Transcranial Magnetic Stimulation-Electroencephalography and Classified Diagnosis of Consciousness
Cheng Pengfei1,2, Ge Xingyu1,2, Gong Anjuan2,3, Wang Qijun2,3, Feng Zhen1,3, Bai Yang1,3*
1(Affiliated Rehabilitation Hospital,Jiangxi Medical College, Nanchang University, Nanchang 330006, China) 2(The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310000, China) 3(Rehabilitation Medicine Clinical Research Center of Jiangxi Province, Nanchang 330006, China)
Abstract:In recent years, there has still been a lack of an objective measure for the level of consciousness in specific states such as sleep, anesthesia, and disorders of consciousness. Attention has increasingly focused on non-invasive techniques for examining brain states. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as one of the most effective techniques in this field. TMS-EEG has become a promising brain assessment tool in contemporary brain science and clinical neuroscience research. This paper presented a systematic review of the development of TMS-EEG technology, focusing on the combination of TMS and EEG, denoising techniques, and characterization methods, as well as summarizing important research advances in the use of TMS-EEG for consciousness grading. The application of the perturbational complexity index (PCI) in differentiating levels of consciousness across wakefulness, different types of anesthesia and sleep, as well as in quantifying the grading diagnosis of patients with disorders of consciousness, has demonstrated that TMS-EEG is poised to become an objective gold standard for consciousness grading and diagnosis. Examples of objective metrics such as TMS-evoked potentials (TEP), global mean field power (GMFP), and the fractional dimensional index of perturbation complexity (FDI) for grading levels of consciousness in patients with disorders of consciousness, as well as for differentiating between healthy controls, were briefly described. The strengths, shortcomings and future directions of TMS-EEG were also summarized.
成鹏飞, 葛星宇, 龚安娟, 王琦鋆, 冯珍, 白洋. 经颅磁融合脑电技术与意识分级诊断[J]. 中国生物医学工程学报, 2024, 43(6): 720-729.
Cheng Pengfei, Ge Xingyu, Gong Anjuan, Wang Qijun, Feng Zhen, Bai Yang. Transcranial Magnetic Stimulation-Electroencephalography and Classified Diagnosis of Consciousness. Chinese Journal of Biomedical Engineering, 2024, 43(6): 720-729.
[1] Ilmoniemi RJ, Virtanen J, Ruohonen J, et al. Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity [J]. Neuroreport, 1997, 8(16): 3537-3540. [2] Noda Y. Toward the establishment of neurophysiological indicators for neuropsychiatric disorders using transcranial magnetic stimulation-evoked potentials: a systematic review [J]. Psychiatry Clin Neurosci, 2020, 74(1): 12-34. [3] Allan HP. Adams and Victor's Principles of Neurology(Seventh Edition) [M]. New York: McGraw-Hill Education, 2019: 375. [4] Stamm M, Aru J, Rutiku R, et al. Occipital long-interval paired pulse TMS leads to slow wave components in NREM sleep [J]. Conscious Cogn, 2015, 35: 78-87. [5] Ferrarelli F, Massimini M, Sarasso S, et al. Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness [J]. Proc Natl Acad Sci USA, 2010, 107(6): 2681-2686. [6] Massimini M, Ferrarelli F, Huber R, et al. Breakdown of cortical effective connectivity during sleep [J]. Science, 2005, 309(5744): 2228-2232. [7] Giacino JT, Fins JJ, Laureys S, et al. Disorders of consciousness after acquired brain injury: the state of the science [J]. Nat Rev Neurol, 2014, 10(2): 99-114. [8] Schiff ND, Plum F. The role of arousal and "gating" systems in the neurology of impaired consciousness [J]. J Clin Neurophysiol, 2000, 17(5): 438-452. [9] Fins JJ. The minimally conscious state: definition and diagnostic criteria [J]. Neurology, 2002, 59(9): 1473; author reply 1473-1474. [10] Laureys S, Celesia GG, Cohadon F, et al. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome [J]. BMC Med, 2010, 8: 68. [11] Schnakers C, Vanhaudenhuyse A, Giacino J, et al. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment [J]. BMC Neurol, 2009, 9: 35. [12] Ragazzoni A, Pirulli C, Veniero D, et al. Vegetative versus minimally conscious states: a study using TMS-EEG, sensory and event-related potentials [J]. PLoS ONE, 2013, 8(2): e57069. [13] Rosanova M, Gosseries O, Casarotto S, et al. Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients [J]. Brain, 2012, 135(Pt 4): 1308-1320. [14] Casali AG, Gosseries O, Rosanova M, et al. A theoretically based index of consciousness independent of sensory processing and behavior [J]. Sci Transl Med, 2013, 5(198): 198ra105. [15] Daskalakis ZJ, Farzan F, Radhu N, et al. Combined transcranial magnetic stimulation and electroencephalography: its past, present and future [J]. Brain Res, 2012, 1463: 93-107. [16] Ilmoniemi RJ, Kicic D. Methodology for combined TMS and EEG [J]. Brain Topography, 2010, 22(4): 233-248. [17] Thut G, Ives JR, Kampmann F, et al. A new device and protocol for combining TMS and online recordings of EEG and evoked potentials [J]. J Neurosci Methods, 2005, 141: 207-217. [18] Cracco RQ, Amassian VE, Maccabee PJ, et al. Comparison of human transcallosal responses evoked by magnetic coil and electrical stimulation [J]. Electroencephalogr Clin Neurophysiol, 1989, 74(6): 417-424. [19] Ilmoniemi RJ, Ruohonen J, Karhu J. Transcranial magnetic stimulation-a new tool for functional imaging of the brain [J]. Crit Rev Biomed Eng, 1999, 27(3-5): 241-284. [20] Lioumis P, KiciAć1 D, Savolainen P, et al. Reproducibility of TMS-evoked EEG responses [J]. Hum Brain Mapp, 2009, 30(4): 1387-1396. [21] Casarotto S, Romero Lauro LJ, Bellina V, et al. EEG responses to TMS are sensitive to changes in the perturbation parameters and repeatable over time [J]. PLoS ONE, 2010, 5(4): e10281. [22] Massimini M, Tononi G, Huber R. Slow waves, synaptic plasticity and information processing: insights from transcranial magnetic stimulation and high-density EEG experiments [J]. Eur J Neurosci, 2009, 29(9): 1761-1770. [23] Pellicciari MC, Veniero D, Miniussi C. Characterizing the cortical oscillatory response to TMS pulse [J]. Front Cell Neurosci, 2017, 11: 38. [24] Bortoletto M, Veniero D, Thut G, et al. The contribution of TMS-EEG coregistration in the exploration of the human cortical connectome [J]. Neuroscience and Biobehavioral Reviews, 2015, 49: 114-124. [25] Chung SW, Rogasch NC, Hoy KE, et al. Measuring brain stimulation induced changes in cortical properties using TMS-EEG [J]. Brain Stimulation, 2015, 8(6): 1010-1020. [26] Barr MS, Farzan F, Davis KD, et al. Measuring GABAergic inhibitory activity with TMS-EEG and its potential clinical application for chronic pain [J]. J Neuroimmune Pharmacol, 2013, 8(3): 535-546. [27] Korhonen RJ, Hernandez-Pavon JC, Metsomaa J, et al. Removal of large muscle artifacts from transcranial magnetic stimulation-evoked EEG by independent component analysis [J]. Med Biol Eng Comput, 2011, 49(4): 397-407. [28] Mutanen TP, Kukkonen M, Nieminen JO, et al. Recovering TMS-evoked EEG responses masked by muscle artifacts [J]. Neuroimage, 2016, 139: 157-166. [29] Komssi S, Aronen HJ, Huttunen J, et al. Ipsi and contralateral EEG reactions to transcranial magnetic stimulation [J]. Clin Neurophysiol, 2002, 113(2): 175-184. [30] Kähkönen S, Komssi S, Wilenius J, et al. Prefrontal transcranial magnetic stimulation produces intensity-dependent EEG responses in humans [J]. NeuroImage, 2005, 24(4): 955-960. [31] Silvanto J, Cattaneo Z. Transcranial magnetic stimulation reveals the content of visual short-term memory in the visual cortex [J]. NeuroImage, 2010, 50(4): 1683-1689. [32] Nikouline V, Ruohonen J, Ilmoniemi RJ. The role of the coil click in TMS assessed with simultaneous EEG [J]. Clin Neurophysiol, 1999, 110(8): 1325-1328. [33] Fuggetta G, Fiaschi A, Manganotti P. Modulation of cortical oscillatory activities induced by varying single-pulse transcranial magnetic stimulation intensity over the left primary motor area: a combined EEG and TMS study [J]. Neuroimage, 2005, 27: 896-908. [34] Paus T, Sipila PK, Strafella AP. Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study [J]. Journal of Neurophysiology, 2001, 86(4): 1983-1990. [35] ter Braack EM, de Vos CC, van Putten MJAM. Masking the auditory evoked potential in TMS-EEG: a comparison of various methods [J]. Brain Topography, 2015, 28(3): 520-528. [36] Russo S, Sarasso S, Puglisi GE, et al. TAAC-TMS adaptable auditory control: a universal tool to mask TMS clicks [J]. Journal of Neuroscience Methods, 2022, 370: 109491. [37] Ilmoniemi RJ, Hernandez-Pavon JC, Makela NN, et al. Dealing with artifacts in TMS-evoked EEG [C]//The 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Milan: IEEE, 2015: 230-233. [38] Gordon PC, Jovellar DB, Song Y, et al. Recording brain responses to TMS of primary motor cortex by EEG - utility of an optimized sham procedure [J]. Neuroimage, 2021, 245: 118708. [39] Song Y, Gordon PC, Metsomaa J, et al. Evoked EEG responses to TMS targeting regions outside the primary motor cortex and their test-retest reliability [J]. Brain Topogr, 2024, 37(1): 19-36. [40] Rogasch NC, Thomson RH, Farzan F, et al. Removing artefacts from TMS-EEG recordings using independent component analysis: importance for assessing prefrontal and motor cortex network properties [J]. Neuroimage, 2014, 101: 425-439. [41] Hernandez-Pavon JC, Metsomaa J, Mutanen T, et al. Uncovering neural independent components from highly artifactual TMS-evoked EEG data [J]. J Neurosci Methods, 2012, 209: 144-157. [42] ter Braack EM, de Jonge B, van Putten MJ. Reduction of TMS induced artifacts in EEG using principal component analysis [J]. IEEE Trans Neural Syst Rehabil Eng, 2013, 21(3): 376-382. [43] Maki H, Ilmoniemi RJ. Projecting out muscle artifacts from TMS-evoked EEG [J]. Neuroimage, 2011, 54(4): 2706-2710. [44] Metsomaa J, Sarvas J, Ilmoniemi RJ. Multi-trial evoked EEG and independent component analysis [J]. J Neurosci Methods, 2014, 228: 15-26. [45] Metsomaa J, Sarvas J, Ilmoniemi RJ. Blind source separation of event-related EEG/MEG [J]. IEEE Trans Biomed Eng, 2017, 64(9): 2054-2064. [46] Casula EP, Bertoldo A, Tarantino V, et al. TMS-evoked long-lasting artefacts: a new adaptive algorithm for EEG signal correction [J]. Clinical Neurophysiology, 2017, 128: 1563-1574. [47] Freche D, Naim-Feil J, Peled A, et al. A quantitative physical model of the TMS-induced discharge artifacts in EEG [J]. PLoS Comput Biol, 2018, 14(7): e1006177. [48] Morbidi F, Garulli A, Prattichizzo D, et al. Off-line removal of TMS-induced artifacts on human electroencephalography by Kalman filter [J]. J Neurosci Methods, 2007, 162: 293-302. [49] Vafidis P, Kimiskidis VK, Kugiumtzis D. Evaluation of algorithms for correction of transcranial magnetic stimulation-induced artifacts in electroencephalograms [J]. Med Biol Eng Comput, 2019, 57(12): 2599-2615. [50] Hernandez-Pavon JC, Veniero D, Bergmann TO, et al. TMS combined with EEG: recommendations and open issues for data collection and analysis [J]. Brain Stimul, 2023, 16: 567-593. [51] Hill AT, Rogasch NC, Fitzgerald PB, et al. TMS-EEG: a window into the neurophysiological effects of transcranial electrical stimulation in non-motor brain regions [J]. Neuroscience and Biobehavioral Reviews, 2016, 64: 175-184. [52] Rosanova M, Casali A, Bellina V, et al. Natural frequencies of human corticothalamic circuits [J]. J Neurosci, 2009, 29(24): 7679-7685. [53] Kirschstein T, Köhling R. What is the source of the EEG? [J]. Clin EEG Neurosci, 2009, 40(3): 146-149. [54] Luck SJ, Kappenman ES. Electroencephalography and event-related brain potentials [M]//Handbook of Psychophysiology//Cambridge: Cambridge University Press, 2017:74-100. [55] Mueller JK, Grigsby EM, Prevosto V, et al. Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates [J]. Nat Neurosci, 2014, 17: 1130-1136. [56] Murphy SC, Palmer LM, Nyffeler T, et al. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites [J].eLife Sciences, 2016, 5: e13598. [57] Komssi S, Kähkönen S, Ilmoniemi RJ. The effect of stimulus intensity on brain responses evoked by transcranial magnetic stimulation [J]. Hum Brain Mapp, 2004, 21(3): 154-164. [58] Komssi S, Kahkonen S. The novelty value of the combined use of electroencephalography and transcranial magnetic stimulation for neuroscience research [J]. Brain Research Reviews, 2006, 52: 183-192. [59] Gosseries O, Sarasso S, Casarotto S, et al. On the cerebral origin of EEG responses to TMS: insights from severe cortical lesions [J]. Brain Stimulation, 2015, 8(1): 142-149. [60] Canali P, Casarotto S, Rosanova M, et al. Abnormal brain oscillations persist after recovery from bipolar depression [J]. Eur Psychiatry, 2017, 41: 10-15. [61] Herring JD, Thut G, Jensen O, et al. Attention modulates TMS-locked alpha oscillations in the visual cortex [J]. J Neurosci, 2015, 35(43): 14435-14447. [62] Van der Werf YD, Paus T. The neural response to transcranial magnetic stimulation of the human motor cortex I. Intracortical and cortico-cortical contributions [J]. Experimental Brain Research, 2006, 175(2): 231-245. [63] Pigorini A, Casali AG, Casarotto S, et al. Time-frequency spectral analysis of TMS-evoked EEG oscillations by means of Hilbert-Huang transform [J]. Journal of Neuroscience Methods, 2011, 198(2): 236-245. [64] Giovanni A, Capone F, di Biase L, et al. Oscillatory activities in neurological disorders of elderly: biomarkers to target for neuromodulation [J]. Front Aging Neurosci, 2017, 9: 189. [65] Cao KX, Ma ML, Wang CZ, et al. TMS-EEG: an emerging tool to study the neurophysiologic biomarkers of psychiatric disorders [J]. Neuropharmacology, 2021, 197: 108574. [66] Tremblay S, Rogasch NC, Premoli I, et al. Clinical utility and prospective of TMS-EEG [J]. Clin Neurophysiol, 2019, 130: 802-844. [67] Guidali G, Zazio A, Lucarelli D, et al. Effects of transcranial magnetic stimulation (TMS) current direction and pulse waveform on cortico-cortical connectivity: a registered report TMS-EEG study [J]. Eur J Neurosci, 2023, 58: 3785-3809. [68] Fernandez L, Biabani M, Do M, et al. Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: a feasibility study [J]. Journal of Neurophysiology, 2021, 125: 1768-1787. [69] Tononi G, Boly M, Massimini M, et al. Integrated information theory: from consciousness to its physical substrate [J]. Nat Rev Neurosci, 2016, 17(7): 450-461. [70] Sarasso S, Rosanova M, Casali AG, et al. Quantifying cortical EEG responses to TMS in (un)consciousness [J]. Clin EEG Neurosci, 2014, 45(1): 40-49. [71] Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia [J]. Science, 2008, 322(5903): 876-880. [72] Franks NP. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal [J]. Nat Rev Neurosci, 2008, 9(5): 370-386. [73] Casali AG, Casarotto S, Rosanova M, et al. General indices to characterize the electrical response of the cerebral cortex to TMS [J]. Neuroimage, 2010, 49(2): 1459-1468. [74] Massimini M, Ferrarelli F, Sarasso S, et al. Cortical mechanisms of loss of consciousness: insight from TMS/EEG studies [J]. Arch Ital Biol, 2012, 150(2-3): 44-55. [75] Sarasso S, Boly M, Napolitani M, et al. Consciousness and complexity during unresponsiveness induced by propofol, xenon, and ketamine [J]. Curr Biol, 2015, 25(23): 3099-3105. [76] Ruiz de Miras J, Soler F, Iglesias-Parro S, et al. Fractal dimension analysis of states of consciousness and unconsciousness using transcranial magnetic stimulation [J]. Comput Methods Programs Biomed, 2019, 175: 129-137. [77] Tononi G. An information integration theory of consciousness [J]. BMC Neurosci, 2004, 5: 42. [78] Massimini M, Ferrarelli F, Esser SK, et al. Triggering sleep slow waves by transcranial