Brain networks in epilepsy: Endophenotypes and generative models

Lead Research Organisation: King's College London
Department Name: Clinical Neuroscience

Abstract

Epilepsy is the commonest serious brain disease, affecting 750,000 people in the UK. It causes catastrophic seizures, resulting in at least 1000 deaths per year in the UK. It is the commonest cause of repeated admission to hospital. About 1 in 3 of all people with epilepsy do not respond to any medication, and continue to have uncontrolled seizures. The personal, social and economic costs of epilepsy are very high.

It is not yet known how epileptic seizures start. There are clues from experiments in animals and genetic studies in people which suggest that epilepsy can be caused by a wide range of disturbances in brain cell function. Furthermore, there are different patterns of epileptic seizure, which occur in different combinations in different people, and associated with other specific findings in clinical tests. This has given rise to the view that epilepsy is at least 20 different diseases (or types of epilepsy), and that each type of epilepsy might have a different cause.

However, this does not explain some well-recognised aspects of epilepsy:

Firstly, although there may appear to be many causes, there are only small number of types of epileptic seizure; and an individual with epilepsy may suffer from several different types of seizure.
Secondly, epilepsy may sometimes be inherited within a family; if epilepsy were a set of entirely different diseases, it might be expected that within one family all affected members would have the same type of epilepsy. On the contrary, it is known that within some families there are affected individuals who have completely different types of epilepsy.
Thirdly, drugs for the treatment of epilepsy have broadly similar therapeutic effects across all types of seizure and epilepsy, with very few exceptions.

These observations suggest that there must be important mechanisms in common between different seizure types, and between different types of epilepsy.

It is increasingly recognised that functions of the brain are properties of complex networks of brain cells. We have worked for several years on new methods to identify whether brain networks in people with epilepsy have abnormal properties, and whether these properties allow seizures to occur. Using MRI brain scans, we have shown abnormalities of specific brain regions and their connections. Using electrical recordings of brain waves (EEG) we have shown that brain networks differ between people with epilepsy and people who do not have epilepsy; and that unaffected relatives of people with epilepsy may have similar brain networks to their affected relatives. Using computer models of how EEG activity is produced, we have shown that these inherited networks have an abnormal ability to suddenly switch to seizure activity.

In this Programme we build on this background, to examine four questions:
(1) Are brain networks which have an abnormal ability to generate seizures found across a range of common types of epilepsy?
(2) Are these network abnormalities inherited?
(3) Does successful treatment act by altering the properties of these brain networks?
(4) In people whose epilepsy spontaneously goes away, is this accompanied by a change in the properties of these brain networks?

We will collect MRI brain scans and EEGs from more than 150 people with epilepsy, in addition to their close family relatives, and a "control" group of people who have no personal or family connection with epilepsy. We will develop new methods to identify the relevant brain networks from MRI and EEG, and examine how these networks differ between people with epilepsy, their relatives and controls. We will also examine how these networks change over time (and how quickly they change) in response to starting treatment, and as a result of spontaneous remission of epilepsy. A special focus of this Programme is the development of new computer-based methods to identify the mechanisms by which seizures arise in these highly complex networks of the brain.

Technical Summary

We aim to explain the emergence of epileptic seizures from the interplay between dynamic properties of localised brain regions and network structures connecting them, using a combination of methods from connectomics and dynamic modelling.

We will develop MRI methods to describe distributed abnormalities of grey matter, structural connectivity and functional connectivity in the human brain, using T1-weighted MRI, diffusion tensor imaging and resting-state functional MRI. We will develop EEG methods to describe brain networks. From these data, we will identify candidate brain networks which generate seizures.

We will employ our successful phenomenological and physiological models of EEG, which capture the patterns of onset and evolution of human ictal EEG activity. We will adopt a novel formalism to investigate brain networks: generalized dynamic graphs with active network topology. We will combine forward modelling (physiological generative models), and backwards modelling (Bayesian inversion of generative models) to determine which candidate network is most likely to explain imaging and EEG observations.

We introduce the new concept of Brain Network Ictogenicity (BNI) - the propensity of brain networks to generate seizures. We will implement and further develop our novel approach to estimating BNI in real brain networks, based on combining a dynamic model with real network structures inferred from data.

In data from human patients with epilepsy, their relatives, and normal controls, we will investigate networks which generate seizures and the BNI of these networks. In appropriate subject groups, we will examine the familial basis of brain network properties; we will explain how a familial ictogenic network endophenotype may be further modified to allow seizures to be manifest; and we will reveal the network-level effects of successful drug treatment, natural remission and epilepsy surgery.

