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| Name | Class |
|---|---|
| Michigan Pioneer Fellowship | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High DC LIFU then Sham | Experimental |
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| Sham then High DC LIFU | Sham Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High DC LIFU | Device | 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. |
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
Note: participants who cannot undergo MRI may complete the other portions of the study.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hasini Weerathunge, Ph.D. | Contact | 734-232-5748 | weerathh@umich.edu | |
| Soo-Eun Chang, Ph.D. | Contact | 734-232-0300 | sooeunc@umich.edu |
| Name | Affiliation | Role |
|---|---|---|
| Hasini Weerathunge, Ph.D. | University of Michigan | Principal Investigator |
| Soo-Eun Chang, Ph.D. | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
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| ID | Term |
|---|---|
| D013342 | Stuttering |
| ID | Term |
|---|---|
| D013064 | Speech Disorders |
| D007806 | Language Disorders |
| D003147 | Communication Disorders |
| D019954 | Neurobehavioral Manifestations |
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This is a two-period, two-sequence crossover design. All participants receive both active LIFU and sham stimulation across two sessions. Participants randomized to Arm 1 receive High duty cycle (DC) LIFU in Session 1 followed by Sham in Session 2; those randomized to Arm 2 receive Sham in Session 1 followed by High DC LIFU in Session 2. The order is counterbalanced across participants to control for order effects. Participants also complete a baseline session where a T1 MRI structural image will be collected for VIM-LIFU targeting, and baseline versions of the outcome measures will also be collected.
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The Speech-Language Pathologist (SLP) conducting and scoring the speech samples to determine stuttering severity will be blind to the condition. A second SLP will score a subset of the speech samples to document reliability.
The BrainSonix BXPulser 10002 brain stimulation system does not contain a blinded mode for double blinding. 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. A study team member not directly involved in any participant interaction or data analysis will randomize sessions and assign sham vs active sessions accordingly.
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| Sham | Device | 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. |
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| 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. |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |