Use of TMS-EEG to directly assess cerebral neurophysiology in healthy humans

Transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) has shown promising results to study cortical neurophysiology in humans. TMS-EEG allows studying directly in real-time cortical activity through the intact scalp, which permits to record of cerebral responses like TMS-evoked potentials (TEPs) and cortical oscillation. This opens up new possibilities for exploring human cerebral networks, including recording activity of remote areas and real-time high-temporal resolution acquisition of cortical connectivity. However, some Authors pointed out that TMS-EEG outcomes could be influenced by several confounding factors, including acoustic and somatosensory inputs. For this reason, the aim of the first experiment of this thesis is to measure separately the contribution of auditory and somatosensory stimulation caused by TMS and to assess their contribution to the TEP waveform, when stimulating the motor cortex. Seven different EEG recording blocks were performed. To assess auditory responses was used a standard TMS figure of eight coil, with and without noise masking. In subsequential blocks, a standard TMS coil placed on a pasteboard cylinder was used, with and without noise masking. Finally, a possible contribution of somatosensory activation was tested using electrical stimulation of the scalp. The results showed that auditory stimulation induced a known pattern of EEG responses that appropriate noise masking could suppress. Electrical stimulation of the scalp alone only induces similar and non-specific EEG responses. Real TMS, coupled with appropriate noise and sensory input masking, elicited specific and lateralized responses at the stimulation site. In conclusion, if carefully controlled, TMS over the motor cortex can generate genuine lateralized EEG activity, while auditory and somatosensory inputs can confound TEPs waveform if masking procedures are not properly used. Furthermore, TMS-EEG allows to explore functional connections between the motor cortex and remote areas, including cerebellar-cerebral pathways. TMS-EEG, compared to classical neurophysiology outcomes, like cerebellar brain inhibition (CBI), records pure cerebral activity and permits to explore cerebellar connections to motor and non-motor areas of the cortex. For this, in the second experiment, TMS- EEG was used to detect cerebral activity on the whole brain following TMS of the cerebellum. Also, was explored if these responses could be influenced by motor learning paradigms. To do that, different recording blocks were performed to collect EEG responses with a) real TMS cerebellar; b) combined auditory and somatosensory inputs. Furthermore, was tested if cerebellar responses could be behaviourally sensitive by assessing subjects before and after learning a visuomotor reach adaptation task. The results showed that after real cerebellar stimulation could be recorded a specific and lateralized neural activity that could not be recorded after mixed auditory-somatosensory stimulation, suggesting that this EEG waveform reflects pure cerebellar stimulation. These cerebellar TEPs are influenced by different stages of learning. In conclusion, TMS-EEG is a novel and powerful technique which allows to explore genuine cortical responses, including those from remote areas. A standardization of TMS-EEG procedures is required to improve acquisition and analysis, the accuracy of collecting data, and to avoid of misinterpretation of the results due to confounding factors.