Transcranial Focused Ultrasound for Impulsivity
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Mary Phillips, MD MD (Cantab)
Must not be taking: Psychotropics, Stimulants
Disqualifiers: MDD, Psychosis, Bipolar, Epilepsy, others
No Placebo Group
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.12345
Is transcranial focused ultrasound (tFUS) safe for humans?
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.45111213
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
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Trial 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 (Procedure)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: VS tFUS/Sham tFUSExperimental Treatment2 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 tFUSExperimental Treatment2 Interventions
VS tFUS (tFUS applied to the ventral striatum) Sham tFUS (go through the motions of applying tFUS to the VS)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMCPittsburgh, PA
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Who Is Running the Clinical Trial?
Mary Phillips, MD MD (Cantab)Lead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
References
Computerized neuropsychological examination of impulsiveness: A selective review. [2015]There is a rapidly accumulating body of knowledge related to the neurobiology of impulsiveness from multidisciplinary neuropsychological and neuroimaging studies. This paper reviews recent research on impulsiveness in the context of neuropsychological theory and research. It has been emphasized that the controversy regarding the results of neuropsychological studies is related to different aspects of impulsiveness. The term "impulsivity" is related to more than one anatomical network among several brain regions. Impaired inhibition control, which has cognitive and behavioral dimensions, has a heterogeneous nature. Analysis of performance suggests that impulsivity includes three cognitive mechanisms: "prepotent inhibition," "interruptive inhibition" and "interference control,' each having separate neurological bases. Based on neuropsychological data it has been stated that both the orbitofrontal cortex, dorsolateral prefrontal cortex and anterior cingulate cortex are functionally disturbed among impulsive individuals. Bringing together knowledge from clinical experience, neuroimaging examination and neuropsychological assessment will lead to better and wider understanding of behavioral symptoms in clinical psychiatric practice.
Transcranial Direct Current Stimulation (tDCS) paired with a decision-making task reduces risk-taking in a clinically impulsive sample. [2019]Impulsivity is a multidimensional personality trait observed across a variety of psychiatric disorders. Transcranial direct current stimulation (tDCS) applied over dorsolateral prefrontal cortex (DLPFC) has shown promise as an intervention to reduce impulsivity.
Impulsivity. [2022]Disorders characterized by impulsivity include disorders of impulse control (intermittent explosive disorder, pyromania, kleptomania, pathological gambling and trichotillomania), paraphilias, sexual impulsions and sexual addictions and impulsive aggression personality disorders (borderline, antisocial, histrionic and narcissistic personality disorders). Impulsivity has a substantial impact on both individuals and society. Impulse control disorders may be conceptualized as a subset of the obsessive-compulsive spectrum. In this article, we examine the genetic and neurobiological aetiology of these disorders and possible treatment options. The link between serotonergic dysfunction and the pathophysiology of impulsivity is discussed, and studies that examine the efficacy of various selective serotonin reuptake inhibitors and other alternatives in the treatment of impulsive disorders such as pathological gambling, sexual addictions and borderline personality disorder are presented.
White matter integrity in the fronto-striatal accumbofrontal tract predicts impulsivity. [2019]Frontostriatal projections have been shown to mediate impulsivity. Recent findings have demonstrated that the projection from the prefrontal cortex to the nucleus accumbens (the accumbofrontal tract) can be isolated by using probabilistic tractography on human brain MRI data, specifically, diffusion tensor images (DTI). Using DTI tractography, we isolated the tract and tested its association with the impulsivity. DTI data from 143 individuals obtained from Nathan Kline Institute-Rockland Sample was used along with the impulsivity measure assessed by the UPPS (urgency, premeditation, perseverance, and sensation seeking) impulsive behavior total score. Probabilistic tractography was first performed between the prefrontal cortex and nucleus accumbens, then, as a measure of white matter integrity in the tract, fractional anisotropy was calculated for each individual's tract. In the multiple regression, accumbofrontal FA showed significant positive association with the impulsivity, suggesting that the accumbofrontal tract integrity may contribute to individual differences in impulsivity. This study bridges the literature in rodents, in which this glutamatergic projection has been shown to mediate impulsive behavior, and the findings in humans which allow the in-vivo isolation of the tract and comparison with behavior.
Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans. [2023]Recent reviews highlighted low-intensity transcranial focused ultrasound (TUS) as a promising new tool for non-invasive neuromodulation in basic and applied sciences. Our preregistered double-blind within-subjects study (N = 152) utilized TUS targeting the right prefrontal cortex, which, in earlier work, was found to positively enhance self-reported global mood, decrease negative states of self-reported emotional conflict (anxiety/worrying), and modulate related midfrontal functional magnetic resonance imaging activity in affect regulation brain networks. To further explore TUS effects on objective physiological and behavioral variables, we used a virtual T-maze task that has been established in prior studies to measure motivational conflicts regarding whether participants execute approach versus withdrawal behavior (with free-choice responses via continuous joystick movements) while allowing to record related electroencephalographic data such as midfrontal theta activity (MFT). MFT, a reliable marker of conflict representation on a neuronal level, was of particular interest to us since it has repeatedly been shown to explain related behavior, with relatively low MFT typically preceding approach-like risky behavior and relatively high MFT typically preceding withdrawal-like risk aversion. Our central hypothesis is that TUS decreases MFT in T-maze conflict situations and thereby increases approach and reduces withdrawal. Results indicate that TUS led to significant MFT decreases, which significantly explained increases in approach behavior and decreases in withdrawal behavior. This study expands TUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct TUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Ultimately, this can serve as a foundation for future clinical work to establish TUS interventions for emotional and motivational mental health.
Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. [2022]Transcranial focused ultrasound (tFUS) is an emerging form of non-surgical human neuromodulation that confers advantages over existing electro and electromagnetic technologies by providing a superior spatial resolution on the millimeter scale as well as the capability to target sub-cortical structures non-invasively. An examination of the pairing of tFUS and blood oxygen level dependent (BOLD) functional MRI (fMRI) in humans is presented here.
Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. [2023]Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively.
Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. [2021]Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing.
Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. [2020]Low-intensity transcranial focused ultrasound stimulation (TFUS) holds great promise as a highly focal technique for transcranial stimulation even for deep brain areas. Yet, knowledge about the safety of this novel technique is still limited.
Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. [2023]Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity.
Cognitive impulsivity in Parkinson's disease patients: assessment and pathophysiology. [2014]Impulsivity may be induced by therapeutic interventions (dopamine replacement therapies and sub-thalamic nucleus (STN) stimulation) in patients with Parkinson's disease (PD). The present review has two goals. First, to describe the most frequently encountered facets of cognitive impulsivity and to stress the links between cognitive impulsivity and aspects such as reward-related decision making, risk-taking, and time-processing in healthy population. The most widely used related cognitive impulsivity paradigms are presented. Second, to review the results of studies on cognitive impulsivity in healthy volunteers and in patients with PD, the latter support the applicability and clinical relevance of this construct in PD population. Data show that PD treatments may favor impulsivity via different mechanisms. Suggestions on the roles of dopamine and STN in the pathophysiology of cognitive impulsivity are proposed.
Neuroanatomical correlates of impulsive traits in children aged 9 to 10. [2021]Impulsivity refers to a set of traits that are generally negatively related to critical domains of adaptive functioning and are core features of numerous psychiatric disorders. The current study examined the gray and white matter correlates of five impulsive traits measured using an abbreviated version of the UPPS-P (Urgency, (lack of) Premeditation, (lack of) Perseverance, Sensation-Seeking, Positive Urgency) impulsivity scale in children aged 9 to 10 (N = 11,052) from the Adolescent Brain and Cognitive Development (ABCD) study. Linear mixed effect models and elastic net regression were used to examine features of regional gray matter and white matter tractography most associated with each UPPS-P scale; intraclass correlations were computed to examine the similarity of the neuroanatomical correlates among the scales. Positive Urgency showed the most robust association with neuroanatomy, with similar but less robust associations found for Negative Urgency. Perseverance showed little association with neuroanatomy. Premeditation and Sensation Seeking showed intermediate associations with neuroanatomy. Critical regions across measures include the dorsolateral prefrontal cortex, lateral temporal cortex, and orbitofrontal cortex; critical tracts included the superior longitudinal fasciculus and inferior fronto-occipital fasciculus. Negative Urgency and Positive Urgency showed the greatest neuroanatomical similarity. Some UPPS-P traits share neuroanatomical correlates, while others have distinct correlates or essentially no relation to neuroanatomy. Neuroanatomy tended to account for relatively little variance in UPPS-P traits (i.e., Model R2 < 1%) and effects were spread throughout the brain, highlighting the importance of well powered samples. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Networks underlying trait impulsivity: Evidence from voxel-based lesion-symptom mapping. [2020]Impulsivity is considered a multidimensional construct that encompasses a range of behaviors, including poor impulse control, premature decision-making, and the inability to delay gratification. In order to determine the extent to which impulsivity and its components share a common network, a voxel-based lesion-symptom mapping (VLSM) analysis was performed in a large sample of patients (N = 131) with focal, penetrating traumatic brain injuries (pTBI). Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), a standard self-report measure that allows for unique estimates of global impulsivity and its factor analysis-derived components (e.g., "motor impulsivity"). Heightened global impulsivity was associated with damage to multiple areas in bilateral prefrontal cortex (PFC), left superior, middle and inferior temporal gyrus, and left hippocampus. Moreover, a cluster was identified within the left PFC associated specifically with motor impulsivity (defined as "acting without thinking"). The results were consistent with the existing literature on bilateral prefrontal cortical involvement in behavioral impulsivity, but also provided new evidence for a more complex neuroanatomical representation of this construct, characterized by left-lateralized temporal and hippocampal involvement, as well as a left-lateralized prefrontal network specifically associated with motor impulsivity. Hum Brain Mapp 38:656-665, 2017. © 2016 Wiley Periodicals, Inc.