Closed-loop Brain StimulationCLIBMNCT07671079
Closed-loop tES-non-invasive Stimulation
A study testing Transcranial low intensity focused ultrasound (FUS), transcranial electrical stimulation and Magnetic Resonance Imaging in people with Closed-loop Brain Stimulation, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Closed-loop Brain Stimulation
- What is being tested?
- Transcranial low intensity focused ultrasound (FUS), transcranial electrical stimulation and Magnetic Resonance Imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2026to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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).
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
University of Nottingham
Nottingham
Alicia Dr. Falcon Caro, alicia.falconcaro@nottingham.ac.uk
About this study
Official title: 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?
Read more
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
Read the 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.
- Conditions
- Closed-loop Brain Stimulation
- Being tested
- Transcranial low intensity focused ultrasound (FUS), transcranial electrical stimulation, Magnetic Resonance Imaging
- Keywords
- neuromodulation, electrical stimulation, transcranial low-intensity focused ultrasound stimulation, closed-loop neuromodulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial low intensity focused ultrasound (FUS)Other
Also called LIFU, tFUS, TUS
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
transcranial electrical stimulationOther
Also called tES
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).
Magnetic Resonance ImagingProcedure or surgery
Also called MRI
We obtain baseline functional, metabolic and structural information through MRI and MRS scanning
| Study group | Role | What they receive |
|---|---|---|
| Open-loop transcranial low-intensity FUS | Active comparator | 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 Receives: Other: Transcranial low intensity focused ultrasound (FUS); Procedure: Magnetic Resonance Imaging |
| Closed-loop transcranial low-intensity FUS | Experimental | 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 Receives: Other: Transcranial low intensity focused ultrasound (FUS); Other: transcranial electrical stimulation; Procedure: Magnetic Resonance Imaging |
| tES alone | Active comparator | tACS or TI delivered through a Digitimer DS5 for brain entrainment phase-locked on peak or trough Receives: Other: transcranial electrical stimulation; Procedure: Magnetic Resonance Imaging |
| Sham FUS | Active comparator | FUS delivered to ventricles or FUS and tACS located on head, one of them on or off depending on sham, or active. Receives: Other: Transcranial low intensity focused ultrasound (FUS); Procedure: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in EEG Power in Alpha Band (8-12Hz)
Measured: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in EEG Power in Theta Band (4-7Hz)
Measured: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in EEG Power in Beta Band (13-30Hz)
Measured: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Change from Baseline in EEG Power in Gamma Band (31-45Hz)
Measured: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Changes from Baseline in EEG-derived spectral power
Measured: 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))
Measured: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Average Reaction time (ms) measured from the Visual Working memory task
Measured: Baseline to 10 weeks, measured immediately before, during, and immediately after stimulation
Average Overall accuracy (%) measured from Visual Working Memory task
Measured: 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)
Measured: Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Changes from Baseline in Functional Connectivity calculated from functional Magnetic Resonance Imaging (fMRI)
Measured: 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
Measured: Baseline (Day 1) to immediately after closed-loop post-stimulation intervention
Secondary outcomes (1)
Structured questionnaire assessing adverse effects of the intervention
Measured: Immediately after stimulation, 24 hours after stimulation and 1 week after stimulation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2026
- Study startSep 2026 (estimated)
- Primary completionAug 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Closed-loop Brain StimulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marcus Kaiser, University of Nottingham
- Investigators
- Marcus Kaiser, PhD, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07671079
- Sponsor's protocol ID
- F1708
- Acronym
- CLIBM
- Status last verified
- Aug 2026
- First submitted
- 22 Jun 2026
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zhai Z, Ren L, Song Z, Xiang Q, Zhuo K, Zhang S, Li X, Zhang Y, Jiao X, Tong S, Sun J, Liu D. The efficacy of low-intensity transcranial ultrasound stimulation on negative symptoms in schizophrenia: A double-blind, randomized sham-controlled study. Brain Stimul. 2023 May-Jun;16(3):790-792. doi: 10.1016/j.brs.2023.04.021. Epub 2023 Apr 29. No abstract available.
PubMed 37121354Sarica C, Nankoo JF, Fomenko A, Grippe TC, Yamamoto K, Samuel N, Milano V, Vetkas A, Darmani G, Cizmeci MN, Lozano AM, Chen R. Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety. Brain Stimul. 2022 May-Jun;15(3):737-746. doi: 10.1016/j.brs.2022.05.002. Epub 2022 May 6.
PubMed 35533835Raco V, Bauer R, Tharsan S, Gharabaghi A. Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study. Front Cell Neurosci. 2016 May 25;10:143. doi: 10.3389/fncel.2016.00143. eCollection 2016.
PubMed 27252625Briley PM, Boutry C, Webster L, Veniero D, Harvey-Seutcheu C, Jung J, Liddle PF, Morriss R. Intermittent theta burst stimulation with synchronised transcranial alternating current stimulation leads to enhanced frontal theta oscillations and a positive shift in emotional bias. Imaging Neurosci (Camb). 2024 Jan 25;2:imag-2-00073. doi: 10.1162/imag_a_00073. eCollection 2024.
PubMed 40800403Nakazono H, Ogata K, Takeda A, Yamada E, Oka S, Tobimatsu S. A specific phase of transcranial alternating current stimulation at the beta frequency boosts repetitive paired-pulse TMS-induced plasticity. Sci Rep. 2021 Jun 23;11(1):13179. doi: 10.1038/s41598-021-92768-x.
