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. 
 
Title The Cerebral City - Exhibition 
Description The Cerebral City was showcased on the 24th January at the Inigo Rooms, Somerset House along with the other Arts in Mind Innovation Scheme projects. The exhibition comprised the final Cerebral City film cut edited by Matthew Maxwell; a 'sound shower' of spoke memories collected by scientist Dr Eugenio Abela as part of his 'walking' exercise; an aluminium light box depicting the pantones collected by artist Matthew Maxwell; and three printed portraits taken by photographer Jason mcGlad. The event was attended by invited individuals with specialist interest in science, the arts, and health. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2018 
Impact The Cerebral City team were approached by interested parties to collaborate on similar larger projects requiring further grant funding to be obtained. 
URL https://www.kcl.ac.uk/Cultural/Cultural-Institute/Innovation/Arts-in-mind.aspx
 
Title The Cerebral City - Film 
Description The cerebral city emerged from a long-standing collaboration between artist Matthew Maxwell and the Richardson Research Lab at King's College London. Matthew's artistic interests include the concept of psychogeography, which involves arbitrarily superimposing maps of two different regions onto each other as a way of reimagining an environment or place. The Richardson Lab's research interests include understanding how the brain is 'wired' through neural networks, and how these networks differ in people with epilepsy and people without epilepsy. Using the neuroimaging technique tractography, the Richardson Lab is investigating how information in the brain travels through neural tracts, or 'pathways', and also how epileptic seizures spread through these pathways. Drawing on psychogeography and tractography, Matthew and the Richardson Lab posited the idea that pathways in the brain (viewed by tractographic imaging) can be reimagined as a city-brain-map, or a 'cerebral city'. Like a city, the brain comprises millions of pathways that connect the areas of the brain just as streets and paths connect areas of the city. In this project, the human brain was reimagined by superimposing tractograms taken from magnetic resonance imaging (MRI) scans of three subjects: an artist, a scientist and a photographer (who has epilepsy), onto a map of London, creating personalised pathways (which may differ depending on how their brains are wired). These pathways were physically walked and documented according to each subject's map, the results providing a unique insight into the psychogeographic experience of a shared urban habitat: what is heard, what is seen and what is encountered as each subject navigates the passageways of their cerebral city. 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact Film footage and photography collected as part of the cerebral city walking exercise formed an immersive visual installation (film) that engages the viewer in an artistic representation of the human brain and the technologies used in epilepsy research to better understand it. 
URL https://www.kcl.ac.uk/Cultural/-/Projects/The-Cerebral-City.aspx
 
Description "Translational Research Exchange at Exeter"
Amount £1,500,000 (GBP)
Funding ID ISSF3 
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom
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
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
Start 06/2016 
End 01/2017
 
Description EPSRC Centre for Predictive Modelling in Healthcare
Amount £2,008,955 (GBP)
Funding ID EP/N014391/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 01/2016 
End 10/2020
 
Description Is epilepsy a progressive disease? - seeking markers of disease-­stage and treatment responsiveness
Amount £56,904 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2020
 
Description King's College London Confidence in Concept
Amount £56,904 (GBP)
Funding ID MC_PC_16048 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2017 
End 05/2019
 
Description MRC Centre for Neurodevelopmental Disorders
Amount £1,467,740 (GBP)
Funding ID MR/N026063/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2016 
End 10/2021
 
Description Marie Sklodowska-Curie Individual Fellowship - European Commission
Amount £146,591 (GBP)
Funding ID 750884 
Organisation European Commission H2020 
Sector Public
Country Belgium
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
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
Start 04/2016 
End 03/2019
 
Description Seeking brain network markers which predict response to first antiepileptic drug in new-onset treatment-naive Idiopathic Generalised Epilepsy
Amount £29,172 (GBP)
Funding ID PGE1402 
Organisation Epilepsy Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2014 
End 06/2016
 
Description Sensory system abnormalities in childhood dystonia / dystonic cerebral palsy - are sensory networks modulated by Deep Brain Stimulation?
Amount £408,778 (GBP)
Funding ID MR/P006868/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2016 
End 08/2020
 
Description Travel Award (IP)
Amount £800 (GBP)
Funding ID not known 
Organisation Guarantors of Brain 
Sector Charity/Non Profit
Country United Kingdom
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
Start 09/2016 
End 09/2016
 
Title Tensor Decomposition in TMS/EEG 
Description This tool was developed under the principle of tensor decomposition which is equivalent PCA inn higher dimensional space. This can discriminate between post-TMS effect of different drug intake. This tool requires a three dimensional space data that is EEG channel frequency and time. By stacking a combination of these matrices for all patient subjects and conditions we can decompose the difference between condition and subject over the three main dimensions (space, frequency, time). The advantages of using this technique over the conventional TMS/EEG analysis techniques is that we do not need to preselect time or frequency of interest. Thus its purely data driven process. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2018 
Provided To Others? No  
Impact Currently this tool has not yet ben used by others as it is still under development. We would like to validate this tool with a larger set of data. Ultimately, we would like this tool to be used in clinical practice. 
 
