Closed-loop tES-non-invasive Stimulation (CLIBM)

August 15, 2026 updated by: Marcus Kaiser, University of Nottingham

Closed-loop Non-invasive Stimulation for Improving Brain and Mental Health in Healthy Individuals

The goal of this study is to establish if non-invasive closed-loop neuromodulation is an effective approach to enhance cognitive function in healthy 18-40 years old volunteers. The main questions it aims to answer are:

  • Can closed-loop stimulation increase stimulation effectiveness?
  • Can closed-loop focused ultrasound specifically engage with excitatory or inhibitory neural populations in the target structure as measured through MRS?
  • Can observed stimulation outcomes for FUS be predicted through connectome analysis and computational models of indirect changes?

Researchers will compare different closed-loop options to their open-loop counterpart to see if closed-loop approaches can increase efficacy and reduce the variability of the stimulation compared to open-loop approaches.

Participants will:

  • Answer some questionnaires at the start of the study and after each intervention session.
  • Undertake a MRI scanning session.
  • Undertake one open-loop FUS session.
  • Undertake one tES session.
  • Undertake one closed-loop FUS sessions involving tES and FUS, followed by a MRI scanning
  • Undertake one sham FUS session
  • Attend one visit in person to assess eligibility through questionnaires and one cognitive task

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Closed-loop approaches may offer greater efficacy and lower variability across individuals compared to current open-loop stimulation approaches, yet they remain a relatively new approach, with no studies evaluating closed-loop transcranial low-intensity focused ultrasound stimulation (FUS) yet.

For this reason, we will collect and evaluate cognitive, biological and metabolic data from healthy participants, before and after closed-loop and open-loop stimulation interventions. This will allow us to compare our proposed closed-loop stimulation approach to stablished non-invasive techniques and to investigate the underlying mechanisms through which FUS can alter brain activity.

For this study, participants will attend multiple visits. To assess eligibility, participants will attend one initial session in-person before the start of the study.

Following safety guidelines, each participant will receive a maximum of two 1-hour MRI scanning sessions in a single week.

This study will be separated into two blocks of stimulation sessions: one block for tACS-FUS, and another block for TI-FUS. Participants will be randomly allocated to receive one of the blocks.

Before the during recruitment, participants will be asked to complete online some baseline questionnaires such as the O-Life inventory, BECK, MAIA, or STAI. Furthermore, full eligibility will be assessed in person.

At the first appointment, participants will have a brain scan at Sir Peter Mansfield Imaging Centre or Queen's Medical Centre, Nottingham, UK. This will help us to apply the brain stimulation to the right part of the participant's brain, as well as obtain baseline functional, metabolic and structural information.

Participants will be randomly allocated to either receive open-loop FUS (FUS with Sham tES), closed-loop FUS (dual FUS-tES), tES with Sham FUS, or double sham FUS-tES, in the second appointment and the other interventions in the subsequent visits for their assigned block. During all stimulation sessions, we will use an AntNeuro neuronavigation system to guide the location of the transducer.

During either of the stimulation visits, participants will have physiological (EEG) and cognitive markers recorded. Some emotional assessments (i.e., through a short STAI) will be performed before and after stimulation. EEG recordings will be conducted before, during and after stimulation on the same day. Rest-state EEG will be recorded pre-stimulation before the start of the cognitive tasks, and post-stimulation after the end of the cognitive tasks.

The participant will then undergo one cognitive assessment, which will consists on a visual working memory task (delayed-spatial-estimation-task). The task involves visual stimuli, with responses recorded via keyboard. The task is designed to take approximately 5-15 minutes to complete on pre and post-stimulation. The duration of the task during stimulation will be adapted to the duration of the stimulation. Following this, participants will receive the allocated intervention.

Participants will have the same physiological and cognitive assessments recorded during the stimulation and after the stimulation has been completed. For the closed-loop stimulation, participants will also undergo an MRI scanning after the stimulation.

The first visit, consisting of brain scan, will be separated by at least 24 hours from the second visit. Subsequent visits will be separated by at least one week from each other.

During each consecutive appointment, participants will be asked about any changes to their eligibility and continued consent.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation in the study
  • Aged between 18 and 40
  • Good general health
  • Not consume alcohol 48 hours prior study visit
  • Not currently taking any medications (except contraceptive pills) or if on long-term medication for a non-neurological/non-psychiatric condition (r.g. inhalers) to be considered otherwise healthy and stable with no symptoms
  • Be right handedness

Exclusion Criteria:

