Cortical reorganization and plasticity In the healthy brain

健康大脑中的皮质重组和可塑性

• 批准号: 10708601
• 负责人: Leonardo Gregorio Cohen
• 金额: $ 189.14万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708601
• 关键词: Address; Adult; Age; Anterior; Area; Basic Science; Behavior; Behavioral; Biological Markers; Brain; Brain Diseases; Brain Injuries; Brain region; COVID-19 pandemic; COVID-19 patient; Central Nervous System; Chronic; Clinical; Cognition; Development; Disease; Electrodes; Electroencephalography; Event; Evoked Potentials; Family; Goals; Health; High Prevalence; Hour; Human; Individual; International; Journals; Knowledge; Lateral; Learning; Learning Skill; Left; Lesion; Long COVID; Measures; Memory; Memory impairment; Mission; Modeling; Motor; Motor Cortex; Motor Skills; Motor output; Movement; Muscle Contraction; Neurologic Symptoms; Neurologist; Neurology; Neurons; Neurosciences; Outcome; Patients; Pattern; Performance; Physiology; Process; Protocols documentation; Psychologist; Publishing; Recovery; Recovery of Function; Reporting; Research; Role; Scalp structure; Skeletal Muscle; Societies; Source; Spinal Cord; Stroke; Surveys; Symptoms; System; Techniques; Training; Transcranial magnetic stimulation; Translating; Traumatic Brain Injury; Work; acute infection; acute stroke; base; brain fog; classical conditioning; design; economic implication; effective intervention; electrical potential; evidence base; healthy volunteer; hippocampal pyramidal neuron; improved; meetings; motor deficit; motor function recovery; motor impairment; motor learning; neuroimaging; neurological rehabilitation; neurophysiology; neuroregulation; novel; novel therapeutics; physical therapist; programs; psychologic; sex; skill acquisition; social implication; source localization; tool

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.

背景资料： 皮质重组发生在成年中枢神经系统，特别是在运动技能获得过程中。这种可塑性有助于各种形式的人类行为，包括技能学习和记忆形成，巩固，再巩固以及短期和长期保留。了解这些不同的行为过程的作用以及这些不同形式的人类可塑性在技能获得过程中的机制对于改善健康成年人的技能学习和记忆非常重要。 今年的发现： 我们继续在开发和完善脑状态依赖性刺激方案方面取得进展，这些方案旨在大幅提高经颅磁刺激（TMS）等脑刺激技术的神经调节作用。沿着这些路线的进展对于将我们的基础研究工作转化为治疗脑损伤或中风等疾病引起的运动缺陷的新疗法至关重要。沿着这些思路，我们在过去的一年里在《临床神经生理学杂志》上发表了一项研究，该研究调查了与初级运动皮层（M1）中皮质脊髓神经元激活直接相关的脑电图（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是一种用于临床环境的非侵入性神经成像技术，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。更好地理解与大脑运动输出相关的EEG特征以及它们如何与TMS产生的大脑内的感应电流方向相关，将改善用于刺激模式的大脑生物标志物的精确表征，这些刺激模式旨在改善神经调节效应，并最终改善临床结果。在这项研究中，我们研究了10名健康志愿者的皮层诱发电位与TMS诱导的不同成分的脑电图特征。以诱导具有P25的后-前或前-后电流方向EEG特征的方式应用TMS（即刺激后25 ms处的正峰）和N45（即-刺激后45 ms处的负峰值）在左侧M1上的电极处记录的分量（即国际10-20系统中的电极C3）诱导后-前电流方向大于诱导前-后电流方向，而在FC 1电极记录的具有P180和N280分量的信号（C3的前部和侧面，和覆盖交界处的M1和前运动皮层）更突出的诱导前-后电流方向比诱导后-M1的前向电流。源定位分析，直接模拟在头皮上测量的电流作为一个功能的基础神经元活动，揭示了诱发的EEG签名的来源时，TMS引起的前-后电流分布在M1和运动前皮质，而签名与诱导的后-前电流方向集中在M1内。基于这些结果，我们的结论是，激活皮质脊髓锥体神经元在M1的局部皮层内电路的相互作用的结果，M1是修改的输入从运动前皮质不同的敏感性，以TMS在相反的电流方向。 过去一年，我们在COVID-19疫情相关的研究工作方面也取得了进展。在新冠肺炎大流行的早期，开始出现患者在急性感染（通常被称为长期新冠肺炎）后恢复后仍有持续症状的报告。尽管在长期新冠肺炎中，脑雾和记忆功能障碍等神经系统症状的患病率很高，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。之前没有研究检查过长期Covid患者学习和巩固程序性运动技能的能力。我们正在一组长期新冠肺炎患者和年龄和性别匹配的对照组中解决这个问题。