Planned Impact

(In accord with MRC guidance, this section emphasises impact for non-academic beneficiaries)

The new knowledge generated in the short-term by this Programme will bring benefits to a much wider group than only the academic community: a better understanding of brain network dynamics, and approaches to modelling such dynamics based on integrating data with dynamic models through the framework of generalised dynamic graphs with active network topology, will provide a novel approach to a range of brain diseases. This enhanced knowledge and new multidisciplinary methodological approach is likely to be of interest to commercial sector R&D, especially in the pharmaceutical industry and medical devices industry. For example, the ability to characterise the effects of a drug or neuromodulation device through parameter evolution of a generative model extracted from experimental or clinical data will be of benefit to commercial-sector pharmaceutical manufacturers, where they will be able to plan phase 3 trials to include data-derived prognostic biomarkers. This will be achieved using our platform to either develop their own generative models or use ours; such markers may become useful stratification markers or surrogate outcomes. Similarly, it may be possible to develop biomarkers of response to newly developed compounds in early-stage trials, based upon evolution of parameters of a suitable generative model. We have already taken steps to protect intellectual property through a patent application around the concept that changes over time in a phenomenological network model of EEG may predict clinical outcomes (joint patent application submitted by the University of Exeter and King's College London). These impacts could be felt early after the Programme completes.

The development of multidisciplinary researchers through this Programme will have an early impact which may extend for the length of the researchers' careers. The consequent enhancement of UK scientific competitiveness may be felt in academic and commercial sectors.

Science funding policy in the UK and worldwide increasingly emphasises collaboration between biomedicine and maths / engineering / computer science, but the development of such science would benefit from increasing multidisciplinary expertise and awareness amongst reviewers of funding proposals, and amongst funding panels and policy-makers. In the short term, we will seek to interact with funders to enhance the development of such multidisciplinarity.

We aim for a major impact within 5-10 years for patients with epilepsy and professionals providing healthcare in epilepsy. If successful, our framework will ultimately provide the opportunity both for a more definitive diagnosis and also more accurate prognosis for treatment response and remission. This will enable a rapid and definitive choice of treatment for patients, resulting in improvements to the health and quality of life of patients, reducing mortality and morbidity. This will be achieved through the uptake of our platform by experimental and clinical researchers, and the consequent filtering through of research findings into the clinic. For a new approach to be taken up in the clinic will require engagement with healthcare managers and policy-makers, which will be enabled through translational research following completion of the Programme.

In the short to medium term we intend an impact on public understanding of science, through public meetings we will hold throughout the duration of the programme.

Publications


10 25 50
 
Title "Beyond My Control" 
Description Science meets theatre in this interactive modelling performance about epilepsy, excitability and all things neurological. Can mathematicians at the University of Exeter abandon their computers and recreate complex brain networks using theatre improvisation techniques? Can the logical world of mathematics and the unpredictable world of theatre come together to help us see what's really going on inside our heads? We think so. Why not come and see for yourself as we combine improvised scenes, verbatim testimony and top mathematical research in a unique theatrical experience engaging with epilepsy. Audience members will be invited to offer feedback and the chance to interact with the performance, as we explore just how much control we have over our brains. This IMPACT workshop is funded by the EPSRC (Engineering & Physical Sciences Research Council). IMPACT is a collaborative programme using the medium of performance to facilitate public engagement for the University of Exeter's world class research. 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2017 
Impact With strong last day sales and walk-ups there were over 300 people at the theatre! It was a pretty amazing experience, and we got some incredible feedback from people with lived experience of epilepsy - one lady in front of everyone said that how we had presented the piece captured exactly how she felt in the build up to a seizure and added "i wished this could be boxed up and shown to everyone" We also got some really good feedback from parents and children on the maths side about how it was great to see how mathematics could be used to understand an important problem. We're off to schools next week to trial a version in mainly GCSE / A level classes, but with one primary school version too 
URL https://exeternorthcott.co.uk/calendar/beyond-my-control/
 
Title Epilepsy and the science of wiring and firing in the brain: Utopia 2016 (AC) 
Description How is your brain wired up? Richardson Lab is proud to present an audio-visual installation that brings together MRI and EEG imaging, at once clinically informative and optically breathtaking, and deeply personal stories from epilepsy patients in a fusion of light and sound that permits us to delve into the enigmas of cognitive function and discover the synaptic pathways that make each of our brains unique. Epilepsy is a severely misunderstood condition that affects one in every hundred people in the UK. Richardson Lab aims to map the brain almost as a programmer might map a circuit board or a cartographer a web of streets, visualising the brain as a network of wired connections, so as to understand where and how epilepsy is generated in the brain, and more importantly, how it can be treated. The Richardson Lab collaborated with the Utopia Lab, a King's Cultural Institute initiative bringing together artists and science, to bring an art installation at that reflects both the science involved in the Richardson Lab projects including neuroimaging techniques (MRI and EEG) together with the patients and their relatives/carers who have taken part in research studies. The installation was situated at Somerset House, London for two weeks during September 2016. 
Type Of Art Artwork 
Year Produced 2016 
Impact Members of the public engaged with stories from persons with epilepsy and their families and images of MRI scans from patients with epilepsy. 
URL http://epilepsy-london.org/paths-utopia-2016/
 
