Trial Outcomes & Findings for Temporal Interference Methods for Non-invasive Deep Brain Stimulation, Study 1.1 (NCT NCT07215299)

Last Updated: 2026-08-03

Results Overview

Brain activity in the nucleus accumbens was measured using functional magnetic resonance imaging (fMRI) during active temporal interference (TI) brain stimulation compared to sham stimulation. Activity change from baseline (no stimulation) was quantified using region-of-interest (ROI) beta estimates extracted from the nucleus accumbens. The beta estimates were derived from blood-oxygen-level-dependent (BOLD) signal changes measured during fMRI and reflect the magnitude of task-related neural activation within the ROI. Higher beta values indicate greater task-related activation. Whole-brain voxelwise analyses did not identify statistically significant activation clusters after correction for multiple comparisons; therefore, descriptive ROI-level beta estimates are reported.

Recruitment status

COMPLETED

Study phase

Target enrollment

30 participants

Primary outcome timeframe

During fMRI scanning for each study session (active and sham stimulation), approximately 60 minutes

Results posted on

2026-08-03

Participant Flow

Participants were recruited from November 2025 to February 2026 through community and campus advertisements, including Craigslist, flyers posted in Bloomington community locations and on the Indiana University campus, All IN for Health online ads, and Facebook posts from the Cognitive Control Lab page.

Participants completed eligibility and MRI safety screening before assignment. This within-subject crossover study assigned all participants to receive TI Active, TI Sham, No-TI Active, and No-TI Sham once each, with the order counterbalanced across 22 randomized block sequences. There was no separate run-in or washout period before assignment. This record reports results for Study 1.1 only; additional studies described in the protocol are reported separately.

Participant milestones

Participant milestones
Measure	All Participants All participants received active temporal interference (TI) stimulation, sham TI stimulation, active no-temporal interference (no-TI) high-frequency stimulation, and sham no-TI high-frequency stimulation targeting the nucleus accumbens during a single fMRI session. Each participant received all four stimulation conditions once, with the order of the stimulation blocks counterbalanced across 22 randomized stimulation sequences. This record reports participants enrolled in Study 1.1 only. Additional studies described in the protocol are reported separately.
Overall Study STARTED	30
Overall Study Received TI Active	30
Overall Study Received TI Sham	30
Overall Study Received No-TI Active	30
Overall Study Received No-TI Sham	30
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=30 Participants All participants received active TI stimulation, sham TI stimulation, active no-TI high-frequency stimulation, and sham no-TI high-frequency stimulation targeting the nucleus accumbens during the fMRI session. The order of stimulation conditions and starting on/off stimulation state were counterbalanced across participants.
Age, Categorical <=18 years	1 Participants n=20 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=20 Participants
Age, Categorical >=65 years	0 Participants n=20 Participants
Sex: Female, Male Female	20 Participants n=20 Participants
Sex: Female, Male Male	10 Participants n=20 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=20 Participants
Race (NIH/OMB) Asian	12 Participants n=20 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants
Race (NIH/OMB) Black or African American	1 Participants n=20 Participants
Race (NIH/OMB) White	16 Participants n=20 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=20 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=20 Participants

PRIMARY outcome

Timeframe: During fMRI scanning for each study session (active and sham stimulation), approximately 60 minutes

Population: Participants contributed data to both active TI and sham TI conditions as part of the within-subject crossover design. Three participants were excluded from the outcome analysis because complete usable imaging and behavioral data were not available for analysis.

Outcome measures

Outcome measures
Measure	Sham TI Stimulation n=27 Participants BOLD signal in the nucleus accumbens measured during sham 20 Hz temporal interference stimulation.	Active TI Stimulation n=27 Participants BOLD signal in the nucleus accumbens measured during active 20 Hz temporal interference stimulation.
Change From Baseline (no Stimulation) in Brain Activity in the Nucleus Accumbens During Active Versus Sham Stimulation	0.038843657 Nucleus accumbens beta estimate Standard Error 0.029097707	0.044393334 Nucleus accumbens beta estimate Standard Error 0.056429912

SECONDARY outcome

Timeframe: During fMRI scanning for each study session (active and sham no-TI stimulation conditions), approximately 60 minutes

Population: Participants contributed data to both active no-TI and sham no-TI conditions as part of the within-subject crossover design. Three participants were excluded from the outcome analysis because complete usable imaging and behavioral data were not available for analysis.

