The spectral features of EEG responses to transcranial magnetic stimulation of the primary motor cortex depend on the amplitude of the motor evoked potentials

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD-peaking at ~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation

Beyond alpha power: EEG spatial and spectral gradients robustly stratify disorders of consciousness.

peer reviewedNeurophysiological markers can overcome the limitations of behavioural assessments of Disorders of Consciousness (DoC). EEG alpha power emerged as a promising marker for DoC, although long-standing literature reported alpha power being sustained during anesthetic-induced unconsciousness, and reduced during dreaming and hallucinations. We hypothesized that EEG power suppression caused by severe anoxia could explain this conflict. Accordingly, we split DoC patients (n = 87) in postanoxic and non-postanoxic cohorts. Alpha power was suppressed only in severe postanoxia but failed to discriminate un/consciousness in other aetiologies. Furthermore, it did not generalize to an independent reference dataset (n = 65) of neurotypical, neurological, and anesthesia conditions. We then investigated EEG spatio-spectral gradients, reflecting anteriorization and slowing, as alternative markers. In non-postanoxic DoC, these features, combined in a bivariate model, reliably stratified patients and indexed consciousness, even in unresponsive patients identified as conscious by an independent neural marker (the Perturbational Complexity Index). Crucially, this model optimally generalized to the reference dataset. Overall, alpha power does not index consciousness; rather, its suppression entails diffuse cortical damage, in postanoxic patients. As an alternative, EEG spatio-spectral gradients, reflecting distinct pathophysiological mechanisms, jointly provide a robust, parsimonious, and generalizable marker of consciousness, whose clinical application may guide rehabilitation efforts

TMS-evoked EEG responses over left M1: Comparison between high-MEP and low-MEP conditions.

<p><b>(A)</b> Left panel shows the distribution of the peak-to-peak MEPs amplitude of the all artifact-free trials for one representative subject. Blue bars correspond to 100 trials in which TMS elicited the smallest APB motor responses (low-MEP) and red bars corresponds to 100 trials in which TMS generated the largest APB motor responses (high-MEP). Then, from left to right, the EEG single trials (thin lines) and the average response (thick line) of the channel closest to the stimulation site (C3 scalp derivation) and the corresponding ERSP are shown. <b>(B)</b> For the same representative subject of Panel A, low-MEP (top panel) and high-MEP conditions (bottom panel) are compared. From left to right, the average MEP, the EEG single trials (thin lines) and average TEPs (thick line) recorded from the electrode closest to the stimulation site (C3 scalp derivation) and the corresponding ERSPs are shown. <b>(C)</b> MEP, LMFP and averaged ERSP derived from low-MEP (blue) and high-MEP (red) trials are compared. Each thick line indicates the grand-average across subjects (±SE, color-coded shaded regions). The averaged ERSP traces are enlarged in the inset (time scale from 150 to 350 ms; power scale from -1 to 1 dB). <b>(D)</b> From left to right: average (±SE) across subjects of the MEP peak-to-peak amplitude, individual averaged LMFP between 8 and 350 ms and the individual averaged ERSP between 200 and 350 ms are presented. Small circles and grey lines indicate single subject values, while large circles and black lines indicate grand-average values across subjects. Statistical analysis by means of Wilcoxon signed rank test resulted in significant differences for MEP (p<0.05), LMFP (p<0.05) and ERSP (p<0.05).</p

Comparison of TMS-evoked EEG potentials recorded from different cortical areas employing Local Mean Field Power (LMFP) and event-related spectral perturbation (ERSP).

<p><b>(A)</b> For each stimulated area, TMS-evoked EEG responses are shown from one representative subject. Butterfly plots of all channels are displayed (top panels, grey traces), together with the corresponding LMFP (bottom panels, black traces). The dashed vertical line indicates the timing of the TMS pulse. <b>(B)</b> Grand-average of LMFP for each stimulated area. Thick traces indicate the grand-average LMFP across subjects (±SE, color-coded shaded regions). Responses recorded after the stimulation of different cortical areas are color coded as follows: motor in black, prefrontal in yellow, premotor in red, parietal in green. <b>(C)</b> For each stimulated area, the LMFP values averaged between 8 and 350 ms post-TMS are shown in the bar histogram (mean ± SE). Asterisks indicate statistically significant differences (* p<0.05, Wilcoxon signed rank test). Bars are color coded as in Panel B. <b>(D)</b> Black traces represent TMS-evoked EEG responses of a representative subject (same as in panel A) for one of the four channels closest to the stimulation site, with the corresponding ERSP shown below. A Wavelet Transform (Morlet, 3.5 cycles) has been applied at the single trial level. Significance threshold for bootstrap statistics is set at α < 0.01. Non-significant activity is set to zero (green), red colors indicate a significant increase with respect to the baseline, while blue colors indicate a significant reduction compared to the baseline. As in Panel A, the dashed vertical line indicates the time of the TMS pulse. <b>(E)</b> The averaged ERSP of the four channels located under the stimulation coil (between 8 and 45 Hz) is presented for each stimulated area (color coding as in panel B and C). Each thick line indicates the grand-average across subjects (± SE, color-coded shaded regions). The same traces are enlarged in the inset (time scale from 150 to 350 ms; power scale from -2 to 2 dB). The dashed vertical line indicates the average time in which the ERD occurs. <b>(F)</b> Using the same color coding as in panel B, C and E, bars indicate, for each stimulated area, the grand-average (±SE) of the averaged ERD (ERSP between 200 and 350 ms post-TMS). Asterisks indicate statistically significant differences (* p<0.05, Wilcoxon signed rank test).</p

Comparison between low-MEP and high-MEP conditions across channels and frequency bands.

<p><b>(A)</b> The broadband (8–45 Hz) ERD topography (ERSP averaged between 200 and 350 ms) of the grand-average across subjects derived from both low-MEP (left) and high-MEP conditions (right) is shown. <b>(B)</b> Topographic distribution of the z-values from a Wilcoxon signed rank test (p<0.05) together with the statistical differences between the broadband ERD in the two conditions. The statistically significant electrodes (white dots) indicate that this broadband reduction was confined over the motor area (C3, C5, Cz, FC2, FC3 and FC5 scalp derivations). <b>(C)</b> For the significant channels of Panel B, the ERSP averaged between 200 and 350 ms across channels in the low-MEP (blue) and high-MEP (red) conditions over four EEG frequency bands (8-15Hz, 15-20Hz, 20-30Hz, 30–45 Hz) are shown in the bar histogram (±SE). Asterisks indicate statistically significant differences (* p<0.05, Wilcoxon signed rank test).</p