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

Developmental Stuttering, Stuttering

Low Intensity Focused Ultrasound, Thalamus, Neuromodulation

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 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.

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United States