Title simultaneous TMS EEG to measure drug effect in brain networks 
Description Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has been used to characterize the effects of antiepileptic drugs (AEDs) in healthy participants and, based on TMS-EMG measurement, to predict the therapeutic response to AEDs in patients. However, TMS-EMG measures derive from peripheral responses (hand muscle), which only indirectly refer to brain mechanisms. We recently showed that the recording of TMS responses directly from the brain via electroencephalography (TMS-EEG) provides a measure of drug activity in healthy volunteers. The EEG response to single-pulse TMS stimulation produces a sequence of positive and negative peaks on the EEG at specific latencies (i.e. P25, N45, P70, N100 and P180), named TMS-evoked EEG potentials (TEPs). Building on our recent work, we aspire to take TMS-EEG to the next level with the aim of translating it into a clinical tool, which can directly measure the pharmacological effects of AEDs in the human brain. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2017 
Provided To Others? Yes  
Impact This tool has great potential to develop reliable and valid markers for antiepileptic drug activity in the healthy human brain. These markers of drug activity attracted pharmaceutical industries as they can be used as a screening tool for early-stage clinical trials. We are now employing our tool to determine pharmacodynamics properties of a newly developed antiepileptic drug in a first-in-human Phase I clinical trial. In addition, these markers will be then associated with therapeutic response in epilepsy patients and will be employed in late-stage studies. The results may open an opportunity for TMS-EEG to be integrated in clinics for a personalized/stratified treatment approach in epilepsy practice 
 
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 and 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 
Year Produced 2018 
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 and Multiscale brain imaging data processing and 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 
Sector Hospitals 
PI Contribution Liverpool and Bonn have collected data closely related to the aims of the Programme. We have brought theory and methods from the Programme to develop hypotheses and analyse the Liverpool-Bonn data.
Collaborator Contribution Liverpool/Bonn provided exceptionally high-quality data from patients with temporal lobe epilepsy.
Impact Five publications (with S Keller, B Weber). The collaboration is multidisciplinary: MRI engineering (Bonn), signals processing (Liverpool), clinical science (King's).
Start Year 2014
 
Description Bonn-Liverpool Collaboration 
Organisation The Walton Centre NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Liverpool and Bonn have collected data closely related to the aims of the Programme. We have brought theory and methods from the Programme to develop hypotheses and analyse the Liverpool-Bonn data.
Collaborator Contribution Liverpool/Bonn provided exceptionally high-quality data from patients with temporal lobe epilepsy.
Impact Five publications (with S Keller, B Weber). The collaboration is multidisciplinary: MRI engineering (Bonn), signals processing (Liverpool), clinical science (King's).
Start Year 2014
 
Description Bonn-Liverpool Collaboration 
Organisation University of Bonn
Country Germany 
Sector Academic/University 
PI Contribution Liverpool and Bonn have collected data closely related to the aims of the Programme. We have brought theory and methods from the Programme to develop hypotheses and analyse the Liverpool-Bonn data.
Collaborator Contribution Liverpool/Bonn provided exceptionally high-quality data from patients with temporal lobe epilepsy.
Impact Five publications (with S Keller, B Weber). The collaboration is multidisciplinary: MRI engineering (Bonn), signals processing (Liverpool), clinical science (King's).
Start Year 2014
 
Description Directed Influence Brain Network: Hangzhou Normal University Collaboration 
Organisation Hangzhou Normal University, China
Country China 
Sector Academic/University 
PI Contribution King's provided clinical expertise and brain network theory related to epilepsy
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 Publication (Liao et al)
Start Year 2014
 
Description Dr Laurent Sheybani 
Organisation University of Geneva
Country Switzerland 
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". Dr Sheybani has shared data from his project and expertise in the methods to obtain the data.
Collaborator Contribution We have provided expertise in network dynamic models, which we have applied to these animal data. This collaboration is a key opportunity to tet model predictions in invasive animal data, an opportunity not available in non-invasive human data.
Impact We have a manuscript ready for submission and a second manuscript in preparation. The project is multidisciplinary: clinical science (King's), engineering (King's, Geneva), computational modelling (King's, Geneva, Exeter).
Start Year 2016
 
