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Temporal Interference Methods for Non-invasive Deep Brain Stimulation, Study 1.2

Temporal Interference Methods for Non-invasive Deep Brain Stimulation

Status
Recruiting
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07339072
Enrollment
30
Registered
2026-01-14
Start date
2026-02-03
Completion date
2027-04-08
Last updated
2026-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Keywords

Temporal Interference, fMRI, BOLD Signal, Cognitive Control, Dorsal Anterior Cingulate Cortex, Non-invasive deep brain stimulation, Neurostimulation

Brief summary

In its totality, this grant aims to develop a line of research using temporal interference (TI) electrical neurostimulation technology to understand the causal role of deep brain structures in cognition. In the short term, the investigators aim to validate and characterize the effects of TI on brain activity as measured by fMRI and demonstrate its ability to focally stimulate deep brain regions without affecting overlying cortex. In the longer term, investigators aim to use these data to resolve longstanding debates about the function of deeper brain regions and lay the foundation for future clinical applications of TI for treating addiction, Obsessive-Compulsive Disorder (OCD), Parkinson's disease, and other disorders involving deep brain dysfunction. The grant supports 2 distinct aims, each of which will be evaluated through a series of independent studies.

Detailed description

Through the grant's duration, the investigators hypothesize that temporal interference (TI) electrical neurostimulation will be well tolerated and effective at focally manipulating deep brain activity as measured by functional MRI (fMRI) BOLD signals. The investigators will investigate whether TI stimulation can increase BOLD activity in targeted deep brain regions including the nucleus accumbens (NAcc) and dorsal anterior cingulate cortex (dACC), and whether this stimulation can influence cognitive functions controlled by these regions. TI works by applying alternating currents of slightly different frequencies through multiple electrode pairs, creating an interference pattern that can stimulate deep brain regions without significantly affecting superficial cortical areas. This method is similar to traditional transcranial direct current stimulation (tDCS), however TI can stimulate deeper brain structures that tDCS cannot reach effectively. The study is broken up into two main aims with multiple sub-studies. In Aim 1, the investigators will characterize the effects of TI on fMRI BOLD signals, test different beat frequencies, and compare TI effects in the nucleus accumbens versus dorsal anterior cingulate cortex. In Aim 2, the investigators will apply TI to the dorsal anterior cingulate cortex to test causal theories about its role in cognitive control, conflict monitoring, risk avoidance, and foraging behavior using established cognitive tasks while subjects undergo fMRI scanning. Study 1.2 (Aim 1, Study 12) will test the ability to focally activate the nucleus accumbens without activating the overlying cortex, and also its effects on functional connectivity. Healthy subjects (n=30) will present for a single study visit during which they will be placed in the fMRI scanner and administered a temporal interference protocol. Specifically, subjects will have four pairs of carbon fiber electrodes attached to the scalp with conductive gel. They will receive one 8-minute block of stimulation at 2mA per electrode pair. The stimulation sequence will be 2 minutes on, 2 minutes off, 2 minutes on, and 2 minutes off with 30 second ramp up and ramp down beginning at the start of each 2-minute period. For Study 1.2, two TI beat frequencies will be evaluated: 5 Hz (produced by channels at 2000 Hz and 2005 Hz) and 10 Hz (produced by channels at 2000 Hz and 2010 Hz). Each beat frequency will have an Active block (30-second ramp to 2 mA, 2 min on / 2 min off cycles) and a matching Sham block where the stimulation immediately ramps down as soon as it reaches 2 mA after ramp up. The order of blocks and whether the "on" or "off" condition occurs first will be counterbalanced across subjects.

Interventions

DEVICETemporal Interference (TI) Electrical Stimulation - NAcc 5 Hz TI Active

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies at up to 2 mA per electrode. For the NAcc 5 Hz TI Active condition, one channel will deliver 2000 Hz and the other 2005 Hz, producing a 5 Hz beat frequency that focally stimulates deep brain regions without activating overlying cortex. Stimulation is administered in 2-minute on / 2-minute off cycles with a 30-second ramp up and ramp down beginning at the start of each 2-minute period.

DEVICETemporal Interference (TI) Electrical Stimulation - NAcc 5 Hz TI Sham

Same setup as the 5 Hz TI Active condition, except that the stimulation immediately ramps down as soon as it reaches 2 mA after ramp up, producing a sham condition.

