Focused Ultrasound for Bipolar Disorder

Overseen By Darin Dougherty, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Neurological disorder, Psychosis, MRI contraindications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with bipolar disorder using transcranial focused ultrasound (tFUS) to target the amygdala, a brain region involved in emotion regulation. Researchers aim to determine if this approach can alter brain activity and improve mood symptoms. Participants must have a diagnosis of bipolar disorder (either BD-I or BD-II) and experience significant mood symptoms. This trial may suit those with bipolar disorder seeking new treatment options. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that transcranial focused ultrasound is safe for treating bipolar disorder?

Studies have shown that low-intensity transcranial focused ultrasound (tFUS) can reduce activity in the amygdala, the brain region involved in processing emotions. This non-invasive technique does not require surgery or entering the body. Research indicates that previous small studies have generally found this method safe and well-tolerated. However, its specific use for bipolar disorder remains under investigation, with limited safety information available for this condition. The current trial phase primarily aims to ensure the treatment's safety and practicality before progressing to larger studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar disorder?

Low-Intensity Focused Ultrasound (tFUS) for Bipolar Disorder is unique because it uses sound waves to target the amygdala directly, unlike standard medications such as mood stabilizers and antipsychotics, which affect brain chemistry more broadly. This non-invasive technique offers a novel mechanism by modulating specific brain regions associated with mood regulation without the systemic side effects common in traditional drugs. Researchers are excited because this method could provide quicker relief with potentially fewer side effects, offering a more precise approach to managing bipolar disorder.

What evidence suggests that transcranial focused ultrasound is effective for bipolar disorder?

Research has shown that using focused ultrasound on the amygdala may help reduce mood and anxiety symptoms. One study found that participants experienced less severe depression symptoms, as measured by a specific test, and showed changes in brain activity. Another study found that this treatment reduced general distress symptoms. In this trial, participants will receive low-intensity focused ultrasound on the amygdala to evaluate its effect on mood and anxiety, which are important symptoms in bipolar disorder. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with bipolar disorder. Participants should be able to undergo an emotion regulation task and have their brain activity monitored. Details on specific inclusion or exclusion criteria are not provided, but typically these would involve age, health status, and severity of bipolar disorder.

Inclusion Criteria

YMRS ≤ 12

BDI ≥ 14

I have been diagnosed with Bipolar Disorder, either Type I or II.

Exclusion Criteria

YMRS > 13

BDI < 14

Current psychosis symptoms

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants complete clinical assessments and practice sessions of the MSIT task, undergo MRI scans, and receive initial tFUS sonication

1 week

1 visit (in-person)

Treatment

Participants receive tFUS sonication and complete clinical assessments over multiple visits

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for changes in mood symptoms and corticolimbic network connectivity

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Low-Intensity Focused Ultrasound of the Amygdala

Trial Overview The study is testing the use of a device called BrainSonix Pulsar 1002 to apply low-intensity focused ultrasound (tFUS) to the amygdala in the brain. The goal is to see if this can affect emotional regulation and improve mood symptoms in people with bipolar disorder.

How Is the Trial Designed?

Group I: Active transcranial focused ultrasound (tFUS) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Children with pediatric bipolar disorder had significantly smaller overall brain sizes compared to healthy controls, suggesting potential structural differences associated with the disorder.

However, the study found no significant differences in the volumes of key brain regions like the amygdala, thalamus, or hippocampus among the pediatric bipolar disorder group, risk group, and healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative analysis of the amygdala, thalamus and hippocampus on magnetic resonance images in paediatric bipolar disorders and compared with the children of bipolar parents and healthy control. Akbaş, S., Nahir, M., Pirzirenli, ME., et al.[2018]

In a study of 16 adolescents and young adults with bipolar disorder compared to 21 healthy controls, there was a trend indicating smaller left amygdala volumes in bipolar patients, suggesting potential neurodevelopmental abnormalities associated with the disorder.

The study found a unique correlation in bipolar patients where left amygdala volume increased with age, contrasting with healthy controls who showed a decrease, indicating that bipolar disorder may involve atypical brain development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder. Chen, BK., Sassi, R., Axelson, D., et al.[2007]

A wearable low-intensity pulsed ultrasound (LIPUS) device was developed and tested, showing it can safely deliver ultrasound to the brain without causing significant thermal injury.

The study suggests that LIPUS has potential as a safe transcranial treatment for neurological diseases, which could help alleviate symptoms of mental illnesses like depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of a Wearable Low-Intensity Pulsed Ultrasound Device for Relieving Mental Illness Symptoms. Qi, S., Chen, J.[2020]

In a study of 54 bipolar disorder patients and 41 healthy controls, it was found that bipolar patients experienced a reduction in amygdala volume as they aged, while healthy controls did not show this change.

The findings suggest that dysfunction in the amygdala may play a significant role in bipolar disorder, particularly in older patients, potentially contributing to mood regulation issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age-dependent reduction of amygdala volume in bipolar disorder. Doty, TJ., Payne, ME., Steffens, DC., et al.[2021]

Children and adolescents with bipolar disorder have smaller amygdala volumes compared to their peers without the disorder, indicating potential structural abnormalities associated with mood dysregulation.