Description Dr Saroosh Afyouni (Phd) 
Organisation University of Warwick
Department School of Life Sciences
Country United Kingdom 
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. The project is multidisciplinary: clinical science (King's), engineering (Warwick).
Start Year 2016
 
Description EEG modelling and source localisation: Geneva collaboration 
Organisation University of Geneva
Country Switzerland 
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 EEG networks as a potential predictor for treatment response to antiepileptic drugs (Edin) 
Organisation Wellcome Trust
Department Wellcome Trust Centre for Cell Biology
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution The collaboration intends to develop a novel approach to analysing high-dimensional TMS-EEG data, in order to extract biomarkers of antiepileptic drug effects in the brain. We are contributing simultaneous TMS-EEG data collected through the MRC Programme, and expertise in epilepsy, as well as the time of Programme-funded researchers.
Collaborator Contribution The Muir Maxwell Epilepsy Centre at the University of Edinburgh (Dr Richard Chin) and the School of Engineering at the University of Edinburgh (Dr Javier Escudero) are providing expertise in tensor factorisation applied to EEG, including analysis code and personal time. £4,400 was awarded to support this new collaboration between Edinburgh and KCL. This short-term data analysis project was organised around two visits by researchers from the Richardson Lab at KCL with the MMEC in Edinburgh. Together we have developed a novel tool to analyse TMS/EEG data set using tensor decomposition technique.
Impact Together these teams have developed a novel tool to analyse TMS/EEG data set using tensor decomposition technique in MATLAB. One or more publications expected. The project is multidisciplinary: clinical science (King's), engineering (Edinburgh).
Start Year 2017
 
Description Generative models for identifying seizure focus from stimulated intracranial EEG: University of Minnesota Collaboration 
Organisation University of Minnesota
Country United States 
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 Inferring Brain States from Intracranial EEG Using Directed Information 
Organisation King's College London
Department Department of Mathematics
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide preprocessed intracranial EEG time-sereis data from epilepsy patients, suggest clinically relevant research hypotheses, interpret results and participate in writing papers.
Collaborator Contribution Advanced time-series analysis using measures derived from information theory, method development and testing, writing lab reports and papers.
Impact No impact yet.
Start Year 2018
 
Description Professor Steve Schiff - University of Penn State 
Organisation Penn State University
Department Department of Engineering Science and Mechanics
Country United States 
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 outcome yet. The project is multidisciplinary: clinical science (King's), engineering (Penn State).
Start Year 2016
 
Description data sharing with ENIGMA consortium 
Organisation University College London
Department Institute of Neurology
Country United Kingdom 
Sector Academic/University 
PI Contribution ENIGMA is a large multicentre partnership which pursues meta-analyses and mega-analyses of neuroimaging data and genomics data. We have shared data collected through the programme and contributed scientific direction.
Collaborator Contribution ENIGMA has contributed multicentre data and a data analysis protocol.
Impact Publication: Whelan et al.
Start Year 2015
 
Description qEEG correlates of neuropsychological outcome in temporal lobe epilepsy 
Organisation University of Lisbon
Department Faculty of Medicine
PI Contribution We have provided scientific collaboration through jointly developing the research questions and sharing data obtained through the MRC Programme.
Collaborator Contribution A researcher fro the University of Lisbon, Dr Pedro Viana, is based in the Richardson Lab at King's College London as a research visitor. His interest is in cognitive consequences of temporal lobe epilepsy. We have combined his expertise in psychology with ours in quantitative EEG, to investigate qEEG correlates of neuropsychological outcome in temporal lobe epilepsy.
Impact No outputs yet. The project is multidisciplinary: clinical science (King's), signals processing (King's), psychology (Lisbon).
Start Year 2017
 
Title Gazele: Microscale Brain Network Dynamics 
Description Software package for the complete study, data manipulation and modelling of the dynamics and structure of complex brain networks. It requires zero knowledge of programming or scripting and consists of two standalone applications, Gazele and Coconi. 
Type Of Technology Webtool/Application 
Year Produced 2019 
Impact None yet as still undergoing release. 
 
