Mechanistic clinical trial of individualized tDCS for hallucinations in schizophrenia

个体化 tDCS 治疗精神分裂症幻觉的机制临床试验

基本信息

批准号：
9892248
负责人：
Michael Avissar
金额：
$ 19.25万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892248
关键词：
Acoustic Stimulation Acute Affect Aftercare Aggressive behavior Anatomy Anterior Antipsychotic Agents Attention Auditory Auditory Evoked Potentials Auditory Hallucination Auditory Perception Auditory area Basic Science Behavior Behavioral Biological Markers Brain Characteristics Clinical Clinical Trials Clinical Trials Design Cognitive Computer Models Data Disease Distress Dose Effectiveness Electrodes Etiology Fellowship Frequencies Functional Magnetic Resonance Imaging Functional disorder Future Generations Hallucinations Individual Inferior Influentials Insula of Reil Intervention Language Left Loudness Magnetic Resonance Imaging Measures Mediating Modeling Modification Monitor Morbidity - disease rate Neurobiology Paper Participant Patient Self-Report Patients Perception Pharmaceutical Preparations Physiologic Monitoring Physiological Physiology Play Pre-Post Tests Professional Competence Program Development Psychotic Disorders Randomized Refractory Reporting Research Research Domain Criteria Research Personnel Resistance Rest Role Schizophrenia Sensory Severities Social Environment Source Specific qualifier value Standardization Structure Suicide Symptoms System Techniques Testing Training Transcranial magnetic stimulation Use of New Techniques Verbal Auditory Hallucinations Work base burden of illness career career development deviant electric field experience frontal lobe improved mortality neuroimaging neuromechanism neurophysiology neuropsychiatric disorder neuropsychiatric symptom novel patient oriented potential biomarker relating to nervous system response skills social deficits suicide rate theories treatment effect treatment response

Acoustic Stimulation Acute Affect Aftercare Aggressive behavior Anatomy Anterior Antipsychotic Agents Attention Auditory Auditory Evoked Potentials Auditory Hallucination Auditory Perception Auditory area Basic Science Behavior Behavioral Biological Markers Brain Characteristics Clinical Clinical Trials Clinical Trials Design Cognitive Computer Models Data Disease Distress Dose Effectiveness Electrodes Etiology Fellowship Frequencies Functional Magnetic Resonance Imaging Functional disorder Future Generations Hallucinations Individual Inferior Influentials Insula of Reil Intervention Language Left Loudness Magnetic Resonance Imaging Measures Mediating Modeling Modification Monitor Morbidity - disease rate Neurobiology Paper Participant Patient Self-Report Patients Perception Pharmaceutical Preparations Physiologic Monitoring Physiological Physiology Play Pre-Post Tests Professional Competence Program Development Psychotic Disorders Randomized Refractory Reporting Research Research Domain Criteria Research Personnel Resistance Rest Role Schizophrenia Sensory Severities Social Environment Source Specific qualifier value Standardization Structure Suicide Symptoms System Techniques Testing Training Transcranial magnetic stimulation Use of New Techniques Verbal Auditory Hallucinations Work base burden of illness career career development deviant electric field experience frontal lobe improved mortality neuroimaging neuromechanism neurophysiology neuropsychiatric disorder neuropsychiatric symptom novel patient oriented potential biomarker relating to nervous system response skills social deficits suicide rate theories treatment effect treatment response

