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

NCT ID: NCT07339072

Last Updated: 2026-02-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-03
• Study Completion Date: 2027-04-08

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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

NAcc 5 Hz TI Active, then NAcc 5 Hz TI Sham, then NAcc 10 Hz TI Active, then NAcc 10 Hz TI Sham

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the nucleus accumbens using two pairs of carbon fiber electrodes in the following order: 5 Hz TI Active, 5 Hz TI Sham, 10 Hz TI Active, then 10 Hz TI Sham.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

NAcc 5 Hz TI Sham, then NAcc 5 Hz TI Active, then NAcc 10 Hz TI Sham, then NAcc 10 Hz TI Active

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the nucleus accumbens using two pairs of carbon fiber electrodes in the following order: 5 Hz TI Sham, 5 Hz TI Active, 10 Hz TI Sham, then 10 Hz TI Active.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

NAcc 10 Hz TI Sham, then NAcc 10 Hz TI Active, then NAcc 5 Hz TI Sham, then NAcc 5 Hz TI Active

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the nucleus accumbens using two pairs of carbon fiber electrodes in the following order: 10 Hz TI Sham, 10 Hz TI Active, 5 Hz TI Sham, then 5 Hz TI Active.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

NAcc 10 Hz TI Active, then NAcc 10 Hz TI Sham, then NAcc 5 Hz TI Active, then NAcc 5 Hz TI Sham

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the nucleus accumbens using two pairs of carbon fiber electrodes in the following order: 10 Hz TI Active, 10 Hz TI Sham, 5 Hz TI Active, then 5 Hz TI Sham.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

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

Intervention Type: DEVICE

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.

Interventions

Temporal 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.

Intervention Type: DEVICE

Temporal 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.

Intervention Type: DEVICE

Temporal 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.

Intervention Type: DEVICE

Temporal 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.

Intervention Type: DEVICE

Other Intervention Names

TI Electrical Neurostimulation; TI Neurostimulation; TI Electrical Neurostimulation; TI Neurostimulation; TI Electrical Neurostimulation; TI Neurostimulation; TI Electrical Neurostimulation; TI Neurostimulation

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Joshua Brown, PHD

Professor of Pyschological and Brain Science

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua W Brown, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University, Bloomington

Locations

Indiana University Bloomington, Imaging Research Facility

Bloomington, Indiana, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Joshua W Brown, PhD

Role: CONTACT

jwmbrown@iu.edu

812-855-9282

Kendall E Moore, BS

Role: CONTACT

kem12@iu.edu

812-856-1846

Facility Contacts

Josh W Brown, PhD

Role: primary

cclab@iu.edu

812-856-1846

Kendall E Moore, BS

Role: backup

kem12@iu.edu

(812) 856-1846

References

Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19. Erratum In: Nat Neurosci. 2023 Dec;26(12):2252. doi: 10.1038/s41593-023-01517-y.

Reference Type: BACKGROUND

PMID: 37857775 (View on PubMed)

Modak P, Fine J, Colon B, Need E, Cheng H, Hulvershorn L, Finn P, Brown JW. Temporal interference electrical neurostimulation at 20 Hz beat frequency leads to increased fMRI BOLD activation in orbitofrontal cortex in humans. Brain Stimul. 2024 Jul-Aug;17(4):867-875. doi: 10.1016/j.brs.2024.07.014. Epub 2024 Jul 24.

Reference Type: BACKGROUND

PMID: 39059712 (View on PubMed)

Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.

Reference Type: BACKGROUND

PMID: 28575667 (View on PubMed)

Related Links

https://ccsrv1.psych.indiana.edu/cclab/

Lab website for study. The Cognitive Control Lab aims to understand the neural mechanisms of goal-directed behavior, using a combination of fMRI, computational neural modeling, and neurostimulation methods in healthy and clinical human populations.

https://reporter.nih.gov/project-details/11119339

Project details for the NIMH-funded study on temporal interference stimulation, including abstract, funding, and key personnel.

Other Identifiers

1R21MH140210-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

26941, Study 1.2

Identifier Type: -

Identifier Source: org_study_id