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 13th ECE: A first-in-human Phase I study to assess the pharmacodynamic profile of a novel potassium channel opener (XEN1101) on human cortical excitability with TMS-EEG and TMS-EMG - Poster (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: 13th European Congress on Epileptology.
XEN1101 is a novel voltage-gated potassium channel opener, which has been developed by Xenon Pharmaceuticals as a treatment for seizures partial onset (focal) seizures. Entering a first-in-human Phase I trial, it is yet unclear to which extent XEN1101 will impact human cortical excitability and at which specific dosage. The non-invasive transcranial magnetic stimulation (TMS) combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) allows measuring the pharmacological effect of drugs acting in the human brain. The resting motor threshold (RMT) and TMS-evoked EEG potentials (TEPs) are readouts associated with corticospinal and cortical excitability, respectively. Several antiepileptic drugs (AEDs) significantly increased RMT values and modulated TEPs indicating a shift towards inhibition. To evaluate whether XEN1101 has entered to brain to act at the intended target, we tested the effects of three different dosages of the active compound (10, 15 and 20mg) on TMS-EEG and TMS-EMG measures for the first time in humans.
Method
A total of eight healthy right-handed male subjects were enrolled in the open-label pilot study. TMS- evoked EEG potentials and RMT were registered before, 2 and 4 hours after the intake XEN1101. The effects of medications on TEPs amplitude were analysed at single-subject level by applying multiple independent sample t-tests. Further, a cluster-based permutation analysis approach was implemented to correct for multiple comparison.
Results
In line with previous TMS investigation of AEDs, the amplitude of TEPs occurring at late latencies (80- 300ms after TMS) were significantly suppressed by 20mg of XEN1101 in each participant at 4 hours post-dose measurement. The two lower XEN1101 drug dosage did not show significant and robust TEP modulation. Further, a trend for RMT increase was observed.
Conclusion
This TMS-EEG protocol provided compelling evidence that 20mg of XEN1101 reached the human cortex to suppress cortical and corticospinal excitability in line with the effects of other AEDs.
Year(s) Of Engagement Activity 2018
 
Description 13th ECE: Motor Network Hypersynchrony as an Endophenotype in Families with Genetic Generalised Epilepsy: a resting state fMRI 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 Introduction: Genetic generalised epilepsy (GGE) is a type of epilepsy which is believed to be inherited through family members [1]. Using fMRI, hypersynchrony was found across motor-related areas in patients with GGE and their first degree relatives, while performing cognitive-motor task [2]. In this study, we are interested if this hypersynchrony could be found during rest to detect baseline values of the synchronicity not influenced by motor task.
Methods : We acquired data from thirteen patients diagnosed with JME and GTCSO, 17 first degree unaffected relative, and 18 age-matched healthy controls (mean age = ~24, ~40 and ~24 years, respectively). Each participant underwent two 10 minutes-EPI fMRI resting scans eyes closed (3.3 x 3.3 x 4 mm effective resolution with a FOV=210 mm TR=2.160s, TE=30, flip angle = 75, number of slices = 30, slice thickness = 3 mm).

For each participant, the BOLD signals were bandpass filtered between 0.04-0.07 Hz. Following brain pracellation in accordance with AAL atlas, the first principal component of each brain region was taken and Hilbert transform was applied to estimate instantaneous phase. Series of 90x90x296 adjacency binary matrices of value equal to 1 if phase difference was < p/6 were estimated. To calculate the temporal averaged brain synchrony, the average across 296 time-points was taken resulting in a 90x90 matrix.
At the single subject level, we estimated the mean degree from (1) a whole-brain network, (2) a motor network including precentral cortex, supplementary motor cortex, and postcentral gyrus) and (3) the occipital network including calcarine, cuneus, lingual, and all occipital cortex.
Data were corrected using non-parametric ranking of covariance (Quade's test) and controlled for age using Mann-Whitney test.
Results: Significant difference among the three groups was found only in the Motor network, with the highest in patients diagnosed with GGE, followed by the first degree relatives, and then the healthy controls. The average mean degrees in both patients with GGE and first degree relatives were both significantly higher than that in healthy controls.
Conclusion:Our results suggested that the motor network presents hypersynchrony different from healthy controls in GGE patients and unaffected relatives during rest. This suggests that this phenomena might be a genetic trait of generalised epilepsy.
Year(s) Of Engagement Activity 2018
 