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项目摘要

The large majority of patients with schizophrenia (Sz) experience auditory verbal hallucinations (AVH) as a core feature of their disorders. AVH can be associated with increased aggression, distress, suicide rates, and difficulty navigating the social environment. They are refractory to treatment with antipsychotics in ~30% of patients. Physiological dysfunction of posterior auditory/language regions, such as left auditory cortex and temporoparietal junction, and anterior language regions, such as left inferior frontal cortex and anterior insula, is thought to play a major role in generating AVH. Noninvasive brain stimulation (NIBS) approaches such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS) have shown promise in treating AVH but have been difficult to reproduce often due to lack of individualized targeting and lack of target engagement biomarkers. This project investigates individualized high-definition tDCS (HD-tDCS), a novel technique that produces a more focal electrical field than conventional tDCS, for treatment of AVH. Inhibitory HD-tDCS is used to test hypotheses regarding two targets, posterior (PosT) and anterior (AntT) auditory/language regions, and their role in influencing the sensory features (e.g. loudness) and evaluative features (e.g. salience) of AVH, respectively. Participants are randomized to receive either sham, active conventional, active PosT, or active AntT stimulation. Individualized targeting and standardized dosing is achieved by MR-guided computational modeling of electrical fields produced in each participant’s brain anatomy. Furthermore, functional target engagement is verified by measuring pre/post treatment changes in elevated resting state functional connectivity (rsFC) within and between PosT and AntT. Etiological biomarkers that track source monitoring, prediction error, and neurophysiological abnormalities associated with AVH are also tested pre/post treatment. The project builds on the candidate’s background in basic auditory neurophysiology, clinical expertise in psychotic disorders and noninvasive brain stimulation, and more recent fellowship training in basic neuroimaging and neurophysiology. The application proposes a 5-year career development program which will provide essential and additional training in basic science of AVH, clinical trials design and implementation, translational neuroimaging, translational neurophysiology, noninvasive brain stimulation, and academic career skills. The acquired skills will allow the candidate to transition into an independent patient-oriented researcher investigating individualized noninvasive brain stimulation for treatment of neuropsychiatric symptoms and disorders. During the project he will work directly with experts in Sz, AVH, fMRI, rsFC, aEPs, computational modeling, NIBS, and clinical trial design. The results of the proposed clinical trial will guide future novel interventions for neuropsychiatric disorders using individualized targeting and target engagement biomarkers. In addition the findings will have the potential to relieve the burden of illness imposed by persistent AVH in Sz.

绝大多数精神分裂症患者（SZ）经历了听觉言语幻觉（AVH）他们的疾病的核心特征。 AVH可能与增加的攻击性，困扰，自杀率和艰难的导航社会环境。它们对用抗精神病药的治疗难治性约30％患者。后验听觉/语言区域的生理功能障碍，例如左听觉皮层和颞parietal结和前语言区域，例如左下额皮层和前岛，被认为在产生AVH方面起着重要作用。无创脑刺激（NIB）方法，例如跨界磁刺激和thrancranial直流电流刺激（TDC）在治疗AVH，但由于缺乏个性化的靶向和缺乏目标，因此很难繁殖参与生物标志物。该项目调查了个性化的高清TDC（HD-TDCS），这是一种小说与常规TDC相比，用于治疗AVH的技术比常规TDC更具局灶性电场。抑制性 HD-TDCS用于测试有关两个目标的假设，即后（后）和前（ANTT）听觉/语言区域及其在影响者中的角色（例如响度）中的作用并进行了评估 AVH的特征（例如显着性）。参与者是随机接收假的，主动的常规，主动柱或主动的ANTT刺激。个性化的靶向和标准化给药是通过在每个参与者大脑中产生的电场的MR引导计算建模实现解剖学。此外，通过测量治疗前/治疗后的变化来验证功能目标参与升高的静息状态功能连通性（RSFC）在邮政和邮政和ANTT之间。病因生物标志物与AVH相关的轨道源监测，预测误差和神经生理异常是还测试了治疗前/治疗后。该项目以基本听觉的候选人背景为基础神经生理学，精神疾病和无创脑刺激的临床专业知识以及最新的基本神经影像学和神经生理学的奖学金培训。申请提案为期5年的职业生涯开发计划将提供AVH基础科学基础科学的必要和额外培训设计和实施，翻译神经影像学，转化神经生理学，无创大脑刺激和学术职业技能。获得的技能将使候选人能够过渡到独立以患者为导向的研究人员研究个性化的无创脑刺激治疗神经精神症状和疾病。在项目期间，他将直接与AVH SZ的专家合作 fMRI，RSFC，AEPS，计算建模，NIBS和临床试验设计。提议的临床结果试验将使用个性化靶向和目标指导神经精神疾病的未来新颖干预措施参与生物标志物。此外，调查结果将有可能挽救施加疾病的烧伤通过SZ的持久性avh。