Stimulating language recovery after stroke: Tailored non-invasive electrical stimulation of the domain-general frontoparietal network.

英国有120万中风幸存者，每年的社会成本为260亿英镑。语言障碍（失语症）是中风后残疾的主要原因，影响了三分之一的患者。目前治疗失语症的治疗策略要么收效甚微，要么需要长期和强化的言语和语言治疗，这在NHS内是不可行的。这些治疗策略大多集中在改善残余的语言特定过程或支持它们的大脑区域。然而，我已经证明，中风后的残余语言功能也依赖于所谓的脑域通用区域的支持，该区域调节一般认知过程，如注意力、工作记忆和技能的学习（或再习得）。重要的是，已建立的双侧额顶叶脑网络（FPN）的域内活动增加已被证明与中风后语言功能的更好恢复有关，这为其作为预后生物标志物和治疗靶点的潜力奠定了基础。这项建议的总体目标是调查和优化这一领域一般大脑网络在中风后语言功能恢复中的代偿作用。Objectives1。使用快速实时脑成像方案来测量脑卒中患者在广泛的语言和非语言任务中的域通用FPN功能。根据初步结果，预计与对照组相比，FPN功能相似的患者在中风后的语言预后最好。相反，那些FPN功能特征与对照组不同的患者将有更差的结果。2 .结合实时脑成像和非侵入性脑刺激，快速识别个性化脑刺激设置，最大限度地发挥每个患者的域通用FPN功能。目的：探讨使用个性化脑刺激域通用FPN是否能改善脑卒中患者的行为表现。方法采用先进的核磁共振成像技术对脑结构和功能进行研究。重要的是，我将使用一种新颖的技术，当参与者在扫描仪中执行任务时，实时分析大脑功能。这将允许在广泛的实验条件下快速评估FPN的域通用脑区域的功能。我在病人的初步研究中使用了这项技术，以显示FPN在一系列语言和非语言任务中的活动模式，与中风后语言障碍的程度有关。我将对50名中风患者使用同样的技术，并将他们的成像测量与中风后的语言功能联系起来。在第二项研究中，我将使用相同的实时脑成像技术结合非侵入性脑刺激，为每个患者确定最佳的脑刺激设置，最大限度地激活他们的域-通用FPN。在这里，大脑刺激的最佳阶段和频率将为每个病人确定。在第三个研究中，我将对每个患者使用个性化的刺激设置来应用大脑刺激，以改善行为表现。潜在的应用和益处中风后的语言障碍很常见，目前还不清楚如何最好地恢复个人。识别个体将受益于支持其残余语言功能的脑区域的康复将提供新的治疗途径。使用个性化的非侵入性大脑模拟来证明这些区域的调节不仅有利于语言障碍患者，而且对广泛的脑缺陷和损伤的康复具有深远的影响。

Context There are 1.2 million stroke survivors in the UK with a societal cost of £26 billion a year. Language impairment (aphasia) is a major cause of disability after stroke affecting a third of all patients. Current therapeutic strategies for treating aphasia have either had little success or demand prolonged and intensive speech and language therapy which is not feasible within the NHS. Most of these therapeutic strategies have largely focused on improving the residual language-specific processes or brain regions that support them. However, I have shown that residual language function after stroke is also dependent on support from the so-called domain-general brain regions that mediate general cognitive processes such as attention, working memory, and learning (or reacquisition) of a skill. Importantly, increased activity within the domain-general regions of a well-established bilateral frontoparietal brain network (FPN) has been shown to be associated with better recovery of language function after stroke, building a case for its potential as a prognostic biomarker and therapeutic target. The overall aim of this proposal is to investigate and to optimise the compensatory role of this domain-general brain network in recovery of language function after stroke. Objectives1. To use a rapid real-time brain imaging protocol to measure the function of the domain-general FPN across a wide range of language and non-language tasks in patients after stroke. Based on preliminary results, it is expected that patients who have a similar FPN function compared to the controls, will have the best language outcomes following their stroke. Conversely, those patients with a dissimilar FPN functional profile to the controls will have the worse outcomes.2. To combine real-time brain imaging and non-invasive brain stimulation to rapidly identify personalised brain stimulation settings that maximise the function of the domain-general FPN for each individual patient.3. To investigate whether the use of personalised brain stimulation of the domain-general FPN improves behavioural performances in patients after stroke. MethodI will use advanced magnetic resonance imaging (MRI) to study brain structure and function. Importantly I will use a novel technique that analyses brain function in real-time whilst participants perform tasks in the scanner. This will allow for a rapid assessment of the function of domain-general brain regions of the FPN across a wide range of experimental conditions. I have used this technique in a pilot study of patients to show that the pattern of activity of the FPN across a range of language and non-language tasks, is related to the degree of language impairment after stroke. I will use the same technique on a group of 50 patients following a stroke, and relate their imaging measures to their language function after the stroke. In a second study, I will use the same real-time brain imaging technique combined with non-invasive brain stimulation, to identify for each individual patient the optimal brain stimulation settings that maximally activate their domain-general FPN. Here, the optimal phase and frequency of the brain stimulation will be identified for each individual patient. In the third study, I will apply brain stimulation using the personalised stimulation settings for each patient, to improve behavioural performances.Potential applications and benefitsLanguage impairment after stroke is common, and it is unclear how best to rehabilitate individuals. Identifying individuals who will benefit from rehabilitation of domain-general brain regions that support their residual language function will provide a new therapeutic avenue. Demonstration of modulation of these regions using a personalised non-invasive brain simulation will not only benefit patients with language impairment, but will have far reaching implications for rehabilitation across a wide range of brain deficits and injuries.