The sensorimotor mu-rhythm as cholinergically controlled pulsed inhibition

在清醒和健康的人脑的脑电图（EEG）中可观察到的最显著的神经元振荡是8-14 Hz α振荡。在感觉运动皮层中，作为这个项目的模型区域，它被称为μ节律。最初被认为只是反映了皮层的闲置，现在认为α/μ振荡是大脑中信息流的主动门控。有影响力的脉冲抑制假说假设α/μ振荡是不对称的，由反复发作的抑制组成，随着振幅的增加而变得更强，从而有节奏地抑制与任务无关的皮层区域的神经处理。然而，所提出的振荡的不对称性和抑制性从未被直接证明。此外，α/μ振荡必须受到注意力自上而下的控制，因为仅仅对即将到来的刺激的预期就已经调节了它们的振幅。然而，其自上而下控制的神经元实现仍然是未知的。据推测，从前额皮质-皮质的预测调节局部释放的乙酰胆碱从上升基底前脑胆碱能神经元的感觉皮层通过轴-轴突触。已知乙酰胆碱调节神经元活动的去同步化。因此，前额叶介导的局部感觉α/μ振荡的胆碱能调制的瞬态变化，从而皮质兴奋性可能代表的神经机制，潜在的感知注意门控以及由此产生的刺激诱导的突触可塑性。我将测试的假设脉冲抑制和前额叶控制胆碱能α调制的模型情况下的感觉运动μ节律。初级运动皮层的经颅磁刺激（TMS）与感觉运动μ节律的并发EEG评估的组合允许在人脑中以幅度和相位依赖的方式无创地研究皮层兴奋性和皮层内抑制。该项目由两个主要部分组成。首先，我将使用实时EEG触发的单脉冲和双脉冲TMS研究介导自发感觉运动μ节律的相位和振幅波动的神经机制及其对突触可塑性诱导的影响。其次，我将采用（抗）胆碱能药物干预和虚拟损伤的方法，使用重复TMS揭示神经机制介导的自上而下的控制的μ节奏的触觉空间注意力任务的背景下。该项目预计将为alpha/mu振荡的神经生理学基础提供全新的见解，它们在门控信息处理和突触可塑性中的作用，以及它们的注意力自上而下控制的前额叶和胆碱能机制。

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.