Description 13th ECE: Poor seizure control in common epilepsies associates with slower and frontally-shifted alpha rhythm (EA) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Purpose: Recent studies indicate that the EEG alpha rhythm decelerates and shifts anteriorly in both focal and idiopathic generalised epilepsies, and computational models suggest that such a low-frequency alpha regime might reflect a seizure-prone state. We therefore tested the hypothesis that alpha deceleration and spatial redistribution is associated with poor seizure control.
Methods: We conducted a prospective EEG study in n = 63 epilepsy patients and n = 18 matched healthy controls (HC). EEG data consisted of 20-second recordings of eyes-closed wakefulness without interictal abnormalities. We used a Fast Fourier Transform to power spectra from 2-20 Hz with 1 Hz resolution for each participant, and then transformed these spectra into three dimensional space-frequency power images. We calculated t-tests on these images to examine differences between HC and patients, IGE (n=23) and FE (n = 39) and patients with poor (PSZ, n = 38, > 4 seizures / month) versus those with good seizure control (GSZ, n = 24, < 4 seizures / month), including age, gender, and drug load as covariates. Statistical inference over space and frequency was performed using cluster-based permutation statistics with false-discovery rate (FDR) correction.
Results: We found a statistically significant increase in EEG power between 5-9 Hz and a decrease at 11 Hz in all epilepsy patients compared to HC (pFDR = .015, effect size d = 0.70). Comparison of PSZ versus GSZ patients revealed a power increase in the same low-alpha frequency band for poorly controlled patients (5-8 Hz, pFDR = .015, d = 0.94); this effect was seen across the whole scalp, with maxima at T3, T5 and F3. No statistically significant effects were found when comparing syndrome subgroups, or when correlating against drug load and disease duration. Conclusions: Spatio-spectal shifts of the alpha rhythm seem to be a generic marker of seizure control across epilepsy syndromes.
Year(s) Of Engagement Activity 2018
URL https://scholar.google.com/scholar?cluster=18437135214864715386&hl=en&oi=scholarr
 
Description 6th Science Factory: TMS Summer School and Workshop: The Outlook of Pharmaco-TMS EEG (IP) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Isabella has been invited to deliver a lecture and teaching session, as a TMS expert, at a highly regarded annual TMS summer school in Finland.
Year(s) Of Engagement Activity 2018
URL https://www.fens.org/News-Activities/Calendar/Training/2018/05/6th-Science-Factory-TMSEEG-Summer-Sch...
 
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 2018: Dynamic network characterisation of icEEG interictal spike events in TLE patients may associate with surgical outcome (DS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Purpose
Microstructural EEG elements and their functional networks relate to many neurophysiological functions of the brain and may reveal abnormalities. The Interictal Epileptiform Discharge (IED), a hallmark graphoelement of epileptic EEG, is thought to play a key role in the formation and evolution of pathogenic networks in epilepsy. Although IEDs have previously been studied, their network attributes are still to be fully elucidated. Here, we perform a dynamic network characterisation of IEDs with high temporal selectivity, regarding this as a readily available window into the epileptic brain state.

Methods

Commonly, brain connectivity studies of epilepsy using  EEG analyse either entire recordings, including pathogenic but also normal brain activities, or lengthy rare events, such as epileptic seizures. For the first time here, we estimate pathogenic networks that characterise very brief IEDs lasting a few 10's of milliseconds, alone. We use an inverse power method for estimation of sparse principal component analysis in order to reveal connectivity properties that are consistent across subjects. Finally, we employ centrality measures (eg. betweenness, eigencentrality, closeness) to identify areas that are either influential or play an important role in the IED network function.

Results

In a preliminary analysis of four exemplar patients, we examined their first EEG at initial epilepsy onset; subsequently, two proved to be treatment-responsive and two were treatment-resistant. We show a difference in their network features. Specifically, IED networks differ in their modularity.

Conclusion

We conclude that network investigation of IEDs may reveal predictive biomarkers for early identification of treatment outcome.
Year(s) Of Engagement Activity 2018
 
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 2018 
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 is a thriving forum which brings together biologists, mathematicians, clinicians, physicists, and computer scientists who are interested in dynamics and networks in the biological and medical sciences. Dynamic phenomena are ubiquitous in biological systems and span multiple, interacting spatiotemporal scales. There is growing appreciation that quantifying them accurately will lead to deeper insights into human disease and even inspire novel therapies - but doing so is challenging, and will likely need innovative cross-disciplinary approaches and tools. We will showcase some of the very best cross-disciplinary research in this rapidly expanding field, with a focus on how the study of biological dynamics, and the mechanistic understanding it provides, can be used for clinical translation and patient-specific therapeutics. This year Biodynamics covered a range of topics from microscopic scales - how molecular dynamics influence disease phenotypes - to macroscopic scales - how neural, humoral and cardiovascular dynamics affect human health and disease. Specific themes covered: Motor Neuroscience; Molecular Mechanisms and Modelling of Diseases; Neural Oscillations in health and Disease; Stress and the Brain; Patient Specific Modelling
Year(s) Of Engagement Activity 2018
URL https://biodynamics2018.co.uk
 
