SERENE Low-Intensity Focused Ultrasound for Cognitive Control

November 2, 2026 updated by: University of Minnesota

Suicide-related Experience Reduction Via Enhancement of Neuroplasticity

SERENE is an experimental study evaluating low-intensity focused ultrasound neuromodulation of cognitive control circuitry in adults with a lifetime history of suicide attempt or suicidal ideation, but without current suicidality.

Participants will complete screening, cognitive control tasks, MRI/fMRI, ecological momentary assessments, and low-intensity focused ultrasound neuromodulation using the DIADEM system. The study will examine whether low-intensity focused ultrasound (LIFU) neuromodulation changes cognitive control performance measured by the Multi-Source Interference Task (MSIT) and EEG event-related spectral power in the alpha and theta frequency bands.

The study will also examine the time course of LIFU effects and explore whether changes in cognitive control circuitry relate to self-reported experiences, including mood, anxiety, psychosis symptoms, suicidal ideation, and emotion regulation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

SERENE is an experimental study designed to test a personalized, non-invasive neuromodulation technique to investigate the neural basis of cognitive control.

The study will enroll adults with a lifetime history of suicide attempt or suicidal ideation, but without current suicidal ideation or behavior. Participants will be screened using the Columbia-Suicide Severity Rating Scale to confirm suicide history and exclude current suicidality. Participants will also complete MRI/fMRI-based cognitive control screening to identify cognitive control circuit function.

Participants will complete baseline cognitive and self-report assessments, including computerized cognitive tasks and clinical/self-report measures. Ecological momentary assessments will be completed before and after neuromodulation to assess symptoms and daily-life experiences related to cognitive control, including mood, anxiety, psychosis-related symptoms, suicidal ideation, and emotion regulation.

The study intervention is low-intensity focused ultrasound neuromodulation delivered using the DIADEM system. LIFU will be applied to deep brain regions involved in cognitive control, including subregions of the internal capsule and connected brain regions. During LIFU visits, participants will complete the Multi-Source Interference Task to assess cognitive control. EEG and fMRI may also be collected to evaluate neurocircuitry changes associated with LIFU.

The primary objective is to evaluate the effect of LIFU on cognitive control and associated circuitry. The study will also examine the time course of this effect, whether responses differ by baseline cognitive control circuit function, and whether changes in circuitry relate to self-reported experiences.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Michael V Bronstein, PhD
  • Phone Number: 781-492-5644
  • Email: brons139@umn.edu

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Institute for the Developing Brain
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Lifetime history of suicide attempt or suicidal ideation, as determined by the Columbia-Suicide Severity Rating Scale
  • Score in specified ranges on measures of cognitive control behavior and/or cognitive control circuit function
  • No current suicide ideation or behavior within the past 3 months, as determined by the Columbia-Suicide Severity Rating Scale
  • Age 18 to 65 years
  • Speaks and understands English
  • Primary user of a smartphone

Exclusion Criteria:

  • Under age 18
  • Neurological disorder that may affect fMRI scan results or cause reaction to LIFU to differ from healthy adults
  • Regular use of psychoactive medication, except PRN use if the participant is willing and able to abstain during the study period
  • Psychiatric hospitalization within the past 3 months
  • Contraindication to fMRI scanning, including claustrophobia, unremovable piercings, pregnancy, medical devices such as pacemakers, or a movement or sleep disorder
  • Pregnant or may have reason to believe they are pregnant
  • Diagnosis of certain psychiatric conditions, such as schizophrenia, bipolar disorder, or a developmental disorder other than ADHD
  • Any other neurological, autoimmune, or medical disorder that may inhibit participation
  • Children
  • Pregnant women/persons
  • Fetuses
  • Neonates
  • Prisoners
  • Adults lacking capacity to consent or adults with diminished or fluctuating capacity to consent
  • Non-English speakers
  • Individuals unable to read
  • Employees of the researcher
  • Students of the researcher
  • Individuals approached during a stressful situation, such as an emergency room setting or childbirth
  • Individuals with fear of negative consequences for not participating
  • Any other circumstance that could increase vulnerability to coercion or exploitation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DIADEM LIFU Neuromodulation

Participants will receive low-intensity focused ultrasound neuromodulation using the DIADEM device while completing cognitive control tasks. Stimulation may be applied to subregions of the internal capsule and connected brain regions to identify targets that modulate cognitive control performance or circuitry.
Device: DIADEM Low-Intensity Focused Ultrasound Neuromodulation

Low-intensity focused ultrasound neuromodulation will be delivered using the SPIRE DIADEM device. LIFU will be applied to subregions of deep brain circuitry involved in cognitive control, including regions within the dorsal or ventral internal capsule, surrounding striatal nuclei, and/or connected brain areas. Stimulation will be delivered by trained study staff according to device safety and screening procedures.

