Biomedical Engineering - Theses
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ItemNeuronal networks in absence epilepsy : dynamics of seizure transitions( 2021)Epilepsy is the most common recurrent neurological condition, affecting a little over 1\% of the world's population. It is often debilitating because of significant psychological, social and cognitive burdens apart from the seizures themselves. Advancing treatment options for generalised epilepsy syndromes has proven a challenging problem, since they are often refractory to treatment with anti-epileptic medication, and are currently not amenable to surgical treatment, so that it is rarely ethical to conduct invasive intracranial EEG studies in human patients with these conditions in order to study them further. Although there has been controversy over the origin and networks involved in absence seizures, previous work by our group has shown that alternative areas of somatosensory cortex are important parts of the thalamocortical circuit in the generation of seizures. The work of this thesis aims to extend those studies by showing that the coupling between cortex and thalamus is altered during seizures. It is established that there is a process of resonance ocurring prior to and during seizures in relevant deep layers of cortex, and the mechanisms behind this are studied. Novel aspects of the work presented in this thesis include the examination of the EEG in the GAERS rat, a whole animal model of absence epilepsy, at the scales of both individual cortical microcircuits and whole cortical areas using simultaneous depth electrodes, and also at both very fine and long time scales. The studies described in this thesis show that the somatosensory cortex leads the thalamus in the first second of seizure onset, in agreement with the results of previous work. To account for the mechanisms behind this increased coupling at seizure onset, an analysis of the properties of resonance in different parts of cortex is presented. This indicates altered phase coupling prior to seizures, in the form of increased phase entrainment, phase coherence, and cross-frequency coupling. These changes are most marked in the junction between primary and secondary somatosensory cortex, with earlier, larger increases prior to seizures, and earlier decoupling at seizure termination. Dynamical analysis points to a number of processes underlying such increases in cortical resonance. Alterations in scaling behaviour are observed in different cortical regions, and also prior to seizures. Analysis of the Lyapunov spectrum of cortical depth and tetrode EEG data shows evidence for a separation in timescales of dynamics at seizure onset, and changes consistent with critical slowing. Further, gradual changes in the statistics of the largest exponents are seen with approaching seizures, suggesting an alteration in dynamical properties giving rise to critical slowing. The results of this thesis support the recently proposed cortical focus theory of absence seizure generation in GAERS rats, and provide new insight into cortical network changes relevant to seizures. This work provides a basis to explore the mode of action of antiepileptic drugs, and more targeted therapy for generalised absence seizures.