Title Murmuration 
Description Murmuration is a unique partnership between three diverse disciplines to produce one unified artistic output. An individual's brainwaves will be recorded using an adapted Electroencephalographic (EEG) headset and transposed into a dynamic animation of flocking starlings. The flock's form and sound will change in response to the brain activity provoked by performing a set of cognitive tasks, giving the subject the sense of seeing and hearing their own brain activity as it happens. This project will be delivered through a collaboration of the Department of Basic and Clinical Neuroscience, Kings College London, the artist and designer Matthew Maxwell, and interactive architects Cinimod Studio and sound designers North V South to align biomedical research, contemporary art practice and software development. This alignment of science, art and technology will reveal aspects of neuroscience research methods in a compelling and beautiful form. The aim of this project is to engage and stimulate both the general public and epilepsy patients who have undergone EEG for research and clinical purposes. It will also provide a rare opportunity to convey, in an observable way, and to a wide and diverse audience, the complexity of brain activity and the unique ways it can be captured and understood. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2015 
Impact The project application was unsuccessful. 
 
Title NHS Choices: Epilepsy and Research a short film 
Description King's College London Epilepsy Research group in collaboration with NHS choices are working with epilepsy patients and their family/carers tp produce a short film about epilepsy and research. 
Type Of Art Film/Video/Animation 
Year Produced 2016 
Impact This short video aims to engage the public about current research into epilepsy, what it is like to be diagnosed with and to live with epilepsy, and will be available on the NHS Choices website. 
 
Description "Translational Research Exchange at Exeter"
Amount £1,500,000 (GBP)
Funding ID ISSF3 
Organisation The Wellcome Trust Ltd 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2016 
End 09/2021
 
Description Bursary for the 'Meeting of Minds' symposium (ML)
Amount £100 (GBP)
Funding ID not known 
Organisation British Neuroscience Association 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2016 
End 09/2016
 
Description Confidence in Concept Award: "Computer Aided Diagnosis and Prognosis of Epilepsy"
Amount £49,816 (GBP)
Funding ID not known 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 06/2016 
End 01/2017
 
Description Marie Curie Fellowship
Amount € 0 (EUR)
Funding ID
Organisation Marie Curie Actions 
Sector Academic/University
Country Global
Start 10/2017 
End 09/2019
 
Description Quantifying uncertainty in perturbed brain networks: towards a decision support tool for epilepsy surgery (MG)
Amount £100,000 (GBP)
Funding ID not known 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 07/2017 
End 06/2019
 
Description Revealing the dynamic mechanisms of seizures: An integrated mathematical and clinical approach (WW)
Amount £325,507 (GBP)
Funding ID MR/N01524X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2016 
End 03/2019
 
Description Travel Award (IP)
Amount £800 (GBP)
Funding ID not known 
Organisation Guarantors of Brain 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2016 
End 11/2016
 
Description Travel Grant for the participation at the Bernstein Conference 2016 (ML)
Amount € 500 (EUR)
Funding ID not known 
Organisation Bernstein Network Computational Neuroscience 
Sector Public
Country Germany, Federal Republic of
Start 09/2016 
End 09/2016
 
Title Control subject EEG fMRI data set 
Description 25 EEG fMRI Control subject data sets available for anonymous sharing. Not made publicly available. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact No notable impacts as of yet. 
 
Title EEG Processing & Analysis: pipeline, scripts and toolbox functions 
Description EEG - Definition of Sets of Electrodes of Interest (EOI) - Initial data processing (pre-processing stage) - EEG data - real dimensionality - EEG presentation in Time-frequency domain (spectrograms) - Definition of Frequency intervals - Filtering in defined frequency bands - Synchrony analysis using 5 synchronisation models Models description: Phase locking factor - Undirected. Maximum normalised correlation (cross-covariance) - Undirected / Directed. Relative synchronisation speed - Directed. H2 - non-linear association index - Directed. - Definition of a set of basic structural network metrics - Inferring functional networks for each synchrony model and each frequency band - For each network calculate network measures - Statistical analysis of the results - in progress 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact none noted as of yet. 
 
