms from intermittent TI sessions, not as readily seen in weekly in person clinical assessments.
Interventions
Temporal Interference (TI) stimulation is a non-invasive neuromodulation method which allows focal electrical stimulation of deep brain structures without affecting overlying cortical regions. Areas will be targeted based on tasks being administered under TI and will include areas associated with fear/anxiety expression and inhibition, reward, and general affective processing including cortical areas. Two carrier electric fields offset by a small amount (5-130Hz) will occur during stimulation. Stimulation will be applied between the pairs of electrodes with a current up to a maximum of between 8mA (TI outside the scanner) and 10mA (TI inside the scanner) with envelope frequencies between 1hz-200hz. Multipolar TI will also be used with multiple locations that can be targeted for stimulation by adding more pairs of electrodes.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent. * Fluent English speaker. * Both sexes and all ethnic origins, between 18 and 65 years old. * Absence of current moderate to severe illicit drug use as assessed by subject history (AUDIT\>=8 and/or DAST\>2).
Exclusion criteria
* Pregnant or currently breast-feeding women or any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant, as assessed by subject report and/or urine pregnancy screen. * Contraindications to MRI scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia, as assessed with the standard MRI screening form from the CABI, FERN or CSI. * Unable to fit comfortably in the scanner. * Contraindication to TI and/or TMS (including history of epilepsy, metallic implants in the head and/or neck, brain stimulators, vagus nerve stimulators, VP shunt, pacemakers) * Current use of medications that may increase the risk of seizures (e.g., bupropion, varenicline, chlorpromazine, theophylline). * History or current serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease, as assessed by subject history. * History of head injury resulting in more than brief loss of consciousness, as assessed by subject history. * Current cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine), as assessed by subject history. * Evidence of significant inconsistencies in self-report measures. * Non-English speakers will be excluded from this study because the research procedures rely heavily on the administration of validated self-report questionnaires, clinical interviews, and task instructions that at this time, are only available in English. Additionally, study staff are trained to administer these assessments and obtain informed consent in English only. Including non-English speakers would therefore pose a risk of misunderstanding study procedures, consent materials, or questionnaire items, which could affect both participant comprehension and data integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Anxiety Rating Scale (HAM-A) | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Hamilton Anxiety Rating Scale (HAM-A) is a clinician-rated assessment used to quantify the severity of anxiety symptoms. It consists of 14 items, each defined by a series of symptoms that measure both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each of the 14 items is scored on a scale of 0 (not present) to 4 (very severe). Total score ranges from 0 to 56. Higher scores indicate greater anxiety severity. |
| Change in State Trait Anxiety Inventory (STAI) | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The State-Trait Anxiety Inventory (STAI) is a 40-item self-report scale used to measure the intensity of anxiety. Each item is rated on a 4-point Likert scale (e.g., 1 = "not at all" to 4 = "very much so" or 1 = "almost never" to 4 = "almost always"). Total Score ranges from 20-80 with higher scores indicate greater levels of anxiety. |
| Change in Difficulties in Emotion Regulation Scale (DERS) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The DERS is a 36 item instrument that measures emotional dysregulation symptoms. Responses are given on a 5-point scale where 1 = almost never and 5 = almost always. The DERS scales include 1) nonacceptance of emotional responses, 2) difficulty engaging in goal-directed behavior, 3) difficulties with impulse control, 4) limited emotional awareness, 5) limited access to emotion regulation strategies, and 6) lack of emotional clarity. Total scores range from 36 to 180 and higher scores suggest greater problems with emotion regulation. |
| Change in PTSD Symptom Checklist (PCL-5) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The PCL-5 is a 20-item self-report measure that assess the DSM-V symptoms of PTSD. Responses are given on a scale from 0 to 4 where 0 = not at all and 4 = extremely. Total scores range from 0 to 80 where higher scores indicate increased symptoms of PTSD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Multiscale Dissociation Inventory (MDI) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The MDI is a 30-item self-report test of dissociative symptomology and measures six different types of dissociative responses: disengagement, depersonalization, derealization, emotional constriction/numbing, memory disturbance, and identity dissociation. Items are scored on a 5-point scale where 1 = never and 5 = very often. Total dissociation scores range from 30 to 150 where higher scores indicate greater symptoms of dissociation. |
