MR Imaging of Brain Generators in Human Epilepsy
Lead Research Organisation:
University College London
Department Name: UNLISTED
Abstract
New Brain Scans for Epilepsy. Epilepsy is the commonest serious neurological condition in the UK. Although medication can help, it is ineffective in 80,000 people. We propose to use a new kind of brain scan to find the brain area that is responsible for the seizures (epileptic focus) and that could be surgically removed.
The new brain scan technique, called EEG-fMRI, combines the recording of brain waves (electroencephalogram or EEG) with functional magnetic resonance imaging (fMRI). EEG-fMRI has already given promising results but we do not know how useful it is in localising the focus. We will first refine the technique to make it as sensitive and specific as possible and then evaluate its performance by comparing it with the best available data. We propose to develop EEG-fMRI on the most advanced scanners to maximise its sensitivity. We also want to compare the EEG-fMRI measurements with clinical data that is collected by placing electrodes inside the patient’s skull – a complicated and relatively risky procedure, but which, at present, gives the best possible localization of the epileptic focus. We hope to show that EEG-fMRI, a non-invasive and totally painless technique, can give the same kind of information as the invasive technique.
The new brain scan technique, called EEG-fMRI, combines the recording of brain waves (electroencephalogram or EEG) with functional magnetic resonance imaging (fMRI). EEG-fMRI has already given promising results but we do not know how useful it is in localising the focus. We will first refine the technique to make it as sensitive and specific as possible and then evaluate its performance by comparing it with the best available data. We propose to develop EEG-fMRI on the most advanced scanners to maximise its sensitivity. We also want to compare the EEG-fMRI measurements with clinical data that is collected by placing electrodes inside the patient’s skull – a complicated and relatively risky procedure, but which, at present, gives the best possible localization of the epileptic focus. We hope to show that EEG-fMRI, a non-invasive and totally painless technique, can give the same kind of information as the invasive technique.
Technical Summary
Thirty percent of epilepsy patients are intractable to drug treatment, representing approximately one hundred thousand people in the UK. Many patients with intractable epilepsy are currently deemed unsuitable for curative surgery due to the difficulty in identifying the focus. Invasive monitoring is currently the gold standard but disadvantages of this approach include the risk of complication and costs. EEG-correlated fMRI (?EEG-fMRI?) is a non-invasive technique unique in its ability to provide activation maps of the hemodynamic (blood oxygen level-dependent or BOLD) correlates of specific epileptiform discharges. Despite limited sensitivity, concordance with non-invasive electroclinical findings on a lobar basis is frequent. Up to now, validation has relied on comparison with electroclinical findings, which is unsatisfactory as it does not allow to assess the technique?s true added clinical value. The demonstration that fMRI can enhance or even replace invasive monitoring would be a great advance and could significantly increase the proportion of patients in whom surgery is an option. This will require validation based on invasive EEG monitoring and postsurgical outcome findings in a representative group of patients.
Significant improvements in sensitivity will be obtained by implementing EEG-fMRI at high field (4.7T). Furthermore, we will investigate a novel fMRI contrast mechanism that directly reflects neuronal activity. To address scalp EEG?s intrinsic limitations, and in particular its low sensitivity and specificity, we will apply data-driven fMRI analysis techniques to reveal spatio-temporal patterns reflecting epileptogenicity. These developments will greatly benefit from the availability of invasive monitoring data.
fMRI activation patterns will be compared the epileptogenic substrate identified invasively. To further investigate the relationship between epileptogenicity and fMRI, discharges recorded within the brain and fMRI signals will be recorded simultaneously, requiring implementation of intracranial EEG-fMRI. In addition to the obvious interest in improving our understanding of the imaging correlates of epileptogenicity and epileptogenic networks, this presents us with a unique opportunity to improve multimodal forward models of EEG and fMRI and our understanding of fMRI in humans. Furthermore the role of EEG-fMRI in guiding invasive monitoring will be investigated.
This programme of research will result in a major improvement in the fMRI?s sensitivity to epileptiform activity, and provide vital information on EEG-fMRI?s clinical potential. It will also represent a major leap forward in our understanding of the relationship between neuronal activity and fMRI on the other.
Significant improvements in sensitivity will be obtained by implementing EEG-fMRI at high field (4.7T). Furthermore, we will investigate a novel fMRI contrast mechanism that directly reflects neuronal activity. To address scalp EEG?s intrinsic limitations, and in particular its low sensitivity and specificity, we will apply data-driven fMRI analysis techniques to reveal spatio-temporal patterns reflecting epileptogenicity. These developments will greatly benefit from the availability of invasive monitoring data.
fMRI activation patterns will be compared the epileptogenic substrate identified invasively. To further investigate the relationship between epileptogenicity and fMRI, discharges recorded within the brain and fMRI signals will be recorded simultaneously, requiring implementation of intracranial EEG-fMRI. In addition to the obvious interest in improving our understanding of the imaging correlates of epileptogenicity and epileptogenic networks, this presents us with a unique opportunity to improve multimodal forward models of EEG and fMRI and our understanding of fMRI in humans. Furthermore the role of EEG-fMRI in guiding invasive monitoring will be investigated.
This programme of research will result in a major improvement in the fMRI?s sensitivity to epileptiform activity, and provide vital information on EEG-fMRI?s clinical potential. It will also represent a major leap forward in our understanding of the relationship between neuronal activity and fMRI on the other.
Organisations
- University College London, United Kingdom (Lead Research Organisation)
- Hammersmith Hospital (Collaboration)
- Ad-Tech Medical Instrument (Collaboration)
- University of Modena and Reggio Emilia (Collaboration)
- Kiel University, Germany (Collaboration)
- Maastricht University (UM) (Collaboration)
- Frenchay Hospital, United Kingdom (Collaboration)
- Aix-Marseille University, France (Collaboration)
- University of Geneva, Switzerland (Collaboration)
- King's College London, United Kingdom (Collaboration)
Publications

