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Temporal Interference Methods for Non-invasive Deep Brain Stimulation, Study 1.1

NCT ID: NCT07215299

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-03

Study Completion Date

2026-01-21

Brief Summary

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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

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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 1.1 (Aim 1, Study 1) 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 two 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. The first block will apply active TI stimulation with 2000Hz in one channel and 2020Hz in the other channel. The second block will be a sham TI stimulation, identical to the first block but with the "on" condition immediately ramping down as soon as it reaches 2mA after ramp up. The third and fourth blocks will be identical to the first and second blocks, except that both electrode pairs will stimulate at 2000Hz, resulting in a "NO-TI active" and "NO-TI sham" conditions. The order of blocks, and whether the "on" or "off" condition occurs first within a block, will be counterbalanced across subjects.

Conditions

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Healthy Volunteers

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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

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.

Group Type ACTIVE_COMPARATOR

Temporal Interference (TI) Electrical Stimulation - NAcc TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc TI Sham

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

Intervention Type DEVICE

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.

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

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.

Group Type ACTIVE_COMPARATOR

Temporal Interference (TI) Electrical Stimulation - NAcc TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc TI Sham

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

Intervention Type DEVICE

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.

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

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.

Group Type ACTIVE_COMPARATOR

Temporal Interference (TI) Electrical Stimulation - NAcc TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc TI Sham

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

Intervention Type DEVICE

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.

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

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.

Group Type ACTIVE_COMPARATOR

Temporal Interference (TI) Electrical Stimulation - NAcc TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc TI Sham

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Active

Intervention Type DEVICE

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.

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

Intervention Type DEVICE

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.

Interventions

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Temporal Interference (TI) Electrical Stimulation - NAcc 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 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.

Intervention Type DEVICE

Temporal Interference (TI) Electrical Stimulation - NAcc TI Sham

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.

Intervention Type DEVICE

Temporal Interference (TI) Electrical Stimulation - 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.

Intervention Type DEVICE

Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham

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.

Intervention Type DEVICE

Other Intervention Names

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TI Electrical Neurostimulation TI Neurostimulation TI Electrical Neurostimulation TI Neurostimulation TI Electrical Neurostimulation TI Neurostimulation TI Electrical Neurostimulation TI Neurostimulation

Eligibility Criteria

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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

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Indiana University

OTHER

Sponsor Role lead

Responsible Party

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Joshua Brown, PHD

Professor of Pyschological and Brain Science

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Joshua W Brown, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University, Bloomington

Locations

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Indiana University Bloomington, Imaging Research Facility

Bloomington, Indiana, United States

Site Status

Countries

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United States

Central Contacts

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Joshua W Brown, PhD

Role: CONTACT

Phone: 812-855-9282

Email: [email protected]

Kendall E Moore, BS

Role: CONTACT

Phone: 812-856-1846

Email: [email protected]

Facility Contacts

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Josh W Brown, PhD

Role: primary

Macie Schmitt

Role: backup

References

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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.

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)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Informed Consent Statement Aim 2

View Document

Document Type: Informed Consent Form: Informed Consent Statement Aim 1

View Document

Related Links

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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

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1R21MH140210-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

26941, Study 1.1

Identifier Type: -

Identifier Source: org_study_id