Excitatory neurotransmission via NMDA receptors in man: Basic mechanisms and role in epilepsy

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

Nerve cells communicate with each other using neurotransmitters. Glutamate is one of these chemicals, acting at receptors including NMDA. NMDA receptors are important in normal functions like learning, and binding changes are associated with epilepsy and other disorders. We have recently developed [11C] CNS5161 to image the level of NMDA receptor binding in the brain of living humans with positron emission tomography (PET).

We will first investigate NMDA binding in healthy controls while learning and while NMDA receptors are pharmacologically blocked, as well as changes following deep brain stimulation. This knowledge will then be used for the study of patients with focal epilepsies (in whom seizures start locally). If an area that gives rise to seizures can be identified it may help these patients to have an operation to remove this area and become seizure-free. We will also aim to identify common mechanisms of seizure generation by investigating patients with generalised seizures (absences) during absences.

Epilepsy affects about 350,000 people in the UK, and newly develops in 30,000 every year. The NHS spends £585M per year in direct medical costs on epilepsy and social costs are up to 4 times higher. New diagnostic and investigative techniques are urgently needed.

Technical Summary

Epilepsy is the most common serious neurological disorder, affecting 350,000 people in the UK. Current antiepileptic drug treatment does not control seizures in 30%. There is great need for improved diagnosis and therapy. Understanding of mechanisms underlying the generation of seizures is incomplete. The net excitation of neurons in an epileptic focus stems from excess excitation or lack of inhibition. To date, suitable positron emission tomography (PET) tracers for excitatory amino acid receptors have not been available.
Glutamate is the main excitatory neurotransmitter. N-methyl-D-aspartate (NMDA) receptors are a subtype of glutamate receptors. Their activation leads to Ca++ influx and changes synaptic strength, mediating physiological functions including memory. NMDA receptors are overactive in epilepsy and other neurological and mental health conditions. Modulators of NMDA neurotransmission offer an an antiepileptic and neuroprotective approach that could be applied to other brain disorders. NMDA antagonists are effective anticonvulsants in animal models, but have not yet emerged as therapeutic agents.
We have recently developed CNS5161, a specific NMDA receptor antagonist, as a [11C] labelled PET tracer with test-retest variation comparable to other standard ligands. We have a sufficient clinical base to enroll the patients required.
The main objective of this program is to further characterise the in vivo kinetics of [11C] CNS5161, in order to then apply [11C] CNS5161 to the study of epileptic syndromes. Specifically, I will test the hypotheses that:
In controls, cognitive learning paradigms will lead to NMDA channel opening, measurable as a change in binding of [11C] CNS5161, and binding will specifically decrease after pharmacological blockade with ketamine.
In patients with stimulators of the subthalamic nucleus, changes in brain stimulation will be associated with appropriate changes of [11C] CNS5161 binding.
In patients with focal epilepsies, [11C] CNS5161 binding per unit of grey matter will be increased in the epileptogenic area (defined by MRI and EEG), compared with the contralateral side and with controls.
[11C] CNS5161 binding will be increased in parallel to interictal epileptiform activity (spiking).
In patients with idiopathic generalised epilepsy, absence seizures provoked by hyperventilation will activate NMDA receptors, compared with baseline.
This work will contribute to the understanding of NMDA neurotransmission in healthy persons and abnormal neurotransmitter changes underlying common mechanisms of epileptogenesis, and inform the development of novel antiepileptic drugs. In addition, [11C] CNS5161 PET may be a useful diagnostic tool to identify areas of neuronal activation in consideration of epilepsy surgery.

