Interleaved Perfrontal TMS/fMRI in Schizophrenia

交错前额 TMS/fMRI 在精神分裂症中的应用

• 批准号: 6694100
• 负责人: Ziad Nahas
• 金额: $ 18.25万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694100
• 关键词: Interleaved; Perfrontal; TMS; fMRI; Schizophrenia

DESCRIPTION (provided by applicant): Schizophrenia is associated with considerable morbidity and economic burdens. Knowledge about its pathophysiology is still incomplete. Some evidence exists that the brain's dorsolateral prefrontal cortex (DLPFC) may be dysfunctional in schizophrenia. Neuroimaging studies have reported both hypoactive and hyperactive DLPFC in subjects with schizophrenia involved in a cognitive task. These apparent contradictions may be due in part to the subjects' skill, performance and the difficulty of each task. Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that employs a high magnetic field to activate neuron and a direct method of brain stimulation that does not depend on subject's compliance or effort. Our group at MUSC has pioneered the interleaved TMS/fMRI technology to get real-time images of brain activity with TMS. Here, we plan to use interleaved TMS/fMRI in schizophrenia subjects to investigate if DLPFC is truly hypoactive and characterize the Blood Oxygen Level Dependent (BOLD) response to TMS. We hypothesize that in subjects with schizophrenia and prominent negative symptoms (such amotivation and flat affect) will show a weaker rCBF response underneath the TMS coil as compared to matched healthy controls. Specific Methods: In this 3 year grant proposal, we plan enroll 15 schizophrenia males with prominent negative symptoms and neuroleptic free (for at least 2 weeks) and 15 healthy controls matched for age, handedness, parental education and smoking habits. They will be rated for psychosis, mood, extrapyramidal symptoms and cognition. They will undergo a high resolution structural scan to determine the location of left middle frontal gyrus (Brodmann Area 9) and to measure the distance ratio from skull to prefrontal cortex over skull to motor cortex. On a different day, they will undergo an interleaved TMS/fMRI session. We will stimulate intermittently over the left middle frontal gyrus at 1Hz and acquire 'in-the-moment BOLD fMRI scans. Each 21-second epoch of TMS will be preceded and followed by an equal length of no stimulation. TMS will be randomly delivered at 80%, 100% and 120% of motor threshold (intensity necessary to move the thumb). The intensity used will be adjusted relative to the degree of prefrontal atrophy if needed. Changes in rCBF will be the primary outcome measures. Conclusions: This study builds on the Prs preliminary work with interleaved prefrontal TMS/fMRI in healthy subjects and in one case of schizophrenia, as well as TMS research in negative symptoms of schizophrenia. It will assess whether TMS/fMRI is a feasible and safe method in this population. It will characterize the BOLD response to TMS (which is hypothesized to be weaker in schizophrenia subjects compared to controls). This is a necessary first step to better understand neuronal response to non-invasive stimulation in subjects with schizophrenia. In future work, results from this R2I grant will help investigating the functional connectivity of the DLPFC, the relation of TMS to complex cognitive and pharmacological probes and possibly add to the understanding of how to restore DLPFC function in patients with schizophrenia.

描述（由申请人提供）：精神分裂症与相当大的发病率和经济负担有关。关于其病理生理学的知识仍然不完整。一些证据表明，精神分裂症患者的大脑背外侧前额叶皮层 (DLPFC) 可能存在功能障碍。神经影像学研究报告了参与认知任务的精神分裂症患者的 DLPFC 功能低下和功能亢进。这些明显的矛盾可能部分是由于受试者的技能、表现和每项任务的难度造成的。 经颅磁刺激（TMS）是一种非侵入性技术，利用高磁场激活神经元，是一种不依赖于受试者的依从性或努力的直接大脑刺激方法。我们在 MUSC 的团队率先推出了交错 TMS/fMRI 技术，通过 TMS 获取大脑活动的实时图像。在这里，我们计划在精神分裂症受试者中使用交错式 TMS/fMRI 来调查 DLPFC 是否真正功能减退，并表征对 TMS 的血氧水平依赖性 (BOLD) 反应。 我们假设，与匹配的健康对照相比，患有精神分裂症和显着阴性症状（例如缺乏动机和平淡情感）的受试者在 TMS 线圈下会表现出较弱的 rCBF 反应。具体方法：在这项为期 3 年的资助提案中，我们计划招募 15 名具有明显阴性症状且未服用抗精神病药物（至少 2 周）的精神分裂症男性和 15 名年龄、惯用手、父母教育和吸烟习惯相匹配的健康对照。他们将对精神病、情绪、锥体外系症状和认知进行评估。他们将接受高分辨率结构扫描，以确定左额中回（布罗德曼区域 9）的位置，并测量头骨到前额叶皮层与头骨到运动皮层的距离比。在另一天，他们将接受交替的 TMS/fMRI 会议。我们将以 1Hz 的频率间歇性地刺激左侧额中回，并获取“即时 BOLD fMRI 扫描”。每个 21 秒的 TMS 周期之前和之后都会有相同长度的无刺激。 TMS 将以运动阈值（移动拇指所需的强度）的 80%、100% 和 120% 随机发送。如果需要，所使用的强度将根据前额叶萎缩的程度进行调整。 rCBF 的变化将是主要结果指标。 结论：本研究建立在健康受试者和一例精神分裂症患者中使用交错前额叶 TMS/fMRI 的 Prs 初步工作以及阴性患者的 TMS 研究基础上。 精神分裂症的症状。它将评估 TMS/fMRI 是否是该人群中可行且安全的方法。它将表征对 TMS 的大胆反应（假设与对照组相比，精神分裂症受试者的反应较弱）。这是更好地了解精神分裂症患者神经元对非侵入性刺激的反应必要的第一步。在未来的工作中，这项 R2I 资助的结果将有助于研究 DLPFC 的功能连接、TMS 与复杂的认知和药理学探针的关系，并可能增加对如何恢复精神分裂症患者 DLPFC 功能的理解。