NON-INVASIVE SINGLE NEURON ELECTRICAL MONITORING (NISNEM Technology)

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