Publications


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Aljabar P (2007) Classifier selection strategies for label fusion using large atlas databases. in Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
Bhatia KK (2007) Similarity metrics for groupwise non-rigid registration. in Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
Chupin M (2007) Fully automatic segmentation of the hippocampus and the amygdala from MRI using hybrid prior knowledge. in Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
Cross JH (2013) Neurological features of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome. in Developmental medicine and child neurology
 
Description Action Medical Research, Project Grant
Amount £148,510 (GBP)
Funding ID AMR AP 1208 
Organisation Action Medical Research 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start  
 
Description Dunhill Medical Trust Project Grant
Amount £173,262 (GBP)
Organisation The Dunhill Medical Trust 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start  
 
Title Adult brain atlases 
Description We expanded the collection of fully manually labelled human brain atlases based on high-resolution MRI images from 20 to 30 atlases, and refined / expanded the number of regions labelled from 49 to 83 per brain. 
Type Of Material Biological samples 
Year Produced 2006 
Provided To Others? Yes  
Impact As part of the "Imperial Imaging" collaboration, this material has enabled the development of the most accurate whole-brain anatomical segmentation method so far (key paper: Heckemann RA, ..., Hammers A, PMID: 16860573). Multiple other collaborations have ensued. 
URL http://europepmc.org/abstract/MED/16860573
 
Title Anatomical brain atlases for 2-year olds 
Description Automatically defined brain atlases for 2-year olds, validated against manual delineations, and describing the anatomical variability in this age group 
Type Of Material Biological samples 
Year Produced 2008 
Provided To Others? Yes  
Impact It is too early to estimate the impact, but the material has been downloaded approximately 50 times (excluding any duplicates) so should lead to better analyses in those research teams over the next years. 
URL http://www.brain-development.org
 
Title MAPER 
Description I cannot meaningfully fill in the field above because nothing corresponds. PS: O joy of inflexibility, I cannot update the record without choosing something. Please note that the information above is more or less random, but what do you want me to do? Methods developments for the automatic anatomical segmentation of unseen brain magnetic resonance images, including - healthy adults - healthy and preterm 2-year olds - elderly subjects - patients with neurodegenerative diseases 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact The key paper (Heckemann RA et al. 2006, PMID: 16860573) has already been cited over 200 times (Web of Science) / 400 times (Google Scholar Citations), and many other research groups are using similar multi-atlas propagation and enhanced registration techniques now. The techniques have allowed the development of automatic screening techniques for hippocampal atrophy in epilepsy which we aim to implement in a routine neuroradiology reporting service in a university hospital. Further developments allow reduction of sample size in Alzheimer's disease trials (Heckemann RA et al. 2006, PMID: 20114079). The MAPER method (extension of automatic labelling to very old subjects and subjects with dementia) was published in 2010 (Heckemann RA et al. 2010, PMID: 20114079). We have applied the technique to ~1000 brain images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We have published the method (Heckemann RA et al. 2011, PMID: 21397703) and made the ~1000 segmented brain images publicly available via the ADNI website. 
URL http://www.adni-info.org/
 
Description CERMEP 
Organisation CERMEP Imaging Centre
Country France, French Republic 
Sector Academic/University 
PI Contribution Methodological development and implementation in a patient-centered care context; intellectual input; grant application
Collaborator Contribution Intellectual input; access to data; patient recruitment
Impact Implementation of neuroscience method for individual patient care (used in about 100 patients a year now in the presurgical evaluation for epilepsy surgery; direct influence on management in about a third). Novel grant (Fédération pour la Recherche sur le Cerveau, FRC) to examine mechanisms of drug resistance via PET Publications so far: PMID: 18790822 PMID: 18765418 PMID: 21051649
Start Year 2006
 
Description Chiba 
Organisation National Institute of Radiological Science (NIRS)
Department Molecular Imaging Centre (NIRS)
Country Japan 
Sector Public 
PI Contribution Provision of human brain atlases and know-how; intellectual input
Collaborator Contribution Creation of a novel method of partial volume effect correction; integration into other efforts to compare such methods
Impact New method for partial volume effect correction, now being implemented for other PET cameras. Publication: PMID: 18852055
Start Year 2007
 
Description DCEE IoN UCL 
Organisation University College London (UCL)
Department UCL Institute of Neurology
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Multiple research projects in collaboration
Collaborator Contribution Integration in patient care and epilepsy surgery programme, access to patients, help with patient recruitment, access to data, intellectual input
Impact PMID: 18809501 PMID: 17851093 PMID: 17764977 PMID: 17579659 PMID: 17428687 PMID: 17301080 PMID: 16671082
 
