Transcranial Focused Ultrasound for Impulsivity

Overseen By Jill Morris-Tillman

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mary Phillips, MD MD (Cantab)

Must not be taking: Psychotropics, Stimulants

Disqualifiers: MDD, Psychosis, Bipolar, Epilepsy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how transcranial focused ultrasound (tFUS), a non-invasive treatment, affects brain activity related to impulsivity in healthy adults. Participants will receive either the actual tFUS treatment or a sham version that mimics the process without active treatment. The trial seeks individuals with no personal or family history of major mental health disorders, such as depression or bipolar disorder, and who have not recently used substances that increase seizure risk. Participants should be right-handed and able to understand English. As an unphased study, this trial offers participants the chance to contribute to groundbreaking research in understanding brain activity.

Will I have to stop taking my current medications?

The trial requires that participants have not taken any psychotropic medications (drugs that affect mood, perception, or behavior) in the past 3 months.

What prior data suggests that transcranial focused ultrasound is safe for brain activity studies?

Research has shown that transcranial focused ultrasound (tFUS) is generally safe for humans. This non-invasive treatment does not involve surgery or cuts. The procedure uses gentle ultrasound waves to target specific areas of the brain.

Side effects from tFUS are rare. However, using it at very high levels or too frequently can cause issues like bleeding or damage to brain cells. Most studies find that when used properly, tFUS is well-tolerated.

Overall, tFUS appears to be a promising and safe method to stimulate the brain without surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial focused ultrasound (tFUS) for impulsivity because it offers a non-invasive approach that directly targets the brain's ventral striatum, a key area involved in impulse control. Unlike traditional treatments for impulsivity, which might include medications like SSRIs or behavioral therapies, tFUS uses sound waves to modulate brain activity without the need for drugs or surgery. This technique could potentially offer faster results with fewer side effects, making it a promising option for individuals seeking alternative treatments.

What evidence suggests that transcranial focused ultrasound is effective for impulsivity?

Research has shown that transcranial focused ultrasound (tFUS) might offer a promising non-surgical method to stimulate the brain. This trial will compare two approaches: VS tFUS, where tFUS targets the ventral striatum, and Sham tFUS, which simulates the procedure without actual stimulation. Studies have found that tFUS can either activate or calm brain cells, potentially helping to manage impulsive behaviors. However, current safety information is insufficient, and further research is necessary to confirm its efficacy and ensure its safety for individuals. ^{6 7 8 9 10}

Who Is on the Research Team?

Mary L Phillips, MD, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for healthy adults without major mental health issues, no family history of certain psychiatric disorders or epilepsy, and not currently using psychotropic medications. Participants must have normal cognitive function, no recent heavy alcohol use, and cannot be pregnant or have metallic implants.

Inclusion Criteria

No present/lifetime history of major depressive disorder (MDD), psychosis, Bipolar Disorder, Hamilton Depression Rating Scale (HDRS) >7, Young Mania Rating Scale (YMRS) >10, borderline personality disorder, and present suicidal ideation

My family has no history of major depression, psychosis, bipolar disorder, or epilepsy.

Exclusion Criteria

I have a history of depression, psychosis, bipolar disorder, or borderline personality disorder, but not current severe depression or suicidal thoughts.

Binge drinking in the week before, and/or >3 drinks/day for the 3 days before, and/or alcohol in the last 12 hrs before, any alcohol on tFUS scan day

MRI exclusion criteria: metallic objects, e.g., surgical implants, claustrophobia, positive pregnancy test for females or self-report pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial focused ultrasound (tFUS) targeting the ventral striatum (VS) to examine its effect on brain activity

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• tFUS

Trial Overview The study investigates the immediate effects of transcranial focused ultrasound (tFUS) on brain activity compared to a sham treatment. tFUS is a non-invasive technique that targets specific brain areas with sound waves.

How Is the Trial Designed?

Group I: VS tFUS/Sham tFUS Experimental Treatment 2 Interventions

VS tFUS (tFUS applied to the ventral striatum) Sham tFUS (go through the motions of applying tFUS to the VS)

Group II: Sham tFUS/VS tFUS Experimental Treatment 2 Interventions

VS tFUS (tFUS applied to the ventral striatum) Sham tFUS (go through the motions of applying tFUS to the VS)

Who Is Running the Clinical Trial?

