The dynamics of cortico-thalamo-cortical interactions at the transition from pre-ictal to ictal LFPs in absence epilepsy

PurposeGeneralized spike and wave discharges (SWD) are generated within the cortico-thalamo-cortical system. However the exact interactions between cortex and different thalamic nuclei needed for the generation and maintenance of 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.MethodsWAG/Rij rats were equipped with multiple electrodes targeting layers 4 to 6 of the somatosensory-cortex, rostral and caudal RTN, VPM, anterior (ATN)- and posterior (Po) thalamic nucleus. The maximal-association-strength between signals was calculated for pre-ictal → ictal transition periods and in control periods using non-linear-association-analysis. Dynamics of changes in coupling-direction and time-delays between channels were analyzed.ResultsEarliest and strongest increases in coupling-strength were seen between cortical layers 5/6 and Po. Other thalamic nuclei became later involved in SWD activity. During the first 500 ms of SWDs the cortex guided most thalamic nuclei while cortex and Po kept a bidirectional crosstalk. Most thalamic nuclei started to guide the Po until the end of the SWD. While the rostral RTN showed increased coupling with Po, the caudal RTN decoupled. Instead, it directed its activity to the rostral RTN.ConclusionsNext to the focal cortical instigator zone of SWDs, the Po seems crucial for their occurrence. This nucleus shows early increases in coupling and is the only nucleus which keeps a bidirectional crosstalk to the cortex within the first 500 ms of SWDs. Other thalamic nuclei seem to have only a function in SWD maintenance. Rostral and caudal-RTN have opposite roles in SWD occurrence.

►SWD related changes can occur more than a second prior to SWD generalization. ►SWDs generalize to the thalamus when a cortical drive accompanies high cortico-thalamic coupling. ►The posterior thalamic nucleus is important for SWD occurrence. ►Time point of SWD involvement differs between thalamic nuclei. ►Rostral- and caudal-RTN have opposite roles in SWD occurrence.