Title IGE EEG patients and relatives database 
Description Scalp EEG data from 40 patients with IGE, 42 relatives and 35 normal control subjects, shared anonymously. Availability announced with publication of PMID: 25302690 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Publication 
 
Title Multimodal & Multiscale brain imaging data processing & modelling Framework - Matlab® environment based TOOLBOX 
Description Methodology framework: The main goal of the toolbox is to propose a pipeline for data processing and statistical analysis, which could help to find statistically significant differences between groups of subjects (group level biomarkers) as well as to classify subjects (individual level diagnosis and forecasting). Methods & Data: Rationale: Let's assume the following: A) Suppose EEG data from different groups of subjects, where each group contains of subjects (in general ); B) For each subject's data one and the same quantity was measured; Note: The quantity is selected by simulations with "disease specific" mathematical models to real or in silico generated data. Then the questions are: a) Is there a significant difference between the groups based on quantity ? b) Is there a subjects' classifier based on quantity ? The answer of the above questions could be found in three simple steps: 1) Segment selection: To select a subset of the data which is statistically comparable; 2) Data processing and quantification: To compute the quantity for the selected subset; 3) Statistical analysis - To use statistical analysis and to answer the questions. Tre toolbox is a collection of functions, working in MatLab ® environment. The toolbox contains the following main sections: 1. Spectral and Power properties of the Signals (basic properties calculation and normalisation tools) 2. Functional Connectivity - (over 20 linear and non-linear Synchrony Models) 3. Networks - Topology and Spectrum Analysis (over 30 network measures for undirected and directed binary/weighted networks) 4. Mathematical Models - Simulations as neuro-mass models (four models (so far) representing bifurcation or bistability based transitions between different stable states, including corresponding Brain Network Ictogenicity (BNI) calculation) 5. Statistical analysis (basic statistical group level analysis) 6. Common Tools (help and plotting tools) 7. Third parties Tools (collection of existing network analysis & cross-frequency synchrony analysis toolboxes) 8. Examples 
Type Of Material Data analysis technique 
Year Produced 2017 
Provided To Others? Yes  
Impact The toolbox is still being tested by members of the Richardson Lab with promising results. 
 
Title Novel methods to quantify seizure generation in brain networks 
Description We have developed a neural mass model based framework with which to predict most efficacious sites for surgical resection in patients with pharmacologically resistant epilepsies 
Type Of Material Computer model/algorithm 
Provided To Others? No  
Impact We have already extended this framework into other models that enable faster computation of predictions. We have validated model predictions in patient datasets 
 
Title Preoperative EEG database from patients who have undergone surgery 
Description Database of preoperative EEG data from EFE patients who have undergone surgery and have a known postoperative outcome. We have 40 postsurgical outcome cases who have undergone EEG ictal recording prior to resective surgery, and who have 1yr of postoperative follow-up. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact None as of yet. 
 
Title TLE EEG and fMRI patients and relatives database 
Description Scalp EEG and fMRI data from 21 patients and 12 relatives, shared anonymously with collaborative partners. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact no notable impacts at the present time. 
 
Title fMRI Network Analysis toolbox 
Description This is a MatLab based toolbox for analysing temporal changes of fMRI data during resting state. 
Type Of Material Data analysis technique 
Year Produced 2016 
Provided To Others? Yes  
Impact None noted as of yet. 
URL http://epilepsy-london.org
 
Description Bonn-Liverpool Collaboration 
Organisation Liverpool Hospital
Country Australia, Commonwealth of 
Sector Hospitals 
PI Contribution providing data and data analysis opportunities between the groups
Collaborator Contribution providing data and analysis methods, specifically neuroimaging applications.
Impact None yet.
Start Year 2014
 
Description Bonn-Liverpool Collaboration 
Organisation The Walton Centre NHS Foundation Trust
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution providing data and data analysis opportunities between the groups
Collaborator Contribution providing data and analysis methods, specifically neuroimaging applications.
Impact None yet.
Start Year 2014
 
Description Bonn-Liverpool Collaboration 
Organisation University of Bonn
Country Germany, Federal Republic of 
Sector Academic/University 
PI Contribution providing data and data analysis opportunities between the groups
Collaborator Contribution providing data and analysis methods, specifically neuroimaging applications.
Impact None yet.
Start Year 2014
 
Description Directed Influence Brain Network: Hangzhou Normal University Collaboration 
Organisation Hangzhou Normal University, China
Country China, People's Republic of 
Sector Academic/University 
PI Contribution providing data and data analysis opportunities to Hangzhou group.
Collaborator Contribution Providing analysis methods specifically, the development of an open-source MATLAB toolbox (Dynamic Brain Connectome) for tracking brain dynamics using functional MRI.
Impact None yet.
Start Year 2014
 
Description Dr Laurent Sheybani 
Organisation University of Geneva
Country Switzerland, Swiss Confederation 
Sector Academic/University 
PI Contribution Dr Laurent Sheybani, PhD, MD visited the Richardson lab to present his PhD thesis analysis and methods on a mouse-model of MTLE "Large-scale epileptic network in a mouse-model of temporal lobe epilepsy"
Collaborator Contribution Laurent spent 2 days showing members of the Richardson lab how to apply his model to human mesial temporal lobe (mTLE) data collected under the programme.
Impact We found that Laurent's animal model found the same changes as we observed in human IGE data.
Start Year 2016
 
