Summary

评价中的连接有关的大脑兴奋患者癫痫多式联运Imaging-和激励为基础的方法

Published: November 13, 2016
doi:

Summary

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Abstract

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.

Introduction

经颅磁刺激(TMS)是通过电磁感应非侵入性刺激皮质区域的装置。在TMS,一个大的但在空间上受限的磁通用于诱导靶皮层区的电场,并由此调节底层神经组织的活性。 TMS在运动皮层运动诱发的结果,可以通过外围肌电图(EMG)来测量电势。当成对或脉冲三胞胎施加,TMS可以用来评估特定皮质内GABA能和谷氨酸能电路1-3的活性,从而评估兴奋和抑制体内在人类患者中的平衡。在癫痫具体地说,TMS的研究表明,皮质兴奋存在癫痫患者4,5,并且可以与成功的抗癫痫药物治疗正常化,从而预测对药物的反应6。此外,前皮质的TMS措施citability显示在患者的中间值与单一发作7和患者都特发性和获得性局灶性癫痫8兄弟姐妹。这些结果表明,大脑皮层兴奋的TMS措施可能使我们确定癫痫内表。然而,这些措施的敏感性和特异性是有限的,可能是因为TMS-EMG只能与运动皮层电路刺激进行评估,许多癫痫患者有运动皮层外扣押灶。

脑电图(EEG)提供了直接测量对于TMS脑反应的机会,并且可以使用跨越新皮质的广泛领域,以评估脑反应性。有研究整合脑电图(TMS-EEG)TMS表明,TMS产生整个皮层9,10的反响,并且是可重复的,可靠的11-13活动的浪潮。通过评估诱发活性的传播在不同的行为的状态和在不同的任务,TMS脑电图已用于因果探查人类大脑的网络10,14-16的动态有效连接。 TMS-EEG措施,对疾病从精神分裂症17多动症18所示显著异常,意识障碍如持续性植物状态19。此外,一些团体已经确定了双脉冲的EEG相关因素TMS-EMG指标是癫痫患者的异常20,21。特别重要的,以前的研究也表明,异常刺激诱发的脑电活动被认为是在癫痫患者22-25。

评价的脑电路的另一手段是通过静息态的功能连接的MRI(RS-fcMRI),即在血液氧合水平随时间评估的相关性,从不同脑区26依赖性(BOLD)的信号的技术。利用研究RS-fcMRI已经证明,人的大脑组织成相互作用区域26-29的不同的网络,可以由RS-fcMRI 30确定的具体的大型分布式神经网络内发生的神经精神性疾病,以及经由RS-标识的大脑网络fcMRI往往是神经精神疾病状态31,32异常。在潜在的临床应用方面,RS-fcMRI具有比传统的基于任务的功能磁共振成像应用33几个优点,包括对主体合作的依赖,并在变量上表现的关注。因此,最近有研究探索在不同疾病状态RS-fcMRI变化爆炸。然而,RS-fcMRI的局限之一是在确定是否以及如何在BOLD信号相关性(或anticorrelations)用于形成神经元沟通的基础的电相互作用的难度。一个相关的问题是,它是ofteÑ不清楚是否在各种疾病状态看到的RS-fcMRI变化有生理意义。特别是关于癫痫,目前还不清楚的RS-fcMRI异常是否只是为了间痫样瞬变到期,或独立存在这样的电生理异常;需要同时EEG-fMRI来帮助这些可能性34之间评估。

如TMS可用于产生不同的皮层区域的激活瞬时或持续变化,TMS研究提供的因果评估不同静息态功能磁共振成像连接图案的意义的装置。一种方法是使用RS-fcMRI引导在不同的疾病状态的治疗的刺激的努力;它可以预期的TMS定位到该被功能地连接到已知参与不同疾病状态是更可能比TMS靶向区域没有这种函数的治疗有效区域的区域最终的连接,而事实上一些研究发现,初步证据显示此35,36。另一种方法是涉及使用TMS-脑电图因果关系评估不同的静息态fcMRI模式的生理意义。具体地,可以测试,显示在一个特定的疾病状态异常功能连接区应该显示在患者刺激不同的响应比在健康受试者的假设,并且这些生理异常是存在特异性(或主要)与的异常刺激连通区域。