Mary Phillips, MD MD (Cantab)

Lead Sponsor

Trials

4

Recruited

180+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 131 patients with traumatic brain injuries, increased impulsivity was linked to damage in several brain areas, particularly in the bilateral prefrontal cortex and left temporal regions, highlighting the complex neuroanatomy of impulsivity.

A specific area in the left prefrontal cortex was found to be associated with 'motor impulsivity,' which is characterized by acting without thinking, suggesting that different types of impulsivity may have distinct brain correlates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Networks underlying trait impulsivity: Evidence from voxel-based lesion-symptom mapping. McDonald, V., Hauner, KK., Chau, A., et al.[2020]

Using diffusion tensor imaging (DTI) data from 143 individuals, researchers isolated the accumbofrontal tract, which connects the prefrontal cortex to the nucleus accumbens, and found that its integrity is positively associated with impulsivity levels as measured by the UPPS scale.

This study provides evidence that the integrity of the accumbofrontal tract may play a role in individual differences in impulsivity, linking findings from animal studies to human behavior and suggesting a potential target for interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

White matter integrity in the fronto-striatal accumbofrontal tract predicts impulsivity. Ikuta, T., Del Arco, A., Karlsgodt, KH.[2019]

In a study of 11,052 children aged 9 to 10, Positive Urgency was found to have the strongest association with specific brain structures, particularly in areas like the dorsolateral prefrontal cortex and orbitofrontal cortex, indicating a potential neuroanatomical basis for this impulsive trait.

The research suggests that while some impulsivity traits share similar brain correlates, others, like Perseverance, show little to no association with neuroanatomy, highlighting the complexity of impulsivity and the need for large sample sizes to understand these relationships better.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroanatomical correlates of impulsive traits in children aged 9 to 10. Owens, MM., Hyatt, CS., Gray, JC., et al.[2021]

Impulsivity is linked to various disorders, including impulse control disorders and personality disorders, and has significant effects on individuals and society.

The article discusses the role of serotonergic dysfunction in impulsivity and reviews the efficacy of selective serotonin reuptake inhibitors (SSRIs) and other treatments for conditions like pathological gambling and borderline personality disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impulsivity. Hollander, E., Rosen, J.[2022]

In a study with 152 participants, low-intensity transcranial focused ultrasound (TUS) targeting the right prefrontal cortex significantly decreased midfrontal theta activity (MFT), which is linked to emotional conflict and decision-making.

The reduction in MFT correlated with increased approach behavior and decreased withdrawal behavior in a virtual T-maze task, suggesting that TUS could be a promising non-invasive tool for enhancing emotional and motivational responses in mental health interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans. Ziebell, P., Rodrigues, J., Forster, A., et al.[2023]

Transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced risk-taking behavior in Veterans with impulsive behavior, showing a 46% decrease in risky choices after the intervention.

The effects of active tDCS persisted for at least two months after the treatment, indicating its potential as a durable intervention for managing impulsivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation (tDCS) paired with a decision-making task reduces risk-taking in a clinically impulsive sample. Gilmore, CS., Dickmann, PJ., Nelson, BG., et al.[2019]

Transcranial focused ultrasound (tFUS) can selectively target and modulate deep brain structures, such as the amygdala and entorhinal cortex, in healthy adults, leading to significant changes in brain perfusion and activity.

The study demonstrated that tFUS does not activate the auditory cortex, indicating that its effects are due to direct neuromodulation rather than an acoustic response, suggesting potential therapeutic applications for neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. Kuhn, T., Spivak, NM., Dang, BH., et al.[2023]

Recent research indicates that impulsiveness is linked to multiple brain regions and networks, highlighting its complex nature and the need for a nuanced understanding in clinical settings.