| Change in Kentucky Mindfulness Scale (KIMS) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Kentucky Mindfulness Scale is a 39-item scale that assesses skills related to what one does while practicing mindfulness. Items are rated on a 5 point Likert scale ranging from 1 (never or very rarely true) to 5 (almost always or always true). Items reflect either direct descriptions of the mindfulness skills, or they describe the absence of that skill and are reverse scored. Total scores range from 39 to 195 and higher scores reflect more mindfulness. |
| Change in Multidimensional Assessment of Interoceptive Awareness (MAIA) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | This is a clinical measure that assesses various aspects of interoception, including ability to attend to body sensations, regulate distress by attending to body sensations, and experiencing body sensations as safe and trustworthy. The instrument includes 32 items and which are scored from 0 to 5, where 0 = never and 5 = always. Total scores range from 0 to 160 and higher scores indicate greater awareness of body sensations. |
| Change in Attentional Control Scale (ACS) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | This is a 20-item self-report measure that assesses attentional control a 4-point Likert scale, where 1 = almost never and 4 = always. Total scores range from 20 to 80 and higher scores indicate greater difficulty with attentional control. |
| Change in Change in Life Events Checklist Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Life Events Checklist includes 21 items asking respondents if they have been exposed to stressful events in the last 3 to 4 weeks. Participants are also able to list stressful events or experiences that are not specifically listed. Responses are coded as 5 = happened to me, 4 = witnessed it, 3 = learned about it, 2 = part of my job, 1 = not sure, and 0 = does not apply. A total score or composite score is not calculated for the Life Events Checklist, rather this instrument is used to identify if the respondent has experienced traumatic situations. |
| Change in Sense of Agency Rating Scale (SOARS) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The SOARS is a 10-item self-report measure that assess the sense of control one has over their body. Responses are given on a 7-point Likert scale where 1 = strongly disagree and 7 = strongly agree. Total scores range from 10 to 70 where lower scores indicate greater sense of agency. |
| Change in Scale of Body Connection (SBC) Body Awareness Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Scale of Body Connection instrument has 20 items assessing the dimensions of Body Awareness and Bodily Dissociation. Items are scored on a 5-point scale where 0 = not at all and 4 = all of the time. The body awareness dimension has 12 items and the body awareness score is the average of responses to these items. Higher scores indicate greater bodily awareness. |
| Change in Kreek-McHugh-Schluger-Kellogg Scale (KMSK) Alcohol Lifetime Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The KMSK assesses lifetime alcohol use with up to 7 items. Three of the items are scored quantitatively on varying scales. Total scores range from 0 to 13 where higher scores indicate greater lifetime use of alcohol. |
| Change in Patient-Reported Outcomes Measurement Information System - Depression (PROMIS-D) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The PROMIS-D instrument assesses depression with 9 items asking respondents if they have experienced certain symptoms of depression in the past 7 days. Responses are given on a 5-point scale. Total scores are transformed to a t-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate increased depressive symptoms compared to the reference population. |
| PHQ-9 | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Patient Health Questionnaire (PHQ-9) is a 9-item self-report tool used to screen, diagnose, and monitor the severity of depression. Each of the 9 items is scored on a scale of 0 (not at all) to 3 (nearly every day). The individual item scores are summed to provide a total score ranging from 0 to 27. Higher scores indicate greater depression severity. |
| Change in Positive and Negative Affect Schedule - Expanded Form (PANAS-X) Positive Affect (PA) | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Positive and Negative Affect Schedule - Expanded Form (PANAS-X) Positive Affect (PA) Scale is a 10-item self-report subscale used to measure the extent to which a person feels enthusiastic, active, and alert. Each of the 10 items is rated on a 5-point Likert scale, ranging from 1 (very slightly or not at all) to 5 (extremely). The individual item scores are summed to provide a total score ranging from 10 to 50. Higher scores indicate higher levels of energy, pleasurable engagement, and concentration. |
| Positive and Negative Affect Schedule - Expanded Form (PANAS X) Negative | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Positive and Negative Affect Schedule - Expanded Form (PANAS-X) Negative Affect (NA) Scale is a 10-item self-report subscale used to measure a general dimension of subjective distress and unpleasurable engagement. Each of the 10 items is rated on a 5-point Likert scale, ranging from 1 (very slightly or not at all) to 5 (extremely). The individual item scores are summed to provide a total score ranging from 10 to 50. Higher scores indicate greater levels of distress, fear, and dissatisfaction. |