为了说明上述情况,我们由于大脑发育异常结节性脑室周围异位(PNH)37提供最近的一项研究中,RS-fcMRI,TMS和脑电图合并探索癫痫患者皮质兴奋的一个例子。 PNH患者与adolescent-或成人发病的癫痫临床目前,阅读障碍,和正常INTElligence,并有相邻于影像学38,39侧脑室灰质异常结节。以前的研究已经表明,异位灰质这些脑室结节结构上和功能上连接到离散的病灶中的新皮层40,41,并且癫痫发作可以由新皮层区域,灰质异位,或两者同时进行42发出,表明在癫痫这些患者是电路的现象。通过使用静息状态FC-MRI引导TMS脑电图,我们表明,患者的活动性癫痫是由于PNH有皮质过度兴奋的迹象,而这似乎兴奋只限于地区异常功能连接到深的结节。

该协议是在两个单独的会话进行的。在第一届会议上,结构和静息状态下血液氧合水平依赖(BOLD)对比MRI序列被收购(病人),或只是结构性MRI序列(为正常对照组)。在第一和第二会话之间,静息态功能连接分析用于定义为患者的大脑皮质的目标,和MNI坐标获得这些目标。然后,相当于皮质的目标(根据MNI坐标)被确定为每个健康对照者。在第二届会议上,获得了TMS-EEG数据。

在本文给出的实例中,使用内部软件工具箱和在MRI软件43,44进行官能连通的MRI分析。神经导航的TMS与具有实时磁共振神经导航经颅磁刺激进行。脑电图记录,具有60个通道的TMS兼容的系统,它利用一个取样与保持电路由TMS的,以避免放大器饱和。使用MATLAB R201运行自定义脚本和EEGLAB工具箱45(版本12.0.2.4b)脑电数据进行分析2B。

Protocol

这里描述的协议是经贝斯以色列女执事医疗中心和麻省理工学院的机构审查委员会。 1.选题患者选择的研究方案。 确定患者的活动性癫痫(在过去的一年内发作)或远程癫痫病史(前发作,但在过去的五年或关闭不吃药或者发作)和脑室周围异位结节结构性脑成像。 排除患者无癫痫发作的病史。还排除患者癫痫替代可能的病因( 例如,外伤性脑?…

Representative Results

静息态功能连接功能磁共振成像可用于识别证明与异位脑室周围灰质结节高功能连接皮层区域( 图1),以及控制区域没有这种连接。为了确定这种不正常的功能连接是否具有生理意义,与相关静息态活性皮质区域可以选择为neuronavigated TMS的“连接”的目标网站,并诱发脑电图结果相比,通过控制刺激产生的脑电位在同一患者的非相连的目标。此外,同一区域…

Discussion

静息态的功能连接的MRI已经被用于识别网络连接在人的大脑,并以确定发生在不同的疾病状态26,31,32连接的改变。然而,如磁共振成像功能连接是基于在BOLD信号识别相关,以及作为血液氧合变化与底层神经活动,因果意义和这些功能磁共振成像连接的发现的生理相关性的非平凡关系目前还不清楚。 TMS能够在特定皮层区域大脑活动的空间和时间上定位的操作;当与脑电图结合,TMS可以用来评…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

The authors would like to thank Emily L. Thorn, B.A., for her assistance with the Source estimation of evoked electrical activity Section. MMS was supported by a KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100). CJC was supported by a grant from the National Institutes of Health (5K12NS066225). APL was supported in part by grants from the Sidney R. Baer Jr. Foundation, the National Institutes of Health (R01 HD069776, R01 NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616), and Harvard Catalyst/The Harvard Clinical and Translational Science Center (NCRR and the NCATS, NIH UL1 RR025758). BSC was supported by the National Institute of Neurological Disorders and Stroke (R01 NS073601).