Description EURIPIDES 
Organisation University College London (UCL)
Department UCL Institute of Neurology
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Intellectual input; collaboration via one of my project financed outside of the consortium; training of a consortium member
Collaborator Contribution Knowledge transfer on drug resistance imaging; participation in consortium meetingindirect benefit through funded post(s) in collaborating groups, knowledge transfer on drug resistance imaging, financed my participation in a consortium meeting
Impact Hammers A, Bouvard S, Costes N, Pereira de Souza Neto E, Lothe A, Keihaninejad S, Le Bars D, Didelot A, Mauguière F, Koepp MJ, Hirsch E, Ryvlin P. PGP action in temporal lobe epilepsy explored with [18F]MPPF: Intermediate results after blockade of PGP with cyclosporine A. Poster presentation at the 28th International Epilepsy Congress, June 28 - July 2 2009, Budapest, Hungary. "PET imaging of P-gp activity Human", oral presentation, American Epilepsy Society, Boston, Dec 2009 (P Ryvlin) Submitted: "Etude de l'impact de la glycoprotéine P (GPP) sur la fixation du [18F]MPPF dans l'épilepsie temporale humaine pharmacorésistante" Journée de Neurologie en Langue Française. April 2010, Lyon, France. Submitted: "Impact of P-glycoprotein on the distribution of [18F]MPPF in pharmacoresistant temporal lobe epilepsy", European Congress on Epileptology. June 2010, Rhodes, Greece.
Start Year 2007
 
Description EURIPIDES 
Organisation University Lyon 1
Country France, French Republic 
Sector Academic/University 
PI Contribution Intellectual input; collaboration via one of my project financed outside of the consortium; training of a consortium member
Collaborator Contribution Knowledge transfer on drug resistance imaging; participation in consortium meetingindirect benefit through funded post(s) in collaborating groups, knowledge transfer on drug resistance imaging, financed my participation in a consortium meeting
Impact Hammers A, Bouvard S, Costes N, Pereira de Souza Neto E, Lothe A, Keihaninejad S, Le Bars D, Didelot A, Mauguière F, Koepp MJ, Hirsch E, Ryvlin P. PGP action in temporal lobe epilepsy explored with [18F]MPPF: Intermediate results after blockade of PGP with cyclosporine A. Poster presentation at the 28th International Epilepsy Congress, June 28 - July 2 2009, Budapest, Hungary. "PET imaging of P-gp activity Human", oral presentation, American Epilepsy Society, Boston, Dec 2009 (P Ryvlin) Submitted: "Etude de l'impact de la glycoprotéine P (GPP) sur la fixation du [18F]MPPF dans l'épilepsie temporale humaine pharmacorésistante" Journée de Neurologie en Langue Française. April 2010, Lyon, France. Submitted: "Impact of P-glycoprotein on the distribution of [18F]MPPF in pharmacoresistant temporal lobe epilepsy", European Congress on Epileptology. June 2010, Rhodes, Greece.
Start Year 2007
 
Description GEHC / Hammersmith Imanet 
Organisation GE Healthcare
Department Hammersmith Imanet
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Private 
PI Contribution Intellectual input, data acquisition improvement, data acquisition management, "alignment", strategic discussions, etc.
Collaborator Contribution Collaboration on data acquisition, data acquisition management, data improvement, methods development
Impact Improvement of data acquisition. Methodological development. Quantification of patient and healthy volunteer motion during brain PET scanning. An MRes thesis (Correction for head movement in medical imaging with Positron Emission Tomography. Shao-Nan Wang, Imperial College London 2008. Conference contribution: Wang S, Hammers A, Thielemans K. An evaluation of different techniques for head movement correction in Positron Emission Tomography. Poster presentation at the World Molecular Imaging Congress (WMIC), September 10-13, 2008, Nice, France. Publications with GEHC/HI members: PMID: 18809501 PMID: 18786637 PMID: 17764977 PMID: 17301080 PMID: 17204713 PMID: 16671082 PMID: 20870689
 
