Funded projects

Find out below about the projects that Neuromod+ has funded. Click on a project title to see the project summary and project team. You can also click any linked team member to view their Neuromod+ profile in our Member Directory and get in touch with them.

Call 1 - March 2023

Characterization of the clinical and neuromodulatory effects of transcutaneous Spinal Cord Stimulation in Essential Tremor
Dario Farina, Alejandro Pascual Valdunciel – Imperial College London
Anna Latorre, Kailash Bhatia – University College London

Tremor is a motor disorder which can severely affect the quality of life of patients, leading to significant socio-economic impact. In this project we aim to explore a non-invasive and cost-effective solution for mitigating tremor. Particularly, we will investigate the effectiveness of transcutaneous spinal cord stimulation (tSCS) in treating tremor and how this technique interferes with motor control. tSCS involves weak currents delivered through electrodes attached to the skin. It has been proven to modulate the central nervous system and based on our previous research on nerve stimulation, we assume that it could potentially disrupt the tremorgenic oscillations at the spinal cord, preventing them to reach the muscles. We will explore the tremor reduction efficacy and safety of tSCS in Essential Tremor and attempt to characterize the neuromodulatory effects on motor control of different stimulation parameters, including a closed-loop stimulation strategy synced with the tremor.

Developing a dual neuromodulation approach for major depressive disorder: understanding action on frontal cortex using functional near infra-red spectroscopy (fNIRS)
Paul Briley, Richard Morriss – University of Nottingham
Sudheer Lankappa – University of Plymouth
Peter Liddle – University of Oxford

Transcranial magnetic stimulation (TMS) is approved by NICE for the treatment of depression. Clinical TMS uses magnetic pulses to modify activity of frontal brain regions. The amount of benefit that patients get from TMS is variable. We are developing an approach for boosting the effects of TMS by delivering it in synchrony with another neuromodulation technique called transcranial alternating current stimulation (tACS). We are commencing a study of tACS-synchronised TMS (“tsTMS”) in people with depression to understand how the two techniques work together. We are requesting funds to purchase a device for non-invasively monitoring activity within frontal cortex. This device, called “functional near infrared spectroscopy” (fNIRS), is quick to setup and can be used before, during, and after stimulation. This would allow us to study the extent, and region specificity, of tsTMS modulation of frontal cortical activity, beyond that of TMS alone, furthering the development of our approach.

Development of Patient and Public Involvement for Neurotechnologies
Antonio Valentin –  King’s College London
Tamar Makin – University College London
Tiago Da Silva Costa – Newcastle University
Kat Richardson –  CloseNIT Network (Newcastle University)
Amparo Guemes – University of Cambridge

Active Patient and Public Involvement (PPI) is crucial to co-develop user-centred, ethically sound and sustainable neurotechnologies, whilst promoting transparency, accountability and inclusivity. We aim to establish a structured approach to PPI in the development and use of neurotechnologies in the UK, by setting clear principles, guidelines and tools for co-production by stakeholders including patients, clinicians, researchers, regulators, and the public. As a first step, we will host a workshop that celebrates successful PPI initiatives. We will first hear from patients, clinicians, researchers, and regulators about their effective PPI implementation methods. Next, we will discuss the practical steps for establishing PPI. Beyond the networking opportunities, deliverables include the consolidation, in a workshop white paper, of the best existing guidelines, policies, and online resources to support effective PPI strategies. This will form the basis for establishing the first set of guidelines and tools for PPI in neurotechnologies design in the UK.

Neurochemical basis of Focused ultrasound stimulation (FUS) on Memory
JeYoung Jung (University of Nottingham), Marcus Kaiser (University of Nottingham), Matthew Lambon Ralph (University of Cambridge), Elena Stylianopoulou (University of Cardiff)

Dementia affects millions globally and the loss of neurotransmitters is a hallmark of dementia. Decreased excitatory (glutamate) and inhibitory (GABA) neurotransmitters have been linked to cognitive and behavioural symptoms in dementia. Focused ultrasound stimulation modulates neural activity by affecting cell membrane features. Unlike other techniques, FUS has high spatial resolution and can stimulate deep-brain structures involved in dementia. This proposal suggests using FUS combined with neuroimaging for developing personalized dementia treatment. The proposal aims to explore and validate the efficacy of FUS in modulating neurotransmitter systems to improve human memory. It involves investigating neurochemical mechanisms of FUS effects, predicting outcomes based on individual neural characteristics, and developing evidence-based FUS protocols to improve memory. The proposal contributes to understanding FUS effects on memory and potentially lead to new treatments for dementia.

