TMS-EP Probes of Neural Response Mechanisms and Connectivity in Schizophrenia

精神分裂症神经反应机制和连接性的 TMS-EP 探针

• 批准号: 7652300
• 负责人: BRUCE I TURETSKY
• 金额: $ 17.72万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-07 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7652300
• 关键词: Area; Brain; Brain region; Characteristics; Clinical; Clinical Research; Development; Disease; Electrodes; Ethics; Evoked Potentials; Exhibits; Failure; Functional disorder; Funding Mechanisms; Goals; Human; Individual; Investigation; Left; Measures; Methodology; Modeling; Morphology; Neurons; Patients; Physiologic pulse; Population; Prefrontal Cortex; Sampling; Schizophrenia; Specificity; Temporal Lobe; Testing; Time; Transcranial magnetic stimulation; base; brain research; conditioning; design; in vivo; neural circuit; neural patterning; neuromechanism; neuropathology; neurophysiology; novel; public health relevance; regional difference; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): Studies of the neuropathology of schizophrenia have documented a multitude of structural and functional brain abnormalities. The scope of these findings has been vast, and no single set of abnormalities has emerged as being characteristic of, or pathognomonic for, the disorder. However, a few specific themes have received enough empirical support to stand as potential models of the illness, and to offer testable hypotheses of the underlying pathophysiological mechanisms. Among the more robust of these are failures of appropriate neuronal inhibition & excitation and disturbed connectivity across cortical regions. Tests of these mechanisms in patients are limited by the practical constraints of in vivo clinical research and are, therefore, necessarily indirect and inferential. Recent developments in the use of transcranial magnetic stimulation (TMS) as a neurophysiological probe of cortical activity have suggested a means to test the functional integrity and responsivity of neural circuits in a more direct manner. By combining TMS with simultaneous multi-channel evoked potential (EP) recording, we believe that we can assess cortical inhibitory and facilitative mechanisms within localized brain areas, and the neural connectivity across brain regions. This is a novel methodology that has only been applied to a limited extent in the study of healthy individuals. It has been applied even less to the study of clinical populations. Early results, though, have been very promising, and further investigation of its applicability to the study of schizophrenia is clearly warranted. The goal of this project, therefore, is to establish the feasibility and utility of this methodology in the study of schizophrenia. Three experiments will be conducted, each in a sample of 16 schizophrenia patients and 16 healthy subjects. Experiment 1 will characterize the cortical evoked potential response to TMS stimulation, using a broad range of TMS pulse intensities. Experiment 2 will characterize intracortical inhibitory and facilitative mechanisms, using a paired- pulse design in which a suprathreshold TMS pulse is preceded by a subthreshold pulse at various inter-pulse intervals. Experiment 3 will assess regional differences in both the underlying TMS-evoked potential response, and the intracortical facilitation and inhibition of this response through single pulse and paired pulse stimulation of left and right frontal and temporal cortices. Patient-control differences in amplitude, latency and inter-cortical connectivity of the TMS-evoked response will be examined for all three experiments. PUBLIC HEALTH RELEVANCE Despite intensive investigation, the pathophysiology underlying schizophrenia remains unclear. This study will examine the utility of a novel methodology that combines transcranial magnetic stimulation with evoked potential response recording, to investigate the neural mechanisms of cortical inhibition, facilitation and connectivity in schizophrenia patients. This may help to clarify our understanding of the neuropathology of this debilitating disorder.

描述（由申请人提供）：精神分裂症神经病理学的研究已记录了许多结构和功能性脑异常。这些发现的范围很大，没有单一的异常出现是该疾病的特征或病理学的特征。但是，一些特定的主题获得了足够的经验支持，可以作为疾病的潜在模型，并提供了基本病理生理机制的可检验假设。其中更强大的是适当的神经元抑制和激发以及跨皮质区域的连通性的失败。这些机制在患者中的测试受体内临床研究的实际限制受到限制，因此必须间接和推理。使用经颅磁刺激（TMS）作为皮质活性的神经生理探针的最新发展提出了一种以更直接的方式测试神经回路的功能完整性和反应性的手段。通过将TMS与同时诱发潜力（EP）记录相结合，我们认为我们可以评估局部大脑区域内的皮质抑制和促进机制，以及大脑区域之间的神经连通性。这是一种新型方法，在健康个体的研究中仅在有限的程度上应用。它的应用更少地用于临床人群的研究。不过，早期结果非常有前途，并且显然需要进一步研究其对精神分裂症研究的适用性。因此，该项目的目的是确定该方法在精神分裂症研究中的可行性和实用性。将进行三个实验，每个实验在16名精神分裂症患者和16名健康受试者中。实验1将使用广泛的TMS脉冲强度来表征皮质诱发对TMS刺激的潜在反应。实验2将使用成对的脉冲设计表征心地内抑制和促进机制，在该设计中，上方的TMS脉冲在各个脉冲间隔之前先于亚阈值脉冲。实验3将通过单个脉冲和配对的左右额叶和颞皮质刺激来评估潜在TMS诱发的潜在反应的区域差异，以及心脏内促进和抑制此反应的区域差异。对于所有三个实验，将检查患者控制的振幅，延迟和皮质间连通性的差异。公共卫生的相关性尽管进行了深入研究，但精神分裂症的病理生理学仍不清楚。这项研究将研究一种新型方法的实用性，该方法将经颅磁刺激与诱发的潜在反应记录相结合，以研究精神分裂症患者皮质抑制，促进和连通性的神经机制。这可能有助于阐明我们对这种令人衰弱的疾病的神经病理学的理解。