The sensorimotor mu-rhythm as cholinergically controlled pulsed inhibition

在清醒和健康的人脑的脑电(EEG)中可以观察到的最显著的神经元振荡是8-14赫兹的α振荡。在感觉运动皮质中，作为本项目的模型区域，它被称为Mu-节律。起初被认为只是反映了大脑皮层的空转，而阿尔法/微米振荡现在被认为是大脑中活跃的信息流的门。有影响力的脉冲抑制假说认为，α/u振荡是不对称的，由反复发作的抑制组成，随着幅度的增加，抑制会变得更强，从而有节奏地抑制任务无关皮质区域的神经加工。然而，所提出的振荡的不对称和抑制性质从未被直接证明。此外，α/u振荡必须受到自上而下的注意力控制，因为仅仅是对即将到来的刺激的预期就已经调节了它们的幅度。然而，其自上而下控制的神经元实现仍是未知的。已有假说认为，前额叶皮质的皮质投射通过轴-轴突触调节感觉皮质上升的基底前脑胆碱能神经元局部乙酰胆碱的释放。已知乙酰胆碱可调节神经元活动的去同步化。因此，前额叶介导的胆碱能调节局部感觉α/u振荡的瞬时变化，从而可能代表了皮层兴奋性的神经机制，可能是知觉注意门控以及由此产生的刺激诱导的突触可塑性的基础。我将为感觉运动节律的模型案例测试脉冲抑制和前额叶控制的胆碱能阿尔法调制的假设。初级运动皮质的经颅磁刺激(TMS)和感觉运动节律的同步EEG评估相结合，可以在人脑中以幅度和相位依赖的方式无创地研究皮质的兴奋性和皮质内的抑制。该项目由两个主要部分组成。首先，我将使用实时脑电触发的单脉冲和双脉冲TMS来研究调节自发感觉运动节律的相位和幅度波动的神经机制及其在突触可塑性诱导中的意义。其次，我将使用(反)胆碱能药物干预和一种使用重复TMS的虚拟损伤方法来揭示在触觉空间注意任务的背景下调节自上而下控制Mu节律的神经机制。总而言之，该项目有望为阿尔法/单位振荡的神经生理学基础、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自上而下控制的前额叶和胆碱能机制提供新的见解。

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.