Non-invasive Electrical Deep Brain Stimulation Technology

世界人口老龄化对大脑疾病患者的患病率产生了毁灭性影响。随着年龄的增长，最常见的大脑疾病是痴呆症--一种神经退行性疾病，导致认知障碍，逐渐影响日常生活活动，侵蚀独立性，损害生活质量。痴呆症的主要原因是阿尔茨海默病，占所有痴呆症病例的60-70% 1。全世界约有5000万痴呆症患者，预计到2050年这一数字将增加到1.52亿。在英国，大约有85万人患有痴呆症，预计到2040年这一数字将增加到160万（相当于每3分钟就有1例新的痴呆症病例）。据估计，全球每年痴呆症的成本为1万亿美元2。英国痴呆症护理的估计成本为350亿英镑，预计到2040年将急剧上升至950亿英镑。在每一个特定的时间，大约四分之一的NHS医院床位被痴呆症患者占用，从而阻碍了对其他医疗条件的护理。在过去的几十年里，通过药物干预来延迟或阻止阿尔茨海默病引起的痴呆症进展的大规模努力未能产生可行的治疗方法。该项目将开发一种技术，旨在通过在疾病的早期阶段提高最脆弱地区对病理学的恢复力来减缓或逆转阿尔茨海默病的进展。我们的方法是基于对这些脆弱结构中的活动进行非侵入性电刺激，以建立其内在的代谢和能量功能，其方式在概念上类似于运动如何建立肌肉中的代谢和能量功能。为了非侵入性地刺激通常位于深部的目标大脑结构的活动，我们将使用我们最近发现的一种新方法，称为时间干扰（TI）刺激。我们已经在动物模型和健康人中证明了TI刺激可以用来改变海马体的活动，海马体是一种对记忆和认知功能至关重要的深部脑结构，在阿尔茨海默病的早期阶段受到强烈影响。在这个项目中，我们将解决最关键的工程挑战，将我们的概念发展为可靠和精确的非-侵入性脑深部电刺激技术，可用于大规模临床测试。此外，我们将测试和迭代地改善的影响的时间干扰刺激的病理海马在阿尔茨海默氏病的动物模型。最后，我们将开始开发将该技术转化为一种可行的医疗保健治疗方法的途径，该方法采用价格合理的可穿戴硬件，也可以部署在患者家中。时间干扰脑刺激技术具有针对任意脑深部结构的能力，将为开发治疗以这些结构异常活动为基础的多种脑疾病的治疗方法提供平台。这种颠覆性技术的发展将使英国处于神经技术行业的前沿，该行业有望成为医疗行业增长最快的行业。利文斯顿，G.等The Lancet（2017）2.帕特森角World Alzheimer Report 2018，伦敦，英国（2018）. 3. Alzheimer's Society（2009）.

The ageing of the world population has had a devastating impact on the prevalence of people with brain disorders. The most common brain disorder with age is dementia - a neurodegenerative disease that leads to cognitive impairment that progressively affects activities of daily living erodes independence and impairs quality of life. The leading cause of dementia is Alzheimer's disease, accounting for 60-70% of all dementia cases1. There are approximately 50 million people with dementia worldwide, and this number is projected to increase to 152 million by 20502. In the UK there are approximately 850,000 people with dementia, and this number is projected to increase to 1.6 million by 2040 (translating to 1 new dementia case every 3 minutes). The global costs of dementia are estimated to be US$1 trillion annually2. The estimated cost of dementia care in the UK is £35 billion, which is projected to rise sharply to £95 billion by 2040. At every given time, about one out of four beds in the NHS hospitals is occupied by a patient with dementia3, thus impeding care for other medical conditions. During the last decades, large-scale efforts to delay or stop the progression of dementia due to Alzheimer's disease via pharmacological interventions have failed to produce viable treatment. This project will develop a technology that aims to slow or reverse the progression of Alzheimer's disease by boosting the resilience to the pathology in the most vulnerable regions at the early stages of the disease. Our approach is based on non-invasive electrical stimulation of the activity in those vulnerable structures to build up their intrinsic metabolic and energetic functionalities, in a way that is conceptionally similar to how exercise builds up the metabolic and energetic functionalities in the muscles. To non-invasively stimulate the activity at the target brain structures which are often at deep locations, we will use a novel method, called temporal interference (TI) stimulation, that we recently discovered. We have already shown that TI stimulation can be used to change the activity in the hippocampus, a deep brain structure that is critical for memory and cognitive function and strongly affected in the early stages of Alzheimer's disease, in an animal model and in healthy humans.In this project, we will address the most critical engineering challenges to develop our concept to a reliable and precise non-invasive deep brain stimulation technology that can be deployed in large-scale clinical testing. In addition, we will test and iteratively improve the effect of the temporal interference stimulation on the pathology of the hippocampus in animal models of Alzheimer's disease. Finally, we will start developing the pathway to translate the technology to a viable healthcare treatment with affordable and wearable hardware that can also be deployed at the patients' home.The temporal interference brain stimulation technology with its capability to target arbitrary deep brain structures will provide a platform for developing therapies for multiple brain disorders underpinned by aberrant activity in those structures. The development of such a disruptive technology will place the UK at the frontiers of the neurotechnology industry that is poised for the fastest growth in the medical industry.1. Livingston, G. et al. The Lancet (2017)2. Patterson, C. World Alzheimer Report 2018, London, UK (2018).3. Alzheimer's Society (2009).