Adaptive closed-loop brain-computer interface therapeutic intervention in laryngeal dystonia

喉肌张力障碍的自适应闭环脑机接口治疗干预

• 批准号: 10371128
• 负责人: Kristina Simonyan
• 金额: $ 36.13万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10371128
• 关键词: Affect; Base of the Brain; Botulinum Toxins; Brain; Brain imaging; Characteristics; Chronic; Clinical; Clinical Management; Clinical Trials; Communication; Crying; Data; Development; Diagnostic; Disease; Disease Management; Double-Blind Method; Dystonia; Electroencephalography; Experimental Designs; Focal Dystonias; Foundations; Functional disorder; Goals; Human; Impairment; Individual; Inferior; Injections; Intervention; Knowledge; Laryngeal muscle structure; Larynx; Lead; Learning; Life; Link; Methodology; Mission; Movement; Muscle Contraction; Occupational; Outcome; Parietal; Patients; Pattern; Peripheral; Phase; Phase I Clinical Trials; Physiology; Posture; Production; Public Health; Quality of life; Randomized; Rehabilitation therapy; Research; Social isolation; Spasm; Spastic Dysphonias; Specificity; Speech; Stress; Symptoms; Testing; Therapeutic; Therapeutic Effect; Therapeutic Intervention; United States National Institutes of Health; Voice; base; brain abnormalities; brain computer interface; clinical care; design; disability; goal oriented behavior; imaging study; improved; innovation; motor behavior; motor control; motor deficit; motor impairment; motor rehabilitation; motor symptom; multimodality; nervous system disorder; neural patterning; neurofeedback; neuroregulation; neurotechnology; novel; novel therapeutic intervention; novel therapeutics; optimal treatments; psychiatric comorbidity; psychologic; reduce symptoms; relating to nervous system; side effect; tool; translational impact; treatment strategy

PROJECT SUMMARY / ABSTRACT Laryngeal dystonia (LD) is a neurological disorder that selectively affects speech production due to involuntary spasms in the laryngeal muscles. As speech communication is a vital part of our daily existence, LD symptoms have a pervasive effect on the quality of life of the affected individual, often extending beyond speech motor deficits and causing significant occupational disability, psychiatric comorbidities, long-lasting stress, and social isolation. Despite the chronic, debilitating impact of LD, its clinical management remains challenging. The current treatment of LD is mostly limited to the temporary relief of voice symptoms with repeated injections of botulinum toxin into the laryngeal muscles, which, however, are not effective in all patients. Thus, there is an urgent clinical need to develop next-generation therapeutic interventions that are informed by LD-specific pathophysiology for their most effective outcome in the majority of patients. Our long- term goal is to determine the causes and pathophysiology of LD and to establish enhanced diagnostics and treatment of this disorder. The overall objective of this study is to conduct a randomized, double-blind, sham- controlled, parallel design, phase 1 clinical trial to assess the feasibility and efficacy of a neurofeedback brain- computer interface (BCI) paradigm in LD patients that acts upon and modulates the disorder pathophysiology. Our central hypothesis is that the disorder-specific neural patterns, which are distinctly associated with symptomatic speech vs. asymptomatic whisper, maybe successfully targeted and modulated with neurofeedback BCI intervention for rehabilitation of speech production in LD patients. Our central hypothesis will be tested by pursuing two specific aims: (1) develop neural signatures of task-characteristic activity during symptomatic and asymptomatic speech motor behaviors in LD patients, and (2) assess the feasibility and efficacy of neurofeedback BCI therapeutic intervention in LD patients. The rationale for the proposed studies is that delineation of task-specific neural signatures in LD will establish a robust scientific foundation for their utilization as a feasible pathophysiological target of novel BCI therapeutic intervention. This research is significant because it is expected to have a meaningful translational impact by informing the conduct of the next phase of the clinical trial in LD patients and thus directly contribute to closing the critically existing gap in the clinical management of this disorder. The research proposed in this application is innovative because it uses a controlled experimental design and advanced methodologies to target disorder-specific central pathophysiology of LD for the development of new non-invasive treatment for these patients.

项目总结/摘要 喉肌张力障碍（LD）是一种神经系统疾病，选择性地影响语音产生， 喉部肌肉不自主的痉挛由于言语交际是我们日常生活的重要组成部分， LD症状对受影响个体的生活质量具有普遍影响，通常延伸到 言语运动缺陷并导致显著职业残疾、精神共病、长期 压力和社会孤立。尽管LD的慢性，衰弱的影响，其临床管理仍然 挑战性目前对LD的治疗主要限于暂时缓解声音症状， 反复注射肉毒杆菌毒素到喉部肌肉中，然而，这并不是所有人都有效。 患者因此，临床上迫切需要开发下一代治疗干预措施， 根据LD特异性病理生理学，它们在大多数患者中的最有效结局。我们长久以来- 长期目标是确定LD的原因和病理生理学，并建立增强的诊断和 治疗这种疾病。本研究的总体目标是进行一项随机、双盲、假手术， 对照，平行设计，1期临床试验，以评估神经反馈大脑的可行性和有效性， 计算机接口（BCI）范式在LD患者的作用和调节疾病的病理生理。 我们的中心假设是，疾病特异性神经模式，这是明显相关的， 有症状的言语与无症状的耳语，可能成功靶向和调制， 神经反馈脑机接口干预对LD患者言语产生的康复作用我们的核心假设 将通过追求两个具体目标进行测试：（1）开发任务特征活动的神经签名， LD患者的有症状和无症状言语运动行为，和（2）评估可行性， 神经反馈脑机接口治疗LD的疗效。拟议研究的理由是 LD中任务特异性神经信号的描绘将为他们的研究建立坚实的科学基础。 利用作为新的BCI治疗干预的可行的病理生理学靶点。本研究是 重要的是，它预计将通过通知行为的行为产生有意义的翻译影响。 LD患者临床试验的下一阶段，从而直接有助于缩小 这种疾病的临床管理。本申请中提出的研究是创新的，因为它 使用对照实验设计和先进的方法来靶向特定于疾病的中枢神经系统， LD的病理生理学，为这些患者开发新的非侵入性治疗方法。