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

Our vision is to develop clinically applicable, non-invasive single neuron monitoring (NISNEM) technology to advance the frontiers of neural interfacing. NISNEM has the potential to transform healthcare and directly impact the healthcare sector, the research and innovation sector, the medical technology industry as well as the national economy and social wellbeing. We aim to create a broad scientific framework for a revolutionary technology that would potentially impact virtually every field of the medical industry. The advances in understanding, monitoring and treating neurodegenerative diseases that NINSEM would enable will set the basis for a new form of technology-based healthcare. This technology, together with ongoing efforts on artificial intelligence (AI), would position the UK as a world-leader in next generation healthcare.
NISNEM would allow studies that increase our understanding of neurological diseases. Many neurological diseases (e.g., Parkinson's, Alzheimer's, Huntington's) are unique to humans; animal models are extremely useful, but, in reality, limited due to the lack in complexity. Having the means to record from large neural populations in patients would constitute a cornerstone to advance our knowledge on these diseases. This improved understanding would enable new targeted pharmacological and neurotechnology-based treatments that are more effective than current methods at treating neural conditions and have minimal side effects. Neurological diseases and conditions are a vast socioeconomic drain on society. For example, currently in UK there are 1.2 million stroke survivors and >100,000 new stroke cases every year; this incidence rate is forecasted to increase by approximately 60% over the next 20 years (stroke.org.uk, 2019) because of population ageing.
As NISNEM is a non-invasive technology, it holds the potential to extend healthcare from the hospital to the home, enabling continued and personalised healthcare. These achievements will have a tremendous social and economic impact, and imply a radical cultural change in how healthcare is provided.
The proposed research will have dramatic impact on the academia and industry. In particular, it will bring a completely new perspective, new technologies/tools and a complementary knowledge base to the biomedical/neural engineering community. The program will also be extremely relevant for the neuroscience community at large, since the proposed methods will enable a breadth of novel approaches to study the nervous system, especially in humans. The technological advances required to produce NISNEM in conjunction with the diverse applicability of the proposed technology are strong indicators that this project could foster a revolution in neurosciences and neurotechnology, strongly impacting and bridging these large academic communities. The research would also be extremely relevant for academics in the broader healthcare engineering and clinical neurology fields since we will develop and progress new techniques and applications of neural interfacing for clinical use, ultimately conditioning all aspects of healthcare.
The potential impact of the proposed research programme has been recognised by a number of leading companies, which have provided their strong support (~£2M in-kind contribution), and expressed a strong interest in discussing the co-creation phase following the project (see LoS from industries). Moreover, key patients' associations have enthusiastically supported the vision of the project and its focus on clinical viability (see LoS).