Noninvasive Thalamocortical Neuromodulation With Low-Intensity Focused Ultrasound for Persistent Developmental Stuttering
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Hasini Weerathunge, Ph.D.
- Número de telefone: 734-232-5748
- E-mail: weerathh@umich.edu
Estude backup de contato
- Nome: Soo-Eun Chang, Ph.D.
- Número de telefone: 734-232-0300
- E-mail: sooeunc@umich.edu
Locais de estudo
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- Recrutamento
- University of Michigan
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Contato:
- Hasini Weerathunge, Ph.D.
- Número de telefone: 734-232-5748
- E-mail: weerathh@umich.edu
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Investigador principal:
- Hasini Weerathunge,, Ph.D.
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: High DC LIFU then Sham
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Stimulation parameters and target location.
Stimulation will be delivered using the BrainSonix BXPulsar 1002 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.
Stimulation parameters and target location.
Stimulation will be delivered using the BrainSonix BXPulsar 1002 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 reversing the direction of the transducer placed on the head such that no active stimulation will be applied to the participant's head.
But the neuronavigation procedures (targeting VIM) and stimulation parameters will be kept identical such that the participant experiences the same procedure across active and sham conditions.
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Comparador Falso: Sham then High DC LIFU
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Stimulation parameters and target location.
Stimulation will be delivered using the BrainSonix BXPulsar 1002 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.
Stimulation parameters and target location.
Stimulation will be delivered using the BrainSonix BXPulsar 1002 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 reversing the direction of the transducer placed on the head such that no active stimulation will be applied to the participant's head.
But the neuronavigation procedures (targeting VIM) and stimulation parameters will be kept identical such that the participant experiences the same procedure across active and sham conditions.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percentage of stuttered syllables produced during speech sample
Prazo: 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.
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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).
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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.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Stop signal response time (SSRT)
Prazo: 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.
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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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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.
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Rhythm discrimination score (d')
Prazo: 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.
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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.
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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.
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Hasini Weerathunge, Ph.D., University of Michigan
- Investigador principal: Soo-Eun Chang, Ph.D., University of Michigan
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- HUM00274381
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