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： 记忆巩固是大脑通过训练加强和保持对运动技能的记忆的过程。巩固过程对于在人的一生中保持技能和改善脑损伤或疾病后的康复结果至关重要。以前，只有在睡眠或较长的休息时间(包括训练课程之间的几个小时或几天)时才对巩固进行调查。在过去的两年里，我们开发了一种新的调查方法，调查了在单个培训课程中穿插的更短的休息期(大约几秒钟)的整合过程。去年，我们报告称，当人类最初学习一种新的运动技能(即用乐器演奏一段新音乐)时，他们在积极练习时表现没有太大变化。相反，成绩的提高在很大程度上局限于练习之间的短时间休息，我们将这一发现称为微离线学习。在过去的一年里，我们在网上进行的一项大型众包研究中推进了这一研究计划(所有实验的累计N=951)。首先，我们最初基于实验室的发现被成功复制，向在家中(N=389)在自己的计算机上学习相同任务的参与者展示了普适性。其次，通过改变练习周期的长度，我们表明微离线改进在不同的练习周期(N=118)上是相等的。这一发现证实，微离线学习与操作疲劳的简单恢复并不是微不足道的，相反，它是在这些短暂的中间休息期间记忆增强的结果。第三，由于参与者在练习目标技能后立即切换到练习不同的技能，导致追溯干扰降低了学习速度，相对于简单的时间推移(N=373)，证实了微离线学习很可能是运动记忆在几秒钟的时间尺度上稳定的结果。总而言之，这些综合结果支持了一种新的记忆巩固形式在人类早期技能学习中的作用，这种巩固发生在几秒钟的时间尺度上。这项工作的未来方向是开发非侵入性脑刺激干预措施，旨在加强健康人的快速微尺度巩固和学习，并改善神经科患者的治疗结果。 在过去的一年里，我们还继续推进了一项重要的研究计划，旨在表征对非侵入性脑刺激反应的个体内和个体间的差异。这项工作的基本原理是，更全面地了解正在进行的内源性大脑活动如何影响个体对脑刺激的反应，对于开发新的治疗干预措施，使患有神经损伤或疾病的个体患者康复至关重要。感觉运动网络中的内源性脑活动呈现动态振荡，其时相(即活动时序)和功率(即活动大小)随时间变化。去年，我们发现，运动诱发电位(MEPs)，一种衡量大脑和脊髓之间沟通强度的指标，对产生运动至关重要，可以通过感觉运动大脑节奏的振荡阶段和功率之间的相互作用来预测。在感觉运动节律低谷时，大脑和脊髓之间的交流强度高于功率较高时的峰值，而在功率较低时则相反。在过去的一年里，在这项工作的后续工作中，我们试图了解大脑中的非持续节奏信号是如何影响大脑和脊髓交流的。持续时间短的β波(15-30赫兹)仅显示1-2个周期，是感觉运动皮质活动的显著信号。我们评估了β事件特征与健康成人皮质脊髓兴奋性之间的关系。结果表明，经颅磁刺激(TMS)前的β事件的数量、幅度和时间均显著预测运动诱发电位(MEP)的幅度，这提供了短暂的内源性β振荡事件塑造人类皮质脊髓兴奋性的初步证据。这些发现为阐明卒中后运动障碍的病理生理学提供了一个重要的可能的生物标志物。

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: Memory consolidation is the processes through which the brain strengthens and maintains memories of motor skills acquired through training. Consolidation processes are crucial for maintaining skills over ones lifespan and improving recovery outcomes following brain injury or disease. Previously, consolidation has only been investigated during sleep or over longer rest periods consisting of hour or days between training sessions. Over the past two years, we developed a new line of inquiry that investigated consolidation processes over much shorter rest periods (on the order of several seconds) interspersed within a single training session. Last year, we reported that when humans initially learn a novel motor skill (i.e. - playing a new piece of music on an instrument) performance does not change much while they are actively practicing. Instead, performance improvements are largely limited to short periods of rest between practice, a finding we termed micro-offline learning. Over the past year, we advanced this research program in a large crowdsourcing study conducted online (cumulative N over all experiments=951). First, our original lab-based findings were successfully replicated demonstrating generalizability to participants learning the same task on their own computers at home (N=389). Second, by varying the length of the practice period, we showed that micro-offline improvements are equivalent across different practice period durations (N=118). This finding confirmed that micro-offline learning is not trivially related to simple recovery from performance fatigue but is instead the result of memory strengthening that occurs during these short intervening rest periods. Third, retroactive interference resulting from having participants switch to practicing a different variant of the skill immediately following practice of the target skill reduced the learning rate relative to the simple passage of time (N=373), confirming that micro-offline learning is likely the result of stabilization of the motor memory over a timescale of several seconds. In summary, these combined results support the role of a novel form of memory consolidation occurring on the timescale of several seconds in early skill learning in humans. A future direction of this work is to develop non-invasive brain stimulation interventions aimed at enhancing fast micro-scale consolidation and learning in healthy humans and improving therapeutic outcomes in neurological patients. Over the past year, we also continued to advance an important research initiative aimed at characterizing intra- and inter-individual variability in responses to non-invasive brain stimulation. The rationale for this work is that a more complete understanding of how ongoing endogenous brain activity influences an individuals response to brain stimulation is crucial for the development of novel therapeutic interventions for rehabilitation of individual patients suffering from neurological injury or disease. Endogenous brain activity within sensorimotor networks exhibits dynamic oscillations with time-varying changes in phase (i.e. activity timing) and power (i.e activity magnitude). Last year, we found that motor evoked potentials (MEPs), a measure of communication strength between the brain and spinal cord important for generating movements, could be predicted by an interaction between the oscillatory phase and power of the sensorimotor brain rhythm. Communication strength between the brain and spinal cord was higher during sensorimotor rhythm troughs versus peaks when power was high while the opposite was true when power was low. This past year, in a follow-up to this work we sought to understand how non-sustained rhythmic signals in the brain influence brain and spinal cord communication. Short-lasting beta (15-30Hz) oscillations displaying only 1-2 cycles is a prominent signal of sensorimotor cortical activity. We evaluated the relationship between beta event characteristics and corticospinal excitability in healthy adults. Results show that the number, amplitude, and timing of beta events preceding transcranial magnetic stimulation (TMS) each significantly predicted motor-evoked potential (MEP) amplitudes, providing initial evidence that short-lasting endogenous beta oscillatory events shape human corticospinal excitability. These findings provide an important possible biomarker for elucidating the pathophysiology of motor deficits following stroke.