Recent advances in systems neuroscience have shifted our understanding of brain functions from being attributed to individual nuclei or regions, to instead being distributed across multiple interacting anatomical areas or cellular populations. Similarly, it is becoming increasingly clear that in epilepsy, seizures and pathological activity emerge from large-scale cellular networks. Furthermore, seizures often generalize or spread through the brain following specific neuronal pathways. Consequently, abnormal activity in specific brain areas during seizures can lead to comorbidities such as memory loss, sleep pathologies, neurodevelopmental delay and severe autistic behaviours. However, seizures themselves may be a consequence of underlying genetic or physiological changes that can be associated with comorbidities.
As a lab, we study genetic and chemically or electrically induced in vivo animal models of epileptic encephalopathies and temporal lobe epilepsy utilizing cutting edge electrophysiological recording techniques. We are focused on deciphering how seizures emerge and propagate throughout the brain and how these events relate to other behavioural phenotypes. We use multi-site chronic in vivo electrophysiology in combination with automated sleep and seizure classifying software to identify the neuronal circuits responsible for seizure generation and propagation throughout the brain. We quantify which brain regions are more likely to start a seizure or mediate it’s spread, for example hippocampus, somatosensory cortex or thalamic areas.
Through this approach we can then focus on seizure causality by modulating the activity of specific brain regions thought to be critical for seizure initiation or spread through pharmacological, genetic or optogenetic approaches. Additionally, we are in the search of clinically-translatable biomarkers of autism and epilepsy by performing connectivity analyses to understand how ongoing brain activity relates to the disease state.
By identifying brain areas mediating seizure we can then study in both in vivo and in vitro, preparations the activity of individual, using silicone probe recordings or patch-clamp respectively, cells and determine whether their function is compromised in disease. When a cellular population is identified as being abnormal, we then envisage also studying genetic mechanism that may underly the pathological activity through genetic sequencing techniques.
These approaches allow us to continue to develop circuit-based interventions, such as deep brain stimulation or genetic rescue, to ameliorate and reverse epilepsy-related pathologies.