Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor μ-Alpha Rhythm

Abstract

Alpha oscillations (8 -14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression for larger alpha amplitudes due to the assumed amplitude asymmetry of the oscillation. While there is evidence for this hypothesis regarding occipital alpha oscillations, it is less clear for the central sensorimotor -alpha rhythm. Probing corticospinal excitability via transcranial magnetic stimulation (TMS) of the primary motor cortex and the measurement of motor evoked potentials (MEPs), we have previously demonstrated that corticospinal excitability is modulated by both amplitude and phase of the sensorimotor -alpha rhythm. However, the direction of this modulation, its proposed asymmetry, and its underlying mechanisms remained unclear. We therefore used real-time EEG-triggered single-and paired-pulse TMS in healthy humans of both sexes to assess corticospinal excitability and GABA-A-receptor mediated short-latency intracortical inhibition (SICI) at rest during spontaneous high amplitude -alpha waves at different phase angles (peaks, troughs, rising and falling flanks) and compared them to periods of low amplitude (desynchronized) -alpha. MEP amplitude was facilitated during troughs and rising flanks, but no phasic suppression was observed at any time, nor any modulation of SICI. These results are best compatible with sensorimotor -alpha reflecting asymmetric pulsed facilitation but not pulsed inhibition of motor cortical excitability. The asymmetric excitability with respect to rising and falling flanks of the -alpha cycle further reveals that voltage differences alone cannot explain the impact of phase.The pulsed inhibition hypothesis, which assumes that alpha oscillations actively inhibit neuronal processing in a phasic manner, is highly influential and has substantially shaped our understanding of these oscillations. However, some of its basic assumptions, in particular its asymmetry and inhibitory nature, have rarely been tested directly. Here, we explicitly investigated the asymmetry of modulation and its direction for the human sensorimotor -alpha rhythm. We found clear evidence of pulsed facilitation, but not inhibition, in the human motor cortex, challenging the generalizability of the pulsed inhibition hypothesis and advising caution when interpreting sensorimotor -alpha changes in the sensorimotor system. This study also demonstrates how specific assumptions about the neurophysiological underpinnings of cortical oscillations can be experimentally tested noninvasively in humans.

Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm

“…3 mV during triggering (see below). This criterion ensured sufficient accuracy of our phasetrigger algorithm since, unlike the phase-triggered experiments performed in our group previously [14,27,30], no m-power threshold was applied for stimulation in the plasticity experiments in order to achieve a stimulation rate as close as possible to 1 Hz; (3) To ensure that subjects showed a m-rhythm-dependent phase stimulation effect with the positive peak being the low excitability state and the negative peak being the high excitability state [14], the median MEP elicited by TMS pulses triggered at the negative peak had to be larger than the median MEP at the positive peak (no statistical test was performed to screen for this criterion). Two participants were excluded because they did not meet the RMT criterion.…”

Alertness fluctuations when performing a task modulate cortical evoked responses to transcranial magnetic stimulation

“…In particular, trials with higher pre-stimulation alpha power tend to be associated with lower MEP amplitude ( Ogata et al., 2019 ; Sauseng et al., 2009 ; Zarkowski et al., 2006 ), although null findings ( Iscan et al., 2016 ) or a positive rather than negative correlation ( Thies et al., 2018 ; Bergmann et al., 2019 ) have also been reported. The association between pre-stimulus alpha power and MEP amplitude is typically interpreted in terms of spontaneous fluctuation of regional sensorimotor mu-alpha rhythms ( Bergmann et al., 2019 ; Hussain et al., 2018 ; Thies et al., 2018 ; Zrenner et al., 2018 ). Unfortunately, previous TMS investigations have not measured or controlled for changes in alertness in their participants, so it remains unknown whether fluctuations in alertness are systematically associated with changes in TMS-evoked neural activity.…”

“…Further evidence for the contribution of fluctuating levels of alertness might come from studies of MEP amplitudes, which tend to be highly variable from trial to trial ( Ellaway et al., 1998 ; Maeda et al., 2002 ). A significant portion of this variance is related to EEG oscillatory activity in a pre-TMS time window ( Bergmann et al., 2019 ; Hussain et al., 2018 ; Mäki and Ilmoniemi, 2010 ; Madsen et al., 2019 ; Ogata et al., 2019 ; Sauseng et al., 2009 ; Thies et al., 2018 ; Zarkowski et al., 2006 ; Zrenner et al., 2018 ). In particular, trials with higher pre-stimulation alpha power tend to be associated with lower MEP amplitude ( Ogata et al., 2019 ; Sauseng et al., 2009 ; Zarkowski et al., 2006 ), although null findings ( Iscan et al., 2016 ) or a positive rather than negative correlation ( Thies et al., 2018 ; Bergmann et al., 2019 ) have also been reported.…”

“…A significant portion of this variance is related to EEG oscillatory activity in a pre-TMS time window ( Bergmann et al., 2019 ; Hussain et al., 2018 ; Mäki and Ilmoniemi, 2010 ; Madsen et al., 2019 ; Ogata et al., 2019 ; Sauseng et al., 2009 ; Thies et al., 2018 ; Zarkowski et al., 2006 ; Zrenner et al., 2018 ). In particular, trials with higher pre-stimulation alpha power tend to be associated with lower MEP amplitude ( Ogata et al., 2019 ; Sauseng et al., 2009 ; Zarkowski et al., 2006 ), although null findings ( Iscan et al., 2016 ) or a positive rather than negative correlation ( Thies et al., 2018 ; Bergmann et al., 2019 ) have also been reported. The association between pre-stimulus alpha power and MEP amplitude is typically interpreted in terms of spontaneous fluctuation of regional sensorimotor mu-alpha rhythms ( Bergmann et al., 2019 ; Hussain et al., 2018 ; Thies et al., 2018 ; Zrenner et al., 2018 ).…”

Does pericentral mu-rhythm “power” corticomotor excitability? – a matter of EEG perspective

“…Real-time EEG-triggered stimulation systems makes it possible to assess the relationship between mu-oscillatory activity and MEP amplitude more effectively through online targeting of specific oscillation states [13][14][15]. In contrast to the studies using post-hoc grouping, several real-time mu-triggered experiments report a positive relationship between mu-power and MEP amplitude, suggesting mu-facilitation rather than a mu-inhibition in the corticospinal system [23][24][25].…”