Generalized spike-and-wave discharges offset is related to precuneal-posterior cingulate activity.

Introduction: Recent EEG-fMRI studies revealed that a widespread neural network subserves the generation of ictal and interictal activity in patients with generalized epilepsy (1-4). Different studies investigated the hemodynamic changes related to the onset and duration of generalized spike-and-wave discharges (GSWD) in human epilepsy. Conversely, the BOLD signal changes related to GSWD termination has not been addressed to date. Few studies have focused the mechanisms that promote seizures stop at molecular and cellular level (6). In particular, a recent single neuron recording study in human focal epilepsy (7) revealed that neuronal firing patterns change homogeneously at seizure offset suggesting that seizure termination is marked by an abrupt homogeneous change in neuronal firing. These data support a mechanism that acts at the neural network level. The present EEG-fMRI study aimed at evaluating the neural correlates of seizure termination studying the BOLD variations at GSWD offset in a large sample of patients with Idiopathic generalized epilepsy (IGE). Materials and methods: eighteen patients (6 male; mean age 25 yrs.) with IGE were included. Scalp EEG was recorded by means of a 32 channels MRI-compatible EEG recording system. Functional data were acquired with a 3T Philips Intera System (TR=3000 ms) from 30 axial contiguous 4 mm slices (64 x 64 matrix) over two-three 10-min sessions per patient with continuous simultaneous video-EEG recording. Event-related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at a second level random effect analysis. Results: a mean of 17 events for each patient was recorded (mean duration= 4 s). Second-level random effect analysis related to onset and GSWD length confirmed previous findings (5) revealing a thalamus activation and a parietal and precuneus-posterior cingulate deactivation. GSWD onset respect to the offset showed BOLD increases in the prefrontal regions (inferior and middle frontal gyrus) mostly on the left side and in the bilateral primary visual cortex. Conversely, GSWD offset respect to the onset revealed significant hemodynamic changes over the precuneus-posterior cingulate region (Fig. 1). Conclusions: fMRI results showed that the neural network at GSWD termination involved precuneus-posterior cingulate region. These findings confirm an important role of this brain region in GSWD pathophysiology. Particularly, precuneal/posterior cingulate neuronal activity might participate actively to the GSWD termination or it might reflect the recovery of the awareness impaired during the pathological activity. BIBLIOGRAFY 1) Gotman J, Grova C, Bagshaw A, Kobayashi E, Aghakhani Y, Dubeau F. (2005) Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci USA, vol. 102, pp. 15236–15240. 2) Moeller F, Siebner HR, Wolff S, Muhle H, Boor R, Granert O, Jansen O, Stephani U, Siniatchkin M. (2008) Changes in activity of striato-thalamo- cortical network precede generalized spike wave discharges. Neuroimage vol. 39, pp. 1839–1849. 3) Vaudano AE, Laufs H, Kiebel SJ, Carmichael DW, Hamandi K, Guye M, Thornton R, Rodionov R, Friston KJ, Duncan JS, Lemieux L. (2009) Causal hierarchy within the thalamo-cortical network in spike and wave discharges. PLoS ONE vol. 4:e6475. 4) Carney PW, Masterton RA, Harvey AS, Scheffer IE, Berkovic SF, Jackson GD. (2010) The core network in absence epilepsy. Differences in cortical and thalamic BOLD response. Neurology vol. 75, pp. 904–911. 5) Benuzzi F, Mirandola L, Pugnaghi M, Farinelli V, Tassinari CA, Capovilla G, Cantalupo G, Beccaria F, Nichelli P, Meletti S (2012). Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies. Epilepsia, vol. 53(4), pp. 622-30. 6) Fred A. Lado, Solomon L. Moshé (2008). How do seizures stop? Epilepsia, vol. 49 (10), pp. 1651–1664. 7) Wilson Truccolo,Jacob A Donoghue,Leigh R Hochberg, Emad N Eskandar, Joseph R Madsen, William S Anderson, Emery N Brown, Eric Halgren, Sydney S Cash (2011). Single-neuron dynamics in human focal epilepsy, Nature Neuroscience,vol. 14 (5), pp. 635-641.