Allen LA
(2017)
Dysfunctional Brain Networking among Autonomic Regulatory Structures in Temporal Lobe Epilepsy Patients at High Risk of Sudden Unexpected Death in Epilepsy.
in Frontiers in neurology


Blinowska K
(2009)
Multimodal imaging of human brain activity: rational, biophysical aspects and modes of integration.
in Computational intelligence and neuroscience

Caballero-Gaudes C
(2013)
Mapping interictal epileptic discharges using mutual information between concurrent EEG and fMRI.
in NeuroImage

Carmichael DW
(2010)
Feasibility of simultaneous intracranial EEG-fMRI in humans: a safety study.
in NeuroImage

Carmichael DW
(2008)
Safety of localizing epilepsy monitoring intracranial electroencephalograph electrodes using MRI: radiofrequency-induced heating.
in Journal of magnetic resonance imaging : JMRI

Carmichael DW
(2008)
An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity.
in Magnetic resonance imaging

Carmichael DW
(2007)
Functional MRI with active, fully implanted, deep brain stimulation systems: safety and experimental confounds.
in NeuroImage

Carmichael DW
(2012)
Simultaneous intracranial EEG-fMRI in humans: protocol considerations and data quality.
in NeuroImage

Centeno M
(2011)
Epilepsy causing pupillary hippus: an unusual semiology.
in Epilepsia
Description | Action Medical Research, Project Grant |
Amount | £200,000 (GBP) |
Organisation | Action Medical Research |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2009 |
End | 04/2012 |
Description | Brain Research Trust Equipment Grant |
Amount | £40,550 (GBP) |
Organisation | Brain Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2009 |
End | 04/2011 |
Description | NATIONAL INSTITUTE FOR HEALTH RESEARCH |
Amount | £77,077 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 04/2013 |
End | 12/2016 |
Description | PhD studentship |
Amount | £100,000 (GBP) |
Organisation | Government of Pakistan |
Sector | Public |
Country | Pakistan |
Start | 09/2008 |
End | 09/2011 |
Title | Dynamic Causal Modelling of Human EEG-fMRI Epilepsy Data |
Description | These methods (developed within the Wellcome trust Centre for Neuroimaging) allow the inference of the initiators of a network of generators of brain activity that is form by a network of areas. |
Type Of Material | Model of mechanisms or symptoms - human |
Provided To Others? | No |
Impact | By applying this method to generalised epilepsy cases EEG-fMRI data a new model of what was required for 'absence' seizures was infered. |
Title | EEG-fMRI database in epilepsy patients |
Description | The data was acquired in patients undergoing presurgical evaluation. All patients either had or will have epilepsy surgery. |
Type Of Material | Database/Collection of Data/Biological Samples |
Year Produced | 2008 |
Provided To Others? | Yes |
Impact | Development of the methods and algorithms for localisation of epileptic foci and investigation of the dynamics of epileptic networks. |
Title | ICA of FMRI |
Description | We were the first to apply the data-driven analysis technique ICA to fMRI data of the resting state to detect epileptic patterns. |
Type Of Material | Data analysis technique |
Provided To Others? | No |
Impact | The publication of our work has resulted in publications from other investigators along similar lines. |
Title | ICEEG-fMRI |
Description | We have developed and implemented the technique of intra-cranial EEG-fMRI in humans and established the relevant safety parameters. |
Type Of Material | Database/Collection of Data/Biological Samples |
Provided To Others? | No |
Impact | This is a world first, with no published articles describing this technique to date. We anticipate that the resulting data will revolutionise our understanding of the physiological substrate of spontaneous brain activity in particular epilepsy. |
Description | Ad-Tech Medical |
Organisation | Ad-Tech Medical Instrument |
Country | United States |
Sector | Private |
PI Contribution | This company has provided hardware in the form of products for us to test. In addition a partnership has been developing with funding applied for a collaborative partnership aimed at developing improved products. |
Collaborator Contribution | Provided free samples for testing. |
Impact | Grant nenewal application includes this industrial partnership |
Start Year | 2008 |
Description | Christian Albrechts University Kiel |
Organisation | University of Kiel |
Department | Neuropediatric Department Kiel |
Country | Germany |
Sector | Academic/University |
PI Contribution | We developed, implemented and applied a novel approach to analyse the EEG-fMRI data acquired in patients with frequent epileptic spikes aiming at direct detection of the neuronal currents in the fMRI data. |
Collaborator Contribution | Provided unique data which we analysed using our methodology |
