Cortical reorganization and plasticity In the healthy brain

背景： 皮质重组发生在成人中枢神经系统，特别是在获得运动技能的过程中。这种可塑性有助于人类行为的各种形式，包括技能学习和记忆形成、巩固、再巩固以及短期和长期保持。了解这些不同的行为过程在技能获得过程中的作用以及这些不同形式的人类可塑性背后的机制对于改善健康成年人的技能学习和记忆是非常重要的。 今年的调查结果： 我们继续在开发和完善依赖于大脑状态的刺激方案方面取得进展，旨在显着提高经颅磁刺激(TMS)等脑刺激技术的神经调制效应的幅度。这些方面的进展对于将我们的基础研究工作转化为治疗由脑损伤或中风等疾病引起的运动障碍的新疗法至关重要。沿着这些思路，我们在过去一年的《临床神经生理学杂志》上发表了一项研究，调查了与初级运动皮质(M1)皮质脊髓神经元激活直接相关的脑电(EEG)特征。M1是大脑的功能区域，直接连接到脊髓中控制随意肌肉收缩的神经元。因此，M1是大脑中最直接控制产生自主运动的区域。EEG是一种非侵入性的神经成像技术，用于临床环境中，通过记录头皮上测量的非常小的电位来间接测量大脑活动。更好地了解与大脑运动输出相关的脑电信号，以及它们与TMS产生的大脑内感应电流的方向之间的关系，将有助于提高用于改善神经调节效果的刺激模式的脑生物标志物的精确特征，并最终改善临床结果。在本研究中，我们研究了10名健康志愿者经TMS诱发的不同成分皮层诱发电位的脑电特征。施加TMS的方式是，在左侧M1上的电极(即国际10-20系统中的电极C3)上记录的具有诱发的前后电流方向的P25(即，刺激后25ms处的正峰)和N45(即刺激后45ms的负峰)的脑电特征信号大于诱导的前后电流方向的EEG特征，而在FC1电极(C3的前面和侧面，以及位于M1和运动前皮质交界处)诱发的前-后电流方向比诱发的后-前电流更显著。源定位分析直接将头皮测量的电流作为潜在神经元活动的函数进行建模，结果表明，TMS诱发前后电流时诱发的EEG特征的来源分布在M1和运动前皮质，而诱导后前电流方向的特征仅集中在M1内。根据这些结果，我们得出结论，M1内皮质脊髓锥体神经元的激活是M1内局部皮质内回路相互作用的结果，这种相互作用被对TMS具有不同敏感性的运动前皮质以相反的电流方向输入所修正。 一年来，新冠肺炎疫情相关研究工作也取得了进展。在Covid大流行早期，开始出现患者从急性感染恢复后出现挥之不去的症状的报告，通常被称为Long Covid。尽管Long Covid的大脑迷雾和记忆障碍等神经系统症状的发生率很高，但大多数研究都依赖于通常用于评估陈述性记忆的调查或临床工具。在此之前，还没有研究过Long Covid患者学习和巩固程序性运动技能的能力。我们正在对一组患有长Covid和年龄和性别匹配的对照组的患者解决这个问题。

Background: Cortical reorganization occurs in the adult central nervous system, especially during motor skill acquisition. This plasticity contributes to various forms of human behavior including skill learning and memory formation, consolidation, reconsolidation and short- and long-term retention. It is very important to understand the role of these different behavioral processes and of the mechanisms underlying these various forms of human plasticity during skill acquisition to improve skill learning and memory in healthy adults. Findings this year: We continue to make progress in the development and refinement of brain-state-dependent stimulation protocols that aim to dramatically improve the magnitude of neuromodulatory effects of brain stimulation techniques such as transcranial magnetic stimulation (TMS). Progress along these lines is critical for translating our basic research work into new therapies for treating motor deficits caused by brain injury or disease such as stroke. Along these lines, we published a study during the past year in the Journal of Clinical Neurophysiology that investigated the electroencephalography (EEG) signatures directly related to activation of corticospinal neurons in the primary motor cortex (M1). M1 is the functional region of the brain that directly connects to neurons in the spinal cord that control voluntary muscle contraction. Thus, M1 is area of the brain most directly in control of generating voluntary movement. EEG is a non-invasive neuroimaging technique used in clinical settings that indirectly measures brain activity via recordings of very small electrical potentials measured on the scalp. Better understanding of EEG signatures related to motor output of the brain and how they relate to the direction of induced current within the brain generated by TMS will improve precise characterization of the brain biomarkers used for stimulation patterns designed to improve neuromodulatory effects, and ultimately clinical outcomes. In this study, we investigated the EEG signatures of cortical evoked potentials with different components induced by TMS in 10 healthy volunteers. The TMS was applied in a manner that induced either posterior-anterior or anterior-posterior current directions EEG signatures with P25 (i.e. - positive peak at 25ms following stimulation) and N45 (i.e. - negative peak at 45ms following stimulation) components recorded at the electrode over the left M1 (i.e. - electrode C3 in the international 10-20 system) with induced posterior-anterior current directions were larger than those with induced anterior-posterior currents, while the signatures with P180 and N280 components recorded at the FC1 electrode (anterior and lateral to C3, and overlying the junction of M1 and premotor cortex) were more prominent for induced anterior-posterior current directions than induced posterior-anterior currents in M1. Source localization analysis, which directly models the electrical currents measured at the scalp as a function of the underlying neuronal activity, revealed that the source of the evoked EEG signature when TMS induced an anterior-posterior current was distributed across both M1 and premotor cortex while the signature with induced posterior-anterior current direction was centered within M1 only. Based upon these results, we concluded that activation of corticospinal pyramidal neurons in M1 is the result of local intracortical circuit interactions within M1 that is modified by inputs from premotor cortex with different sensitivities to TMS in opposite current directions. We also made advances over the past year in our research work related to the COVID-19 epidemic. Early in the Covid pandemic, reports started to emerge of patients with lingering symptoms following recovery from acute infection, often referred to as Long Covid. Despite the high prevalence of neurological symptoms like brain fog and memory dysfunction in Long Covid, most research has relied on surveys or clinical tools typically used to assess declarative memory. No prior studies have examined Long Covid patients ability to learn and consolidate a procedural motor skill. We are addressing this question in a group of patients with Long Covid and age- and sex-matched controls.