Noninvasive Thalamocortical Neuromodulation With Low-Intensity Focused Ultrasound for Persistent Developmental Stuttering
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Hasini Weerathunge, Ph.D.
- 전화번호: 734-232-5748
- 이메일: weerathh@umich.edu
연구 연락처 백업
- 이름: Soo-Eun Chang, Ph.D.
- 전화번호: 734-232-0300
- 이메일: sooeunc@umich.edu
연구 장소
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Michigan
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Ann Arbor, Michigan, 미국, 48109
- 모병
- University of Michigan
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연락하다:
- Hasini Weerathunge, Ph.D.
- 전화번호: 734-232-5748
- 이메일: weerathh@umich.edu
-
수석 연구원:
- Hasini Weerathunge,, Ph.D.
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 크로스오버 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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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가짜 비교기: Sham then High DC LIFU
|
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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percentage of stuttered syllables produced during speech sample
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Stop signal response time (SSRT)
기간: 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')
기간: 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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공동 작업자 및 조사자
수사관
- 수석 연구원: Hasini Weerathunge, Ph.D., University of Michigan
- 수석 연구원: Soo-Eun Chang, Ph.D., University of Michigan
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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