Shafi Mouhsin M, Whitfield-Gabrieli Susan, Chu Catherine J, Pascual-Leone Alvaro, Chang Bernard S
Department of Neurology, Harvard Medical School; Department of Neurology, Beth Israel Deaconess Medical Center; Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center;
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology.
J Vis Exp. 2016 Nov 13(117):53727. doi: 10.3791/53727.
Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.
静息态功能连接磁共振成像（rs-fcMRI）是一种基于血氧水平依赖信号随时间的相关性来识别不同脑区之间连接性的技术。rs-fcMRI已被广泛应用于识别不同神经和精神疾病中的脑连接异常。然而，rs-fcMRI连接异常、脑电生理学和疾病状态之间的关系尚不清楚，部分原因是疾病病理生理学中功能连接改变的因果意义尚未确立。经颅磁刺激（TMS）是一种利用电磁感应非侵入性地在皮质活动中产生局灶性变化的技术。当与脑电图（EEG）结合使用时，TMS可用于评估大脑对外部扰动的反应。在这里，我们提供了一个将rs-fcMRI、TMS和EEG结合起来评估神经精神疾病患者功能连接改变的生理意义的方案。我们提供了一项先前发表的研究的代表性结果，其中rs-fcMRI被用于识别因皮质发育畸形、脑室周围结节性异位症（PNH）导致的癫痫患者中连接异常的区域。与匹配的健康对照患者相同部位的刺激相比，癫痫患者的刺激导致TMS诱发的EEG活动异常，TMS诱发电位的晚期成分异常增加，这与皮质兴奋性过高一致。这种异常特定于静息态功能连接异常的区域。对一名先前记录有癫痫发作的受试者进行的电源分析表明，异常TMS诱发活动的起源与癫痫发作起始区共定位，提示存在致痫回路。这些结果证明了rs-fcMRI、TMS和EEG如何可以一起用于识别和理解人类疾病中异常脑连接的生理意义。
