Functional brain connectivity in a rodent seizure model of autistic-like behavior

Objective: There is increasing evidence that Autism Spectrum Disorder (ASD) is a disorder of functional connectivity with both human and rodent studies demonstrating alterations in connectivity. Here, we hypothesized that early-life seizures (ELS) in rats would interrupt normal brain connectivity and result in autistic-like behavior (ALB). Methods: Following 50 seizures, adult rats were tested in the social interaction and social novelty tests and then underwent qualitative and quantitative intracranial electroencephalography (EEG) monitoring in the medial prefrontal cortex (PFC) and the hippocampal subfields, CA3 and CA1. Results: Rats with ELS showed deficits in social interaction and novelty, and compared with control, rats had marked increases in coherence within the hippocampus (CA3-CA1) and between the hippocampus and PFC during the awake and sleep states indicating hyperconnectivity. In addition, sleep spindle density was significantly reduced in rats with ELS. There were no differences in voltage correlations and power spectral densities between the ELS and control rats in any bandwidths. Conclusion: Taken together, these findings indicate that ELS can result in ALB and alter functional connectivity as measured by coherence and sleep spindle density. These findings implicate altered connectivity as a robust neural signature for ALB following ELS. (C) 2019 Elsevier Inc. All rights reserved.