NON-INVASIVE SINGLE NEURON ELECTRICAL MONITORING (NISNEM Technology)

我们提出了一种新的无创单神经元电监测技术(NISNEM)的开发。目前的非侵入性神经成像技术包括脑电(EEG)、脑磁图(MEG)或功能磁共振成像(FMRI)提供了对大脑中大量神经元活动的间接测量。然而，越来越明显的是，单个神经元水平的信息对于理解、诊断和治疗日益普遍的神经疾病，如中风和痴呆症可能是至关重要的。目前记录单个神经元活动的方法是有创的--它们需要外科植入。植入的电极有可能损害神经组织和/或限制长期稳定性的异物反应。可以理解的是，许多患者并没有选择这种方法；事实上，植入电极技术仅限于在世界各地的少数患者身上进行动物准备或测试。非侵入性地测量单个神经元的活动将改变诊断、监测和治疗神经疾病的方式，并为神经技术在医疗保健中的广泛采用铺平道路。我们建议通过推动电极技术、超低噪声电子学和先进信号处理方面的前沿工程研究来发展NISNEM，并在临床前试验的广泛测试中反复验证。我们将设计和制造干电极阵列，以超高密度的记录点安装在皮肤上。通过积极的小型化，我们将开发微电子芯片，以超过最先进的噪音性能从数千个频道进行录音。我们将在无监督盲源识别方面取得突破性进展，从数万个记录中识别数十到数百个神经元的活动。这项研究将得到对人类和动物的迭代临床前研究的支持，这将是确定需求和完善设计的关键。我们打算展示NISNEM技术的可行性及其成为改变医疗保健方方面面的常规临床工具的潜力。特别是，我们预计它将极大地改善神经疾病的管理方式。鉴于它们是一个巨大的负担，并限制了数百万患者及其家人的生活质量，NISNEM的影响可能是史无前例的。我们预计NISNEM技术将在常规临床基础上应用于：1)诊断(癫痫、震颤、痴呆)；2)监测(中风、脊髓损伤、衰老)；3)干预(大脑活动的闭环调节)；4)增进我们对神经系统的了解(识别病变)；以及5)开发用于交流的神经接口(针对闭锁患者的脑机接口)、控制(神经)假体或替换“缺失的感觉”(如听觉假体)。此外，通过准确检测患者的意图，这项技术可以用来驱动神经可塑性-大脑自我重组的能力-有可能治愈目前无法治愈的疾病，如中风、脊髓损伤或帕金森氏症。NISNEM还提供了将治疗从医院扩展到家庭的机会。例如，中风后的康复主要在医院进行，时间有限；没有家庭康复。NISNEM可以通过使用治疗技术在家中提供持续的康复。神经工程、神经科学和临床神经病学社区都将从这种全新的视角和互补的知识库中受益匪浅。NISNEM将促进神经科学和神经技术的革命，对这些大型学术界和临床部门产生强烈影响。更重要的是，如果成功，它将改善数百万患者及其亲属的生活

We propose the development of a new technology for Non-Invasive Single Neuron Electrical Monitoring (NISNEM). Current non-invasive neuroimaging techniques including electroencephalography (EEG), magnetoencephalography (MEG) or functional magnetic resonance imaging (fMRI) provide indirect measures of the activity of large populations of neurons in the brain. However, it is becoming apparent that information at the single neuron level may be critical for understanding, diagnosing, and treating increasingly prevalent neurological conditions, such as stroke and dementia. Current methods to record single neuron activity are invasive - they require surgical implants. Implanted electrodes risk damage to the neural tissue and/or foreign body reaction that limit long-term stability. Understandably, this approach is not chosen by many patients; in fact, implanted electrode technologies are limited to animal preparations or tests on a handful of patients worldwide. Measuring single neuron activity non-invasively will transform how neurological conditions are diagnosed, monitored, and treated as well as pave the way for the broad adoption of neurotechnologies in healthcare. We propose the development of NISNEM by pushing frontier engineering research in electrode technology, ultra-low-noise electronics, and advanced signal processing, iteratively validated during extensive tests in pre-clinical trials. We will design and manufacture arrays of dry electrodes to be mounted on the skin with an ultra-high density of recording points. By aggressive miniaturization, we will develop microelectronics chips to record from thousands of channels with beyond state-of-art noise performance. We will devise breakthrough developments in unsupervised blind source identification of the activity of tens to hundreds of neurons from tens of thousands of recordings. This research will be supported by iterative pre-clinical studies in humans and animals, which will be essential for defining requirements and refining designs. We intend to demonstrate the feasibility of the NISNEM technology and its potential to become a routine clinical tool that transforms all aspects of healthcare. In particular, we expect it to drastically improve how neurological diseases are managed. Given that they are a massive burden and limit the quality of life of millions of patients and their families, the impact of NISNEM could be almost unprecedented. We envision the NISNEM technology to be adopted on a routine clinical basis for: 1) diagnostics (epilepsy, tremor, dementia); 2) monitoring (stroke, spinal cord injury, ageing); 3) intervention (closed-loop modulation of brain activity); 4) advancing our understanding of the nervous system (identifying pathological changes); and 5) development of neural interfaces for communication (Brain-Computer Interfaces for locked-in patients), control of (neuro)prosthetics, or replacement of a "missing sense" (e.g., auditory prosthetics). Moreover, by accurately detecting the patient's intent, this technology could be used to drive neural plasticity -the brain's ability to reorganize itself-, potentially enabling cures for currently incurable disorders such as stroke, spinal cord injury, or Parkinson's disease. NISNEM also provides the opportunity to extend treatment from the hospital to the home. For example, rehabilitation after a stroke occurs mainly in hospitals and for a limited period of time; home rehabilitation is absent. NISNEM could provide continuous rehabilitation at home through the use of therapeutic technologies.The neural engineering, neuroscience and clinical neurology communities will all greatly benefit from this radically new perspective and complementary knowledge base. NISNEM will foster a revolution in neurosciences and neurotechnology, strongly impacting these large academic communities and the clinical sector. Even more importantly, if successful, it will improve the life of millions of patients and their relatives