# AI-Based Electroencephalogram Analysis in Rodent Models of Epilepsy: A Systematic Review
## 2 Fundamental Concepts and Background
### Rodent Models of Epilepsy  
The rodent models of epilepsy are categorised into genetic and induced (see Figure 1). In both categories of modelled epilepsy, seizures are the fundamental phenotypic feature of assessment. There are three primary ways of inducing epilepsy in animal models: chemo-convulsant (direct or systemic), electrical stimulation, and acoustic stimulation [41]. The most common is the use of chemo-convulsants to mimic epilepsy similar to a particular type of human epilepsy [42].  
The systemic or direct injection of chemo-convulsants (kainic acid, pilocarpine, pentylemetrazol) into the rodent brain and electrical and acoustic brain stimulation induce brain injury [13; 43], resulting in status epilepticus (SE) [41]. SE is a generalised seizure activity that lasts more than 5 min without full recovery [44]. The brain analysis of these animals following the administration of the chemo-convulsants reveals substantial damage in the olfactory cortex, amygdala, thalamus, neocortex, hippocampus and substantia nigra [45]. To reduce the severity of SE that could lead to permanent neuronal damage, the SE is abated with the injection of sedatives, leading to a latent phase before spontaneous recurrent seizure (SRS) begins to manifest days later [46]. Typically, rodents that have been subjected to SE go on to develop epileptiform discharges and chronic SRS [47]. During the chronic phase of SRS, either the pathophysiology of epilepsy is studied or new therapeutic approaches for suppressing SRS are tested [48].  
Although epilepsy is defined clinically as unprovoked seizures from genetic and acquired factors, the studies on epilepsy have traditionally relied on induced acute seizure models. While induced acute seizure models such as maximal electroshock seizure and pentylenetetrazole are invaluable for initial screening of anticonvulsant activity, it is important to note that these models do not fully represent the complex pathophysiology of epilepsy [49]. These models are used primarily for their efficiency in identifying potential ASDs. Advances in genomics have identified genes linked to epilepsy [49]. In genetic mod  
Figure 1: Rodent models of epilepsy: rodent models of epilepsy are categorised into genetic and induced types. Genetic models are created through knockout or knock-in mutagenesis. In induced models, seizures are typically provoked by chemical, electrical, or acoustic stimulation of the brain [41].  
els of epilepsy, clinically relevant mutations are identified and replicated in mice, known as knockout or knock-in mutagenesis [41]. These genetic models provide essential insight regarding the role of mutation in ictogenesis and epileptogenesis [50]. Genetic models such as audiogenic seizure-susceptible DBA/2 mouse is a relevant model for studying sudden death in epilepsy [51] due to its susceptibility to audio generalised seizures evoked by excessive auditory stimulation [52]. The genetic absence seizure rats (GAERS) model in Wistar rats represents a prototypical form of childhood generalised idiopathic epilepsy [53]. Dravet syndrome is an intractable epileptic encephalopathy [54]. Almost 90% of Dravet syndrome patients have de novo heterozygous mutation in the SCN1A gene [55]. Replicating the causal mechanism of Dravet syndrome relies on generating animals with a genetic mutation in the SCN1A gene [49]. Like humans, the SCN1A is expressed throughout the central nervous system of rodents [56].