The Role of the Piriform Cortex in Absence Epilepsy

Abstract

© 2019 James Christopher YoungThe piriform cortex is critically involved in our sense of smell and engages with the olfactory network via specific neural oscillations. It is also considered to be common node of the focal epilepsy network however it is unknown if it plays a role in absence epilepsy. The main focus of this thesis was to determine whether there is any pre-seizure involvement of the piriform cortex in absence epilepsy. Using a rat model of absence epilepsy and non-epileptic controls, multi-channel microelectrode arrays were implanted in the piriform cortex and mediodorsal thalamus, the piriform cortex’s direct link to thalamo-cortical networks underlying absence epilepsy, to record multiunit clusters and field potentials. Three distinct signal processing analyses were developed and applied to the study of the pre-seizure onset connectivity changes in the piriform cortex which encompass four distinct but interrelated research aims. The first aim was to determine the transient firing patterns of multiunit clusters within and between the piriform cortex and mediodorsal thalamus around the onset of absence seizures. The phase locking between multiunit cluster spikes and neural oscillations (spike-LFP phase locking) which govern olfactory network communication was shown to change within the piriform cortex prior to seizure onset, suggesting it contributes to seizure initiation. Early changes in spike-LFP phase locking suggested possible pre-seizure onset changes in local and long range functional connectivity of the piriform cortex and mediodorsal thalamus. A critical issue of analysing functional connectivity using microelectrode arrays is overlapping effect of neighbouring electrodes. Hence the second aim of this thesis was determining the optimal method for resolving the effect of neighbouring electrodes to accurately estimate functional connectivity. Band-amplitude fluctuation orthogonalization followed by inter-site phase clustering estimates was shown to be the optimal method. This finding has important implications for future medical bionics consisting of electrodes with small inter-electrode distances. Following the optimal method of functional connectivity being derived, the third aim of this thesis, determining the local and long range functional connectivity of piriform cortex and mediodorsal thalamus, could be addressed. Results demonstrated pre-seizure onset increase in local functional connectivity within the piriform cortex and increases in long range connectivity with the mediodorsal thalamus in neural oscillatory bands of the olfactory network. The final aim of this thesis was to determine effective connectivity of the piriform cortex to mediodorsal thalamus in order to determine changes in information flow from the piriform cortex to the mediodorsal thalamus in absence epilepsy. A novel method of effective connectivity was developed. The results demonstrated pre-seizure onset increases in effective connectivity of a similar frequency band to where absence seizures localize. This suggests the piriform cortex to mediodorsal thalamus pathway is predisposed to propagating absence seizure activity. Overall, the piriform cortex was discovered to contribute to the initiation of absence seizures and the piriform cortex to mediodorsal thalamus pathway is recruited as part of the absence epilepsy network. The brain connectivity methods developed in this thesis can be applied to the study of brain regions and neural pathways of epilepsy and other neurological disorders

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