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）：精神分裂症与相当高的发病率和经济负担有关。对其病理生理学的认识尚不完整。一些证据表明，脑背外侧前额叶皮层（DLPFC）可能在精神分裂症中功能失调。神经影像学研究报告了参与认知任务的精神分裂症受试者DLPFC的低活性和高活性。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。经颅磁刺激（TMS）是一种利用高磁场激活神经元的非侵入性技术，是一种不依赖于受试者依从性或努力的直接脑刺激方法。我们在MUSC的团队开创了经颅磁刺激/功能磁共振交错技术，通过经颅磁刺激获得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的TMS/fMRI来研究DLPFC是否真的是低活性的，并表征对TMS的血氧水平依赖性（BOLD）反应。我们假设，在精神分裂症和突出的阴性症状（如动机和平坦的情感）的受试者中，与匹配的健康对照相比，TMS线圈下的rCBF反应较弱。具体方法：在这项为期3年的资助计划中，我们计划招募15名具有明显阴性症状且未使用抗精神病药物（至少2周）的精神分裂症男性患者，以及15名年龄、惯用手、父母教育程度和吸烟习惯相匹配的健康对照组。他们将被评定为精神病，情绪，锥体外系症状和认知能力。他们将接受高分辨率的结构扫描，以确定左额叶中回（布罗德曼区9）的位置，并测量从头骨到前额叶皮层的距离比与头骨到运动皮层的距离比。在另一天，他们将接受TMS/fMRI交替测试。我们将以1Hz的频率间歇刺激左额叶中回，并获得“即时BOLD fMRI”扫描。在每次21秒的经颅磁刺激之前和之后，将分别进行相同长度的无刺激。在运动阈值（移动拇指所需的强度）的80%、100%和120%时随机进行TMS。如果需要，使用的强度将根据前额叶萎缩的程度进行调整。rCBF的变化将是主要的结果衡量指标。结论：本研究建立在Prs在健康受试者和1例精神分裂症患者的前额叶经颅磁刺激/功能磁共振交织的初步工作基础上，以及在阴性患者的经颅磁刺激研究基础上