State-dependency of deep-brain transcranial ultrasonic neurostimulation
Miriam Klein-Flugge, Lilian Weber, Johannes Algermissen – University of Oxford
Elsa Fouragnan, Siti Yakuub – University of Plymouth

We aim to further improve iTBS for depression by optimizing the TMS pulse shape. Overcoming the engineering limitations of conventional devices, our novel TMS device can deliver monophasic iTBS. Compared to conventional biphasic, monophasic iTBS induces stronger brain plasticity – key to the antidepressant effects.

Here we will test the hypothesis that monophasic iTBS will reverse cognitive deficits in depression more effectively than conventional biphasic. We will use tasks we have shown to be sensitive to depression and single-dose stimulation (Figure 1). Our project aims to establish proof-of-concept evidence to advance towards a next-step clinical trial.

Ultrasound neuromodulation with real-time 3-photon imaging
Sophie Morse, Simon Schultz, James Choi, Ann Go – Imperial College London

Focused ultrasound is capable of non-invasive neuronal modulation. It can, with high spatial precision, reach deep brain structures normally accessible only through invasive deep brain stimulation. Producing both short and long-lasting changes in neuronal excitability and firing rates, focused ultrasound offers enormous potential as an investigative tool for neuroscience and as a treatment for neurological and psychiatric disorders. How ultrasound induces neuromodulation, however, needs to be better understood in order to develop more precise and effective protocols for the treatment of promising brain disorders. Three-photon microscopy can non-invasively perform deep-tissue, live-cell structural and functional imaging. With its ability to image structures such as the murine hippocampi without the need of a craniotomy, it is an ideal tool to better understand the mechanism of ultrasound neuromodulation. We here propose to build the first simultaneous ultrasound neuromodulation and three-photon imaging system to advance our mechanistic understanding and improve patient treatments.

Call 2 - November 2023

Clinical Trial Readiness for Non-Invasive Therapeutic Neuromodulation in Ataxia Telangiectasia
Rob Dineen, Stephen Jackson, Caroline Blanchard, Alex Turner – University of Nottingham
William Whitehouse – National Paediatric A-T Clinic, Nottingham University Hospitals NHS Trust

Ataxia telangiectasia (A-T) is an inherited cerebellar neurodegenerative disorder. People with A-T experience unwanted involuntary movements (e.g. dystonia, chorea, athetosis and tremors), interfering with daily tasks, social interactions and reducing quality-of-life. Pharmacological treatments are ineffective and limited by side effects.

Non-invasive Median Nerve Stimulation (MNS) suppresses involuntary movements in Tourette syndrome. Based on this, in 2023 we successfully undertook a pilot study (STIM-A-T) of MNS in 5 people with A-T, with video recording during motor tasks with MNS on and off. The video recordings have undergone expert rating for abnormal movements, but this is time-consuming and suffers subjective biases, hence not ideal for large-scale clinical trials.

To support a clinical trial of MNS in people with A-T (grant submission 2024-Q3/Q4), we will work collaboratively with computer scientists and clinical neurologists to develop AI-based quantitative video analysis providing unbiased measures of involuntary movements trained on labelled videos from people with A-T.

Closed-loop focused neuromodulation: Testing different strategies in healthy human participants
Marcus Kaiser, Mohammad Zia Katshu – University of Nottingham
James Choi, Sophie Morse – Imperial College London

Unlike other noninvasive brain stimulation techniques, focused ultrasound can safely reach deep-brain structures. It therefore competes with invasive deep-brain stimulation through implants. One challenge of the field is that stimulation is often inconsistent between participants or patients and that results in the same participant vary between sessions. This has led to the idea of closed-loop approaches which we have already tested in animal studies invasively showing a great increase in stimulation effectiveness (Zaaimi et al., Nature Biomedical Engineering, 2023). Here, we test closed-loop approaches in humans noninvasively, observing the effect of focused ultrasound stimulation. We will test whether closed-loop stimulation, either coupled to ongoing brain rhythms or to task execution, leads to more consistent and stronger changes in cognitive performance.

While we initially test our approaches in healthy participants, our aim is to provide pilot results for future study of interventions in patients.