Description Imperial Imaging 
Organisation Faculty of Engineering
Department Department of Computing
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Use of and further development of our manually constructed atlases, intellectual input, knowledge transfer, clinical / neurological angle on research, neuroanatomical knowledge, methods development, collaboration with students
Collaborator Contribution Knowledge transfer, computing infrastructure, intellectual input, collaborations with multiple studentsKnowledge transfer, computing infrastructure, intellectual input, collaborations with multiple students
Impact Tools for automatic anatomical segmentations of brain MRIs, disease classification tools, etc. Publications: PMID: 19815080 PMID: 19245840 PMID: 18979782 PMID: 18500985 PMID: 18051099 PMID: 18044611 PMID: 17428687 PMID: 17354848 PMID: 17354834 PMID: 16860573 PMID: 20079440 PMID: 20114079 PMID: 20114082 PMID: 20382238
 
Description Imperial Imaging 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Use of and further development of our manually constructed atlases, intellectual input, knowledge transfer, clinical / neurological angle on research, neuroanatomical knowledge, methods development, collaboration with students
Collaborator Contribution Knowledge transfer, computing infrastructure, intellectual input, collaborations with multiple studentsKnowledge transfer, computing infrastructure, intellectual input, collaborations with multiple students
Impact Tools for automatic anatomical segmentations of brain MRIs, disease classification tools, etc. Publications: PMID: 19815080 PMID: 19245840 PMID: 18979782 PMID: 18500985 PMID: 18051099 PMID: 18044611 PMID: 17428687 PMID: 17354848 PMID: 17354834 PMID: 16860573 PMID: 20079440 PMID: 20114079 PMID: 20114082 PMID: 20382238
 
Description King's College London 
Organisation King's College London (KCL)
Department Institute of Psychiatry (IoP)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Methodology to define anatomical cortical regions which has then enabled the definition of thalamic subregions via DTI
Collaborator Contribution Methodology to define anatomical regions by their connectivity patterns
Impact PMID: 20398772
Start Year 2008
 
Description Neonatal Medicine, MRC-CSC 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Knowledge transfer, intellectual input, creation of tools (automatically labelled brain atlases of 2-year old children and one-year old children; manually labelled brain atlases of neonates; work on automatically labelling neonatal brain MRIs)
Collaborator Contribution Knowledge transfer, access to datasets
Impact Tools (automatically labelled brain atlases of 2-year old children and one-year old children; manually labelled brain atlases of neonates; work on automatically labelling neonatal brain MRIs) Publications: PMID: 18234511 PMID: 20079440 Abstracts: Gousias IS, Hammers A, Counsell SJ, Rueckert D, Edwards AD. A new resource for imaging research in neonates: Manually defined brain atlases. Acta Paed 2009, 98, Suppl 460, p. 146-147 Keihaninejad S, Heckemann RA, Aljabar P, Rueckert D, Gousias IS, Hammers A. Automatic volumetry can reveal visually undetected disease features on brain MRI images in temporal lobe epilepsy. Multi-page conference submission to ISBI 2010, November 2010 85. Gousias IS, Hammers A, Heckemann RA, Counsell S, Boardman JP, Edwards AD, Rueckert D. Atlas selection strategy for automatic segmentation of pediatric brain MRIs into 83 ROIs. Presentation at IEEE International Conference on Imaging Systems and Techniques, Thessaloniki, Greece, July 2010. Proceedings of the IEEE International Conference on Imaging Systems and Techniques, July 2010, (DOI: 10.1109/IST.2010.5548493).
 