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 Biodynamics: Control of dynamics revealing a key role of frontal lobes in generating generalised spike and wave discharge (CT) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Introduction: Generalized spike-and-wave discharges (GSW) are one type of EEG abnormality observed in patients with epilepsy. Previously, we investigated fMRI data in a group of patients time locked to GSW events vs a group of controls at rest [1]. During GSW events, we found fifteen standard AAL regions (covering frontal lobes, sensorimotor cortex and precuneus) being synchronized. On the other hand, during rest, the healthy brains were being dominated by the occipital area, where the nodes in this area were highly synchronized. In this study, we are interested to investigate the fifteen GSW nodes and their contribution in generating GSW using a level of energy intakes required to steer the brain from the healthy state (occipital activities) into the GSW state as measure.
Methods: We used an average diffusion tensor imaging (DTI) matrix, representing an anatomical connection among the 90 AAL regions, from 25 subjects. To quantify a contribution of each GSW nodes, we performed 15 simulations. At each simulation, we removed one of the GSW nodes as well as all its connections out of the DTI matrix, then re-estimated the amount of energy needed to steer the brain from the healthy state to the GSW state using control theory [2].
Results: We found the four frontal regions (see Table-1) requiring the highest energy intakes. This may highlight the largest contribution of these regions in generating GSW.
Conclusions: Our results suggested among the regions forming the GSW network the four frontal brain regions may play a vital role in generating GSW.
Year(s) Of Engagement Activity 2018
 
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 Computational Biomarkers in Early Identification and Prediction of Intractable Epilepsy (DS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Purpose
Microstructural EEG elements and their functional networks relate to many neurophysiological functions of the brain and may reveal abnormalities. The Interictal Epileptiform Discharge (IED), a hallmark graphoelement of epileptic EEG, is thought to play a key role in the formation and evolution of pathogenic networks in epilepsy. Although IEDs have previously been studied, their network attributes are still to be fully elucidated. Here, we perform a dynamic network characterisation of IEDs with high temporal selectivity, regarding this as a readily available window into the epileptic brain state.

Methods

Commonly, brain connectivity studies of epilepsy using EEG analyse either entire recordings, including pathogenic but also normal brain activities, or lengthy rare events, such as epileptic seizures. For the first time here, we estimate pathogenic networks that characterise very brief IEDs lasting a few 10's of milliseconds, alone. We use an inverse power method for estimation of sparse principal component analysis in order to reveal connectivity properties that are consistent across subjects. Finally, we employ centrality measures (eg. betweenness, eigencentrality, closeness) to identify areas that are either influential or play an important role in the IED network function.

Results

In a preliminary analysis of four exemplar patients, we examined their first EEG at initial epilepsy onset; subsequently, two proved to be treatment-responsive and two were treatment-resistant. We show a difference in their network features. Specifically, IED networks differ in their modularity.

Conclusion

We conclude that network investigation of IEDs may reveal predictive biomarkers for early identification of treatment outcome.
Year(s) Of Engagement Activity 2018
 
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 ICTALS2017: The Penumbra Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Professor Richardson was an invited member of the organising committee and presented a poster.
Year(s) Of Engagement Activity 2017
URL http://ictals2017.umn.edu/program
 
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 Invited talk: EEG-fMRI maps of GSW BOLD response in the biggest cohort of drug naïve genetic generalised epilepsy patients (SY) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Dr Suejen Perani was invited to give a talk entitled: EEG-fMRI maps of GSW BOLD response in the biggest cohort of drug naïve genetic generalised epilepsy patients at the centre at the MRC Centre for Developmental Disorders at KIng's College London.