Description Dr Richard Chin & Dr Javier Escudero 
Organisation University of Edinburgh
Department Wellcome Trust Centre for Cell Biology
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Presentation by Dr Eugenio Abela (Richardson Lab) giving a detailed overview of Richardson Lab current data collection and analysis methods.
Collaborator Contribution Presentation by Dr Javier Escudero on EEG connectivity analysis: Preliminary results in epilepsy and techniques beyond static analyses - detailed explanation of his approach
Impact Outcome: Javier Escudero will apply for The RS MacDonald Seedcorn Fund that will support the development of neuroscience research projects and collaboration at the University of Edinburgh, mainly funds to enable an exchange between Javier and Chaynin Tangwiriyakasul (Richardson lab) to advance Javier's approach to our data set.
Start Year 2017
 
Description Dr Saroosh Afyouni (Phd) 
Organisation University of Warwick
Department School of Life Sciences Warwick
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Saroosh trained under Dr Andrew Bagshaw at the University of Birmingham and Prof. Thomas Nichols' lab at University of Warwick. Saroosh's PhD project is centred on stochastic block model analysis of the resting-state human brain. Saroosh presented his recently developed model of stochastic equivalent of Rich Club, called Rich Block which detects the core of brain networks by use of wide range of Stochastic Block Models. Rich Block, contrary to Rich Club, can be applied to extraordinarily large network (>30k nodes; voxel-wise). Additional to Rich Block, we also developed a method to correct the bias in degree of freedom due to auto-correlation between BOLD signal lags. The model uses heritability measures to validate the network topological properties with and without correction, applicable to data collected under this programme.
Collaborator Contribution When fully developed Saroosh's model has the potential to be applied to our data.
Impact A potential new model of analysis to apply our data set.
Start Year 2016
 
Description EEG modelling and source localisation: Geneva collaboration 
Organisation University of Geneva
Country Switzerland, Swiss Confederation 
Sector Academic/University 
PI Contribution Providing data and data analysis opportunities to Geneva group
Collaborator Contribution providing analysis methods, specifically (i) source localisation methods (ii) microstate analysis methods (iii) correlation between human data and rodent data
Impact Award of an Epilepsy Research UK grant £149,500 over 36 months, to carry out a project entitled 'An optimal computer model for the diagnosis and prognosis of focal epilepsies'.
Start Year 2014
 
Description Generative models for identifying seizure focus from stimulated intracranial EEG: University of Minnesota Collaboration 
Organisation University of Minnesota
Country United States of America 
Sector Academic/University 
PI Contribution providing data and data analysis opportunities to Minnesota group.
Collaborator Contribution Providing analysis methods, specifically algorithm to extract and classify feature from TMS EEG data, namely artefact rejection and support vector machine for multidimensional EEG data.
Impact None yet.
Start Year 2015
 
Description Professor Steve Schiff - University of Penn State 
Organisation Penn State University
Department Department of Engineering Science and Mechanics
Country United States of America 
Sector Academic/University 
PI Contribution Professor Schiff is a theoretical neuroscientist and systems biologist. Professor Mark Richardson and his team arranged a series of lectures given by Professor Schiff to the Department of mathematics and department clinical neuroscience, King's College London; University College London; University of Liverpool. During Prof Schiff's visit to the Richardson Lab theoretical ideas/expertise for data further analysis were exchanged.
Collaborator Contribution Professor Schiff provided theoretical input/expertise to potential future data analysis and the offer of postdoc visits to his lab.
Impact no outcomes as of yet
Start Year 2016
 
Description "Pint of science" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact "Pint of science": public engagement event presenting brain dynamics to a lay audience
Year(s) Of Engagement Activity 2014
 
Description A neuronal network model of interictal and recurrent ictal activity poster (ML) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Computational Neurology Conference 2017 - Newcastle poster presentation to academic audience - dissemination of current work/findings
Year(s) Of Engagement Activity 2017
URL https://conferences.ncl.ac.uk/compneurology/
 
Description American Epilepsy Society annual scientific meeting, Washington DC, 5-11 December 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Abstracts presented relating to MRC Programme:

2.178 HIPPOCAMPAL VOLUME AND POSTSURGICAL OUTCOME IN INTRACTABLE TEMPORAL LOBE EPILEPSY
Y. Goh, J. C. Schoene-Bake, A. Marson, M. P. Richardson, B. Weber, S. Keller

2.025 SUBCORTICAL ATROPHY IN PATIENTS WITH IGE AND THEIR ASYMPTOMATIC FIRST-DEGREE RELATIVES
M. P. Richardson, S. Keller, A. D. Pawley, L. Nashef, R. Elwes, F. Chowdhury

3.186 SUBCORTICAL SHAPE ANALYSIS IN TEMPORAL LOBE EPILEPSY
S. Keller, J. O Muircheartaigh, C. Traynor, K. Towgood, G. Barker, M. P. Richardson


Discussions with meeting par5ticipants
Year(s) Of Engagement Activity 2013
URL https://www.aesnet.org/sites/default/files/file_attach/Meeting/AES-2013program-bk_Washington%20DC_fi...
 