Description PET Methodology 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Contribution of materials (data, human brain atlases), collaborations on improvements in data collection and corrections (e.g. motion correction, partial volume effect correction).
Collaborator Contribution Methodological and statistical input, intellectual input, important discussions to refine ideas and take them forward
Impact Multiple methodological improvements and new developments. PMID: 18852055 PMID: 18786637 PMID: 17851093 PMID: 17764977 PMID: 17579659 PMID: 17398120 PMID: 17204713 PMID: 16182554 PMID: 20870689
 
Description University of Mainz, Germany 
Organisation The Johannes Gutenberg University of Mainz
Country Germany, Federal Republic of 
Sector Academic/University 
PI Contribution Intellectual input
Collaborator Contribution The strategies for image intensity normalisation we co-developed are useful for many of my studies.
Impact We have co-developed one of the most promising data normalisation strategies to detect abnormalities in brain glucose metabolism measured by FDG-PET. This vastly improves the detection of abnormalities in individual patients with Alzheimer's disease and mild cognitive impairment (PMID: 18691659) and is beginning to be widely used. It may also have applications in epilepsy and other diseases. Publications: PMID: 18930634 PMID: 18691659 PMID: 20109475
Start Year 2006
 
Title Atlas databases 
Description Atlas databases 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2006
Licensed Yes
Impact See other sections As of December 2011, over 100 academic licences have been granted; some atlas resources have been licenced to a company; a software company is in the process of taking a commercial licence. PS: As the atlas databases are automatically copyrighted, the question 8.4.1/8.4.2 makes no sense. The system forced me to give an answer so I put "2006" in.
 
Description Biomedical industry and Council meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Presentation to rerpresentatives of the biomedical industry and the GrandLyon (city and regional authorities)

Several contacts with biomedical industry representatives; now get channeled requests through city and regional authorities
Year(s) Of Engagement Activity 2009
 
Description Brain Week / Semaine du Cerveau 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Hundreds of people passed through the tent; dozens looked at the displays; I had in-depth interaction with under ten, often members of the public with a family member with epilepsy.
2013: Similar to 2012.

I would not know how to quantify the impact.
Year(s) Of Engagement Activity 2012,2013
URL https://www.dropbox.com/s/2ptl2zwsmvh49rh/RapportActivites2013.pdf
 
Description Charing Cross Hospital, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact Where is the brain, and what does it do? Interactive presentation in a public space inside a hospital. Target: patients, staff

I don't think this was well pitched and don't think it had any impact.
Year(s) Of Engagement Activity 2007
 
Description Cybertots Nursery, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Interactive presentation on the brain in a nursery (2-5 year olds)

The nursery teachers learned about, amongst other things, epilepsy which will be useful when they have children with epilepsy. For the toddlers, it is a bit early to say whether they will be more likely to study neuroscience as a result!
Year(s) Of Engagement Activity 2006
 
Description Epilepsy information for school (pupils; teachers) 
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 Following an incident case of epilepsy,
- 30 min presentation to class
- 30 min presentation to staff


I may have saved some teeth by explaining _not_ to put anything into seizing people's mouths.
Especially teachers reported feeling better prepared to deal with epileptic seizures.
Year(s) Of Engagement Activity 2011
 
Description Open University talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk about "The brain and its image" to about 60 participants of an Open University Course in Lyon, France

Very well received, lots of questions, have as a consequence been invited to speak at Lyon's Science University "Scientific Evenings" (2012).
Year(s) Of Engagement Activity 2011
 
Description Outpatients 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact As a Clinician Scientist, I discuss our research regularly with my patients in Outpatient clinics, well beyond recruitment for ongoing studies; they are generally aware of what is going on; and I become aware of what their priorities are.

Realising that for some patients, aspects of their epilepsy other than seizures are at least as important, notably memory impairment, has directly influenced the design of one of our studies. A major study on a particular neurotransmitter receptor class in relation to seizures has also been inspired by literature searches triggered by patient experiences.
Year(s) Of Engagement Activity 2006,2007,2008,2009
 
Description Presidency of Annual Banquet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact >120 former pupils of a Lycée (a form of university college offering 3-year courses after A-levels, including in Medical Imaging) - presented on "Imaging and Epilepsy". Excellent feedback and great interest from public, patients, current students and teachers.