Other Names:
  • SPIRE DIADEM System
  • LIFU Neuromodulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Reaction Time During the Multi-Source Interference Task Following LIFU at Different Internal Capsule Sites
Time Frame: Baseline and during MSIT task blocks corresponding to each internal capsule LIFU sonication site

Cognitive control performance will be assessed using the Multi-Source Interference Task (MSIT), a computerized cognitive control task. Reaction time will be measured in milliseconds. The MSIT will be administered in blocks, with one block corresponding to each internal capsule sonication site. Mean reaction time will be calculated separately for each block and compared with baseline MSIT mean reaction time. Lower reaction times indicate faster task performance.
Baseline and during MSIT task blocks corresponding to each internal capsule LIFU sonication site
Event-Related EEG Alpha-Band Spectral Power Following LIFU
Time Frame: During post-LIFU MSIT assessment at each internal capsule sonication site

EEG alpha-band activity will be assessed using event-related spectral power during the Multi-Source Interference Task (MSIT) following LIFU. Spectral power will be baseline-normalized using a pre-stimulus reference interval from -500 to -100 milliseconds relative to the target event. Baseline normalization will be performed in the linear power domain, with results expressed in decibels (dB).
During post-LIFU MSIT assessment at each internal capsule sonication site
Event-Related EEG Theta-Band Spectral Power Following LIFU
Time Frame: During post-LIFU MSIT assessment at each internal capsule sonication site

EEG theta-band activity will be assessed using event-related spectral power during the Multi-Source Interference Task (MSIT) following LIFU. Spectral power will be baseline-normalized using a pre-stimulus reference interval from -500 to -100 milliseconds relative to the target event. Baseline normalization will be performed in the linear power domain, with results expressed in decibels (dB).
During post-LIFU MSIT assessment at each internal capsule sonication site
Time Course of Mean Reaction Time During the Multi-Source Interference Task Following LIFU
Time Frame: During repeated MSIT assessments across LIFU sonication sessions and through post-treatment follow-up within 2 weeks

The time course of LIFU effects on cognitive control will be evaluated using repeated mean reaction time measurements obtained during the Multi-Source Interference Task (MSIT). Reaction time will be measured in milliseconds and summarized for each assessment block. Mean reaction time will be compared across the repeated assessments to evaluate changes in cognitive control performance over time. Lower values indicate faster task performance.
During repeated MSIT assessments across LIFU sonication sessions and through post-treatment follow-up within 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in MSIT Mean Reaction Time From Baseline Following LIFU at Different Internal Capsule Sites
Time Frame: Baseline and during MSIT task blocks corresponding to each internal capsule LIFU sonication site

Differential response to LIFU across internal capsule stimulation sites will be assessed using mean reaction time during the Multi-Source Interference Task (MSIT), measured in milliseconds. Mean reaction time will be calculated separately for the MSIT block corresponding to each sonication site. Change will be calculated as the mean reaction time following sonication at each site minus the baseline mean reaction time. Negative change values indicate faster responses relative to baseline. Changes will be compared across sonication sites.
Baseline and during MSIT task blocks corresponding to each internal capsule LIFU sonication site
Change in Momentary Active Suicidal Ideation Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary active suicidal ideation will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Passive Suicidal Ideation Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary passive suicidal ideation will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Depression Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary depressive symptoms will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Rumination Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary rumination will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Physical Pain Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary physical pain will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Co-dampening Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary co-dampening will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Hallucination Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary experiences of hallucinations will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU
Change in Momentary Persecutory Experience Rating Measured by Ecological Momentary Assessment
Time Frame: Twice daily for 3 days before and 3 days after LIFU

Momentary persecutory experiences will be assessed using a study-adapted ecological momentary assessment (EMA) item delivered through participants' smartphones. Responses are rated on a 5-point Likert scale from 1 to 5.
Twice daily for 3 days before and 3 days after LIFU

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Investigators

  • Principal Investigator: Michael V Bronstein, PhD, University of Minnesota
  • Study Director: Alik S Widge, MD,PhD, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2027

Primary Completion (Estimated)

September 20, 2028

Study Completion (Estimated)

September 20, 2028

Study Registration Dates

First Submitted

October 13, 2026

First Submitted That Met QC Criteria

November 2, 2026

First Posted (Actual)

November 6, 2026

Study Record Updates

Last Update Posted (Actual)

November 6, 2026

Last Update Submitted That Met QC Criteria

November 2, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00028755

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe