Noninvasive Thalamocortical Neuromodulation With Low-Intensity Focused Ultrasound for Persistent Developmental Stuttering
Purpose
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.
Conditions
- Stuttering
- Developmental Stuttering
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 - Any active, unstable, or inadequately treated psychiatric condition, including but not limited to psychosis, active major depressive episode, bipolar disorder with recent mood episode, or current suicidal ideation. - Current use of antipsychotic medications for treatment of a primary psychotic disorder or bipolar disorder; current use of mood stabilizers (e.g., lithium, valproate) or benzodiazepines. Low-dose adjunctive use of atypical antipsychotics (e.g., brexpiprazole, aripiprazole, quetiapine) for treatment-resistant depression or anxiety is not exclusionary if the participant's condition is stable per the existing ≥2-month stability criterion. - Any condition or medication that lowers seizure threshold, consistent with standard practice across non-invasive brain stimulation protocols. Note: participants who cannot undergo MRI may complete the other portions of the study. For participants who cannot undergo MRI can be targeted for LIFU stimulation using a standard T1 scan. Resting state fMRI measures taken before and after stimulation will also be omitted for these cases. But the behavioral and speech measures can still be completed to provide pre and post-stimulation variations.
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Intervention Model Description
- This is a two-period, two-sequence crossover design. All participants receive both active LIFU and sham stimulation across two sessions. Participants pseudo randomized to Arm 1 receive High duty cycle (DC) LIFU in Session 1 followed by Sham in Session 2; those pseudo 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.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
- Masking Description
- 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 BXPulsar 1002 brain stimulation system does not contain a blinded mode for double blinding. The researchers will be using a passive sham condition where no stimulation will be provided to the participant (by reversing the direction of the transducer but keeping all other parameters and procedures identical). A study team member not directly involved in any participant interaction or data analysis will randomize sessions and assign sham versus active sessions accordingly.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental High DC LIFU then Sham |
|
|
|
Sham Comparator Sham then High DC LIFU |
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Recruiting Locations
Ann Arbor, Michigan 48109
More Details
- Status
- Recruiting
- Sponsor
- University of Michigan
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 safety, feasibility, and precision of individualized, MRI-guided LIFU targeting of the left VIM thalamus using neuronavigation and post-hoc acoustic simulation. Feasibility outcomes include targeting accuracy, protocol adherence, adverse event monitoring, and participant tolerability. Aim 2 is to characterize the acute neural and behavioral effects of excitatory VIM-LIFU relative to a passive sham condition (reverse direction of transducer; no stimulation) using a within-subjects, double-blind crossover design. Primary outcome is the change in speech fluency (stuttered syllable percentage). Secondary outcomes are motor inhibition (stop-signal reaction time), and beat-based rhythm discrimination (d'). Exploratory neural outcomes include pre-to-post changes in resting-state thalamocortical functional connectivity and task-based (stop-signal fMRI) connectivity between VIM and speech motor regions (IFG, STN, pre-SMA). Exploratory analyses will also 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.