Description Biodynamics 2013 http://www.bio-dynamics2013.org/conference-programme.html 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I led, facilitated and contributed to a session on Epilepsy in this meeting. Speakers were invited and costs covered through MRC funding. The programme of this section was:
Session 5a: Epilepsy

5a.1 Emergence of epileptogenic high frequency oscillations from human neuronal networks
M O Cunningham, Newcastle University, UK

5a.2 Peri-ictal dynamics of brain network synchronization
C Rummel, University Institute for Diagnostic and Interventional Neuroradiology,
Inselspital, Switzerland

5a.3 Investigating thalamocortical oscillations in man using MRI and EEG
A P Bagshaw, University of Birmingham, UK

5a.4 Large-scale brain models of epilepsy
M Richardson, King's College London, UK

Multicentre MRC grant proposal under discussion led by Cunningham.

Rummel and co-workers engaged in methods colalboration to benefit MRC Programme.

Bagshaw has invited me to present to Neuroimaging dept at Birmingham Unviersity.
Year(s) Of Engagement Activity 2013
URL http://www.bio-dynamics2013.org/conference-programme.html
 
Description Biodynamics Workshop 2016 
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 BioDynamics Workshop too place in Exeter on 7-9 September 2016. This was the third in a series of international workshops designed to bring together biologists, mathematicians, clinicians, physicists, and computer scientists who are interested in dynamics and networks in the biological and medical sciences. BioDynamics 2016 provided an exciting opportunity for scientists to present both methods and data in a multidisciplinary forum and hear how interdisciplinary collaborations can provide major conceptual advances in our understanding of complex biomedical systems.
Year(s) Of Engagement Activity 2016
URL http://www.bio-dynamics.org/sites/default/files/programme_combined_2016_09_06_0.pdf
 
Description Britain Needs Scientists presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Britain needs scientists: presentation on brain dynamics with the goal to inspire to inspire year 12 students to a career in science
Year(s) Of Engagement Activity 2014
 
Description Collaboration launch meeting: KCL, Exeter, University of Geneva - at KCL 1-2 September 2014 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two-day meeting of research teams involved in MRC Programme and Epilepsy-EEG-imaging research group of University of Geneva (Profs Christoph Michel and Serge Vulliemoz. Extensive discussion of opportunities for data sharing, methods sharing and future research collaborations.

Two research proposals submitted in next 6 weeks, outcomes not yet known.
Year(s) Of Engagement Activity 2014
 
Description Collaboration launch meeting: KCL, University of Berne catalepsy imaging and EEG group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussions between KCL team involved in MRC Programme and group of Prof Kaspar Schindler. Presentation to internal university neuroscience meeting in Berne.

Plans for future collaboration, including hosting visit of Dr Eugenio Abela at KCl for 12 months, as part of MRC Programme (2016)
Year(s) Of Engagement Activity 2014
 
Description Collaboration launch meeting: KCL, University of Bonn epilepsy imaging group, University of Liverpool epilepsy imaging group 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two day meeting with teams of Prof Bernd Weber (Bonn) and Dr Simon Keller (Liverpool) with team working in MRC Programme

Two papers in submission, using Bonn data to address aspects of Programme aims
Year(s) Of Engagement Activity 2014
 
Description Epilepsy Focussed Public Engagement Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Finding out about a patient and carer perspective with respect to diagnostic and prognostic epilepsy in an informal half day group meeting at the University of Exeter.
Year(s) Of Engagement Activity 2015
 
Description Epilepsy Focussed Public Engagement Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Finding out about a patient and carer perspective with respect to diagnostic and prognostic epilepsy in an informal half day group meeting at the University of Exeter.
Year(s) Of Engagement Activity 2016
 
Description European Congress on Epileptology 2014, Stockholm 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The following abstracts presented:

A voxel-based morphometry study of postoperative seizure outcome in temporal lobe epilepsy
Keller SS1,2, Richardson MP2, Schoene-Bake J-C3,4, Elger C3, Weber B3,4

Diffusion tensor imaging in Rolandic epilepsy
McGinnity CJ1, Tyson AL2, Gammerman A1, Gerbase SW3, Elmasri M4, Reed TK5, Said MA1, Pina M6, Barker GJ7, Smith AB1, Richardson MP1, Pal DK1

Simultaneous EEG-fMRI: posterior slow-waves compared with occipital alpha in childhood absence epilepsy
Perani S1,2, Centeno M2, Cross H2, Carmichael DW2, Richardson M1