DEVICETemporal Interference (TI) Electrical Stimulation - NAcc 10 Hz TI Active

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies at up to 2 mA per electrode. For the NAcc 10 Hz TI Active condition, one channel will deliver 2000 Hz and the other 2010 Hz, producing a 10 Hz beat frequency that focally stimulates deep brain regions without activating overlying cortex. Stimulation is administered in 2-minute on / 2-minute off cycles with a 30-second ramp up and ramp down beginning at the start of each 2-minute period.

DEVICETemporal Interference (TI) Electrical Stimulation - NAcc 10 Hz TI Sham

Same setup as the 10 Hz TI Active condition, except that the stimulation immediately ramps down as soon as it reaches 2 mA after ramp up, producing a sham condition.

Sponsors

Indiana University
Lead SponsorOTHER
National Institute of Mental Health (NIMH)
CollaboratorNIH

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)

Intervention model description

This study uses a within-subject crossover design. Participants receive both active temporal interference (TI) stimulation and sham stimulation, in both "on" and "off" conditions during fMRI scanning. The order of active vs. sham stimulation and the order of on vs off conditions is counterbalanced across participants. Beat frequency, electrode placement, and behavioral paradigm vary by sub-study (e.g., reward-related tasks targeting the nucleus accumbens, cognitive control and decision-making tasks targeting the dorsal anterior cingulate cortex). For Study 1.2, two temporal interference beat frequencies (5 Hz and 10 Hz) will be evaluated for their effects on the nucleus accumbens.

Eligibility

Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

* Between the ages of 18 and 50 * Must have at least a 6th grade education * Ability to speak and read English for all phases

Exclusion criteria

* Currently taking psychotropic medications for ADHD, other mental illness, or medications for cancer * History of epilepsy or seizure disorders * History of migraines or other neurological syndromes * History of AIDS (due to potential cognitive deficits) * History of head trauma or cognitive impairments * Personal experiences consistent with symptoms of psychosis (e.g., hallucinations, delusions of control or special powers) * History of skull defects (e.g., holes bored into the skull or known cranial fissures) * Metal implants in the head or under the scalp * Does not meet fMRI safety screening criteria (e.g., metal implants in the body, permanent jewelry, tattoos on the head or neck) * Uses an intrauterine device (IUD) for birth control and cannot provide documentation to verify MRI safety * Pregnancy (self-reported; no pregnancy test administered) * Weight over 440 lbs (scanner weight limit) * Presence of pacemakers

Design outcomes

Primary

MeasureTime frameDescription
Change in brain activity in the nucleus accumbens during 5 Hz versus 10 Hz temporal interference stimulationDuring fMRI scan on study day (approximately 60 minutes)Brain activity in the nucleus accumbens will be measured using functional magnetic resonance imaging (fMRI) during temporal interference (TI) stimulation at 5 Hz compared to 10 Hz. Activity will be reported as the percent change in blood-oxygen-level-dependent (BOLD) signal, which reflects changes in neural activity. Higher BOLD values indicate stronger brain activation.

Secondary

MeasureTime frameDescription
Change in brain activity in the nucleus accumbens during active versus sham stimulation at 5 HzDuring fMRI scan on study day (approximately 60 minutes)Brain activity in the nucleus accumbens will be measured using fMRI during active versus sham temporal interference stimulation at a 5 Hz beat frequency. Activity will be reported as the percent change in blood-oxygen-level-dependent (BOLD) signal.
Change in brain activity in the nucleus accumbens during active versus sham stimulation at 10 HzDuring fMRI scan on study day (approximately 60 minutes)Brain activity in the nucleus accumbens will be measured using fMRI during active versus sham temporal interference stimulation at a 10 Hz beat frequency. Activity will be reported as the percent change in blood-oxygen-level-dependent (BOLD) signal.
Change in brain connectivity between the nucleus accumbens and other brain regions during temporal interference stimulationDuring fMRI scan on study day (approximately 60 minutes)Functional connectivity between the nucleus accumbens and other brain regions will be measured using fMRI-based analyses during active versus sham temporal interference stimulation. Higher correlation values indicate stronger communication between brain regions. The primary test statistic will be the whole-brain psycho-physiological interaction (PPI) between nucleus accumbens BOLD activity and stimulation condition.

Countries

United States

Contacts

CONTACTJoshua W Brown, PhD
jwmbrown@iu.edu812-855-9282
CONTACTKendall E Moore, BS
kem12@iu.edu812-856-1846
PRINCIPAL_INVESTIGATORJoshua W Brown, PhD

Indiana University, Bloomington

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 11, 2026