  • Inability to complete MRI/FUS/TMS/tES safety questionnaire and / or informed consent process.
  • Current or previous diagnosis of a neurological, neurosurgical, psychiatric disorders.
  • Other significant medical condition (specific details to be reviewed by the CI prior to inclusion).
  • Currently pregnant, breast feeding, or on planned pregnancy.
  • Medication intake (such as beta-blocker, glucocorticoids, anti-depressants, anti-inflammatory drugs in the last 7d).
  • Medication intake (such as antidepressants, antipsychotics, anti-epileptics, beta blockers, glucocorticoids, anti-inflammatories, benzodiazepines, hypnotics, sedating antihistamines or any illicit substances in the past seven days).
  • Significant use of medication or recreational drugs that affect the nervous system.
  • Excessive consumption of alcohol.
  • Known allergy to any required consumables (such as aquasonic gel).
  • History of anaphylaxis to any substance
  • Have tightly coiled, curly or voluminous texture hair type (e.g., hair type 3, 4, or afro hair).
  • Having skin disease or sensitive skin on or close to the head.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Open-loop transcranial low-intensity FUS
Transcranial low intensity focused ultrasound stimulation (FUS) with 500kHz transducer for following either the continuous theta burst or intermittent theta burst protocol using the NeuroFus PRO system
Other: Transcranial low intensity focused ultrasound (FUS)
Low intensity focused ultrasound stimulation (FUS) with 500kHz transducer for following either the continuous theta burst or intermittent theta burst protocol using the NeuroFus PRO system
Other Names:
  • TUS
  • LIFU
  • tFUS
Procedure: Magnetic Resonance Imaging
We obtain baseline functional, metabolic and structural information through MRI and MRS scanning
Other Names:
  • MRI
Experimental: Closed-loop transcranial low-intensity FUS
Closed-loop Transcranial Electrical Stimulation by means of tACS or TI delivered through a Digitimer DS5 for brain entrainment phase-locked on peak or trough to transcranial low intensity FUS delivered to dACC through the NeuroFUS PRO system
Other: Transcranial low intensity focused ultrasound (FUS)
Low intensity focused ultrasound stimulation (FUS) with 500kHz transducer for following either the continuous theta burst or intermittent theta burst protocol using the NeuroFus PRO system
Other Names:
  • TUS
  • LIFU
  • tFUS
Procedure: Magnetic Resonance Imaging
We obtain baseline functional, metabolic and structural information through MRI and MRS scanning
Other Names:
  • MRI
Other: transcranial electrical stimulation
Transcranial electrical stimulation (by means of transcranial alternating current stimulation (tACS) or non-invasive temporal interference (TI) electrical stimulation) using the DS5 isolated bipolar constant current stimulator together connected to a wave generator and with two electrodes for tACS (TI implementation will be carried out with two DS5 systems, separate wave generators and four electrodes).
Other Names:
  • tES
Active Comparator: tES alone
tACS or TI delivered through a Digitimer DS5 for brain entrainment phase-locked on peak or trough
Procedure: Magnetic Resonance Imaging
We obtain baseline functional, metabolic and structural information through MRI and MRS scanning
Other Names:
  • MRI
Other: transcranial electrical stimulation
Transcranial electrical stimulation (by means of transcranial alternating current stimulation (tACS) or non-invasive temporal interference (TI) electrical stimulation) using the DS5 isolated bipolar constant current stimulator together connected to a wave generator and with two electrodes for tACS (TI implementation will be carried out with two DS5 systems, separate wave generators and four electrodes).
Other Names:
  • tES
Active Comparator: Sham FUS
FUS delivered to ventricles or FUS and tACS located on head, one of them on or off depending on sham, or active.
Other: Transcranial low intensity focused ultrasound (FUS)
Low intensity focused ultrasound stimulation (FUS) with 500kHz transducer for following either the continuous theta burst or intermittent theta burst protocol using the NeuroFus PRO system
Other Names:
  • TUS
  • LIFU
  • tFUS
Procedure: Magnetic Resonance Imaging
We obtain baseline functional, metabolic and structural information through MRI and MRS scanning
Other Names:
  • MRI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change from Baseline in EEG Power in Alpha Band (8-12Hz)
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in EEG Power in Theta Band (4-7Hz)
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in EEG Power in Beta Band (13-30Hz)
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in EEG Power in Gamma Band (31-45Hz)
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Changes from Baseline in EEG-derived spectral power
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Changes from Baseline in Functional connectivity (e.g., through changes in Phase-locked value (PLV))
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Average Reaction time (ms) measured from the Visual Working memory task
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Average Overall accuracy (%) measured from Visual Working Memory task
Time Frame: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in Target-Region metabolite Concentration measured via Magnetic Resonance Spectroscopy (MRS)
Time Frame: Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Changes from Baseline in Functional Connectivity calculated from functional Magnetic Resonance Imaging (fMRI)
Time Frame: Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Changes from Baseline on Structural connectivity metrics derived from multi-shell diffusion MRI (dMRI) tractography
Time Frame: Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Baseline (Day 1) to immediately after closed-loop post-stimulation intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Structured questionnaire assessing adverse effects of the intervention
Time Frame: Immediately after stimulation, 24 hours after stimulation and 1 week after stimulation
Immediately after stimulation, 24 hours after stimulation and 1 week after stimulation

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nottingham

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marcus Kaiser, PhD, University of Nottingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • F1708

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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