Seizure abatement with Single DC Pulses: is Phase resetting at Play?

Topological approaches for seizure abatement have received scarce attention. The ability to reset the phase of biological oscillations has been widely exploited in cardiology, as evidenced in part by the usefulness of implantable of defibrillators, but not in epileptology. The aim of this work is to investigate the feasibility of seizure blockage using single or brief monophasic (DC) pulse trains. Single DC or brief (0.1 s) pulse trains were delivered manually or automatically to generalized seizures, induced in rats with the convulsant 3-mercaptoprionic acid, a GABA inhibitor. Treatment outcome (blocked vs. not blocked seizures) was ascertained visually and correlated with the "rhythmicity index", an indirect estimate of neuronal synchrony level. Blockage using single or brief (0.1 s) DC pulses was consistently achieved for seizures with a rhythmicity index > 0.6, while seizures with levels <0.6 were not, although transient phase changes in their oscillations were effected. This work reveals that level of neuronal synchronization may be an important factor in determining the probability of seizure blockage. Seizure blockage using single or brief DC pulse trains and its effects on neural tissue merit further investigation. The clinical applicability of this therapeutic modality and means to enhance it are discussed.

[1]  A. Winfree,et al.  Sudden Cardiac Death: A Problem in Topology , 1983 .

[2]  R. Shepherd,et al.  Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli. , 1999, Acta oto-laryngologica.

[3]  Brian Litt,et al.  Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy , 2004, Epilepsia.

[4]  I. Osorio,et al.  Real‐Time Automated Detection and Quantitative Analysis of Seizures and Short‐Term Prediction of Clinical Onset , 1998, Epilepsia.

[5]  R. Lesser,et al.  Brief bursts of pulse stimulation terminate afterdischarges caused by cortical stimulation , 1999, Neurology.

[6]  Daniel R. Merrill,et al.  Electrical stimulation of excitable tissue: design of efficacious and safe protocols , 2005, Journal of Neuroscience Methods.

[7]  D. Contreras,et al.  Synchronized sleep oscillations and their paroxysmal developments , 1994, Trends in Neurosciences.

[8]  D. Durand,et al.  Suppression and control of epileptiform activity by electrical stimulation: a review , 2001, Proc. IEEE.

[9]  P. Gerin Microelectrode investigations on the mechanisms of the electrically induced epileptiform seizure ("afterdischarge") , 1960 .

[10]  M. Kawato,et al.  Biological oscillators can be stopped—Topological study of a phase response curve , 1978, Biological Cybernetics.

[11]  Peter A. Tass,et al.  Desynchronization of brain rhythms with soft phase-resetting techniques , 2002, Biological Cybernetics.

[12]  S. Schiff,et al.  Decreased Neuronal Synchronization during Experimental Seizures , 2002, The Journal of Neuroscience.

[13]  C. Antzelevitch,et al.  Phase resetting and annihilation of pacemaker activity in cardiac tissue. , 1979, Science.

[14]  Warren M. Grill,et al.  Selection of stimulus parameters for deep brain stimulation , 2004, Clinical Neurophysiology.

[15]  Mojgan Hodaie,et al.  Chronic Anterior Thalamus Stimulation for Intractable Epilepsy , 2002, Epilepsia.

[16]  R. Jindra Analysis of the non-stationary EEG by means of an approximate canonical expansion , 1978, Biological Cybernetics.

[17]  B. Werigo Die depressive Kathodenwirkung, ihre Erklärung und ihre Bedeutung für Elektrophysiologie , 1901, Archiv für die gesamte Physiologie des Menschen und der Tiere.

[18]  Ivan Osorio,et al.  Automated seizure abatement in humans using electrical stimulation , 2005, Annals of neurology.

[19]  C D Binnie,et al.  Responses to single pulse electrical stimulation identify epileptogenesis in the human brain in vivo. , 2002, Brain : a journal of neurology.

[20]  Ana Luisa Velasco,et al.  Stimulation of the Central Median Thalamic Nucleus for Epilepsy , 2002, Stereotactic and Functional Neurosurgery.

[21]  Kristl Vonck,et al.  Long‐term amygdalohippocampal stimulation for refractory temporal lobe epilepsy , 2002, Annals of neurology.

[22]  Ivan Osorio,et al.  High Frequency Thalamic Stimulation for Inoperable Mesial Temporal Epilepsy , 2007, Epilepsia.

[23]  Ying-Cheng Lai,et al.  Characterization of synchrony with applications to epileptic brain signals. , 2007, Physical review letters.

[24]  A. Winfree Phase control of neural pacemakers. , 1977, Science.

[25]  B. Pakkenberg,et al.  An efficient method for estimating the total number of neurons in rat brain cortex , 1990, Journal of Neuroscience Methods.