Clinical Applications of EEG-fMRI: Epilepsy Andrew Bagshaw School of Psychology EEG-fMRI in Epilepsy  Generally, we are NOT looking at seizures – Ictal – Interictal    seizures  between seizures (spikes) Patients undergo 1-2 hour EEG-fMRI scanning session with no task Analysis steps: – Artefact removal, identification of spikes and event-related fMRI analysis  Identify voxels whose signal changes reliably whenever an epileptic event occurs  Long term goals: – To aid in pre-surgical evaluation  Placement of intracranial electrodes? – To provide a better understanding of the mechanisms producing epilepsy  Pre-surgical Evaluation  Basic Mechanisms of Epilepsy  Future Directions Pre-surgical Evaluation Temporal Lobe Epilepsy (TLE) The most common form of focal epilepsy  Responds well to surgery  Varied EEG-fMRI responses are observed  What is the significance of the ‘unexpected’ regions? – Can these responses differentiate between patients (surgical outcome etc.)?  Spikes F7T3 Kobayashi et al Epilepsia 47 343-354 (2006) Localisation Accuracy  How is localisation accuracy assessed? – Electro-clinical features (e.g MRI lesions, scalp EEG topography, seizure symptomatology)  See Al Asmi et al Epilepsia 2003, Salek-Haddadi et al Brain Res 2006, Di Bonaventura et al Epilepsia 2006 – EEG source localisation   See Lemieux et al Neuroimage 2001, Bagshaw et al Neuroimage 2006, Leal et al Epilepsia 2006, Boor et al Clin Neurophysiol 2007 Comparison with distributed EEG models is ongoing (Grova et al In press) – Intracranial or stereotaxic EEG (SEEG)   e.g Bénar et al 2006, Laufs et al Magn Reson Imag 2006 For clinical use of EEG-fMRI in pre-surgical evaluation this issue needs to be better addressed Basic Mechanisms of Epilepsy Generalised Epilepsy   Idiopathic generalised epilepsy is characterised interictally by generalised spike and wave (GSW) discharges in the EEG What regions are involved in GSW discharge generation? – Positive EEG-fMRI response  Confirms role of thalamus seen in animal models Aghakhani et al Brain 127 1127-1144 (2004) Generalised Epilepsy    Negative response – Regions involved in default attentional network (Raichle et al PNAS 2001) – See also Archer et al Neuroimage 2003, Gotman et al PNAS 2005, Hamandi et al Neuroimage 2006 – Recently also seen in TLE (Laufs et al Hum Brain Mapp 2007) Suggests that discharges disrupt ongoing brain processes The regions identified by EEG-fMRI relate not only to the generation of the discharges, but their wider effect on brain function Aghakhani et al Brain 127 1127-1144 (2004) Negative BOLD Kobayashi et al Hum Brain Mapp 27 488-497 (2006)  Widely seen in interictal EEG-fMRI – Generally poorer correspondence with electro-clinical features – See Kobayashi et al Hum Brain Mapp 2006, Salek-Haddadi et al Brain Res 2006  What is the neurophysiological and clinical significance of negative responses in epilepsy? Future Directions Ongoing Issues (1)  Interpretation and Validation – Not all regions of activation correspond well with electro-clinical information  e.g extratemporal responses to temporal lobe spikes – Is this new and clinically useful information?  How can a more detailed interpretation of these regions of activation be achieved? – SEEG (but not helpful for non-congruent responses) – MR spectroscopy (NAA, Cho, Cr changes) – Post-surgical outcome… Ongoing Issues (2)  Patient selection – Patients must have interictal activity but rare seizures – 30-40% with discharges in the scanner have no EEG-fMRI responses  Al Asmi et al Epilepsia 2003, Salek-Haddadi et al Brain Res 2006, Di Bonaventura et al Epilepsia 2006  This may be in part be related to SNR issues (Kobayashi et al Neurology 2006) and improve at higher field strengths – How to predict whether a patient will show EEG-fMRI responses beforehand based on the EEG?  More spikes, runs of discharges, less head movement and fewer background abnormalities (Salek-Haddadi et al Brain Res 2006) – Can properties of the EEG other than spikes be used?    Delta (Laufs et al Magn Reson Imag 2006) Gamma (Willoughby et al JNNP 2003) cf HFO from SEEG? Conclusions EEG-fMRI is a robust research tool which can provide new information about the generation and consequences of epileptic activity  It remains a technique with potential in clinical epilepsy management, rather than a widely used tool  Acknowledgements University of Birmingham – Shoumitro Deb, Imad Soryal, Tracy Warbrick Montreal Neurological Institute Jean Gotman, Franỗois Dubeau, Eliane Kobayashi, Christian Bénar, Christophe Grova, Yingli Lu, Colin Hawco  ... Bonaventura et al Epilepsia 2006 – EEG source localisation   See Lemieux et al Neuroimage 2001, Bagshaw et al Neuroimage 2006, Leal et al Epilepsia 2006, Boor et al Clin Neurophysiol 2007 Comparison