magnetic stimulation [J]. Proc Natl Acad Sci USA, 2007, 104(20): 8496-8501. [79] Massimini M, Ferrarelli F, Murphy M, et al. Cortical reactivity and effective connectivity during REM sleep in humans [J]. Cogn Neurosci, 2010, 1(3): 176-183. [80] Lee M, Baird B, Gosseries O, et al. Connectivity differences between consciousness and unconsciousness in non-rapid eye movement sleep: a TMS-EEG study [J]. Scientific Reports, 2019, 9(1): 5175. [81] Tononi G, Massimini M. Why does consciousness fade in early sleep? [J]. Ann N Y Acad Sci, 2008, 1129: 330-334. [82] Civardi C, Collini A, Monaco F, et al. Applications of transcranial magnetic stimulation in sleep medicine [J]. Sleep Med Rev, 2009, 13(1): 35-46. [83] Darracq M, Funk CM, Polyakov D, et al. Evoked alpha power is reduced in disconnected consciousness during sleep and anesthesia [J]. Sci Rep, 2018, 8(1): 16664. [84] Rosanova M, Fecchio M, Casarotto S, et al. Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients [J]. Nat Commun, 2018, 9(1): 4427. [85] Seel RT, Douglas J, Dennison AC, et al. Specialized early treatment for persons with disorders of consciousness: program components and outcomes [J]. Arch Phys Med Rehabil, 2013, 94(10): 1908-1923. [86] Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis [J]. Brain Res Brain Res Rev, 1999, 29(2-3): 169-195. [87] Shou Zeyu, Li Zhilong, Wang Xueying, et al. Non-invasive brain intervention techniques used in patients with disorders of consciousness [J]. Int J Neurosci, 2021, 131(4): 390-404. [88] Bai Yang, Gong Anjuan, Wang Qijun, et al. Breakdown of oscillatory effective networks in disorders of consciousness [J]. CNS Neurosci Ther, 2024, 30(3): e14469. [89] Kondziella D, Bender A, Diserens K, et al. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness [J]. Eur J Neurol, 2020, 27: 741-756. [90] Casarotto S, Comanducci A, Rosanova M, et al. Stratification of unresponsive patients by an independently validated index of brain complexity [J]. Ann Neurol, 2016, 80(5): 718-729. [91] Formaggio E, Cavinato M, Storti SF, et al. Assessment of event-related EEG power after single-pulse TMS in unresponsive wakefulness syndrome and minimally conscious state patients [J]. Brain Topogr, 2016, 29(2): 322-333. [92] Bodart O, Gosseries O, Wannez S, et al. Measures of metabolism and complexity in the brain of patients with disorders of consciousness [J]. Neuroimage Clin, 2017, 14: 354-362. [93] Sinitsyn DO, Poydasheva AG, Bakulin IS, et al. Detecting the potential for consciousness in unresponsive patients using the perturbational complexity index [J]. Brain Sciences, 10(12):917. [94] Comolatti R, Pigorini A, Casarotto S, et al. A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations [J]. Brain Stimulation, 2019, 12(5): 1280-1289. [95] Wang Yong, Niu Zikang, Xia Xiaoyu, et al. Application of fast perturbational complexity index to the diagnosis and prognosis for disorders of consciousness [J]. IEEE Trans Neural Syst Rehabil Eng, 2022, 30: 509-518. [96] Mencarelli L, Biagi MC, Salvador R, et al. Network mapping of connectivity alterations in disorder of consciousness: towards targeted neuromodulation [J]. Journal of Clinical Medicine, 2020, 9(3):828. [97] Bai Yang, Xia Xiaoyu, Kang Jiannan, et al. Evaluating the effect of repetitive transcranial magnetic stimulation on disorders of consciousness by using TMS-EEG [J]. Front Neurosci, 2016, 10: 473. [98] Hernandez-Pavon JC, Kugiumtzis D, Zrenner C, et al. Removing artifacts from TMS-evoked EEG: a methods review and a unifying theoretical framework [J]. J Neurosci Methods, 2022, 376: 109591. [99] McMackin R, Bede P, Pender N, et al. Neurophysiological markers of network dysfunction in neurodegenerative diseases [J]. Neuroimage Clin, 2019, 22: 101706. [100] Esposito R, Bortoletto M, Miniussi C. Integrating TMS, EEG, and MRI as an approach for studying brain connectivity [J]. Neuroscientist, 2020, 26(5-6): 471-486.