Discussions with other participants in the meeting
Year(s) Of Engagement Activity 2014
URL http://www.epilepsystockholm2014.org/scientific-programme/interactive-scientific-programme.831.html
 
Description International day of woman and girls in science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Demonstration of a science experiment to girls from year 4 and 5. There were 4 experiments in total. Our's was about the concept of chemical reactions and involved mixing bicarbonate with different liquids found in the kitchen.
Year(s) Of Engagement Activity 2016
 
Description Investigation of Kuramoto's critical value during generalized spike and wave discharge periods: an EEG-fMRI pilot study (CT) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at BioDynamics Workshop 2016 - dissemination of current findings/results - generated questions about the research.
Year(s) Of Engagement Activity 2016
URL http://www.bio-dynamics.org/events/biodynamics-2016
 
Description Invited Talk (SP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Centre of Neuroimaging Science, King's College London, IoPPN

Title of talk: "studying idiopathic generalised epilepsy using simultaneous EEG-fMRI"
Year(s) Of Engagement Activity 2015
 
Description Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials (IP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at the Society for Neuroscience meeting, 2016, Sand Diego, USA. Dissemination of findings/results.
Year(s) Of Engagement Activity 2016
URL https://www.sfn.org/annual-meeting/neuroscience-2016
 
Description Optimal number of communities extracted from tensor decomposition of resting fMRI data (CT & SNY) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at Resting State and Brain Connectivity conference Sep 21-23 at Vienna - dissemination of current findings/results - generated questions about the research.
Year(s) Of Engagement Activity 2016
 
Description Organiser of: BrainModes international conference: Emergent dynamics from large scale brain networks in health and disease 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 100 people attended the Programme

Thursday 11th December: Methods for large-scale brain modelling

09.00 - 10.00 Registration and coffee

10.00 - 10.15 Welcoming remarks: Mark Richardson & John Terry

10.15 - 11.00 Karl Friston: Dynamic causal modelling and network discovery.

11.00 - 11.45 Klaus Lehnertz: Inferring and interpreting epileptic brain
networks from clinical data.

11.45 - 12.15 Orla Doyle: Application of pattern recognition in brain
networks.

12.15 - 13.45 Lunch

13.45 - 14.30 Petra Ritter: The virtual brain: A framework for collective
multimodal reverse engineering the brain.

14.30 - 15.15 Highlighted Oral

15.15 - 15.45 Coffee

15.45 - 16.30 Andreas Daffertshofer: talk title to be confirmed

16.30 - 17.15 Donald Tournier: Inferring structural connectivity using
diffusion MRI

17.30 - 19.00 Drinks reception

Friday 12th December: Applications

09.30 - 10.00 Coffee

10.00 - 10.45 Maxime Guye: Why are dynamics crucial for defining
connectivity alterations in epilepsy?

10.45 - 11.30 Tjeerd Boonstra: Intrinsic coupling modes in source
reconstructed electroencephalography.

11.30 - 12.00 Highlighted Talk

12.00 - 13.30 Lunch

13.30 - 14.15 Olivier David: Functional brain tractography.

14.15 - 15.00 Beatriz Rico: GABAergic circuitry assembly and schizophrenia.

15.00 - 15.30 Coffee

15.30 - 16.15 Emrah Duezel: Functional imaging of hippocampal networks
and their plasticity in old age.

16.15 - 17.00 John Pierre Lin: Towards a developmental and pathological
model of dsytonia in children: the influence of time, the timing of
deep brain stimulation and new information from brain imaging
intracerebral microelectrode recordings.

17.00 Thanks and close

(not yet known)
Year(s) Of Engagement Activity 2014
URL http://www.kcl.ac.uk/ioppn/depts/cn/brainmodes/index.aspx
 
Description Patient Focus Group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact A focus group event was conducted to consult with epilepsy patients on the contents, tone, visual style of a short video about whats involved when taking part in epilepsy research.
Year(s) Of Engagement Activity 2015
 
Description PhD Student Poster (SNY) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact King's College London Institute of Psychiatry, Psychology and Neuroscience Student Showcase, poster titled Altered Resting State Networks in Patients with JME
Year(s) Of Engagement Activity 2014
 
Description PhD Student Poster (SNY) 2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact American Epilepsy Society Meeting 2015
Poster presentation - Altered Network Hubs in JME
Year(s) Of Engagement Activity 2015
 
Description Pint of Science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Dr Wessel Woldman presented work on behalf of the programme to a lay audience.
Year(s) Of Engagement Activity 2016
 
Description Post-Doctoral Poster (CT) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation:

Title "Comparison between K-mean Clustering and Independent Component Analysis to extract
microstates from resting state EEG" by C. Tangwiriyasakul, A.D. Pawley, S.N. Yaakub, S. Carr and M. Richardson.