Suejen Perani1,2, Maria Centeno2, Elhum Shamshiri2, Tim M Tierney2, Mark P. Richardson1, David W. Carmichael2
1. Basic and clinical neuroscience unit, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 9RX
2. Imaging and Biophysics section, Institute of Child Health, UCL, London, WC1N 1EH.
The network associated with Generalised Spike Waves (GSW) activity has been studied using simultaneous EEG-fMRI (Gotman, Grova et al. 2005, Kay and Szaflarski 2014, Pugnaghi, Carmichael et al. 2014). Overall agreement in the community is that the fMRI response associated with GSW consists of a sub-cortical activation, particularly in the thalamus and in the caudate and deactivation of cortical areas including frontal and default mode brain regions (Gotman, Grova et al. 2005, Kay and Szaflarski 2014). However, the current literature is based on results from patients taking antiepileptic medication (AED). Given there is evidence showing alteration in cerebral blood flow after drug intake (Bartenstein, Ludolph et al. 1991, Gaillard, Zeffiro et al. 1996, Joo, Hong et al. 2006, Spanaki, Siegel et al. 1999) that supports a modification of neuronal functioning related to AEDs that might influence BOLD response, it is crucial to measure GSW BOLD response in a drug naïve population.
32 drug naïve patients diagnosed with GGE (mean age=15.75 years) underwent sedation-free simultaneous EEG-fMRI. A 64-channel MRI compatible system (Brain Products, Munich) was used to record EEG activity and simultaneous fMRI. After standard artefact corrections to the EEG, 116 runs of GSWs (mean duration= 6.1s, SD=5.3) were marked in 21 patients and entered into a general linear model (GLM) using SPM8 (www.fil.ion.ucl.ac.uk) before checking for commonalities across group.
We found that bilateral parietal cortex and posterior cingulate showed a negative BOLD response to GSW whilst mesial frontal cortex and bilateral caudate showed a positive BOLD response. This suggests that the pattern of activity in the functional networks is independent of AED intake.
Year(s) Of Engagement Activity 2017
URL https://devneuro.org/cnd/symposium/symposium.php
 
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 Poster presentation at Biodynamics Conference, London UK, 12-13 Apr 2018: "Sakellariou DF, Vakrinou A, E. Abela, Richardson MP. Dynamic network characterisation of icEEG interictal spike events in TLE patients may associate with surgical outcome." 
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 Conference, London UK, 12-13 Apr 2018: "Sakellariou DF, Vakrinou A, E. Abela, Richardson MP. Dynamic network characterisation of icEEG interictal spike events in TLE patients may associate with surgical outcome."
Year(s) Of Engagement Activity 2018
 
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 TMS-induced oscillations to evaluate pharmacodynamics properties of a newly developed anti- epileptic drug (XEN1101) - poster (IP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact TMS-evoked EEG potentials have been described to reflect cortical inhibitory and excitatory processes and for this reason have been used to investigate the impact of anti-epileptic drugs. In addition to the analysis of TEPs, brain responses to TMS can be quantified in term of EEG rhythm changes. The spatiotemporal profile of oscillations induced (i.e. non-phase locked) by TMS of the human motor cortex was described as a synchronization (30-300ms) - desynchronization (300-500ms) pattern in the alpha and beta-bands. XEN1101 is a novel voltage-gated potassium (Kv7.2/3) channel opener, being developed by Xenon Pharmaceuticals as a treatment for epilepsy. In this Phase I, double-blind, randomized, placebo-controlled trial we aimed to define XEN1101 fingerprints on TMS-induced oscillations.
A total of 20 healthy right-handed male subjects were enrolled in the study. TMS-EEG sessions were recorded before, 2, 4 and 6 hours after the intake of a single oral dose of XEN1101 (20 mg). TMS- induced oscillations were obtained subtracting the average evoked response (TEPs) at single trial level. The effect of XEN1101 on TMS-induced oscillation was evaluated on theta (4 - 8 Hz), alpha (8 - 12 Hz), beta (13 - 30 Hz) power bands, using non-parametric cluster-based permutation analysis technique.
Results showed that the typical TMS-induced pattern of synchronization-desynchronization is followed by a rebound synchronization in the alpha- and beta-bands occurring after 500ms. Relative to time- matched placebo, at peak plasma levels, XEN1101 decreased the power of theta (p<0.001), alpha (p=0.04) and beta (p=0.05) oscillations at early latencies (30-300ms). In the following time window, XEN1101 suppressed the power of theta and alpha (both p=0.04) oscillations whereas no significant differences were observed over late TMS-induced activity (500-800ms).
The possibility to extract drugs profile on TMS-induced brain responses provides a direction for future research on the implementation of these signals as candidate predictive markers of treatment response in epilepsy patients.
Year(s) Of Engagement Activity 2018
 
Description Thalamic Alterations in Patients with IGE: Poster OHBM( (SP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Suejen Perani (Post-doctral research worker) was invited to present a poster on thalamic alterations in Idiopathic Generalised Epilepsy (IGE).
Year(s) Of Engagement Activity 2017
 
