Annika Lüttjohann1, Gilles van Luijtelaar. 1. Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Radboud University Nijmegen, Nijmegen, The Netherlands. a.luttjohann@donders.ru.nl
Abstract
PURPOSE: The site specific effects of two different types of electrical stimulation of the thalamus on electroencephalic epileptic activity as generated in the cortico-thalamo-cortical system were investigated in genetic epileptic WAG/Rij rats, a well characterized and validated absence model. METHODS: First, 12 male rats received low frequency (double-pulse pairs of 2.5Hz, 150 μA intensity and 30s inter-pair-interval) open-loop stimulation to either the Ventral-Postero-Medial (VPM) or the Anterior Thalamic Nucleus (ATN) for 8h. Second, rats received high frequency (130Hz, pulse train of 1s) closed-loop stimulation applied to either VPM or ATN whenever a spike-wave discharge (SWD) was automatically detected. RESULTS: Low frequency stimulation induced 8Hz SWD-like afterdischarges (AD). AD were frequently seen in VPM but rarely in ATN stimulated rats. AD, recorded in cortex and thalamus, showed a strong temporal coherence (visually assessed) and opposite spike polarities. Properties of AD and spontaneous SWD were equally affected by the stimulation. Closed-loop high frequency stimulation disrupted spontaneous SWD with no difference between ATN and VPM stimulated rats. 89% of SWD could be disrupted leading to a decrease in average SWD duration from 9 to 1.5s. CONCLUSION: Low frequency stimulation induced AD, which strongly mimic SWD. Moreover, the effects were site-specific. High frequency thalamic stimulation disrupts ongoing SWD probable by interfering with the slow firing pattern of cortico-thalamo-cortical neurons seen during SWD cycle. The absence of stimulation site specificity for high frequency stimulation might be due to the fact that stimulation only started on average 1s after SWD onset when SWD are already fully expressed in the bidirectional cortico-thalamo-cortical resonance system.
PURPOSE: The site specific effects of two different types of electrical stimulation of the thalamus on electroencephalic epileptic activity as generated in the cortico-thalamo-cortical system were investigated in genetic epileptic WAG/Rij rats, a well characterized and validated absence model. METHODS: First, 12 male rats received low frequency (double-pulse pairs of 2.5Hz, 150 μA intensity and 30s inter-pair-interval) open-loop stimulation to either the Ventral-Postero-Medial (VPM) or the Anterior Thalamic Nucleus (ATN) for 8h. Second, rats received high frequency (130Hz, pulse train of 1s) closed-loop stimulation applied to either VPM or ATN whenever a spike-wave discharge (SWD) was automatically detected. RESULTS: Low frequency stimulation induced 8Hz SWD-like afterdischarges (AD). AD were frequently seen in VPM but rarely in ATN stimulated rats. AD, recorded in cortex and thalamus, showed a strong temporal coherence (visually assessed) and opposite spike polarities. Properties of AD and spontaneous SWD were equally affected by the stimulation. Closed-loop high frequency stimulation disrupted spontaneous SWD with no difference between ATN and VPM stimulated rats. 89% of SWD could be disrupted leading to a decrease in average SWD duration from 9 to 1.5s. CONCLUSION: Low frequency stimulation induced AD, which strongly mimic SWD. Moreover, the effects were site-specific. High frequency thalamic stimulation disrupts ongoing SWD probable by interfering with the slow firing pattern of cortico-thalamo-cortical neurons seen during SWD cycle. The absence of stimulation site specificity for high frequency stimulation might be due to the fact that stimulation only started on average 1s after SWD onset when SWD are already fully expressed in the bidirectional cortico-thalamo-cortical resonance system.
Authors: C Ákos Szabó; Melissa De La Garza; Robert Shade; Alexander M Papanastassiou; Peter Nathanielsz Journal: Epilepsy Behav Date: 2021-05-04 Impact factor: 3.337