It was held at King's College London Neuroscience Symposium (Sep 10th, 2015).
Year(s) Of Engagement Activity 2015
 
Description Post-Doctoral Poster (GP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact (IWSP) 7th Epilepsy Mechanisms, Models, Prediction & Control; poster presentation:

Seizure Dynamics, Network Topology and the Information Spread between different brain regions

Melbourne Brain Centre, University of Melbourne
Year(s) Of Engagement Activity 2015
 
Description Post-Doctoral Poster (GP) 2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Bio Dynamics 2015- where Biology, Medicine & Mathematics meet poster presentation:

Network structure supports faster information flow between brain regions in people with idiopathic generalised epilepsy

John McIntyre Conference Centre, Edinburgh, UK
Year(s) Of Engagement Activity 2015
 
Description Post-Doctoral Poster (GP) 3 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Principles of autonomous neurodynamics 2014: Emergent Dynamics of Complex Biological Networks - oral presentation:

"A computational modelling approach for network structures in idiopathic generalised epilepsy"

Pasteur Institute; Paris; France
Year(s) Of Engagement Activity 2014
 
Description Post-Doctoral Poster (GP) 4 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Bio Dynamics Workshop 2014: Emergent Dynamics of Complex Biological Networks - poster presentation:

"A critical role for network structure in seizure onset: a computational modelling approach"

The Innovation Centre, University of Exeter, UK
Year(s) Of Engagement Activity 2014
 
Description Post-Doctoral Poster (ML) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Melbourne, IWSP7: Epilepsy Mechanisms, Models, Prediction and Control
Poster: "Forecasting epileptic seizures in neuronal networks".
Year(s) Of Engagement Activity 2015
 
Description Post-Doctoral Poster (ML) 2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Brain States Conference: Characterization and Neuromodulation by DBS" (Cologne, Germany)

Poster: "Quantitative Analysis of Epileptic Brain Networks"
Year(s) Of Engagement Activity 2015
 
Description Sidmouth Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Sidmouth science festival: interaction/demo with adults and children on dynamics of the brain in health and disease
Year(s) Of Engagement Activity 2015
 
Description Synchronization in the random-field Kuramoto model on complex networks poster (ML) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Brainmodes Conference 2016: Poster presentation at an academic conference - disseminate current work/findings
Year(s) Of Engagement Activity 2016
URL http://www.da.ugent.be/brainmodes/
 
Description TD-Source: A tool to estimate EEG source localization guided by Time source covariance derived from Tensor decomposition technique (CT) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at Computational Neurology conference, Newcastle 20-21 Feb 2017 - dissemination of current findings/results - generated questions about the research. Won 2nd prize for best poster.
Year(s) Of Engagement Activity 2017
URL https://conferences.ncl.ac.uk/compneurology/
 
Description The role of network topology in epileptiform dynamics and its significance for epilepsy surgery 2 poster (ML) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Bernstein Conference 2016 poster presentation to academic audience - disseminating current work findings
Year(s) Of Engagement Activity 2016
 
Description The role of network topology in epileptiform dynamics and its significance for epilepsy surgery poster (ML) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Meeting of Minds Conference 2016: Poster presentation at an academic conference - disseminate current work/findings
Year(s) Of Engagement Activity 2016
URL https://www.bna.org.uk/meeting-booking/bna-abn-joint-symposium-meeting-of-minds/
 
Description The role of network topology in epileptiform dynamics and its significance for epilepsy surgery poster (ML) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Biodynamics conference 2016 poster presentation to academic audience - dissemination of current work/findings
Year(s) Of Engagement Activity 2016
URL http://www.bio-dynamics.org/events/biodynamics-2016
 
Description Using a tensor decomposition technique to investigate dynamic changes in subnetworks derived from resting state fMRI during generalized spike and wave discharges: an EEG-fMRI pilot study (CT) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at NeuroInformatics 2016 Conference, Reading. This is also published as an abstract in Frontiers in Neuroinformatics, No. 00074, DOI=10.3389/conf.fninf.2016.20.00074 - dissemination of current findings/results - generated questions about the research.
Year(s) Of Engagement Activity 2016
 
Description Young Epilepsy retreat 2017 (SP) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Each year Dr Suejen Perani, is invited to join the delegation of the Young Epilepsy's Paediatric Epilepsy Research Retreat 2017 which was hosted by Professor Helen Cross OBE, The Prince of Wales's Chair of Childhood Epilepsy and led by world renowned paediatric neurologist and senior research fellow, Professor Ingrid Scheffer AO.

Now in its seventh year, this event brought together over 90 of the brightest minds in paediatric epileptology. International researchers, professors, PhD students and research scientists presented and discussed 21 varied current projects which aim to tackle epilepsy, support early intervention and improve long term outcomes for children and young people.
Year(s) Of Engagement Activity 2017
URL http://www.youngepilepsy.org.uk/news-and-events/news/young-epilepsy-paediatric-epilepsy-research-ret...