Brain activity in the nucleus accumbens was measured using functional magnetic resonance imaging (fMRI) during no-temporal interference (no-TI) control stimulation, in which both electrode pairs delivered the same frequency. Change in activity from baseline (no stimulation) was quantified using region-of-interest (ROI) beta estimates extracted from the nucleus accumbens during NO-TI active versus NO-TI sham high-frequency stimulation to determine whether high-frequency stimulation alone altered brain activity. The beta estimates were derived from blood-oxygen-level-dependent (BOLD) signal changes measured during fMRI and reflect the magnitude of task-related neural activation within the ROI. Higher beta values indicate greater task-related activation. Whole-brain voxelwise analyses did not identify statistically significant activation differences after correction for multiple comparisons; therefore, descriptive ROI-level beta estimates are reported.

Outcome measures

Outcome measures
Measure	Sham TI Stimulation n=27 Participants BOLD signal in the nucleus accumbens measured during sham 20 Hz temporal interference stimulation.	Active TI Stimulation n=27 Participants BOLD signal in the nucleus accumbens measured during active 20 Hz temporal interference stimulation.
Change From Baseline (no Stimulation) in Brain Activity in the Nucleus Accumbens During No-TI Active Versus No-TI Sham High-frequency Stimulation	0.022811615 Nucleus accumbens beta estimate Standard Error 0.050208561	-0.038527468 Nucleus accumbens beta estimate Standard Error 0.026485881

SECONDARY outcome

Timeframe: During fMRI scanning for each study session (active TI and active no-TI stimulation conditions), approximately 60 minutes

Population: Participants contributed data to both active TI and active no-TI conditions as part of the within-subject crossover design. Three participants were excluded from the outcome analysis because complete usable imaging and behavioral data were not available for analysis.

Brain activity in the nucleus accumbens was compared between active temporal interference (TI) stimulation and active high-frequency no-temporal interference (no-TI) stimulation using functional magnetic resonance imaging (fMRI). Change in activity from baseline (no stimulation) was quantified using region-of-interest (ROI) beta estimates extracted from the nucleus accumbens to determine whether TI stimulation produced greater task-related activation than high-frequency stimulation alone. The beta estimates were derived from blood-oxygen-level-dependent (BOLD) signal changes measured during fMRI and reflect the magnitude of task-related neural activation within the ROI. Higher beta values indicate greater task-related activation. Whole-brain voxelwise analyses did not identify statistically significant activation differences after correction for multiple comparisons; therefore, descriptive ROI-level beta estimates are reported.

Outcome measures

Outcome measures
Measure	Sham TI Stimulation n=27 Participants BOLD signal in the nucleus accumbens measured during sham 20 Hz temporal interference stimulation.	Active TI Stimulation n=27 Participants BOLD signal in the nucleus accumbens measured during active 20 Hz temporal interference stimulation.
Change From Baseline (no Stimulation) in Brain Activity in the Nucleus Accumbens During Active TI Stimulation Versus Active No-TI Stimulation	-0.038527468 Nucleus accumbens beta estimate Standard Error 0.026485881	0.044393334 Nucleus accumbens beta estimate Standard Error 0.056429912

SECONDARY outcome

Timeframe: During fMRI scanning for each study session (active and sham stimulation conditions), approximately 60 minutes

Population: No participants were analyzed because no significant activation clusters were identified, so a seed region could not be defined for the connectivity (PPI) analysis.

Functional connectivity between the nucleus accumbens and other brain regions was planned to be evaluated using fMRI-based psycho-physiological interaction (PPI) analyses during active versus sham temporal interference (TI) stimulation. Higher correlation values indicate stronger functional connectivity between brain regions. The primary test statistic was the whole-brain interaction term between seed-region BOLD activity and stimulation condition (active vs. sham TI). This analysis was not performed because no statistically significant activation clusters were identified from which to define a seed region.

Outcome measures

Outcome data not reported

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Joshua W. Brown, Principal Investigator

Indiana University Bloomington

Phone: (812) 855-9282

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place