Materials

3T MRI scanner
MRI functional connectivity software
MRI image viewing software MRICron
Transcranial Magnetic Stimulator Nexstim eXimia Stimulator  Can use stimulators from other suppliers e.g. Magventure, Magstim
MRI neuronavigation system Nexstim NBS v3.2.1 Alternative MRI neuronavigation system e.g. Brainsight, Localite
TMS-compatible EEG system Nexstim Eximia EEG Alternatives: Brain Products, Synamps, ANT
Matlab Mathworks R2012b Alternatives: Octave
EEGLab
Minimum Norm Estimate (MNE) software
FreeSurfer

Riferimenti

  1. Florian, J., Müller-Dahlhaus, M., Liu, Y., Ziemann, U. Inhibitory circuits and the nature of their interactions in the human motor cortex a pharmacological TMS study. J. Physiol. 586 (2), 495-514 (2008).
  2. Rotenberg, A. Prospects for clinical applications of transcranial magnetic stimulation and real-time EEG in epilepsy. Brain Topogr. 22 (4), 257-266 (2010).
  3. Cash, R. F. H., Ziemann, U., Murray, K., Thickbroom, G. W. Late cortical disinhibition in human motor cortex: a triple-pulse transcranial magnetic stimulation study. J. Neurophysiol. 103 (1), 511-518 (2010).
  4. Badawy, R. A. B., Curatolo, J. M., Newton, M., Berkovic, S. F., Macdonell, R. A. L. Changes in cortical excitability differentiate generalized and focal epilepsy. Ann. Neurol. 61 (4), 324-331 (2007).
  5. Silbert, B. I., Heaton, A. E., et al. Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy. Seizure. 26, 36-42 (2015).
  6. Badawy, R. A. B., Macdonell, R. A. L., Berkovic, S. F., Newton, M. R., Jackson, G. D. Predicting seizure control: cortical excitability and antiepileptic medication. Ann. Neurol. 67 (1), 64-73 (2010).
  7. Badawy, R. A. B., Vogrin, S. J., Lai, A., Cook, M. J. On the midway to epilepsy: is cortical excitability normal in patients with isolated seizures?. Int. J. Neural Syst. 24 (2), 1430002 (2014).
  8. Badawy, R. A. B., Vogrin, S. J., Lai, A., Cook, M. J. Capturing the epileptic trait: cortical excitability measures in patients and their unaffected siblings. Brain J. Neurol. 136 (Pt 4), 1177-1191 (2013).
  9. Komssi, S., Kähkönen, S., Ilmoniemi, R. J. The effect of stimulus intensity on brain responses evoked by transcranial magnetic stimulation. Hum. Brain Mapp. 21 (3), 154-164 (2004).
  10. Massimini, M., Ferrarelli, F., Huber, R., Esser, S. K., Singh, H., Tononi, G. Breakdown of cortical effective connectivity during sleep. Science. 309 (5744), 2228-2232 (2005).
  11. Lioumis, P., Kicić, D., Savolainen, P., Mäkelä, J. P., Kähkönen, S. Reproducibility of TMS-Evoked EEG responses. Hum. Brain Mapp. 30 (4), 1387-1396 (2009).
  12. Casali, A. G., Casarotto, S., Rosanova, M., Mariotti, M., Massimini, M. General indices to characterize the electrical response of the cerebral cortex to TMS. NeuroImage. 49 (2), 1459-1468 (2010).
  13. Casarotto, S., Romero Lauro, L. J., et al. EEG responses to TMS are sensitive to changes in the perturbation parameters and repeatable over time. PloS One. 5 (4), e10281 (2010).
  14. Morishima, Y., Akaishi, R., Yamada, Y., Okuda, J., Toma, K., Sakai, K. Task-specific signal transmission from prefrontal cortex in visual selective attention. Nat. Neurosci. 12 (1), 85-91 (2009).
