Abstracts

Rationale: Generalized absence seizures are known to be generated within the cortico-thalamo-cortical system. However the exact interactions between the cortex and the different thalamic nuclei, which are needed for the generation and maintenance of spike-wave discharges (SWD) are still to be elucidated. This study aims to shed more light on these interactions via multisite cortical and thalamic local field potential recordings in freely moving, genetic epileptic rats.Methods: 16 WAG/Rij rats were equipped with multiple electrodes targeting layer 4, 5 and 6 of the somatosensory cortex, the rostral and caudal RTN, the VPM, the anterior- (ATN) and posterior (Po) nucleus of the thalamus. The maximal association strength between signals was calculated for pre-ictal -> ictal transition periods and in control periods using nonlinear association analysis (h2). In addition, the dynamics of changes in coupling-direction and time-delays between channels were analyzed.Results: Earliest (1.25sec prior to the first generalized spike) and strongest, significant increases in coupling strength were seen between cortical layer 5/6 and Po. Other thalamic nuclei became only later involved in seizure activity. During the first 500ms of a seizure the cortex guided most thalamic nuclei while cortex and Po kept a bidirectional crosstalk. In addition, the rostral RTN, ATN and VPM started to guide the Po at seizure onset and continued to do so until the end of the seizure. While the rostral RTN showed increased coupling with Po, the caudal RTN decoupled from it and redirected its activity to the rostral RTN. Time-delays gradually increase shortly before seizure onset. Conclusions: Next to the focal cortical generator of SWD, the Po nucleus seems crucial for the occurrence of SWD. This nucleus shows early increases in coupling and is the only nucleus that is capable to respond/give feedback to the cortex within the first 500ms of an SWD. Since their late involvement on seizure activity and their constant input to the Po nucleus, the other thalamic nuclei seem only to have a function in maintenance of SWD. Rostral and caudal RTN have an opposite role in seizure occurrence. The increases in time-delays might represent a phase reset between channels which might partly explain the increase in coupling strength.