NCT07594795

Brief Summary

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
2mo left

Started May 2026

Shorter than P25 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

First Submitted

Initial submission to the registry

May 11, 2026

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 19, 2026

Completed
11 days until next milestone

Study Start

First participant enrolled

May 30, 2026

Expected
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2026

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Last Updated

May 19, 2026

Status Verified

May 1, 2026

Enrollment Period

2 months

First QC Date

May 11, 2026

Last Update Submit

May 11, 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 dorsal anterior cingulate cortex during 20 Hz versus selected comparison frequency temporal interference stimulation

    Brain activity in the dorsal anterior cingulate cortex will be measured using functional magnetic resonance imaging (fMRI) during temporal interference (TI) stimulation at 20 Hz compared to a selected comparison beat frequency. The comparison frequency will be in the 1-100 Hz range. 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.

    During fMRI scan on study day (approximately 60 minutes)

Secondary Outcomes (3)

  • Change in brain activity in the dorsal anterior cingulate cortex during active versus sham stimulation at 20 Hz

    During fMRI scan on study day (approximately 60 minutes)

  • Change in brain activity in the dorsal anterior cingulate cortex during active versus sham stimulation at the selected comparison frequency

    During fMRI scan on study day (approximately 60 minutes)

  • Change in brain connectivity between the dorsal anterior cingulate cortex and other brain regions during temporal interference stimulation

    During fMRI scan on study day (approximately 60 minutes)

Study Arms (4)

dACC 20Hz Active then Sham; Comparison frequency Active then Sham

ACTIVE COMPARATOR

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the dorsal anterior cingulate cortex using two pairs of carbon fiber electrodes in the following order: 20 Hz TI Active, 20 Hz TI Sham, selected comparison frequency TI Active, then selected comparison frequency TI Sham. The comparison frequency will be within the 1-100 Hz range.

Device: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI Sham

dACC 20Hz Sham then Active; Comparison Frequency Sham then Active

ACTIVE COMPARATOR

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the dorsal anterior cingulate cortex using scalp electrodes. The stimulation order is: 20 Hz TI Sham, 20 Hz TI Active, selected comparison frequency TI Sham, then selected comparison frequency TI Active. The comparison frequency will be in the 1-100 Hz range.

Device: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI Sham

dACC Comparison Frequency Sham then Active; 20Hz Sham then Active

ACTIVE COMPARATOR

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the dorsal anterior cingulate cortex using scalp electrodes. The stimulation order is: selected comparison frequency TI Sham, selected comparison frequency TI Active, 20 Hz TI Sham, then 20 Hz TI Active. The comparison frequency will be in the 1-100 Hz range.

Device: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI Sham

dACC Comparison Frequency Active then Sham; 20Hz Active then Sham

ACTIVE COMPARATOR

Participants in this arm receive temporal interference (TI) electrical stimulation targeting the dorsal anterior cingulate cortex using scalp electrodes. The stimulation order is: selected comparison frequency TI Active, selected comparison frequency TI Sham, 20 Hz TI Active, then 20 Hz TI Sham. The comparison frequency will be in the 1-100 Hz range.

Device: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC 20 Hz TI ShamDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI ActiveDevice: Temporal Interference (TI) Electrical Stimulation - dACC Comparison Frequency TI Sham

Interventions

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies at up to ±5 mA per channel, corresponding to 10 mA peak-to-peak. For the dACC 20 Hz TI Active condition, one channel will deliver 2000 Hz and the other 2020 Hz, producing a 20 Hz beat frequency targeting the dorsal anterior cingulate 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.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
dACC 20Hz Active then Sham; Comparison frequency Active then ShamdACC 20Hz Sham then Active; Comparison Frequency Sham then ActivedACC Comparison Frequency Active then Sham; 20Hz Active then ShamdACC Comparison Frequency Sham then Active; 20Hz Sham then Active

Same setup as the dACC 20 Hz TI Active condition, except that stimulation immediately ramps down after reaching the target intensity following ramp up, producing a sham condition.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
dACC 20Hz Active then Sham; Comparison frequency Active then ShamdACC 20Hz Sham then Active; Comparison Frequency Sham then ActivedACC Comparison Frequency Active then Sham; 20Hz Active then ShamdACC Comparison Frequency Sham then Active; 20Hz Sham then Active

Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies at up to ±5 mA per channel, corresponding to 10 mA peak-to-peak. For the dACC comparison frequency TI Active condition, stimulation will be delivered using a selected beat frequency in the 1-100 Hz range. 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.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
dACC 20Hz Active then Sham; Comparison frequency Active then ShamdACC 20Hz Sham then Active; Comparison Frequency Sham then ActivedACC Comparison Frequency Active then Sham; 20Hz Active then ShamdACC Comparison Frequency Sham then Active; 20Hz Sham then Active

Same setup as the dACC comparison frequency TI Active condition, except that stimulation immediately ramps down after reaching the target intensity following ramp up, producing a sham condition.

Also known as: TI Electrical Neurostimulation, TI Neurostimulation
dACC 20Hz Active then Sham; Comparison frequency Active then ShamdACC 20Hz Sham then Active; Comparison Frequency Sham then ActivedACC Comparison Frequency Active then Sham; 20Hz Active then ShamdACC Comparison Frequency Sham then Active; 20Hz Sham then 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. For Study 1.3, TI stimulation will target the dorsal anterior cingulate cortex, and the beat frequency will be selected and adjusted within the 1-100 Hz range. Study 1.3 will also evaluate whether increased stimulation intensity, up to ±5 mA per channel, improves modulation of BOLD activity in the dorsal anterior cingulate cortex.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Pyschological and Brain Science

Study Record Dates

First Submitted

May 11, 2026

First Posted

May 19, 2026

Study Start (Estimated)

May 30, 2026

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

July 31, 2026

Last Updated

May 19, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will not share

Locations