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Der sensomotorische mu-Rhythmus als cholinerg modulierte pulsierende Hemmung

Fachliche Zuordnung Kognitive und systemische Humanneurowissenschaften
Förderung Förderung von 2017 bis 2022
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 362546008
 
Erstellungsjahr 2023

Zusammenfassung der Projektergebnisse

In this project we investigated the function of a specific member of the alpha oscillation family, which is the most pronounced rhythmic activity (around 8-14 waves per second) observable in the healthy human brain with electroencephalographic (EEG) recordings from the scalp. The so-called mu-alpha oscillation is prevalent in the sensorimotor cortex and modulated in its amplitude (power) by shifts in tactile attention or the processing of tactile stimuli. Specifically, we asked (i) how exactly this brain rhythm is linked to fluctuations in cortical excitability and whether it is in agreement with the hypothesis of pulsed inhibition established for alpha in the visual cortex, (ii) how it may regulate synaptic plasticity in the sensorimotor cortex in a phase-dependent manner, (iii) how the neuromodulator acetylcholine is involved in the spontaneous and attention-driven modulation of the mu-alpha rhythm, and (iv) whether the frontal cortex is responsible for regulating this cholinergic mualpha modulation. To answer these questions, we combined real-time EEG analyses to evaluate the ongoing mu-alpha oscillation, with neuronavigated transcranial magnetic stimulation (TMS, a method to non-invasively excite cortical neurons) and electromyography (EMG) of the contralateral hand muscles to measure motor evoked potentials (MEP) as index of corticospinal excitability. With respect to our first question, to our surprise, we found converging evidence across three studies in different samples that, in contrast to the pulsed inhibition associated with alpha oscillations in the visual system, the sensorimotor mu-alpha rhythm was rather linked to a pulsed facilitation of corticospinal excitability. That means that the cortical excitability of the motor cortex is rhythmically increased once per mu-alpha cycle (i.e., once every ~100 ms), but never decreased relative to a desynchronized state with no mu-alpha oscillation present. It is however possible, but yet unclear, that this phenomenon is linked to a rhythmic disinhibitory effect produced by the connected somatosensory cortex with pulsed inhibition remining the major mechanism of the somatosensory mu-alpha oscillation. With respect to our second question, we could unfortunately not demonstrate that repeated sensory afferent input during the more excitable phase of the mu-alpha oscillation, whether in isolation or paired with TMS over M1, would lead to a lasting change in somatosensory or motor cortical excitability according to the recently proposed principle of phase-dependent plasticity. This null finding from two studies should, however, not yet be taken as evidence against phase-dependent plasticity, but may rather be owed to the fact that we did not yet find the optimal stimulation parameters (in terms of stimulation intensity, number of pulses, etc.) to interact with or mimic the internal mechanisms of phasedependent plasticity as well as challenges arising from inter-individual and inter-session variability of mu-alpha power and plasticity effects. Regarding the third question, using the well-established paradigm of short-interval afferent inhibition (SAI), we could obtain first evidence that the cholinergic tone in the human motor cortex actually co-varies with the power of mu-alpha oscillations and that sensory-to-motor (afferent) inhibition (SAI) actually depends on the mu-alpha phase. Detailed analyses of these data as well as the mu-alpha phase-dependency of somatosensory cortex excitability per se is still pending, as is a study testing the top-down attentional modulation of these effects. Unfortunately, we could not investigate the prefrontal control over the above-mentioned cholinergic effects within the funding period. However, beyond these empirical studies, we also developed and published two novel open-source software toolboxes to facilitate the use of the novel approach of EEG-triggered TMS for brain state-dependent brain stimulation. In summary, we successfully employed this novel approach to answer fundamental questions regarding the neurophysiological nature and function of the sensorimotor mu-alpha rhythm in the humans brain and found first evidence for its cholinergic modulation. However, further research is required to better understand its role in gating plasticity and its potential top-down modulation by attention.

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