Fostering Acceptance and Inclusivity of Non-Invasive Neurotechnology in African Ethnic Minority Communities
Mahnaz Arvaneh, Daniel Blackburn – University of Sheffield
Lise Sproson – Sheffield Teaching Hospital NHS FT, NIHR Devices for Dignity Med Tech Cooperative
Ismail Yussuf – Israac Centre, Sheffield

Non-invasive neurotechnology like EEG and brain stimulation can revolutionize healthcare by providing accurate diagnoses and personalized treatments. However, it is crucial to consider the social and cultural implications to ensure inclusivity for historically marginalized groups. In the UK, African ethnic minority communities face health disparities and are often underrepresented in neurotechnology research. Barriers include limited awareness, cultural and language differences, mental health stigma, and design issues. For instance, African-style hair hampers EEG and electrical brain stimulation effectiveness, while wearing hijab poses religious concerns. To address these challenges, this project will investigate the acceptance and inclusivity of neurotechnology among people from Somali heritage. Collaborating with Israac, a Sheffield-based Somali Community association, this study will use user-centered approaches to evaluate existing technology, identify barriers, propose solutions for greater ethnic representation in neurotechnology research, and co-develop alternative designs for better acceptability and inclusivity.

Optimising transcranial electrical stimulation for motor neurone disease
Alekhya Mandali, James Alix – University of Sheffield

Motor neurone disease (MND) is a fatal condition that causes muscle weakness. During the disease, the brain becomes ‘overactive’ well before symptoms start and is critical to disease progression. Over the last 20 years, small electrical currents applied by electrodes on the scalp have been shown to alter the brain’s activity. Recent work shows that these weak currents can dampen down this ‘overactive’ brain, making this approach relevant for MND. A recent randomised-controlled trial using one stimulation form decreased this ‘overactivity’ in MND patients. However, the study was limited to one stimulation type, and it is unknown if other forms of stimulation work better.

This project will compare two stimulation types on healthy participants by measuring a criterion used to assess the brain’s overactivity in MND. The best stimulation will then be tested on a few MND patients. The study outcomes will enable future studies to treat MND using electrical currents.

Remediating depressive cognition using a novel brain stimulation device
Jacinta O’Shea, Tim Denison, Verena Sarrazin, Emile Radyte, Fatima Khokar – University of Oxford
Majid Memarian – Magstim Limited
Michael Browning – Oxford Health NHS Trust

Depression is the leading cause of adult disability worldwide. 1 in 3 patients do not respond to medications/psychotherapy. Transcranial Magnetic Stimulation (TMS) is a promising alternative. A rapid form (intermittent theta burst stimulation, iTBS) delivered in 3 minutes is as effective as conventional 37-minute treatment, and highly intensive multi-session iTBS greatly increases clinical effectiveness.

We aim to further improve iTBS for depression by optimizing the TMS pulse shape. Overcoming the engineering limitations of conventional devices, our novel TMS device can deliver monophasic iTBS. Compared to conventional biphasic, monophasic iTBS induces stronger brain plasticity – key to the antidepressant effects.

Here we will test the hypothesis that monophasic iTBS will reverse cognitive deficits in depression more effectively than conventional biphasic. We will use tasks we have shown to be sensitive to depression and single-dose stimulation (Figure 1). Our project aims to establish proof-of-concept evidence to advance towards a next-step clinical trial.

Sharp-wave ripple triggered neuromodulation for memory enhancement
Simon Schultz, Hayriye Cagnan – Imperial College London
Ashwini Oswal, David Dupret – University of Oxford

Memory disorders are a key component of neurodegenerative disease, and can have a debilitating effect on quality of life. Attempts to alleviate symptoms and enhance memory function using drug-based approaches have had very limited success. In this project we will demonstrate proof of principle for a new approach for enhancing memory performance, which will work by non-invasively amplifying the sharp-wave ripple (SWR) signal that coordinates the transfer of information from the hippocampus into the neocortex in memory consolidation. The project will involve addressing two current hurdles to realising this technology: (i) demonstration of proof of principle in a rodent model, and (ii) non-invasive detection of SWRs in human subjects using magnetoencephalography. Addressing these gaps in the literature will enable follow-on work integrating these techniques with focused ultrasound neurostimulation, in order to treat memory impairment in patients suffering from neurodegenerative disorders.

Understanding the mechanisms by which low intensity focussed ultrasound is able to modulate neural activity
Tracy Farr, Marcus Kaiser, Anna Lion – University of Nottingham
Tim England – Royal Derby Hospital

Many neurological diseases, for example stroke, have very few effective treatments. This represents a significant burden to the individual and society, therefore, novel therapies are required. Low intensity focussed ultrasound stimulation is an emerging neuromodulation technique that can stimulate various pathways with greater accuracy, penetration and potentially fewer side effects compared to conventional neurostimulation methods. Before moving the technology into clinical trials, it is necessary to improve our understanding of the mechanisms by which the stimulation can alter brain function. We aim to develop flexible transducers, focussing devices, and equipment for mechanistic driven research in animal models. This will also facilitate testing of optimal dosing regimens and windows that will inform the design of future clinical studies and could ultimately lead to options for therapies that would benefit patient populations.