Predicting the response to plasticity-inducing protocols of non-invasive brain stimulation (NIBS)

在过去的30年里，我们发明了许多方法，使我们第一次能够刺激健康、有意识的人的部分大脑，而无需切除部分头皮或进行神经外科手术。这是一个显著的进步。更引人注目的是，最近的发展已经使得直接与被称为“突触可塑性”的过程相互作用成为可能，这是我们学习新事物能力的基础。当我们学习新的东西时，大脑中少数神经元连接在一起的方式发生了微妙的变化，这个新的回路被用来存储记忆。新的大脑刺激方法可以巧妙地加速或减缓这一过程。对这种方法的主要兴趣在于它有可能加速脑损伤或疾病后的康复训练。例如，中风后，大脑必须重新学习如何在一组受损的电路中执行任务。物理疗法的工作原理是让病人练习任务，这样他们的大脑就可以通过一套新的连接来重新学习旧的技能。研究表明，使用新的大脑刺激方法可以加快这一过程。尽管这些方法很有吸引力，而且总体上很有效，但它们的一个问题是，它们的有效性因人而异。结果是，在任何临床试验中，一些参与者的表现都比其他人好得多。本建议的目的是更多地了解这种变化产生的原因，更重要的是，设计简单的预测措施，可用于检查个人是否可能对特定方案做出反应，如果找不到合适的替代方案。这项工作将从探索一些简单的方法开始，这些方法已经被报道用来预测对特定大脑可塑性协议的反应，并在对50名健康志愿者进行一系列研究后选择其中最有用的方法。然后，我们将在一组25名慢性中风幸存者中测试这些因素是否也能预测每个患者对单次治疗的临床反应。最后，该项目将探索一个假设，即人与人之间的这些差异取决于大脑解剖结构的细微差异。大脑皮层的折叠模式与每个个体的“平均”模式略有不同。此外，大脑皮层中代表某些功能的区域在个体之间也有一厘米左右的差异。我们将使用复杂的计算机模拟外部大脑刺激可能激活个体大脑区域的方式，并显示激活区域的差异可以解释一个人对每种方案的反应差异。如果是正确的，我们可以在随后的研究中使用这些信息来改变刺激器的设计，这样我们就可以瞄准个体大脑中的“正确”位置，并最大限度地提高对任何给定协议的反应机会。

Over the past 30 years a number of methods have been devised that allow us for the first time to stimulate parts of the brain in healthy, conscious individuals without having to remove part of the scalp or undergo neurosurgery. It is a remarkable advance. Even more strikingly, recent developments have made it possible to interact directly with a process known as "synaptic plasticity" which is fundamental to our ability to learn new things. When we learn anything new, a subtle change is made in the way a small number of neurones connect together in the brain and this new circuit is used to store the memory. The new brain stimulation methods can subtly speed up or slow down this process.The main interest in this method lies in its potential to speed up rehabilitation training after brain injury or disease. For example, after a stroke, the brain has to re-learn how to perform tasks with a damaged set of circuits. Physiotherapy works by giving patients practice in tasks so that their brain can re-learn old skills with a new set of connections. Work has suggested that this process would be speeded up by using the new methods of brain stimulation.Although very attractive, and overall effective, a problem with the methods is that they vary in effectiveness from one individual to another. The result is that in any clinical trial, some participants perform much better than others. The objective of this proposal is to understand more about why this variation arises, and, more importantly, devise simple predictive measures that can be used to check if an individual is likely to respond to a particular protocol, and if not find an appropriate alternative.The work will begin by exploring a number of simple measures that have been reported to predict responses to particular brain plasticity protocols and select the most useful of these after a series of studies in 50 healthy volunteers. We will then test in a group of 25 chronic stroke survivors whether these factors will also predict the clinical response of each patient to a single session of therapy. Finally the project will explore the hypothesis that these differences between people depend on subtle differences in the anatomy of the brain. The pattern of folding of the cerebral cortex varies slightly from the "average" pattern in every individual. In addition, the area of cortex where certain functions are represented also varies within a centimetre or so between individuals. We will use sophisticated computer modelling of the way the external brain stimulation is likely to activate regions in individual brains and show that differences in the regions activated can account for differences in a person's response to each protocol. If correct we can use this information in a subsequent study to change stimulator design so that we can target the "correct" locations in an individual brain and maximise chances of responding to any given protocol.