Abstract
We developed a neural network model that can account for major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus, and postulates a role for synaptic plasticity in the emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this model can provide a roadmap and potentially an in silico testbed for future explorations of seizure mechanisms and clinical therapies.
Highlights
Focal seizures have been recognized for more than 3000 years, with descriptions dating back to ancient Mesopotamia (Worthington, 2005)
Focal seizures can present with a plethora of behavioral manifestations that vary according to the affected cortical regions, there are several consistent clinical and large-scale EEG features (Kotagal et al, 2008): propagation from a focal onset location to large brain regions, widespread neuronal synchronization, a transition from tonic to clonic activity, and a slowing pace of neuronal discharging prior to simultaneous seizure termination
Our recent investigations, utilizing microelectrode array recordings in humans, identified neuronal underpinnings of these common seizure features (Schevon et al, 2012; Smith et al, 2016). Based on these findings and results from animal model studies (Trevelyan et al, 2006; Trevelyan et al, 2007a; Trevelyan et al, 2007b; Wenzel et al, 2017; Wenzel et al, 2019), we proposed a dual spatial structure for focal seizures consisting of a core region of seizing brain bounded by an ictal wavefront surrounded by a passively reactive penumbra
Summary
Focal seizures have been recognized for more than 3000 years, with descriptions dating back to ancient Mesopotamia (Worthington, 2005). Our recent investigations, utilizing microelectrode array recordings in humans, identified neuronal underpinnings of these common seizure features (Schevon et al, 2012; Smith et al, 2016) Based on these findings and results from animal model studies (Trevelyan et al, 2006; Trevelyan et al, 2007a; Trevelyan et al, 2007b; Wenzel et al, 2017; Wenzel et al, 2019), we proposed a dual spatial structure for focal seizures consisting of a core region of seizing brain bounded by an ictal wavefront surrounded by a passively reactive penumbra. Evidence from human (Schevon et al, 2012) and animal studies (Trevelyan et al, 2006; Trevelyan et al, 2007b) suggests that collapse of inhibition is the key element causing ictal wavefront propagation, which leads
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