Lycée asked for formal presentations to their BSc Medical Imaging students; agreement in principle that they can become Summer Students in the lab
Year(s) Of Engagement Activity 2010
 
Description Press conference 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact We presented results obtained so far using PET and MRI in the epilepsies, and plans for the future, to an audience of approx. 40 journalists

Good printed press coverage (e.g. http://www.leprogres.fr/fr/permalien/article/2038818/Doper-la-recherche-pour-qu-elle-profite-plus-vite-au-patient.html) and local television evening news - several requests for further information etc. have resulted.
Year(s) Of Engagement Activity 2009
URL http://www.leprogres.fr/fr/permalien/article/2038818/Doper-la-recherche-pour-qu-elle-profite-plus-vi...
 
Description School Visit 
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 Talk about "The Brain" in front of two classes of 6-7 year olds at an international school in Lyon. Voted Best Presentation of the Term by some pupils.
2011: "The Brain" for Grade 2 (6-7 year olds); again enthusiastic feedback.
2012: From macro to nano: how to visualise subatomic particles? Interactive 30-minute presentation of a PET block detector and photomultiplier tube at ISL (International School of Lyon) as part of a "Unit of enquiry" on nanotechnology, Lyon, Monday 22nd of October, 2012 (for grade 5, i.e. 10/11 year olds - 16 participants).
2013: 19. The brain and its representations: History and application of imaging in epilepsy. Interactive presentation at ISL (International School of Lyon), Monday 18th of March, 2013 (for Intensive Science Course, i.e. 17/18 year olds - 1h20).
2013: 20. Healthy Living - how do physical activity and nutrition affect our brain and nervous system? Filmed interview for the Grade 5 (11 year olds) exhibition at ISL (International School of Lyon), Monday 18th of March, 2013 (0.5h).
2014: 21. What will be the next breakthroughs in neuroscience, and other questions about the brain in children and adults. Filmed interview for the Grade 5 (11 year olds) exhibition at ISL (International School of Lyon), Saturday 12th of April, 2014 (0.5h).

Sparked general interest from pupils and teacher, but pupils are a bit young to become neuroscientists yet.
Update 2014: Have now done many more school events - some children report wanting to become scientists
Year(s) Of Engagement Activity 2009,2011,2012,2013,2014
 
Description School visit (From nano to macro) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact From macro to nano: how to visualise subatomic particles? Interactive 30-minute presentation of a PET block detector and photomultiplier tube at ISL (International School of Lyon) as part of a "Unit of enquiry" on nanotechnology, Lyon, Monday 22nd of October, 2012 (for grade 5, i.e. 10/11 year olds - 16 participants)

Extremely good feedback. Several students wrote to me saying they wanted to work in science afterwards.
Year(s) Of Engagement Activity 2012
 
Description Science Museum, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Where is the brain? What does it do? How does it do that?. Interactive presentation for 8-9 year olds (several runs)

Hard to know. They liked it.
Year(s) Of Engagement Activity 2006
 
Description TV documentary 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Contribution of material and interview to three-minute TV documentary about Lyon's 80M€-bid for an Academic Health Sciences Centre (Institut Hospitalo-Universitaire, IHU) "Brain and Mental Health" (Cerveau et Santé Mentale, CESAME) as part of France's Economic Stimulus Package (Investissements d'Avenir), France 3, Friday 25th of February, 2011, 19h08, http://www.pluzz.fr/jt-19-20-rhone-alpes-2011-02-25-19h00.html.

How to tell? We got 6M of funding in the end, but this was certainly unrelated to the TV documentary.
Acquaintances had seen me by chance on TV, though, and had found the documentary interesting - will have sparked interest in epilepsy and epilepsy surgery.
Year(s) Of Engagement Activity 2011
URL http://www.pluzz.fr/jt-19-20-rhone-alpes-2011-02-25-19h00.html
 
Description University Science Evenings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact "Le cerveau et son image: Histoire et application dans l'épilepsie" [The brain and its image: History and application to epilepsy]. Lyon, Tuesday 17th of April, 2012. About 80 participants.
Lively discussion.

Very good feedback. Otherwise impossible to tell.
Year(s) Of Engagement Activity 2012