  15. Shafi, M. M., Westover, M. B., Fox, M. D., Pascual-Leone, A. Exploration and modulation of brain network interactions with noninvasive brain stimulation in combination with neuroimaging. Eur. J. Neurosci. 35 (6), 805-825 (2012).
  16. Kugiumtzis, D., Kimiskidis, V. K. Direct Causal Networks for the Study of Transcranial Magnetic Stimulation Effects on Focal Epileptiform Discharges. Int. J. Neural Syst. 25 (5), 1550006 (2015).
  17. Radhu, N., Garcia Dominguez, L., et al. Evidence for inhibitory deficits in the prefrontal cortex in schizophrenia. Brain J. Neurol.. 138 (Pt 2), 483-497 (2015).
  18. Bruckmann, S., Hauk, D., et al. Cortical inhibition in attention deficit hyperactivity disorder: new insights from the electroencephalographic response to transcranial magnetic stimulation. Brain J. Neurol. 135 (Pt 7), 2215-2230 (2012).
  19. Rosanova, M., Gosseries, O., et al. Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients. Brain J. Neurol. 135 (Pt 4), 1308-1320 (2012).
  20. Daskalakis, Z. J., Farzan, F., Barr, M. S., Maller, J. J., Chen, R., Fitzgerald, P. B. Long-interval cortical inhibition from the dorsolateral prefrontal cortex: a TMS-EEG study. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 33 (12), 2860-2869 (2008).
  21. Farzan, F., Barr, M. S., et al. The EEG correlates of the TMS-induced EMG silent period in humans. NeuroImage. , (2013).
  22. Valentin, A., Arunachalam, R., et al. Late EEG responses triggered by transcranial magnetic stimulation (TMS) in the evaluation of focal epilepsy. Epilepsia. 49 (3), 470-480 (2008).
  23. Del Felice, ., Fiaschi, A., Bongiovanni, A., L, G., Savazzi, S., Manganotti, P. The sleep-deprived brain in normals and patients with juvenile myoclonic epilepsy: a perturbational approach to measuring cortical reactivity. Epilepsy Res. 96 (1-2), 123-131 (2011).
  24. Julkunen, P., Säisänen, L., Könönen, M., Vanninen, R., Kälviäinen, R., Mervaala, E. TMS-EEG reveals impaired intracortical interactions and coherence in Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1). Epilepsy Res. 106 (1-2), 103-112 (2013).
  25. Kimiskidis, V. K., Koutlis, C., Tsimpiris, A., Kälviäinen, R., Ryvlin, P., Kugiumtzis, D. Transcranial Magnetic Stimulation Combined with EEG Reveals Covert States of Elevated Excitability in the Human Epileptic Brain. Int. J. Neural Syst. 25 (5), 1550018 (2015).
  26. Fox, M. D., Raichle, M. E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8 (9), 700-711 (2007).
  27. Greicius, M. D., Krasnow, B., Reiss, A. L., Menon, V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc. Natl. Acad. Sci. U. S. A. 100 (1), 253-258 (2003).
  28. Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., Raichle, M. E. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl. Acad. Sci. U. S. A. 102 (27), 9673-9678 (2005).
  29. De Luca, M., Beckmann, C. F., De Stefano, N., Matthews, P. M., Smith, S. M. fMRI resting state networks define distinct modes of long-distance interactions in the human brain. NeuroImage. 29 (4), 1359-1367 (2006).
  30. Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., Greicius, M. D. Neurodegenerative diseases target large-scale human brain networks. Neuron. 62 (1), 42-52 (2009).
  31. Greicius, M. Resting-state functional connectivity in neuropsychiatric disorders. Curr. Opin. Neurol. 21 (4), 424-430 (2008).
  32. Zhang, D., Raichle, M. E. Disease and the brain’s dark energy. Nat. Rev. Neurol. 6 (1), 15-28 (2010).
