Epilepsy and Autism

Abstract

Epilepsy and autistic spectrum disorder frequently coexist in the same individual. Electroencephalogram (EEG) epileptiform activity is also present at a substantially higher rate in children with autism than normally developing children. As with epilepsy, there are a multitude of genetic and environmental factors that can result in autistic spectrum disorder. There is growing consensus from both animal and clinical studies that autism is a disorder of aberrant connectivity. As measured with functional magnetic resonance imaging (MRI) and EEG, the brain in autistic spectrum disorder may be under- or overconnected or have a mixture of over- and underconnectivity. In the case of comorbid epilepsy and autism, an imbalance of the excitatory/inhibitory (E/I) ratio in selected regions of the brain may drive overconnectivity. Understanding the mechanism by which altered connectivity in individuals with comorbid epilepsy and autistic spectrum disorder results in the behaviors specific to the autistic spectrum disorder remains a challenge.

Figure 1.

Interictal spikes in normal children without seizures and children with ASD. Note that frontal lobe spikes are more common in children with ASD than controls (based on data in Hashimoto et al. 2001 and Eeg-Olofsson et al. 1971, respectively).

Figure 2.

Sociability and social novelty test. (A) Rectangular wood box with opaque sides divided into three equal squares using removable plastic doors. An unfamiliar male rat is placed in one grated cylinder and an object in the other. (B) Starting point for test with test rat placed in the center square for 5 min. The rat and object cylinders are covered. (C) Once doors are removed, the animal is allowed to wander in the chamber for 10 min (sociability test). In C, the rat is spending time near the object. (D) Rat spending time near the other rat. (E) After 15 min, a new rat replaces the object. (F) The test rat was then tracked for time investigating the new and old rat (social novelty test).

Figure 3.

In the early-life seizure (ELS) model, immature rats are given a series of flurothyl seizures. This results in an imbalance of the excitatory/inhibitory (E/I) ratio, which leads to increased short-term plasticity and an increase in coherence. There is likely a “sweet spot” for coherence in which there is an optimal coherence (green ball). Increased coherence (red ball) may result in overconnectivity as shown by highly coherent wave forms in both the dorsal (DH) and ventral hippocampus (VH) and prefrontal cortex. PFC, Prefrontal cortex; EEG, electroencephalogram.