Description The Developing Brain in Health and Disease Symposium: poster Dynamic Brain Networks during Generalized Spike and Wave Discharges (CT) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Post doctoral research Chayanin Tangwiriyakasul was invited to give a poster presentation titled: Dynamic Brain Networks during Generalized Spike and Wave Discharges: Abstract
Generalized spike-and-wave discharges (GSW) are one type of EEG abnormality observed in patients with epilepsy. Simultaneous EEG-fMRI recording is used to study functional changes in the brain during GSW events. General Linear Model (GLM) is a standard technique used to reveals brain region contributing to a generation of GSW in a static fashion by calculating amplitude differences in the BOLD signal across two states. However, the human brain does function dynamically. For this reason, we applied a phase-based analysis in which we can estimate dynamic changes in the human brain network before, during and after GSW.
19 patients underwent two resting scans (each lasts 10 minutes). 57 GSW events were visually identified. Pre-processed fMRI data were band-pass filtered between 0.04-0.07 Hz [1] and a Hilbert transform was applied. The AAL atlas was used to divide the brain into 90 regions, with each region represented by the first principal component of the instantaneous phase of all voxels in the region. Next, we estimated a binary synchronisation matrix at each time-point with regions considered to synchronise if the phase difference was less than p/6, giving 296 binary synchronisation matrices for each subject [2]. Eigenvector centrality was estimated from each synchronisation matrix. Note that hub node is a node with high eigenvector centrality.
About ten seconds before GSW onset, a system of hub nodes was found over the primary motor cortex. Five seconds later, this system extended to the left prefrontal cortex. During GSW, we observed an elevation in the global network synchrony (as the number of edges across the whole brain increased). At the same time, the GSW network extended to the precuneus. The GSW network (covering the left prefrontal cortex, primary motor cortex, and precuneus) persisted around six seconds after the termination of GSW. This shows that GSW is a dynamic phenomenon as the brain network changes dynamically before, during, and after GSW.
[1] Glereen et al. 2011
[2] Ponce-Alvarez et al. 2014
Year(s) Of Engagement Activity 2017
 
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 Xenon: TMS-EEG and TMS-EMG to assess the pharmacodynamic profile of a novel potassium channel opener (XEN1101) on human cortical excitability - Poster (IP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Poster: Xenon Pharmaceuticals Inc., Canada
Transcranial magnetic stimulation (TMS) combined with electromyography and electroencephalography allows measurement of resting motor threshold (RMT) and TMS-evoked EEG potentials (TEPs), readouts associated with corticospinal and cortical excitability, respectively. Several antiepileptic drugs (AEDs) significantly increase RMT values and modulate TEPs indicating a shift towards inhibition. TMS may therefore be used to assess target engagement of newly developed AEDs in early stage trials. XEN1101 is a novel voltage-gated potassium (Kv7.2/3) channel opener, being developed by Xenon Pharmaceuticals as a treatment for epilepsy. In a first-in-human Phase 1 open-label study, TMS readouts showed that 20mg of XEN1101 crosses the human blood brain barrier and significantly impacts cortical excitability compared to lower dosages (10 and 15mg). TMS was then used to assess pharmacodynamics properties of XEN1101 (20mg) on 20 healthy right- handed male subjects compared to placebo.
RMT and TEPs were recorded before and at 2, 4 and 6 hours after dosing. The effects of XEN1101 on TEP amplitudes were analysed by applying a cluster-based permutation analysis approach.
XEN1101 elevated RMT by 1.5±0.4% (p<0.05), 3.0±0.7% (p<0.01) and 4.3±0.8% (p<0.01) compared to time matched placebo changes of 0.4±0.3%, 0.7±0.4% and 0.9±0.3%. Further, the RMT increase positively correlated with drug plasma level underlying a strong relationship between pharmacokinetic and pharmacodynamics drug's profiles. Relative to time-matched placebo, at peak plasma levels, XEN1101 decreased the amplitude of TEPs measured at 25 ms (N15-P25: 4.5 vs 6.0µV, p<0.05), 45 ms (N45: -2.3 vs -3.0µV, p<0.01) and 180 ms (P180: 2.2 vs 3.0µV, p<0.01) after the TMS pulse.
This study showed that active XEN1101 doses produce significant plasma concentration dependent reduction of corticospinal (RMT) and cortical (TEP) excitability and these results support the further development of XEN1101 in patients with epilepsy.
Year(s) Of Engagement Activity 2019
 
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...