| Generalized Anxiety Disorder-7 (GAD-7) | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item, self-administered patient questionnaire used to measure the severity of anxiety symptoms over the past two weeks. Each item identifies a specific symptom (e.g., feeling nervous, anxious, or on edge). Each of the 7 items is rated on a 4-point Likert scale (0 = Not at all,1 = Several days, 2 = More than half the days, 3 = Nearly every day). The individual item scores are summed to provide a total score ranging from 0 to 21. Higher scores indicate greater anxiety severity. |
| Change in Childhood Trauma Questionnaire (CTQ) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Childhood Trauma Questionnaire (CTO) has 28 items asking respondents if they experienced situations of trauma as a child or teenager. Responses are given on a 5-point scale (1= never true and 5 = always true). There are subscales for sexual abuse, physical abuse, emotional abuse, emotional neglect, and physical neglect, and a total trauma score is calculated. Total scores range from 28 to 140 where higher scores indicate more severe trauma. |
| Change in Motivation and Pleasure Scale Self-Report (MAP-SR) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The MAP-SR is an 18-item questionnaire assessing the degree of pleasure experienced with social, work or recreational, and family situations and the amount of motivation to engage in activities. Responses are given on a 5-point scale where 0 = no pleasure or no motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 72. Scoring for certain items is reversed so that higher scores indicate increased pleasure and motivation. |
| Change in Ruminative Responses Scale Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Ruminative Responses Scale is a 22-item instrument assessing different things that people do when they feel depressed. Responses are given on a 4-point scale where 1 = almost never and 4 = almost always. Total scores range from 22 to 88 and higher scores indicate greater rumination on depressive symptoms, potentially prolonging depressive episodes. |
| Change in Everyday Discrimination Scale (EDS) Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The original Everyday Discrimination Scale includes 9 items asking respondents how often they experience certain situations of discrimination. Responses are given on a 6-point scale where 1 = never and 6 = almost everyday. Total scores range from 9 to 54 where higher scores indicate experiencing increased discrimination. |
| Change in Experiences of Discrimination (EOD) Scale Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Experiences of Discrimination Questionnaire is an 11-item instrument assessing experiences of discrimination because of race, ethnicity, or color. Respondents indicate if they have or have not experienced 9 situations of discrimination (no = 0 and yes = 1), and then there are two questions about how often respondents feel that discrimination occurs that are score as 1 = never and 4 = often. Total scores range from 2 to 17 where higher scores indicate greater experiences of discrimination. |
| Alcohol Use Disorders Identification Test (AUDIT) score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item self-report or clinician-administered questionnaire designed to identify hazardous and harmful patterns of alcohol consumption. It covers three domains: alcohol consumption, dependence symptoms and harmful alcohol use. Each of the 10 items is scored on a scale of 0 to 4. The individual item scores are summed to provide a total score ranging from 0 to 40. A higher score indicates a greater likelihood of hazardous and harmful drinking or alcohol dependence. |
| Drug Abuse Screening Test (DAST-10) score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Drug Abuse Screening Test (DAST-10) is a 10-item self-report scale designed to provide a brief instrument for clinical screening and treatment evaluation of drug use (excluding alcohol and tobacco) during the past 12 months. Each item is answered with a binary "Yes" (1) or "No" (0). The individual item scores are summed to provide a total score ranging from 0 to 10. Higher scores indicate a greater degree of problem severity related to drug use. |
| Change in Epworth Sleepiness Scale Score | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | The Epworth Sleepiness Scale is an 8-item instrument assessing level of daytime sleepiness. Responses are given on a 4-point scale where 0 = would never doze and 3 = high chance of dozing. Total scores range from 0 to 24, where scores between 0 and 10 are considered normal and scores above 16 are indicative of high levels of excessive daytime sleepiness. |
| Change in Penn Computerized Neuropsychological Battery (Penn CNP) Performance | Baseline, 2-5 weeks post-intervention, 6 weeks post-intervention | This is a computerized neuropsychological assessment that is designed to examine different domains of cognitive functioning. The executive functioning and memory components of this battery (which include measures of sustained attention and working memory) will be administered, which take approximately 30 minutes to complete. |
Countries
United States
Contacts
CONTACTRachel Jones
CONTACTAlisha Sylvester
PRINCIPAL_INVESTIGATORNegar Fani, PhD, ABPP
Emory University
Outcome results
None listed