  33. Fox, M. D., Greicius, M. Clinical applications of resting state functional connectivity. Front. Syst. Neurosci. 4, 19 (2010).
  34. Centeno, M., Carmichael, D. W. Network Connectivity in Epilepsy: Resting State fMRI and EEG-fMRI Contributions. Front. Neurol. 5, 93 (2014).
  35. Fox, M. D., Buckner, R. L., White, M. P., Greicius, M. D., Pascual-Leone, A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol. Psychiatry. 72 (7), 595-603 (2012).
  36. Fox, M. D., Buckner, R. L., Liu, H., Chakravarty, M. M., Lozano, A. M., Pascual-Leone, A. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases. Proc. Natl. Acad. Sci. U. S. A. 111 (41), E4367-E4375 (2014).
  37. Shafi, M. M., Vernet, M., et al. Physiological consequences of abnormal connectivity in a developmental epilepsy: Cortical Connectivity. Ann. Neurol. 77 (3), 487-503 (2015).
  38. Chang, B. S., Ly, J., et al. Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia. Neurology. 64 (5), 799-803 (2005).
  39. Battaglia, G., Granata, T. Periventricular nodular heterotopia. Handb. Clin. Neurol. 87, 177-189 (2008).
  40. Chang, B. S., Katzir, T., et al. A structural basis for reading fluency: white matter defects in a genetic brain malformation. Neurology. 69 (23), 2146-2154 (2007).
  41. Christodoulou, J. A., Walker, L. M., et al. Abnormal structural and functional brain connectivity in gray matter heterotopia. Epilepsia. 53 (6), 1024-1032 (2012).
  42. Tassi, L., Colombo, N., et al. Electroclinical, MRI and neuropathological study of 10 patients with nodular heterotopia, with surgical outcomes. Brain J. Neurol. 128 (Pt 2), 321-337 (2005).
  43. Rorden, C., Brett, M. Stereotaxic display of brain lesions). Behav. Neurol. 12 (4), 191-200 (2000).
  44. Rorden, C., Karnath, H. -. O., Bonilha, L. Improving lesion-symptom mapping. J. Cogn. Neurosci. 19 (7), 1081-1088 (2007).
  45. Delorme, A., Makeig, S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J. Neurosci. Methods. 134 (1), 9-21 (2004).
  46. Dill, T. Contraindications to magnetic resonance imaging: non-invasive imaging. Heart Br. Card. Soc. 94 (7), 943-948 (2008).
  47. Rossi, S., Hallett, M., Rossini, P. M., Pascual-Leone, A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 120 (12), 2008-2039 (2009).
  48. Whitfield-Gabrieli, S., Nieto-Castanon, A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2 (3), 125-141 (2012).
  49. Chai, X. J., Castañòn, A. N., Ongür, D., Whitfield-Gabrieli, S. Anticorrelations in resting state networks without global signal regression. NeuroImage. 59 (2), 1420-1428 (2012).
  50. Behzadi, Y., Restom, K., Liau, J., Liu, T. T. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. NeuroImage. 37 (1), 90-101 (2007).
  51. Mutanen, T., Mäki, H., Ilmoniemi, R. J. The effect of stimulus parameters on TMS-EEG muscle artifacts. Brain Stimulat. 6 (3), 371-376 (2013).
  52. Sekiguchi, H., Takeuchi, S., Kadota, H., Kohno, Y., Nakajima, Y. TMS-induced artifacts on EEG can be reduced by rearrangement of the electrode’s lead wire before recording. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 122 (5), 984-990 (2011).
  53. Keel, J. C., Smith, M. J., Wassermann, E. M. A safety screening questionnaire for transcranial magnetic stimulation. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 112 (4), 720 (2001).
