Seizures and the Brain: The Role of Perturbed Dynamic Networks

Lead Research Organisation: University of Birmingham
Department Name: School of Mathematics

Abstract

Accurate diagnosis, prognosis and management of epilepsy is a significant unmet medical need. Epilepsy is a serious brain condition whereby susceptible individuals have recurrent seizures. It affects almost 1% of the UK population at some point in their lives. Every year 125,000 people attend first seizure clinics across the UK. Of these, 40,000 eventually receive a confirmed diagnosis of epilepsy, typically following an average delay of a year (Joint Epilepsy Council, September 2011). Whilst two-thirds of these confirmed cases can ultimately be controlled by anti-epilepsy drugs (AED), approximately 50% remain uncontrolled a year after commencing treatment, with no clear indicators of choice of AED or dose. Treatment response is currently a case of "watchful waiting" to see whether further seizures occur and adjusting choice of medication and dose accordingly. For those who do not respond they continue to have seizures, apparently at random, which leads to a significant reduction in quality and quantity of life. Every year over 1,000 people die in the UK as a direct consequence of epilepsy.

I propose an exciting programme of research in which mathematical models and computer algorithms will be developed to improve our understanding of how seizures occur. These models will describe how different regions of the brain interact with each other and how internal and external stimuli can influence these interactions. The interplay between neural activity within brain regions and the connections between regions critically determines whether seizures can occur and how frequently they are likely to happen. Having developed this fundamental understanding, computer algorithms can be developed to inform key parameters of these models directly from clinical recordings collected from people with epilepsy. This makes the models personalised and therefore suitable to address key questions for people with (suspected) epilepsy:

- is the diagnosis accurate?
- are the drugs being prescribed effective?
- will exposure to stress make seizures more likely?
- can I know when my seizures are most likely to happen?
- will surgery stop my seizures happening?

I will work with a software engineer and people with epilepsy to translate this understanding into a prototype tools to address these questions. For example, developing a tool that can aid a multi-disciplinary clinical team in determining where in the brain seizures originate from and using this information to better plan for surgery. Alternatively, a smart-phone based app that receives electrical brain recordings from a wireless headset to provide a forecast of seizure risk. Co-designing and developing these prototypes with people with lived experience and clinicians will maximise the likelihood of their leading to impact of the fundamental research.

Planned Impact

There are many groups who will benefit from the research I plan in this Fellowship. These include clinicians and allied healthcare professionals; people with epilepsy and their families and friends; MedTech companies; health sector managers and health insurers; as well as policy makers and research funders.

To ensure these broad classes of stakeholders benefit from my research, I plan a range of activities including:

- a lived experience group consisting of people with epilepsy, their carers and family members. This group will help to shape the research through advice and guidance to researchers. Additionally they will play a key role in designing prototypes in the context of seizure forecasting and trialling them in the community.

- a visitor programme that will enable neurologists and other relevant healthcare professionals to interact with members of my team for periods of up to six months. This will enable them to introduce key concepts, as well as to benefit from developing understanding of state of the art in relation to perturbed dynamic networks, seizure generation and epilepsy.

- "hot topics" workshops will enable researchers (both academic and industry), as well as clinicians and regulators to focus on emerging research challenges throughout the lifetime of the Fellowship. Building close collaborations between these key stakeholders will accelerate research and realise impact on people with epilepsy more quickly.

- involvement in policy making will maximise the likelihood of findings from my research to impact on clinical decision making. For example, I am a member of the International League Against Epilepsy (ILAE)'s Task Force on the Network Basis of Disease. This new task force was established in late 2017 with a focus on developing quantitative descriptors for the network basis of seizures and epilepsy. My membership increases the likelihood of dynamic network markers of seizures ultimately being adopted in ILAE guidelines.

- through my continued involvement in research funder strategy and decision making knowledge and expertise generated through this Fellowship will impact on the broader research community. In this regard I currently serve on the Healthcare Technologies Strategic Advisory Team for EPSRC; a role I have been asked to extend for an additional year to the end of 2020. I am currently a member of the MRC's Senior Non-Clinical and Career Development Panel and am also a member of the Scientific Advisory Committee of Epilepsy Research UK. I will look to regularly invite funders to engage with our team during the course of the Fellowship.

- the proposed research offers the opportunity to advance both diagnosis, prognosis and management of epilepsy. Successful delivery of this research will lead to increased efficacy and efficient of treatment. This will lead to savings in the cost of treatment, positively impacting on health sectors managers and health insurers.

Within my broader research Centre we have a number of additional mechanisms for facilitating impact including the "research incubator". This brings together researchers from quantitative disciplines and those from healthcare backgrounds, supported by expertise from researchers within the Centre, to accelerate emerging research opportunities with a focus on delivering impact through involvement of relevant industry partners.

Publications

10 25 50
 
Title Artist in Residence Programme 
Description Four Artists in Residence were appointed to work with our researchers to develop artistic outputs as part of a multidisciplinary research team in this Sci-Art collaboration 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2021 
Impact Showcasing event held March 2021 
 
Description Member of the Epilepsy Research UK Scientific Advisory Committee
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Theme lead for Epilepsy Research Institute UK
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
URL https://epilepsy-institute.org.uk/eri/research/research-themes/enabling-technologies/
 
Description Defining and validating a digital biomarker of epilepsy in children
Amount £96,950 (GBP)
Funding ID SBRIH23P1016 
Organisation Small Business Research Initiative (SBRI) 
Sector Public
Country United Kingdom
Start 02/2024 
End 08/2024
 
Description Determining the clinical utility of BioEP: a multisite, prospective, study
Amount £350,000 (GBP)
Funding ID 10090508 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 02/2024 
End 02/2026
 
