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

We are proposing to take a new and creative approach to the way in which the brain is imaged and useful information is delivered to both doctors and patients. We will develop a suite of entirely novel compact, non-invasive and lightweight brain imaging systems which will allow patients to be monitored in a range of environments. This will open up new possibilities for how we guide the management of patients with brain injury and develop technologies which may assist profoundly disabled patients to interact with the world around them. Our imaging systems will combine two technologies: near infrared spectroscopy which measures how oxygen is delivered and utilised by different regions of the brain, and electroencephalography which measures brain electrical activity. The combination of these technologies will provide a powerful tool to assess the effects of brain injury and its response to therapy, and to capture information about how well the brain is working which can be used to aid the patient. The systems will be wearable, and importantly, comfortable to wear for extended periods of time. One system will be optimised for studies of brain injured patients outside of intensive care environments (when they may be semi mobile) during the critical rehabilitation stage of their management. The system will be specifically designed to help doctors to optimise the type and duration of therapies, minimise the risk of further injury to the brain, and thus improve the likelihood of patient recovery. Another system will be designed to monitor patients who have chronic brain or other neurological injury which means they are severely physically disabled but still have some degree of brain function. For these patients we will optimise our brain imaging system to measure the activation of their brain during specific tasks and investigate whether we can use these measured signals to help the patients communicate with, and control, their environments - so called brain computer interfacing. No other brain imaging systems currently exist which are capable of delivering this type of information, in this range of patient groups. In addition to building the new imaging systems, we will also develop computer programmes which are essential to extract the relevant information from the measured signals from the brain. This will involve developing routines for delivering images in real time, and incorporating a computer model of the brain to help us understand the meaning of the signals and images. We will test our systems and methods on healthy volunteers before moving on to studies in patients with brain injury. Our group has a long and successful track record of this type of translational research, i.e. the combined approach of hardware and software engineering of novel brain imaging technologies targeted at specific applications in healthcare, and introduction into clinical use. We have assembled a multidisciplinary team to meet the challenges of this ambitious project including engineers, mathematicians, clinicians, physicists and neuroscientists, and we have attracted the interest of an industrial project partner for potential commercial exploitation of our developed systems.