The sensorimotor mu-rhythm as cholinergically controlled pulsed inhibition

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The most pronounced neuronal oscillation observable in the electroencephalography (EEG) of the awake and healthy human brain is the 8-14 Hz alpha oscillation. In the sensorimotor cortex, serving as the model region in this project, it is called the mu-rhythm. Initially thought to simply reflect cortical idling, alpha/mu oscillations are nowadays believed to actively gate information flow in the brain. The influential Pulsed Inhibition Hypothesis assumes that the alpha/mu oscillation is asymmetric and composed of recurring bouts of inhibition, which become stronger with increasing amplitude, thereby rhythmically suppressing neural processing in task-irrelevant cortical regions. However, the proposed asymmetric and inhibitory nature of the oscillation has never been directly demonstrated. Moreover, alpha/mu oscillations must be under top-down control of attention, since the mere anticipation of an upcoming stimulus already modulates their amplitude. Yet, also the neuronal implementation of its top-down control is still unknown. It has been hypothesized that cortico-cortical projections from the prefrontal cortex modulate the local release of acetylcholine from ascending basal forebrain cholinergic neurons in the sensory cortices via axo-axonal synapses. Acetylcholine is known to regulate the de /synchronization of neuronal activity. Therefore, prefrontally mediated transient changes in the cholinergic modulation of local sensory alpha/mu oscillations and thus cortical excitability may represent the neural mechanism, underlying the attentional gating of perception as well as resulting stimulus-induced synaptic plasticity. I will test the hypotheses of pulsed inhibition and a prefrontally controlled cholinergic alpha modulation for the model case of the sensorimotor mu-rhythm. The combination of transcranial magnetic stimulation (TMS) of the primary motor cortex with concurrent EEG assessment of the sensorimotor mu-rhythm allows to noninvasively study cortical excitability and intra-cortical inhibition in an amplitude and phase-dependent manner in the human brain. The project is composed of two major parts. Firstly, I will use real-time EEG-triggered single- and paired-pulse TMS to study the neural mechanisms mediating fluctuations in phase and amplitude of the spontaneous sensorimotor mu-rhythm and their implication for the induction of synaptic plasticity. Secondly, I will employ (anti )cholinergic pharmacological interventions and a virtual lesion approach using repetitive TMS to uncover the neural mechanisms mediating top-down control of the mu-rhythm in the context of a tactile spatial attention task. Together the project is expected to provide fundamentally new insights into the neurophysiological underpinnings of the alpha/mu oscillations, their role in gating information processing and synaptic plasticity, and the prefrontal and cholinergic mechanisms of their attentional top-down control.