PubMed 34162993Zrenner C, Desideri D, Belardinelli P, Ziemann U. Real-time EEG-defined excitability states determine efficacy of TMS-induced plasticity in human motor cortex. Brain Stimul. 2018 Mar-Apr;11(2):374-389. doi: 10.1016/j.brs.2017.11.016. Epub 2017 Nov 24.
PubMed 29191438Gold JM. Cognitive deficits as treatment targets in schizophrenia. Schizophr Res. 2004 Dec 15;72(1):21-8. doi: 10.1016/j.schres.2004.09.008.
PubMed 15531404
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-loop Non-invasive Stimulation for Improving Brain and Mental Health in Healthy Individuals
- ClinicalTrials.gov ID
- NCT07671079
- Acronym / sponsor ID
- CLIBM / F1708
- Conditions
- Closed-loop Brain Stimulation
- Keywords
- neuromodulation, electrical stimulation, transcranial low-intensity focused ultrasound stimulation, closed-loop neuromodulation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 26 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Open-loop transcranial low-intensity FUS | Active comparator | Other: Transcranial low intensity focused ultrasound (FUS), Procedure: Magnetic Resonance ImagingTranscranial 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 |
| Closed-loop transcranial low-intensity FUS | Experimental | Other: Transcranial low intensity focused ultrasound (FUS), Other: transcranial electrical stimulation, Procedure: Magnetic Resonance ImagingClosed-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 |
| tES alone | Active comparator | Other: transcranial electrical stimulation, Procedure: Magnetic Resonance ImagingtACS or TI delivered through a Digitimer DS5 for brain entrainment phase-locked on peak or trough |
| Sham FUS | Active comparator | Other: Transcranial low intensity focused ultrasound (FUS), Procedure: Magnetic Resonance ImagingFUS delivered to ventricles or FUS and tACS located on head, one of them on or off depending on sham, or active. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial low intensity focused ultrasound (FUS)Also: LIFU, tFUS, TUSLow 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 | Closed-loop transcranial low-intensity FUS, Open-loop transcranial low-intensity FUS, Sham FUS |
| transcranial electrical stimulationAlso: tESTranscranial 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 | Closed-loop transcranial low-intensity FUS, tES alone |
| Magnetic Resonance ImagingAlso: MRIWe obtain baseline functional, metabolic and structural information through MRI and MRS scanning | Procedure or surgery | Closed-loop transcranial low-intensity FUS, Open-loop transcranial low-intensity FUS, Sham FUS, tES alone |
Primary outcome
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
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
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
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
Changes from Baseline in EEG-derived spectral power
Time frame: 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
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
Average Overall accuracy (%) measured from Visual Working Memory task
Time frame: 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
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
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
1 secondary outcome
Structured questionnaire assessing adverse effects of the intervention
Time frame: Immediately after stimulation, 24 hours after stimulation and 1 week after stimulation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Background: PubMed 37121354Zhai Z, Ren L, Song Z, Xiang Q, Zhuo K, Zhang S, Li X, Zhang Y, Jiao X, Tong S, Sun J, Liu D. The efficacy of low-intensity transcranial ultrasound stimulation on negative symptoms in schizophrenia: A double-blind, randomized sham-controlled study. Brain Stimul. 2023 May-Jun;16(3):790-792. doi: 10.1016/j.brs.2023.04.021. Epub 2023 Apr 29. No abstract available.
- Background: PubMed 35533835Sarica C, Nankoo JF, Fomenko A, Grippe TC, Yamamoto K, Samuel N, Milano V, Vetkas A, Darmani G, Cizmeci MN, Lozano AM, Chen R. Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety. Brain Stimul. 2022 May-Jun;15(3):737-746. doi: 10.1016/j.brs.2022.05.002. Epub 2022 May 6.
- Background: PubMed 27252625Raco V, Bauer R, Tharsan S, Gharabaghi A. Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study. Front Cell Neurosci. 2016 May 25;10:143. doi: 10.3389/fncel.2016.00143. eCollection 2016.
- Background: PubMed 40800403Briley PM, Boutry C, Webster L, Veniero D, Harvey-Seutcheu C, Jung J, Liddle PF, Morriss R. Intermittent theta burst stimulation with synchronised transcranial alternating current stimulation leads to enhanced frontal theta oscillations and a positive shift in emotional bias. Imaging Neurosci (Camb). 2024 Jan 25;2:imag-2-00073. doi: 10.1162/imag_a_00073. eCollection 2024.
- Background: PubMed 34162993Nakazono H, Ogata K, Takeda A, Yamada E, Oka S, Tobimatsu S. A specific phase of transcranial alternating current stimulation at the beta frequency boosts repetitive paired-pulse TMS-induced plasticity. Sci Rep. 2021 Jun 23;11(1):13179. doi: 10.1038/s41598-021-92768-x.
- Background: PubMed 29191438Zrenner C, Desideri D, Belardinelli P, Ziemann U. Real-time EEG-defined excitability states determine efficacy of TMS-induced plasticity in human motor cortex. Brain Stimul. 2018 Mar-Apr;11(2):374-389. doi: 10.1016/j.brs.2017.11.016. Epub 2017 Nov 24.
- Background: PubMed 15531404Gold JM. Cognitive deficits as treatment targets in schizophrenia. Schizophr Res. 2004 Dec 15;72(1):21-8. doi: 10.1016/j.schres.2004.09.008.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marcus Kaiser, PhD principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial low intensity focused ultrasound (FUS), transcranial electrical stimulation and Magnetic Resonance Imaging in people with Closed-loop Brain Stimulation, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. Falcon Caro (+44 115 823 2866, alicia.falconcaro@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07671079, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.