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。有一些证据表明，精神分裂症的大脑背侧前额叶皮层（DLPFC）可能是功能失调的。神经影像学研究报道了患有精神分裂症的受试者参与认知任务的受试者中的低血球和多活跃DLPFC。这些明显的矛盾可能部分归因于主题的技能，表现和每个任务的难度。 经颅磁刺激（TMS）是一种非侵入性技术，它采用高磁场来激活神经元和直接的脑刺激方法，不取决于受试者的依从性或努力。 MUSC的小组率先开创了交错的TMS/fMRI技术，以获取使用TMS的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织的TMS/fMRI研究DLPFC是否真正低连接，并表征了对TMS的血氧水平（BOLD）反应。 我们假设，与匹配的健康对照组相比，在精神分裂症和明显的负面症状受试者和明显的负面症状（此类动机和平坦的影响）中，TMS线圈下的RCBF反应较弱。具体方法：在这三年的赠款建议中，我们计划招募15名具有明显的负面症状和无神经摄影的精神分裂症男性（至少2周）和15种健康对照，并且适合年龄，惯用性，父母教育和吸烟习惯。它们将被评为精神病，情绪，锥体外症状和认知。他们将接受高分辨率的结构扫描，以确定左中间回回（Brodmann区域9）的位置，并测量从头骨到颅骨前额叶皮层的距离比在头骨到运动皮层的距离。在不同的一天，他们将进行交错的TMS/fMRI会议。我们将在1Hz处间歇性地刺激左中额回，并获取“命中式大胆的fMRI扫描”。每个21秒的TMS时期将在之前，然后是相等的无刺激长度。 TMS将以80％，100％和120％的运动阈值（移动拇指所需的强度）随机交付。如果需要，使用的强度将相对于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：这项研究基于PRS的初步工作，在健康受试者和一种精神分裂症的一种情况下，前额叶的TMS/fMRI以及负面的TMS研究。 精神分裂症的症状。它将评估TMS/fMRI在该人群中是否是可行且安全的方法。它将表征对TMS的粗体反应（与对照相比，这在精神分裂症受试者中较弱）。这是更好地了解精神分裂症受试者非侵入性刺激的神经元反应的必要第一步。在未来的工作中，该R2I赠款的结果将有助于研究DLPFC的功能连通性，TMS与复杂的认知和药理学探针的关系，并可能增加了对精神分裂症患者中如何恢复DLPFC功能的理解。