Transcranial magnetic stimulation in assessment of cortical network properties

Aalto University, P.O. Box 11000, FI-00076 Aalto www.aalto. fi Author Pantelis Lioumis Name of the doctoral dissertation Transcranial magnetic stimulation in assessment of cortical network properties Publisher School of Science Unit Department of Biomedical Engineering and Computational Science Series Aalto University publication series DOCTORAL DISSERTATIONS 164/2012 Field of research Tfy-99 Biomedical Engineering Manuscript submitted 1 June 2012 Date of the defence 3 December 2012 Permission to publish granted (date) 17 August 2012 Language English Monograph Article dissertation (summary + original articles) Abstract This Thesis demonstrates the way to combine navigated transcranial magnetic stimulation (nTMS) with electrophysiological techniques, such as electroencephalography (EEG) and magnetoencephalo graphy (MEG). This technical and neurophysiological possibility allows the assessment of cortical excitability and functional connectivity with the advantage of high spatiotemporal resolution. Investigation of these cortical network properties can lead in deeper understanding of sensorimotor and speech networks and bridge the gap between basic research and clinical applications by means of TMS. First, we examined whether nTMS–EEG can be used as a marker of cortical excitability changes by investigating the reproducibility of EEG after TMS. We showed that reproducibility is a feature of TMS-evoked EEG responses if the parameters of the stimulation and coil orientation are kept the same. Utilization of navigation is crucial for such test–retest paradigms. The second part of the thesis elaborated the effect of neuronal state prior to TMS on cortico–cortical excitability. We demonstrated modulation of excitability not only of the contrabut also of the ipsilateral hemisphere during preparation and execution of unilateral movements. We also tested the methodology to measure the time onset of cortical activation by grading the levels of its modulation with TMS–EEG. Next, we utilized MEG to detect sensorimotor cortical sources. nTMS was used to target these sources and modulate their activity during a motor task after a sensory stimulation. We demonstrated that stimulation of the secondary somatosensory cortex can influence the primary one and amplify somatosensory processing. By this study, we set the methodological standards on how to use nTMS and MEG in mapping the sensorimotor cortex. Therefore, we applied our experience in presurgical mapping of epileptic patients before cortical resection. By combining the nTMS and MEG advantages, we created a noninvasive methodology to map the sensorimotor cortex. The results were as accurate as electrical cortical stimulation in most patients. Thus, it may be possible to replace costly invasive standard procedures, which pose a high risk for the patient, when the epileptic focus is near sensorimotor cortex and accessible to MEG. This motivated us to create another nTMS paradigm for mapping speech-related areas. We combined an object naming paradigm and repetitive TMS to find cortical sites sensitive to interference during the task. We recorded video of the experiment to evaluate the effect of TMS on the subjects’ performance. The results show that this method may map speech-related areas successfully. All in all, we show that recent advances in TMS set new standards in basic research and clinical applications, such as preoperative workup and test–retest pharmacological studies. Crossmodal nTMS applications open new avenues in studying cortical network parameters.This Thesis demonstrates the way to combine navigated transcranial magnetic stimulation (nTMS) with electrophysiological techniques, such as electroencephalography (EEG) and magnetoencephalo graphy (MEG). This technical and neurophysiological possibility allows the assessment of cortical excitability and functional connectivity with the advantage of high spatiotemporal resolution. Investigation of these cortical network properties can lead in deeper understanding of sensorimotor and speech networks and bridge the gap between basic research and clinical applications by means of TMS. First, we examined whether nTMS–EEG can be used as a marker of cortical excitability changes by investigating the reproducibility of EEG after TMS. We showed that reproducibility is a feature of TMS-evoked EEG responses if the parameters of the stimulation and coil orientation are kept the same. Utilization of navigation is crucial for such test–retest paradigms. The second part of the thesis elaborated the effect of neuronal state prior to TMS on cortico–cortical excitability. We demonstrated modulation of excitability not only of the contrabut also of the ipsilateral hemisphere during preparation and execution of unilateral movements. We also tested the methodology to measure the time onset of cortical activation by grading the levels of its modulation with TMS–EEG. Next, we utilized MEG to detect sensorimotor cortical sources. nTMS was used to target these sources and modulate their activity during a motor task after a sensory stimulation. We demonstrated that stimulation of the secondary somatosensory cortex can influence the primary one and amplify somatosensory processing. By this study, we set the methodological standards on how to use nTMS and MEG in mapping the sensorimotor cortex. Therefore, we applied our experience in presurgical mapping of epileptic patients before cortical resection. By combining the nTMS and MEG advantages, we created a noninvasive methodology to map the sensorimotor cortex. The results were as accurate as electrical cortical stimulation in most patients. Thus, it may be possible to replace costly invasive standard procedures, which pose a high risk for the patient, when the epileptic focus is near sensorimotor cortex and accessible to MEG. This motivated us to create another nTMS paradigm for mapping speech-related areas. We combined an object naming paradigm and repetitive TMS to find cortical sites sensitive to interference during the task. We recorded video of the experiment to evaluate the effect of TMS on the subjects’ performance. The results show that this method may map speech-related areas successfully. All in all, we show that recent advances in TMS set new standards in basic research and clinical applications, such as preoperative workup and test–retest pharmacological studies. Crossmodal nTMS applications open new avenues in studying cortical network parameters.