  54. Huber, R., Mäki, H., et al. Human cortical excitability increases with time awake. Cereb. Cortex N. Y. N. 1991. 23 (2), 332-338 (2013).
  55. Ter Braack, E. M., de Vos, C. C., van Putten, M. J. A. M. Masking the Auditory Evoked Potential in TMS-EEG: A Comparison of Various Methods. Brain Topogr. 28 (3), 520-528 (2015).
  56. Groppa, S., Oliviero, A., et al. A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 123 (5), 858-882 (2012).
  57. Clin Neurophysiol, S. u. p. p. l. . 56, 13-23 (2003).
  58. Rosanova, M., Casali, A., Bellina, V., Resta, F., Mariotti, M., Massimini, M. Natural frequencies of human corticothalamic circuits. J. Neurosci. Off. J. Soc. Neurosci. 29 (24), 7679-7685 (2009).
  59. Rothwell, J. C., Hallett, M., Berardelli, A., Eisen, A., Rossini, P., Paulus, W. Magnetic stimulation: motor evoked potentials. The International Federation of Clinical Neurophysiology. Electroencephalogr. Clin. Neurophysiol. Suppl. 52, 97-103 (1999).
  60. Rogasch, N. C., Thomson, R. H., et al. Removing artefacts from TMS-EEG recordings using independent component analysis: importance for assessing prefrontal and motor cortex network properties. NeuroImage. 101, 425-439 (2014).
  61. Hernandez-Pavon, J. C., Metsomaa, J., et al. Uncovering neural independent components from highly artifactual TMS-evoked EEG data. J. Neurosci. Methods. 209 (1), 144-157 (2012).
  62. Mognon, A., Jovicich, J., Bruzzone, L., Buiatti, M. ADJUST: An automatic EEG artifact detector based on the joint use of spatial and temporal features. Psychophysiology. 48 (2), 229-240 (2011).
  63. Lehmann, D., Skrandies, W. Reference-free identification of components of checkerboard-evoked multichannel potential fields. Electroencephalogr. Clin. Neurophysiol. 48 (6), 609-621 (1980).
  64. NeuroImage, . 62 (2), 774-781 (2012).
  65. Hämäläinen, M. S., Sarvas, J. Realistic conductivity geometry model of the human head for interpretation of neuromagnetic data. IEEE Trans. Biomed. Eng. 36 (2), 165-171 (1989).
  66. Gramfort, A., Luessi, M., et al. MNE software for processing MEG and EEG data. NeuroImage. 86, 446-460 (2014).
  67. Nikouline, V., Ruohonen, J., Ilmoniemi, R. J. The role of the coil click in TMS assessed with simultaneous EEG. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 110 (8), 1325-1328 (1999).
  68. Gosseries, O., Sarasso, S., et al. On the Cerebral Origin of EEG Responses to TMS: Insights From Severe Cortical Lesions. Brain Stimulat. 8 (1), 142-149 (2015).
  69. Premoli, I., Castellanos, N., et al. TMS-EEG signatures of GABAergic neurotransmission in the human cortex. J. Neurosci. Off. J. Soc. Neurosci. 34 (16), 5603-5612 (2014).
  70. Farzan, F., Barr, M. S., et al. Evidence for gamma inhibition deficits in the dorsolateral prefrontal cortex of patients with schizophrenia. Brain J. Neurol. 133 (Pt 5), 1505-1514 (2010).
  71. Wang, J. X., Rogers, L. M., et al. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 345 (6200), 1054-1057 (2014).
check_url/it/53727?article_type=t

Play Video

Citazione di questo articolo
Shafi, M. M., Whitfield-Gabrieli, S., Chu, C. J., Pascual-Leone, A., Chang, B. S. A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy. J. Vis. Exp. (117), e53727, doi:10.3791/53727 (2016).

View Video