NCT07215299

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for not_applicable healthy-volunteers

Timeline
9mo left

Started Nov 2025

Typical duration for not_applicable healthy-volunteers

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress43%
Nov 2025Feb 2027

First Submitted

Initial submission to the registry

September 29, 2025

Completed
11 days until next milestone

First Posted

Study publicly available on registry

October 10, 2025

Completed
1 month until next milestone

Study Start

First participant enrolled

November 12, 2025

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 2, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 2, 2027

Last Updated

February 10, 2026

Status Verified

February 1, 2026

Enrollment Period

1.2 years

First QC Date

September 29, 2025

Last Update Submit

February 6, 2026

Conditions

Keywords

Temporal InterferencefMRIBOLD SignalCognitive ControlDorsal Anterior Cingulate CortexNon-invasive deep brain stimulationNeurostimulation

Outcome Measures

Primary Outcomes (1)

  • Change in brain activity in the nucleus accumbens during active versus sham stimulation

    Brain activity in the nucleus accumbens will be measured using functional magnetic resonance imaging (fMRI) during active temporal interference (TI) brain stimulation compared to sham (placebo) stimulation. Activity will be reported as the percent change in blood-oxygen-level-dependent (BOLD) signal, which reflects changes in brain activity. Higher BOLD values indicate stronger brain activation.

    During fMRI scan on study day (approximately 60 minutes)

Secondary Outcomes (3)

  • Change in brain activity in the nucleus accumbens during no-TI active versus no-TI sham high-frequency stimulation

    During fMRI scan on study day (approximately 60 minutes)

  • Change in brain activity in the nucleus accumbens during active TI stimulation versus active no-TI stimulation

    During fMRI scan on study day (approximately 60 minutes)

  • Change in brain connectivity between the nucleus accumbens and other brain regions during stimulation

    During fMRI scan on study day (approximately 60 minutes)

Study Arms (4)

NAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI Sham

ACTIVE COMPARATOR

Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI Sham.

Device: Temporal Interference (TI) Electrical Stimulation - NAcc TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI Sham

ACTIVE COMPARATOR

Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI Sham.

Device: Temporal Interference (TI) Electrical Stimulation - NAcc TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

NAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active

ACTIVE COMPARATOR

Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active.

Device: Temporal Interference (TI) Electrical Stimulation - NAcc TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

NAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI Active

ACTIVE COMPARATOR

Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI Active.

Device: Temporal Interference (TI) Electrical Stimulation - NAcc TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

Interventions

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Active condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI ShamNAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI ActiveNAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI ShamNAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Sham condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the Active TI condition), the stimulation in the NAcc TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI ShamNAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI ActiveNAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI ShamNAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Active condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI ShamNAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI ActiveNAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI ShamNAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Sham condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the NAcc No-TI Active condition), the stimulation in the NAcc No-TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI ShamNAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI ActiveNAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI ShamNAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Indiana University Bloomington, Imaging Research Facility

Bloomington, Indiana, 47408, United States

RECRUITING

Related Publications (3)

  • 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.

    PMID: 37857775BACKGROUND
  • 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.

    PMID: 39059712BACKGROUND
  • 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.

    PMID: 28575667BACKGROUND

Related Links

Study Officials

  • Joshua W Brown, PhD

    Indiana University, Bloomington

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua W Brown, PhD

CONTACT

Kendall E Moore, BS

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: 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 1.1, a 20Hz beat frequency will be evaluated for its effect on the nucleus accumbens.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Pyschological and Brain Science

Study Record Dates

First Submitted

September 29, 2025

First Posted

October 10, 2025

Study Start

November 12, 2025

Primary Completion (Estimated)

February 2, 2027

Study Completion (Estimated)

February 2, 2027

Last Updated

February 10, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations