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: 10176816
• 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/10176816
• 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; comorbidity; 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; 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.

项目摘要/摘要 喉肌张力障碍(LD)是一种神经疾病，由于以下原因而选择性地影响言语产生 喉部肌肉不由自主的痉挛。由于语音交流是我们日常生活中至关重要的一部分， LD症状对受影响个人的生活质量具有普遍影响，其影响范围通常不止于此 言语运动障碍并导致严重的职业残疾，精神疾病，长期存在 压力和社会孤立。尽管LD有慢性的、令人衰弱的影响，其临床管理仍然 很有挑战性。目前对LD的治疗大多局限于暂时缓解发音症状， 反复向喉部肌肉注射肉毒杆菌毒素，但并不是完全有效。 病人。因此，迫切需要开发下一代治疗干预措施，这些干预措施是 通过LD特定的病理生理学了解其在大多数患者中的最有效结果。我们的长- 学期目标是确定LD的原因和病理生理学，并建立增强的诊断和 治疗这种疾病的方法。本研究的总体目标是进行随机、双盲、假研究。 对照，平行设计，第一阶段临床试验，以评估神经反馈脑- LD患者的计算机接口(BCI)范例，作用于并调节紊乱的病理生理学。 我们的中心假设是，特定于疾病的神经模式，明显与 有症状的言语与无症状的窃窃私语，可能成功地定向和调节了 神经反馈脑-机接口干预对学习障碍患者言语产生的康复作用。我们的中心假设 将通过追求两个具体目标进行测试：(1)发展任务特征活动的神经特征 有症状和无症状的LD患者的言语运动行为，以及(2)评估 神经反馈脑-机接口治疗干预对学习障碍患者的疗效建议进行研究的理由是 在学习记忆中描绘特定任务的神经特征将为他们的 作为新型脑梗塞治疗干预的一个可行的病理生理学靶点。这项研究是 重要，因为预计它将通过通知 在LD患者中进行下一阶段的临床试验，从而直接有助于缩小 这种疾病的临床治疗。本申请中提出的研究具有创新性，因为它 使用受控实验设计和先进的方法来针对特定于障碍的中枢 LD的病理生理学为这些患者开发新的非侵入性治疗方法。