Three distinct cognitive mechanisms of impulsivity—'prepotent inhibition,' 'interruptive inhibition,' and 'interference control'—each have unique neurological underpinnings, suggesting targeted approaches may be necessary for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized neuropsychological examination of impulsiveness: A selective review. Kertzman, S., Grinspan, H., Birger, M., et al.[2015]

Transcranial focused ultrasound (tFUS) is a promising non-surgical technique for neuromodulation that offers better spatial resolution compared to traditional electro and electromagnetic methods.

tFUS can effectively target sub-cortical brain structures non-invasively, and its combination with BOLD functional MRI allows for enhanced examination of brain activity in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. Leo Ai, ., Mueller, JK., Grant, A., et al.[2022]

In a study involving eight patients with refractory temporal lobe epilepsy, Transcranial Focused Ultrasound (tFUS) at intensities up to 5760 mW/cm2 showed no significant tissue damage in histological analyses, indicating potential safety for neuromodulation.

Neuropsychological testing revealed no major changes in cognitive function post-tFUS, except for a slight decrease in one test, suggesting that tFUS may be a safe method for brain modulation, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. Stern, JM., Spivak, NM., Becerra, SA., et al.[2021]

A systematic review of 33 studies on low-intensity transcranial focused ultrasound stimulation (TFUS) indicates that adverse effects are very rare, with most studies showing no significant negative outcomes even when safety limits were exceeded.

However, at high stimulation intensities, TFUS can potentially cause serious issues like hemorrhage, cell death, and unintended blood-brain barrier opening, highlighting the need for further research to establish clear safety guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Pasquinelli, C., Hanson, LG., Siebner, HR., et al.[2020]

Transcranial focus ultrasound stimulation (tFUS) can significantly modulate excitability in the human motor cortex, with different parameters leading to either increased or decreased excitability, as shown in a study involving 10 subjects.

The study revealed that tFUS affects neurotransmitter levels, decreasing GABA and increasing glutamate concentrations, which suggests it alters the balance of excitatory and inhibitory signals in the brain, potentially impacting motor function and plasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. Zhang, T., Guo, B., Zuo, Z., et al.[2023]

Therapeutic interventions for Parkinson's disease, such as dopamine replacement therapies and sub-thalamic nucleus (STN) stimulation, can induce cognitive impulsivity, affecting decision-making and risk-taking behaviors.

The review highlights that cognitive impulsivity in Parkinson's patients may arise from different mechanisms related to dopamine and STN activity, emphasizing the need for awareness of these effects in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive impulsivity in Parkinson's disease patients: assessment and pathophysiology. Robert, G., Drapier, D., Verin, M., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05875181?term=AREA%5BConditionSearch%5D(%22Impulsive%20Behavior%22)&rank=2

Examining the Impact of Transcranial Focused Ultrasound ... The investigators aim to examine the immediate effect of transcranial focused ultrasound (tFUS) on brain activity and emotions in healthy adults as a first ...

2. withpower.com withpower.com/trial/phase-impulsive-behavior-8-2024-bd7c1

Transcranial Focused Ultrasound for Impulsivity Research on transcranial focused ultrasound (tFUS) suggests it is a promising non-invasive brain stimulation technique, but safety data is still limited.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8507972/

Transcranial Focused Ultrasound Neuromodulation: A Review ... This review synthesizes animal and human research outcomes and offers an integrated description of the excitatory and inhibitory effects of tFUS.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772528625000196

Optimizing transcranial focused ultrasound parameters: A ... This paper presents a novel computational-experimental technique to improve tFUS parameters, addressing significant constraints in accuracy, efficacy, and ...

5. nature.com nature.com/articles/s41467-021-22743-7

Intrinsic functional neuron-type selectivity of transcranial ... We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599299/

Safety of Clinical Ultrasound Neuromodulation - PMC Transcranial ultrasound holds much potential as a safe, non-invasive modality for navigated neuromodulation, with low-intensity focused ultrasound (FUS) and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05792020

Study Details | NCT05792020 | Safety, Parameterization ... All participants will receive three sessions of Focused Ultrasound Stimulation to their motor hotspot. This stimulation cycle will operate at a 50% duty cycle.

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

Low-intensity transcranial focused ultrasound amygdala ... Safety of transcranial focused ultrasound stimulation: a systematic review of the state of knowledge from both human and animal studies.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25003055

A roadmap for focused ultrasound applications in psychiatry Transcranial focused ultrasound (FUS) is an emerging neuromodulation modality that enables incisionless, spatially precise targeting of deep brain ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31401074/

Safety of transcranial focused ultrasound stimulation Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood- ...