In contrast, adults with bipolar disorder do not show significant differences in amygdala size compared to control adults, suggesting that these structural changes may be more pronounced in younger populations and could serve as biomarkers for the illness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of amygdala volumes in children and adolescents with bipolar disorder. Pfeifer, JC., Welge, J., Strakowski, SM., et al.[2008]

Individuals diagnosed with bipolar spectrum disorders (BSD) have larger overall amygdala volumes compared to those at low risk for the disorder, indicating a potential biomarker for BSD.

Examining specific amygdala subnuclei revealed that those with BSD had larger volumes in certain subnuclei compared to high-risk individuals, suggesting that these subnuclei may play a critical role in the disorder's development and progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion-based subsegmentation and a high-risk design. Damme, KSF., Alloy, LB., Young, CB., et al.[2021]

Transcranial focused ultrasound technology can temporarily and reversibly disrupt the blood-brain barrier in a highly controlled, noninvasive manner, which is promising for delivering therapies to treat neurological and psychiatric conditions.

This technique is being studied in both nonhuman primates and humans, indicating its potential for clinical applications, as it may allow for the transfer of therapeutic agents across the blood-brain barrier to modulate brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potentials of Localized Blood-Brain Barrier Disruption by Noninvasive Transcranial Focused Ultrasound: A Technical Review. Cammalleri, A., Croce, P., Lee, W., et al.[2022]

MR-guided focused ultrasound (MRgFUS) shows promise in treating neuropsychiatric disorders like obsessive-compulsive disorder (OCD) and depression, with preliminary studies indicating improvements in symptoms, although more rigorous trials are needed.

Low-intensity MRgFUS may help open the blood-brain barrier and modulate brain activity, but current evidence is limited, necessitating further comparative studies to evaluate its effectiveness against other treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incisionless MR-guided focused ultrasound: technical considerations and current therapeutic approaches in psychiatric disorders. Kinfe, T., Stadlbauer, A., Winder, K., et al.[2021]

Unmedicated bipolar disorder (BD) patients showed significantly smaller amygdala volumes compared to healthy controls, suggesting a potential structural brain difference associated with the disorder.

Medicated BD patients (treated with lithium or divalproex) exhibited larger amygdala volumes than unmedicated patients, indicating that mood stabilizing medications may promote neuroplastic changes in the amygdala.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: the impact of medication. Savitz, J., Nugent, AC., Bogers, W., et al.[2021]

Focused ultrasound ablation (FUSA) of the anterior nucleus of the thalamus (ANT) is a promising treatment for patients with treatment-refractory epilepsy, showing significant reduction in seizure frequency in a pilot study of two adult subjects.

The procedure was well-tolerated with no serious adverse events, although one patient experienced a decline in certain cognitive functions, highlighting the need for careful monitoring of potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy. Krishna, V., Mindel, J., Sammartino, F., et al.[2023]

In a study involving 36 patients with essential tremor, the accumulated thermal dose (ATD) during MR-guided focused ultrasound (MRgFUS) thalamotomy was found to correlate with the size of brain lesions, helping to predict treatment outcomes.

The optimal ATD values for predicting lesion size were identified as 100 and 200 cumulative equivalent minutes at 43°C, providing valuable insights for determining effective treatment endpoints in future MRgFUS procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting lesion size by accumulated thermal dose in MR-guided focused ultrasound for essential tremor. Huang, Y., Lipsman, N., Schwartz, ML., et al.[2019]

Youths with bipolar disorder showed significantly smaller hippocampal volumes compared to healthy peers, particularly among female participants, suggesting a potential link between hippocampal abnormalities and the disorder's pathophysiology.

Both male and female youths with bipolar disorder also exhibited reduced overall cerebral volumes, indicating broader brain structural changes associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. Frazier, JA., Chiu, S., Breeze, JL., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06482762

Low-Intensity Focused Ultrasound of the Amygdala for ... The specific aim of this proposed study is to investigate the feasibility and therapeutic potential of transcranial focused ultrasound (tFUS) as a treatment ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11321877/

Effect of Low-Intensity Transcranial Focused Ultrasound ... Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, ...

3. nature.com nature.com/articles/s41380-025-03033-w

Low-intensity transcranial focused ultrasound amygdala ... There were significant reductions on the primary outcome (Mood and Anxiety Symptom Questionnaire General Distress subscale; p = 0.001, Cohen's d ...

4. fusfoundation.org fusfoundation.org/posts/clinical-trial-results-focused-ultrasound-neuromodulation-improves-mood-anxiety-and-trauma-related-disorders/

Clinical Trial Results Clinical Trial Results: Focused Ultrasound Neuromodulation Improves Mood, Anxiety, and Trauma-Related Disorders. Published: September 19, 2025.

5. fusfoundation.org fusfoundation.org/diseases-and-conditions/bipolar-disorder/

Bipolar Disorder Learn about clinical trials that are investigating the use of focused ultrasound to treat Bipolar Disorder.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12162705/

Low-intensity transcranial focused ultrasound of the amygdala ... Our results indicate that LIFU of the amygdala acutely dampens amygdala reactivity during active socio-emotional processing.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0022395623004776

A pilot study of low-intensity focused ultrasound for ... Conversely, low-intensity transcranial focused ultrasound (tfUS) is a non-invasive deep brain stimulation technique that has recently demonstrated safety and ...

8. fusfoundation.org fusfoundation.org/posts/clinical-trial-investigates-low-intensity-focused-ultrasound-for-depression/

Clinical Trial Investigates Low-Intensity ... A clinical trial is investigating the safety and feasibility of using low-intensity focused ultrasound to address anxiety and depression.