rTMS Clinical Trial for Auditory Hallucinations

rTMS 治疗幻听的临床试验

• 批准号: 7030666
• 负责人: RALPH Edward HOFFMAN
• 金额: $ 46.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7030666
• 关键词: auditory cortex; behavioral /social science research tag; bioengineering /biomedical engineering; brain mapping; clinical research; clinical trials; hallucinations; human subject; human therapy evaluation; nervous system disorder therapy; patient oriented research; psychophysiology; schizophrenia; speech recognition; temporal lobe /cortex; transcranial magnetic stimulation

DESCRIPTION (provided by applicant): Studies suggest that speech processing areas of the brain play an important role in producing auditory hallucinations (AHs). The PI has reported that delivering 1-Hertz repetitive transcranial magnetic stimulation (rTMS) to the left temporoparietal cortex - a brain region underlying speech perception - produces statistically significant improvements in AHs relative to sham simulation. In a follow-up study, the PI used individualized fMRI maps of abnormal speech processing neurocircuitry to position rTMS in multiple cortical sites, and has found that targeting Wernicke's region and a homologous right-sided region in the superior temporal gyrus (STG) optimized clinical improvement of AHs. The proposed study will enroll 90 patients with a diagnosis of schizophrenia and medication-resistant AHs in a more extended, double- masked rTMS trial. Stimulation will be positioned using structural MRI over the left Wernicke's site and right-sided STG site previously found to have optimized clinical response. Specific Aim #1 is to demonstrate that MRI-positioned 1-Hz rTMS, delivered to the Wernicke's and right STG sites, each for 5 sessions in randomized order, results in greater clinical improvement in AHs compared to sham stimulation. Specific Aim #2 is to determine if alterations in cerebral laterality predict optimal hemisphere of stimulation in reducing AHs, and the degree of improvement elicited by rTMS at each of the two sites. Specific Aim #3 is to demonstrate that a third 5-session series of active rTMS directed to the left/right site found to optimize clinical improvement in the first 10 sessions produces greater improvements in AHs compared to sham stimulation positioned according to the same algorithm. Specific Aim #4 is to demonstrate prospectively that a higher level of hallucination frequency at baseline is a statistical moderator of 1-Hz rTMS in reducing AHs. This study will provide critical information regarding positioning strategies that optimize rTMS for AHs, as well as new insights regarding underlying pathophysiology.

描述（由申请人提供）：研究表明大脑的语音处理区域在产生幻听（AH）方面发挥着重要作用。 PI 报告称，向左颞顶皮层（负责言语感知的大脑区域）提供 1 赫兹重复经颅磁刺激 (rTMS)，相对于假模拟，AH 会产生统计上显着的改善。在后续研究中，PI 使用异常语音处理神经回路的个性化 fMRI 图将 rTMS 定位在多个皮质部位，并发现针对 Wernicke 区域和颞上回 (STG) 中的同源右侧区域优化了临床改善受影响户的情况。拟议的研究将招募 90 名被诊断为精神分裂症和耐药性 AH 的患者参加一项更广泛的双盲 rTMS 试验。将使用结构 MRI 将刺激定位在左侧 Wernicke 部位和右侧 STG 部位，此前发现这些部位具有优化的临床反应。具体目标 #1 是证明，与假刺激相比，将 MRI 定位的 1-Hz rTMS 传送到 Wernicke 和右侧 STG 部位（每个部位按随机顺序进行 5 个疗程）可带来更大的 AH 临床改善。具体目标#2 是确定大脑偏侧性的改变是否可以预测减少 AH 的最佳半球刺激，以及 rTMS 在两个部位引起的改善程度。具体目标 #3 是证明，与根据相同算法定位的假刺激相比，针对左/右部位的第三个 5 疗程系列的主动 rTMS 优化了前 10 疗程中的临床改善，可产生更大的 AH 改善。具体目标#4 是前瞻性地证明基线时较高水平的幻觉频率是 1-Hz rTMS 在减少 AH 方面的统计调节因素。这项研究将提供有关优化 AH rTMS 的定位策略的关键信息，以及有关潜在病理生理学的新见解。