Impact | A paper has been accepted for publication in an imprtant peer-reviewed journal. |
Start Year | 2007 |
Description | Geneva |
Organisation | University of Geneva |
Department | Epilepsy Unit |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | We provided data, expertise in EEG-fMRI data fusion and manpower. |
Collaborator Contribution | Provided part-time clinical research fellow for a period of 18 months. and EEG analysis software and expertise. |
Impact | New methodology, greater insight into the generators of epileptic activity based on EEG-fMRI data. Three joint publications to date (PMID: 19408351, 19817805, 19948231 and one publication in press), with more in preparation. |
Start Year | 2007 |
Description | Hammersmith Hospital |
Organisation | Hammersmith Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | We provided manpower to develop and run computer simulations. |
Collaborator Contribution | Expertise in modellng of electromagnetic and thermal effects on human body and implants related to MR |
Impact | Simulation results. No joint publication to date, but at least one planned. |
Description | Kings team |
Organisation | King's College London |
Department | Institute of Psychiatry, Psychology & Neuroscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We acquired data from patients recruited by the collaborator and analysed it. |
Collaborator Contribution | Recruited patients for our study and provided data and clinical expertise. |
Impact | A significant amount of new data. Publications are under preparation with one currently in press. |
Start Year | 2006 |
Description | Maastricht |
Organisation | Maastricht University (UM) |
Department | Faculty of Psychology and Neuroscience |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | We provided the data and manpower to run the analysis, with the help of our collaborators who supplied the methodology. |
Collaborator Contribution | Provided the projejct with new methodology to analyze our data and support, resulting in one publication to date and more being prepared. |
Impact | Entirely novel way of analysing our data. A joint publication in an important peer-reviewed journal resulted (PMID: 17889566). |
Start Year | 2006 |
Description | Marseille team |
Organisation | Aix-Marseille University |
Department | INSERM U751 (Stereotactic & Functional Neurosurgery) |
Country | France |
Sector | Academic/University |
PI Contribution | We acquired data on patiens recruited by the collaborator and analysed the data. |
Collaborator Contribution | Provided human subjects, data and expertise. |
Impact | Publicartions to date: PMID: 19408351, 19649252, 19948231, with two in press and many more in preparation. |
Description | Modena |
Organisation | University of Modena and Reggio Emilia |
Country | Italy |
Sector | Academic/University |
PI Contribution | Data sharing and analysis |
Collaborator Contribution | Exchange of research staff. |
Impact | None yet. |
Start Year | 2010 |
Description | North Bristol NHS Trust |
Organisation | Frenchay Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | We acquired data from the patients recruited by the collaborator and analysed and interpreted it, jointly with our collaborator. |
Collaborator Contribution | Recruited patients for our study and provided clinical data and expertise. |
Impact | EEG-fMRI data from 6 patients. One joint publication in press, with more in preparation. |
Start Year | 2007 |
Title | EEG-fMRI |
Description | Scalp EEG-fMRI for pre-surgical assessment of patients with drug-resistant epilepsy. |
Type | Diagnostic Tool - Imaging |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2009 |
Development Status | Under active development/distribution |
Impact | Funding as recently been obtained to conduct a hospital-based prospective study on the technique's efficacy at providing localisaing information in patients with drug-resistant epilepsy. The project started in May 2009. |
Description | Review article in professional journal |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Primary Audience | Health professionals |
Results and Impact | Article on "EEG, FMRI and Their Combination in the Study of Epilepsy" in Advances in Clinical Neuroscience & Rehabilitation journal. None know to date. |
Year(s) Of Engagement Activity | 2008 |
Description | Wikipedia article on EEG-fMRI |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Primary Audience | Public/other audiences |
Results and Impact | I wrote the article on EEG-fMRI in Wikipedia, and improved a number of articles in related areas. The article has been edited by other people suggesting it is being consulted. We do not know whether data is available on the number of times an article is browsed. |
Year(s) Of Engagement Activity | 2006 |