Direct electrical cortical stimulation to reconstruct epileptiform afterdischarge networks Lorenzo Caciagli 1, Roman Rodionov 1, Catherine Scott 2, Tim Wehner 1,2, Andrew McEvoy 1,3, Louis Lemieux 1, Beate Diehl 1,2, Gerold Baier 4 1 UCL Institute of Neurology, Department of Clinical and Experimental Epilepsy, Queen Square, London, UK; 2 Department of Clinical Neurophysiology and 3 Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; 4 Department of Cell and Developmental Biology, University College London, Gower Street, London, UK UCL INSTITUTE OF NEUROLOGY NHNN – QUEEN SQUARE BACKGROUND Extra-operative direct electrical cortical stimulation (DCS) is widely employed to map eloquent cortex in patients with intracranial EEG electrodes undergoing pre-surgical assessment for refractory epilepsy 1. It can be performed as bipolar DCS, which involves the stimulation of adjacent electrode pairs, or monopolar DCS, during which the stimulated channel pair is represented by one electrode referenced to a distant electrode overlying non-eloquent cortex 2. Some DCS trials evoke local paroxysms of epileptiform activity, known as afterdischarges (ADs) 3,4, in stimulated and non-stimulated EEG channels. There is limited understanding of the neurophysiological underpinnings and network properties of ADs, and more generally of the effects of DCS on local neural dynamics 3-5. PURPOSE To compare AD- and non-AD-containing post-stimulation epochs against baseline activity to quantify AD-specific power spectral changes. To devise an algorithm for the reconstruction of AD-underlying networks. To compare AD-related networks obtained after bipolar DCS with those derived for ADs occurring after monopolar DCS. CONCLUSIONS Afterdischarges are associated with a statistically significant increase in the proportion of slow components in the EEG power spectrum. Fraction of channels containing ADs varied between 2.4 and 24.7%. The newly developed algorithm reliably allows us to define the network of nodes that participate in afterdischarges across multiple frequency bands. Patterns of AD-related networks evoked after monopolar vs bipolar DCS overlap only marginally. Network properties in the beta and gamma range (“attenuation networks”) are instead more uniform, with nodal distribution involving a set of nodes located in the more rostral portion of the main electrode grid. RESULTS References: 1) Stephani and Lüders, John Libbey Eurotext, 2011; 2) Kovac et al., Clin Neurophysiol 2014; 3) Blume et al., Clin Neurophysiol 2004; 4) Kalamangalam et al., Clin Neurophysiol 2013; 5) Borchers et al., Nat Rev Neurosci METHOD iEEG recordings (subdural grid and depth electrodes) in 3 patients with pharmacoresistant frontal lobe epilepsy secondary to cortical dysplasia POWER SPECTRAL CHANGES POWER SPECTRUM EXTRACTION for delta (0.5- 4Hz), theta (4-7.5Hz), alpha (8-13Hz), beta (13-30Hz) and gamma (31-60Hz) bands Channel defined as “POSITIVE” NODE if its band-specific power value was higher than the highest corresponding value of the baseline segment. Channel defined as “NEGATIVE” NODE if its band-specific power value of a channel was lower than the lowest corresponding baseline one. Channels Time Comparison of 4 AD-containing traces obtained with bipolar vs. 4 AD- containing traces obtained using monopolar DCS * ** * * p < 0.01, Mann- Whitney U ** p < 0.001, Mann-Whitney U Analysis on 37 AD and 41 non-AD traces. On y axis, median number of channels (expressed in percentage) emerging as nodes compared with baseline 64s BASELINE TRACE4s AD EPOCHS4s PAIRED NON-AD EPOCHS For each subject For each frequency band EDGES of AD networks derived by comparing their covariance matrices with Fourier-adjusted surrogate data Pilot analysis suggests focusing on positive nodes for delta, theta and alpha Pilot analysis suggests focusing on negative nodes for gamma and beta GA17-GA31 Patient 1 GA17-GA32 Patient 1 GA31-GA32 Patient 1 GA17-GA31 Patient 1 GA17-GA32GA31-GA32 EXAMPLES OF AD - UNDERLYING NETWORKS - DELTA BAND EXAMPLES OF AD - UNDERLYING NETWORKS - BETA BAND Electrodes/channelsNodes Stimulated channel pairIctal onset zone White arrows indicate central sulcus MONOPOLAR BIPOLAR Patient 1 BIPOLARMONOPOLAR Patient 1 and 2, all trials with ADs compared to all trials without ADs Significant increase in delta, theta and alpha band power in stimulation trials with ADs Trend towards a decrease in beta band power in stimulation trials with ADs DCS features 50 Hz, 1-7 mA, max 5s