Non-invasive brain stimulation equipment is a fundamental tool in neuroscience that allows activity in specific brain regions to be temporally altered. This is important for both basic neuroscience (i.e., understanding the role of a brain region during behaviour by temporally altering its activity) and in the clinical treatments of neurological/psychiatric conditions (i.e., rebalancing the activity of a brain region which is affected by disease). However, existing non-invasive techniques are restricted to brain areas close to the scalp and are unable to target critical deep (subcortical) brain structures. Given the essential role these areas play within behaviour and neural disorders, it is vital for new equipment to be developed that bridges this technological gap. Transcranial focused ultrasound stimulation (FUS) has recently revolutionised the field by allowing, for the first time, the accurate and safe non-invasive stimulation of deep brain structures. Whilst FUS is now an established technique, combining it with neuroimaging techniques (i.e., magnetic resonance imaging), is not. The ability to perform FUS concurrently with neuroimaging opens an exciting window of opportunity to casually map human brain function during behaviour/cognition at a level of detail never previously achieved in health and disease. In addition, it will allow novel interventions to be developed for clinical populations. For example, ongoing brain activity (measured by neuroimaging) could be used as a signal to deliver temporally specific FUS (i.e., closed-loop stimulation) in order to restore normal brain activity/function. This application sets out the case for the purchase of the first commercially available system that enables FUS to be combined with neuroimaging techniques. The state-of-the-art combination of FUS-brain imaging promises novel insight across a large range of scientific areas (learning, memory, consciousness, attention) and neural disorders (Depression, Parkinson's disease, Disorders of Consciousness, Dystonia, Autism). The new equipment will be placed in a specialist facility in the University of Birmingham that is dedicated to the study of human brain health. This facility houses 5 separate brain imaging modalities/techniques alongside specialist trained staff. This will ensure that the equipment will be used rapidly and by the largest possible number of researchers in order to make the greatest possible advances in science and medicine.

Non-invasive brain stimulation equipment is a fundamental tool in neuroscience that allows activity in specific brain regions to be temporally altered. This is important for both basic neuroscience (i.e., understanding the role of a brain region during behaviour by temporally altering its activity) and in the clinical treatments of neurological/psychiatric conditions (i.e., rebalancing the activity of a brain region which is affected by disease). However, existing non-invasive techniques are restricted to brain areas close to the scalp and are unable to target critical deep (subcortical) brain structures. Given the essential role these areas play within behaviour and neural disorders, it is vital for new equipment to be developed that bridges this technological gap. Transcranial focused ultrasound stimulation (FUS) has recently revolutionised the field by allowing, for the first time, the accurate and safe non-invasive stimulation of deep brain structures. Whilst FUS is now an established technique, combining it with neuroimaging techniques (i.e., magnetic resonance imaging), is not. The ability to perform FUS concurrently with neuroimaging opens an exciting window of opportunity to casually map human brain function during behaviour/cognition at a level of detail never previously achieved in health and disease. In addition, it will allow novel interventions to be developed for clinical populations. For example, ongoing brain activity (measured by neuroimaging) could be used as a signal to deliver temporally specific FUS (i.e., closed-loop stimulation) in order to restore normal brain activity/function. This application sets out the case for the purchase of the first commercially available system that enables FUS to be combined with neuroimaging techniques. The state-of-the-art combination of FUS-brain imaging promises novel insight across a large range of scientific areas (learning, memory, consciousness, attention) and neural disorders (Depression, Parkinson's disease, Disorders of Consciousness, Dystonia, Autism). The new equipment will be placed in a specialist facility in the University of Birmingham that is dedicated to the study of human brain health. This facility houses 5 separate brain imaging modalities/techniques alongside specialist trained staff. This will ensure that the equipment will be used rapidly and by the largest possible number of researchers in order to make the greatest possible advances in science and medicine.

The Neuromod+ network will represent UK research, industry, clinical and patient communities, working together to address the challenge of minimally invasive treatments for brain disorders. Increasingly, people suffer from debilitating and intractable neurological conditions, including neurodegenerative diseases and mental health disorders. Neurotechnology is playing an increasingly important part in solving these problems, leading to recent bioelectronic treatments for depression and dementia. However, the invasiveness of existing approaches limits their overall impact. Neuromod+ will bring together neurotechnology stakeholders to focus on the co-creation of next generation, minimally invasive brain stimulation technologies. The network will focus on transformative research, new collaborations, and facilitating responsible innovation, partnering with bioethicists and policy makers. As broadening the accessibility of brain modification technology my lead to unintended consequences, considering the ethical and societal implications of these technological development is of the utmost importance, and thus we will build in bioethics research as a core network activity. The activities of NEUROMOD+ will have global impact, consolidating the growing role of UK neurotechnology sector.

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

Hospital neurology and neurophysiology services are increasingly overwhelmed. With a growing and ageing population, the incidence of many brain conditions (such as dementia and epilepsy) are rapidly increasing. Compounded by the COVID-19 pandemic, there are now over 10,000 people in the UK waiting more than a year for an appointment with a neurologist. Things must change! The purpose of our Network is to address these challenges through the development of new technologies that enable diagnosis and management in the community. These services could be provided in a community diagnostic hub, by high-street healthcare professionals, in a GP surgery, in a mobile unit or even in the home environment. Our focus will be on new digital solutions built around neural interfacing, signal processing, machine learning and mathematical modelling. We will work closely with partners developing technologies for measuring brain, eye, spinal, and peripheral nerve activity using wearable technology and minimally invasive devices. Collectively, this will contribute to a significant increase in capacity that will augment the expertise provided in neurology services. To achieve this, we will build a network of partners with backgrounds spanning academia, industry, hospitals and GP surgeries, charities and policy makers. Crucially we will ensure that people with lived experience of neurological conditions are at the heart of our network. Their experience will inform debate and shape our research priorities, ensuring feasibility and acceptability of emerging technologies. We will empower people from different backgrounds and career stages to work together on challenging problems whose solutions will lead to societal benefit. To enable this we plan a suite of activities built around the principles of connect, communicate and collaborate. To connect people we will build a website and social media presence, create a public representation group and build new parnterships. We will establish a mentorship scheme and post opportunities for people at different career stages to undertake secondments with partner organisations. To facilitate communication, we will engage with stakeholders including the public, people with neurological conditions, healthcare providers and policy makers. We will host workshops on emerging areas of interest, as well as an annual conference to celebrate findings from across the network. To enable collaboration we will host events including stake-holder led study groups, sandpits and research incubators: where teams of partners will work collaboratively in a facilitated environment, conducting feasibility studies over 6-9 months.