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

Trial Summary

What is the purpose of this trial?

The investigators aim to examine the immediate effect of transcranial focused ultrasound (tFUS) on brain activity in healthy adults.

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 data supports the effectiveness of the treatment Transcranial Focused Ultrasound Stimulation (tFUS) for impulsivity?

Research shows that Transcranial Focused Ultrasound (TUS) can influence brain activity related to decision-making and behavior. A study found that TUS decreased certain brain activity linked to conflict and increased approach behavior, suggesting it might help manage impulsivity by affecting how the brain processes decisions. ^{1 2 3 4 5}

Is transcranial focused ultrasound (tFUS) safe for humans?

Research on transcranial focused ultrasound (tFUS) suggests it is a promising non-invasive brain stimulation technique, but safety data is still limited. Some studies have explored its use in humans, including those with epilepsy, but more research is needed to fully understand its safety. ^{6 7 8 9 10}

How is the treatment tFUS different from other treatments for impulsivity?

Transcranial Focused Ultrasound Stimulation (tFUS) is unique because it uses low-intensity ultrasound waves to non-invasively target specific brain areas, like the prefrontal cortex, to modulate brain activity and behavior. This approach is different from traditional treatments as it directly influences brain function without the need for medication or invasive procedures. ^{4 5 11 12 13}

Research Team

Mary L Phillips, MD, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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]

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]

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]

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]

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]

References

1. Israel pubmed.ncbi.nlm.nih.gov

Computerized neuropsychological examination of impulsiveness: A selective review. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation (tDCS) paired with a decision-making task reduces risk-taking in a clinically impulsive sample. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Impulsivity. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

White matter integrity in the fronto-striatal accumbofrontal tract predicts impulsivity. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. [2021]

9. United States 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. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Cognitive impulsivity in Parkinson's disease patients: assessment and pathophysiology. [2014]

12. United States pubmed.ncbi.nlm.nih.gov

Neuroanatomical correlates of impulsive traits in children aged 9 to 10. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Networks underlying trait impulsivity: Evidence from voxel-based lesion-symptom mapping. [2020]