Professor Matthias Koepp

Matthias J. Koepp, MD PhD FRCP

Our research uses advanced MRI modalities (functional magnetic resonance tomography (fMRI), dynamic contrast-enhanced (DCE) MRI and positron emission tomography (PET) to better understand mechanisms of seizure development and suppression, cognitive and affective comorbidities, and to predict cognitive, mood and seizure outcome following therapeutic interventions.

Imaging neurotransmitter fluxes

We have used PET to image specific neurotransmitter release following seizures (opioids), through behavioural challenges (dopamine), and most recently during a working memory task (glutamate). The goal is to identify mechanisms of drug resistance in epilepsy, and to find out how epilepsy affects behaviour and cognition.

Legend:  PET scan with 18F-GE179 to image activated, open NMDA receptors in NMDA-antibody encephalitis

Imaging accelerated ageing in epilepsy

Funded by the Wellcome Trust, we currently use tau-PET to investigate the bi-directional link between epilepsy and Alzheimer’s Disease (AD). We identified progressive cortical atrophy in longitudinal studies of focal epilepsies
 

Legend: Progressive cortical atrophy occurs in longitudinal studies of focal epilepsies, which resembles the atrophy patterns seen in AD. (Braak stages on the right)

Using Artificial Intelligence, we determined from a single MRI scan that atrophy of the brain progresses in three distinct patterns, suggesting that fundamental processes underly the progression of epilepsy-related brain atrophy. 

Legend: patterns of atrophy of cortex, basal ganglia and hippocampus in individuals with epilepsy. 

Imaging of Area tempestas - the master-switch 

We have the aim to reduce “trial-and-error” when choosing how to best treat individuals with epilepsy. Analysing MRI brain scans before and after anterior temporal lobe epilepsy resections, we showed that resection of the temporal portion of the piriform cortex gave a much higher seizure freedom rate.

Legend: Surgical removal of the temporal portion of the piriform cortex (red) greatly increases the chances of being seizure free.

Imaging the effects of drugs

We have shown that MRI brain imaging can be used to predict the effects of antiseizure medications. Using a verbal fluency task and fMRI, control of focal to bilateral tonic-clonic seizures with the AMPA-antagonist Perampanel was associated with activation of thalamus and caudate, and undesired side-effects of anger and aggression with increased activation in the orbitofrontal cortex.

Legend: Changes in verbal fluency fMRI activation patterns before and after treatment with Perampanel.

Post-mortem brain imaging

We have developed non-invasive post-mortem-MRI, which will identify and validate risk-biomarkers for SUDEP, and also reduce the additional burden of invasive-post-mortem examinations for bereaved families. 
We have developed non-invasive post-mortem-MRI, which will identify and validate risk-biomarkers for SUDEP, and also reduce the additional burden of invasive-post-mortem examinations for bereaved families. 
 

Legend: Post mortem MRI of the brain of an individual with chronic encephalitis Pathology-confirmed left atrophy, and the pathological and histological examinations. 

Selected Recent Publications 

  • Galovic M, Al-Diwani A, Vivekananda U, Walker MC, Irani SR, Koepp MJ; NEST Investigators. In Vivo N-Methyl-d-Aspartate Receptor (NMDAR) Density as Assessed Using Positron Emission Tomography During Recovery From NMDAR-Antibody Encephalitis. JAMA Neurol. 2023 Feb 1;80(2):211-213.
  • Galovic M, Baudracco I, Wright-Goff E, Pillajo G, Nachev P, Wandschneider B, Woermann F, Thompson P, Baxendale S, McEvoy AW, Nowell M, Mancini M, Vos SB, Winston GP, Sparks R, Prados F, Miserocchi A, de Tisi J, Van Graan LA, Rodionov R, Wu C, Alizadeh M, Kozlowski L, Sharan AD, Kini LG, Davis KA, Litt B, Ourselin S, Moshé SL, Sander JWA, Löscher W, Duncan JS, Koepp MJ. Association of Piriform Cortex Resection With Surgical Outcomes in Patients With Temporal Lobe Epilepsy. JAMA Neurol. 2019 Jun 1;76(6):690-700.
  • Galovic M, de Tisi J, McEvoy AW, Miserocchi A, Vos SB, Borzi G, Cueva Rosillo J, Vuong KA, Nachev P, Duncan JS, Koepp MJ. Resective surgery prevents progressive cortical thinning in temporal lobe epilepsy. Brain. 2020 Dec. 5;143(11):3262-3272.
  • Xiao F, Caciagli L, Wandschneider B, Fleury M, Binding L, Giampiccolo D, Hill A, Galovic M, Foong J, Zhou D, Sander JW, Duncan JS, Koepp MJ. Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy. Epilepsia. 2023 Feb;64(2):e9-e15.
  • Xiao F, Caciagli L, Wandschneider B, Sone D, Young AL, Vos SB, Winston GP, Zhang Y, Liu W, An D, Kanber B, Zhou D, Sander JW, Thom M, Duncan JS, Alexander DC, Galovic M, Koepp MJ. Identification of different MRI atrophy progression trajectories in epilepsy by subtype and stage inference. Brain. 2023 Nov 2;146(11):4702-4716.