Noninvasive Thalamocortical Neuromodulation With Low-Intensity Focused Ultrasound for Persistent Developmental Stuttering

This research is studying the use of low-intensity focused ultrasound (LIFU; a mild, noninvasive acoustic stimulation technique) in a small number of people to learn about its safety as a treatment for stuttering. LIFU is a small, safe sound signal that produces a gentle, pulsing flow of acoustic waves to help different parts of the brain communicate with each other. Researchers want to understand how the mild, non-invasive brain stimulation affects speech relevant brain areas, which may in turn affect speech fluency and speaking-related brain activity in people who stutter.

Study Overview

• Status: Not yet recruiting
• Conditions: Stuttering; Developmental Stuttering
• Intervention / Treatment: Device: High DC LIFU; Device: Sham

Detailed Description

This study will investigate whether Low-Intensity Focused Ultrasound (LIFU; also known as transcranial ultrasound stimulation, TUS) targeting the ventral intermediate (VIM) nucleus of the thalamus can safely and feasibly modulate neural activity and improve speech fluency in adults with Persistent Developmental Stuttering (PDS).

Adult participants with PDS will be recruited through community advertisements and from existing institutional research registries, including individuals who have previously participated in noninvasive neuromodulation studies and have consented to be re-contacted for future research. All participants will complete an informed consent process prior to any study procedures.

This is a within-subject, sham-controlled study in which participants will attend multiple study visits. Study procedures include: (1) baseline behavioral and speech assessments; (2) magnetic resonance imaging (MRI), including structural imaging and diffusion tractography, to localize individualized stimulation targets; (3) functional MRI (fMRI) to assess brain connectivity; (4) neuronavigation-guided LIFU stimulation targeting the VIM thalamic nucleus; and (5) concurrent and pre/post behavioral tasks assessing speech production, reading, and rhythm perception. Participants will receive both active and sham LIFU stimulation in separate sessions.

Aim 1 is to evaluate the precision and feasibility of individualized, MRI-guided LIFU targeting of the VIM using neuronavigation and acoustic modeling. Outcomes will include alignment between intended and estimated stimulation targets and associated changes in behavioral performance and speech fluency.

Aim 2 is to identify neural biomarkers associated with response to LIFU using fMRI. Analyses will examine whether baseline thalamocortical connectivity predicts changes in functional connectivity and behavioral outcomes following stimulation.

The study is noninvasive and does not involve surgical procedures or implantation. Data collected will include neuroimaging, behavioral performance, and speech recordings. The results of this study will inform the feasibility and potential efficacy of noninvasive subcortical neuromodulation for PDS.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hasini Weerathunge, Ph.D.; Phone Number: 734-232-5748; Email: weerathh@umich.edu
• Study Contact Backup: Name: Soo-Eun Chang, Ph.D.; Phone Number: 734-232-0300; Email: sooeunc@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
      • Contact: Hasini Weerathunge, Ph.D.; Phone Number: 734-232-5748; Email: weerathh@umich.edu
      • Principal Investigator: Hasini Weerathunge,, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• have normal language, hearing and cognition
• speak English as their primary language
• currently stutter
• score at least 10 (very mild) on the Stuttering Severity Instrument (SSI-4) or exhibit greater than 3% stuttered syllables during at least one of the first 3 speech samples
• have not receive any treatment for stuttering within the past year

Exclusion Criteria:

• History of seizures
• Major medical or neurological illness (e.g., stroke, serious head trauma, brain infection, Parkinson's disease, etc.)
• History of closed head injury with loss of consciousness (e.g., concussion)
• Metal or electronic implants such as cochlear implants and pacemakers
• Braids or other hair styling that prevents direct access to the scalp (if removal not possible)
• Current or planned pregnancy

Note: participants who cannot undergo MRI may complete the other portions of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High DC LIFU then Sham	Device: High DC LIFU; Stimulation parameters and target location. Stimulation will be delivered using the BrainSonix BXPulser 10002 System (BrainSonix Corporation, Sherman Oaks, CA, USA). Sonication Parameters will be as follows. Fundamental frequency: 650 kHz; pulse repetition frequency: 10Hz; pulse duration: 100ms; DC: 70% (yielding pulse width of 70 ms); sonication duration: 30 s; inter-sonication interval: 30s; LIFU-ON epochs per block: 12 epochs (Jang et al., 2025). During active stimulation a total of 4.2 min stimulation will be applied across all LIFU-ON epochs. Both active and sham stimulation sessions will last ~12 mins each. The researchers will be targeting ventral intermediate nucleus (VIM) region of the thalamus for the active stimulation.; Device: Sham; Stimulation parameters and target location. Stimulation will be delivered using the BrainSonix BXPulser 10002 System (BrainSonix Corporation, Sherman Oaks, CA, USA). Sonication Parameters will be as follows. Fundamental frequency: 650 kHz; pulse repetition frequency: 10Hz; pulse duration: 100ms; DC: 70% (yielding pulse width of 70 ms); sonication duration: 30 s; inter-sonication interval: 30s; LIFU-ON epochs per block: 12 epochs (Jang et al., 2025). During sham stimulation a total of 4.2 min stimulation will be applied across all LIFU-ON epochs. Both active and sham stimulation sessions will last ~12 mins each. The researchers will be targeting anterior nucleus of thalamus (ANT) as the sham control with previous literature utilizing ANT-LIFU as a non-motor thalamus modulation.
Sham Comparator: Sham then High DC LIFU	Device: High DC LIFU; Stimulation parameters and target location. Stimulation will be delivered using the BrainSonix BXPulser 10002 System (BrainSonix Corporation, Sherman Oaks, CA, USA). Sonication Parameters will be as follows. Fundamental frequency: 650 kHz; pulse repetition frequency: 10Hz; pulse duration: 100ms; DC: 70% (yielding pulse width of 70 ms); sonication duration: 30 s; inter-sonication interval: 30s; LIFU-ON epochs per block: 12 epochs (Jang et al., 2025). During active stimulation a total of 4.2 min stimulation will be applied across all LIFU-ON epochs. Both active and sham stimulation sessions will last ~12 mins each. The researchers will be targeting ventral intermediate nucleus (VIM) region of the thalamus for the active stimulation.; Device: Sham; Stimulation parameters and target location. Stimulation will be delivered using the BrainSonix BXPulser 10002 System (BrainSonix Corporation, Sherman Oaks, CA, USA). Sonication Parameters will be as follows. Fundamental frequency: 650 kHz; pulse repetition frequency: 10Hz; pulse duration: 100ms; DC: 70% (yielding pulse width of 70 ms); sonication duration: 30 s; inter-sonication interval: 30s; LIFU-ON epochs per block: 12 epochs (Jang et al., 2025). During sham stimulation a total of 4.2 min stimulation will be applied across all LIFU-ON epochs. Both active and sham stimulation sessions will last ~12 mins each. The researchers will be targeting anterior nucleus of thalamus (ANT) as the sham control with previous literature utilizing ANT-LIFU as a non-motor thalamus modulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of stuttered syllables produced during speech sample	The study will calculate the percentage of stuttered syllables (out of total syllables) in two speech samples (one before LIFU and one sample after LIFU) per each stimulation session. Decreased stuttered syllables represents better outcomes (greater reduction in stuttering). Two samples are collected during session 1 and two samples are collected during session 2. An additional baseline sample is collected at the baseline session (on a separate day before the two stimulation sessions).	Baseline, and immediately before and after LIFU stimulation during Stimulation Session 1 and Stimulation Session 2 (sessions occurring a minimum of 2 days apart and a maximum of 1 week apart), for a total of 5 assessments over an estimated 2-3 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stop signal response time (SSRT)	The study will measure the Stop signal response time (SSRT) from the stop signal fMRI task (one before LIFU and one sample after LIFU) per each stimulation session. Two SSRT outcomes are collected during session 1 and two SSRT outcomes are collected during session 2. An additional baseline SSRT is collected at the baseline session (on a separate day before the two stimulation sessions). SSRT will be measured 5 times total.	Baseline, and immediately before and after LIFU stimulation during Stimulation Session 1 and Stimulation Session 2 (sessions occurring a minimum of 2 days apart and a maximum of 1 week apart), for a total of 5 assessments over an estimated 2-3 weeks.
Rhythm discrimination score (d')	The study will compare the rhythm discrimination behavioral task from before and after LIFU during both session 1 and 2 for a total of 4 measurements. This is measured by the signal direction measures d' that will be calculated to quantify perceptual sensitivity (d'). Apart from the stimulation sessions, the baseline session will also collect this measure. Thus, assessed 5 times in total, considering the baseline session and stimulation sessions 1 and 2.	Baseline, and immediately before and after LIFU stimulation during Stimulation Session 1 and Stimulation Session 2 (sessions occurring a minimum of 2 days apart and a maximum of 1 week apart), for a total of 5 assessments over an estimated 2-3 weeks.

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Michigan Pioneer Fellowship
• Investigators: Principal Investigator: Hasini Weerathunge, Ph.D., University of Michigan; Principal Investigator: Soo-Eun Chang, Ph.D., University of Michigan

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 19, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Thalamus; Low Intensity Focused Ultrasound
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Communication Disorders; Language Disorders; Speech Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stuttering
• Other Study ID Numbers: HUM00274381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No