Description Digital Healthcare: A vehicle for capacity building in ICT skills and public engagement
Amount £170,511 (GBP)
Funding ID EP/W033593/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2023 
End 02/2025
 
Description EPSRC Network+: Neurotechnology for enabling community-based diagnosis and care
Amount £1,232,804 (GBP)
Funding ID EP/W035030/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2022 
End 09/2025
 
Description Military Traumatic Brain Injury Biomarker Study, a prospective cohort biomarker study of military and civilian participants with mTBI
Amount £1,551,109 (GBP)
Funding ID MoD Predict 
Organisation Ministry of Defence (MOD) 
Sector Public
Country United Kingdom
Start 12/2021 
End 11/2029
 
Description Prototyping a wearable solution for epileptic seizure forecasting: A transdisciplinary project (ATMOSPHERE)
Amount £34,472 (GBP)
Organisation University of Bristol 
Sector Academic/University
Country United Kingdom
Start 08/2023 
End 08/2024
 
Description Proximity to Discovery Fund for Knowledge Exchange and Dissemination "Quantifying the impact of seizure triggers"
Amount £2,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 11/2022 
End 05/2023
 
Description Research England QR Enhancing Research and Knowledge Exchange Funding Programme
Amount £40,799 (GBP)
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 01/2022 
End 03/2022
 
Description Travel Grant YF Joint Annual Meeting of the Korean Society for Mathematical Biology and the Society for Mathematical Biology (KSMB-SMB)
Amount € 350 (EUR)
Organisation European Society for Mathematical and Theoretical Biology 
Sector Learned Society
Country Germany
Start 05/2024 
End 07/2024
 
Description Travel ward for "Retreat for Women in Applied Mathematics"
Amount £900 (GBP)
Organisation International Centre for Mathematical Sciences 
Sector Public
Country United Kingdom
Start 01/2023 
End 01/2023
 
Description N-CODE Network+ 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Research team provides research expertise in epilepsy research and neurotechnology
Collaborator Contribution N-CODE provides the platform for collaborative working between the partners and funding opportunities for collaborative research.
Impact None as yet
Start Year 2022
 
Description N-CODE Network+ 
Organisation University of Plymouth
Country United Kingdom 
Sector Academic/University 
PI Contribution Research team provides research expertise in epilepsy research and neurotechnology
Collaborator Contribution N-CODE provides the platform for collaborative working between the partners and funding opportunities for collaborative research.
Impact None as yet
Start Year 2022
 
Description N-CODE Network+ 
Organisation University of Warwick
Department Warwick Evidence
Country United Kingdom 
Sector Academic/University 
PI Contribution Research team provides research expertise in epilepsy research and neurotechnology
Collaborator Contribution N-CODE provides the platform for collaborative working between the partners and funding opportunities for collaborative research.
Impact None as yet
Start Year 2022
 
Description Neuronostics Ltd 
Organisation Neuronostics Limited
Country United Kingdom 
Sector Private 
PI Contribution Collaborative research using mathematical analysis of routinely acquired clinical data to enhance diagnosis and prognosis of epilepsy
Collaborator Contribution Collaborative research using mathematical analysis of routinely acquired clinical data to enhance diagnosis and prognosis of epilepsy
Impact None to date. Ongoing. Multidisciplinary: clinical research and mathematical and computational modelling
Start Year 2021
 
Description University of Michigan - William Stacey/Matthew Szuromi 
Organisation University of Michigan
Country United States 
Sector Academic/University 
PI Contribution Joint research collaboration
Collaborator Contribution Joint research collaboration
Impact Publication https://www.biorxiv.org/content/10.1101/2023.11.03.565450v1
Start Year 2023
 
Description University of Surrey - Anne Skeldon 
Organisation University of Surrey
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative research partner
Collaborator Contribution Collaborative research partner
Impact Joint paper https://www.biorxiv.org/content/10.1101/2023.11.03.565450v1 Mathematics
Start Year 2022
 
Description Epilepsy Action Awareness Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Around 50-60 supporters of Epilepsy Action attended an information event in Leeds to find out more about epilepsy and mathematical research being undertaken
Year(s) Of Engagement Activity 2022
 
Description HealthTech Integrates 2023 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Took part in a panel discussion on the use of digital tools for biomarkers of neurological health
Year(s) Of Engagement Activity 2023
URL https://www.lifescienceintegrates.com/event/healthtech-integrates-2023/
 
Description Perturbations in Epilepsy workshop 2023 JT/AKK/YF 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Scientific 2 day workshop bringing together researchers, industry, clinicians and patients with lived experience of epilepsy to discuss "Quantifying the impact of seizure triggers". Included a early careers workshop to discuss career development opportunities for early career researchers.
Year(s) Of Engagement Activity 2023
URL https://esmtb.org/event-5289816
 
Description Phase Transitions in Electrophysiological Systems - Mini Symposium organisation at SIAM AKK/YF 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Postdocs Dr Aravind Kumar Kamaraj and Dr Yingjing Feng organised a two day mini symposium "Phase Transitions in Electrophysiological Systems" at SIAM Applications of Dynamical Systems conference, Portland, USA. May 2023.
Year(s) Of Engagement Activity 2023
URL https://www.siam.org/conferences/cm/conference/ds23
 
Description Presentation at Epilepsy Research UK's Shape Network 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Gave an invited talk at the inaugural Epilepsy Research UK Shape Network event in London in May 2023
Year(s) Of Engagement Activity 2022
URL https://epilepsyresearch.org.uk/shape-network-live-signup-form/
 
Description Purple Day with Epilepsy Research UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact We hosted a joint event at the University of Birmingham with Epilepsy Research UK and Epilepsy Action to raise awareness of Epilepsy on the national epilepsy day (purple day)
Year(s) Of Engagement Activity 2022