Neural Mechanisms Underlying Functional Plasticity of the Human Brain

学习和技能获得在很大程度上依赖于与意识无关的内隐过程，无论是在短时间还是长时间范围内。一个短时间尺度的例子是重复启动(RP)，在重复相同或相关的刺激时，提高了识别、产生或分类刺激的性能。神经成像显示，RP经常伴随着重复抑制(RS)，降低了大脑中对手头任务至关重要的部分的神经激活。尽管进行了20年的研究，但RP和RS之间的联系仍然难以捉摸。许多理论都聚焦于离散大脑区域内局部活动的变化。然而，另一种解释是，RS可能是跨大规模皮质网络进行更有效通信的结果。根据这一解释，重复导致大脑区域之间更有效的耦合(功能连接：FC)，这同时减少了局部神经活动，提高了认知能力。然而，到目前为止，几乎没有直接证据支持这一假设。因此，迫切需要直接验证这一假说的研究，以阐明这一基本过程背后的神经机制。关于更长的时间尺度，有证据表明，大规模网络中大脑活动的自发波动在学习和技能获得中也发挥着基础性作用。虽然这些活动模式持续存在，在很大程度上独立于正在进行的想法，但它们在某种程度上也受到经验的调节，这种调节对未来的行为和表现有影响。关于这种内在活动如何与RP或RS相互作用我们知之甚少，但这可能是大脑长期功能可塑性的基本机制；因此，迫切需要研究阐明重复体验、内在活动模式和长期行为促进之间的关系。这项研究提案有两个主要目标： 1)使用功能磁共振成像技术，确定RP和RS是否反映了FC增强所致的神经效率，以及它们是否与由内在活动反映的长期神经认知可塑性相互作用。 2)通过经颅磁刺激实验调节大脑活动，建立导致短期和长期神经认知可塑性的皮质-皮质和大脑行为之间的因果关系。 长期目标是开发一个全面的模型，描述和量化不同时间尺度上作用的内隐过程之间的因果关系，了解神经认知可塑性如何随着时间的推移塑造认知表现。这项工作将对这些我们目前知之甚少的基本过程产生迫切需要的洞察，并将对人类学习和认知领域产生重大影响。

Learning and skill acquisition rely to a large extent on implicit processes that occur independent of conscious awareness, both on short and long timescales. An example on a short timescale is repetition priming (RP) improved performance in identifying, producing, or classifying a stimulus upon repetition of the same or a related stimulus. Neuroimaging reveals that RP is often accompanied by repetition suppression (RS) reduced neural activation in parts of the brain that are critical for the task at hand. Despite 20 years of research, the link between RP and RS remains elusive. Many theories have focused on changes in local activity within discrete brain regions. However, an alternative explanation is that RS might be a consequence of more efficient communication across large-scale cortical networks. By this account, repetition leads to more efficient coupling across brain regions (functional connectivity: FC), which simultaneously reduces local neural activity and enhances cognitive performance. However, there is little direct evidence to support this hypothesis to date. Thus, there is a critical need for studies that directly test this hypothesis to elucidate the neural mechanism underlying this fundamental process. Regarding longer timescales, evidence demonstrates that spontaneous fluctuations of brain activity across large-scale networks play a fundamental role in learning and skill acquisition as well. While these patterns of activity persist, largely independent of ongoing thoughts, they are also modulated by experienc to some extent, and this modulation has an impact on future behaviour and performance. Little is known about how this intrinsic activity interacts with RP or RS, but this could be a fundamental mechanism underlying long-term functional plasticity in the brain; thus, there is a critical need for studies that elucidate the relationship between repeated experiences, patterns of intrinsic activity, and long-term behavioural facilitation. This research proposal has 2 primary objectives: 1) To determine if RP and RS reflect neural efficiency due to enhanced FC, and if they interact with long-term neurocognitive plasticity reflected by intrinsic activity, using fMRI. 2) To establish causal cortico-cortical and brain-behaviour relationships that lead to both short- and long-term neurocognitive plasticity by experimentally modulating brain activity using transcranial magnetic stimulation. The long-term objective is to develop a comprehensive model that characterizes and quantifies the causal interrelationships between implicit processes acting on different timescales, to understand how neurocognitive plasticity shapes cognitive performance over time. This work will produce critically needed insight into these fundamental processes, of which we currently know little, and will have a significant impact on the fields of human learning and cognition.