Mechanistic Validation of Human Multipolar TES-TI: Amplitude Modulation, Frequency, and Benchmarking

Обзор

This study is to find out whether and how a type of non-invasive electrical brain stimulation called transcranial electrical stimulation with temporal interference (TES-TI) can temporarily change brain activity in healthy adults. A structural MRI scan will be used to customize where the stimulation electrodes are placed for each participant to deliver TES-TI during three afternoon sessions at rest with eyes closed. Brain activity is recorded with high-density EEG. Up to 24 participants will be enrolled and on study for 3 to 12 weeks.

Подробное описание

This is an experimental study using a within-subject, single-blind, randomized, counterbalanced crossover design in which each participant serves as their own control. Healthy adults will complete (or provide an existing) structural MRI scan (T1/T2) to support individualized electric-field modeling and personalized montage optimization for thalamic targeting, followed by three afternoon stimulation sessions with simultaneous high-density EEG during eyes-closed wakefulness; sessions will be scheduled on separate days at least one week apart. Each session includes four stimulation conditions administered in randomized/counterbalanced order, with each condition consisting of a fixed 3-minute pre-stimulation baseline, 3-minute stimulation period, and 3-minute post-stimulation recording to enable STIM-PRE and POST-PRE comparisons.

* Session A tests amplitude-modulation specificity (in-phase mTI, a mixed unipolar+HF condition with the same montage/current, a carrier-only HF control, and sham) * Session B benchmarks in-phase mTI against unipolar TES-TI at 5 mA and 8 mA (plus sham); and * Session C characterizes frequency dependence of in-phase mTI (10, 50, 130 Hz; plus sham).

Primary Objectives:

1. Determine whether active multipolar TES-TI (mTI) produces envelope-driven EEG effects (primary contrast: STIM-PRE) by comparing in-phase mTI to SHAM, to a carrier-only no-envelope high-frequency (HF) control, and to a mixed unipolar+HF condition (same montage/current; one pair as unipolar TES-TI producing an AM envelope, the other pair as a non-interacting HF carrier with no envelope contribution). 2. Benchmark mTI against unipolar TES-TI across stimulation intensity by comparing in-phase mTI to unipolar TES-TI at 5 mA and 8 mA, each evaluated relative to SHAM (primary contrast: STIM-PRE), and estimating effect sizes to inform future study design. 3. Characterize envelope-frequency dependence of in-phase mTI effects by comparing EEG spectral power changes across 10, 50, and 130 Hz conditions (each relative to SHAM; primary contrast: STIM-PRE).

Secondary Objectives: 4. Assess persistence of stimulation-related EEG changes by quantifying post-stimulation effects (POST-PRE) across conditions (in-phase, mixed unipolar+HF, HF, unipolar) and sessions

Вмешательства

• Устройство TES-TI with hdEEG
  4 conditions per session. Each condition will follow a standardized block structure consisting of 3 minutes pre-stimulation baseline, 3 minutes stimulation, and 3 minutes post-stimulation recording (PRE, STIM, POST)

Первичные конечные точки

• Change in band-limited, topography-resolved EEG spectral power during stimulation for conditions in Session A [Срок оценки: data collected for 3 minutes prior to stimulation and 3 minutes during stimulation for each of 4 conditions during Session A (approximately 3 hours long)]
• Change in band-limited, topography-resolved EEG spectral power during stimulation for conditions in Session B [Срок оценки: data collected for 3 minutes prior to stimulation and 3 minutes during stimulation for each of 4 conditions during Session B (approximately 3 hours long)]
• Change in band-limited, topography-resolved EEG spectral power during stimulation for conditions in Session C [Срок оценки: data collected for 3 minutes prior to stimulation and 3 minutes during stimulation for each of 4 conditions during Session C (approximately 3 hours long)]

Вторичные конечные точки (1)

• Change in band-limited, topography-resolved EEG spectral power in the post-stimulation interval (POST-PRE) across all tested conditions [Срок оценки: data collected for 3 minutes prior to stimulation and 3 minutes post stimulation for each of 4 conditions during each of 3 sessions (each session is approximately 3 hours long, with at least one week between sessions)]

Критерии участия

Критерии включения

• Medically healthy (based on self-report and study team review)
• U.S. citizen or holding permanent resident status
• English-speaking (able to provide consent and complete questionnaires)

Критерии исключения

• Current or past history of clinically significant neurological disorder or acquired neurological disease (e.g., stroke, traumatic brain injury), including intracranial lesions (including clinically significant findings identified on the structural MRI)
• History of inpatient psychiatric hospitalization
• History of head trauma resulting in prolonged loss of consciousness; or a history of >3 grade I concussions
• Current poorly controlled headaches, including intractable or frequent 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 seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG, or family history of treatment resistant epilepsy except for 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 (self reported)
• Any metal in the head
• Any medical devices or implants (i.e. cardiac pacemaker, medication infusion pump, cochlear implant, vagal nerve stimulator)
• Dental implants
• Permanent retainers
• Any hair braid, dreadlocks, hair pieces, or extensions which cannot be taken out before the study sessions
• Any head coverings or headdress that participant feels uncomfortable removing for the purposes of study sessions
• Current use of medications known to substantially lower seizure threshold, specifically chlorpromazine, clozapine, bupropion, clomipramine, or maprotiline; or other medications at doses known to substantially lower seizure threshold in the judgment of the PI
• Active scalp lesions, broken skin, or skin conditions at planned electrode sites that would preclude safe electrode application
• Claustrophobia (a fear of small or closed places)
• Back problems that would prevent lying flat for up to two hours

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• University of Wisconsin - Madison — Madison

Идентификаторы

NCT: NCT07752745 · 2026-1006 · R&D funding · Protocol Version · SMPH | Psychiatry

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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