Seizures Alter Cortical Representations for Complex Movements

Abstract

Alterations in the functional organization of motor cortex and interictal motor deficits are observed in people with epilepsy. While seizures in the rat lead to more cortical area devoted to simple cortical forelimb movement representations (motor maps) assessed using short-duration intracortical microstimulation (ICMS), the effect of seizures on complex movements derived with long-duration ICMS is unknown. Further, the relationship between motor map expression and motor impairment is not well understood. We used long-duration ICMS in the rat to test the hypothesis that repeated seizure activity (cortical kindling) increases the extent of overlapping cortical representation where multiple forelimb movements are evoked to stimulation. Cortical kindling (n = 7) significantly expanded (100%) forelimb motor maps characterized by a proportional increase in both complex and simple movement representation areas, and significantly increased (285%) overlapping forelimb representation compared to sham-kindled controls (n = 5). In a second experiment, motor maps were derived with long-duration ICMS under acute cortical application of bicuculline (n = 6) to reduce intracortical inhibition or saline control (n = 10). Bicuculline also significantly expanded forelimb motor maps (108%) but without increasing representational overlap. Moreover, expanded map areas in bicuculline rats evoked qualitatively distinct forelimb movements to long-duration, but not short-duration (n = 5), ICMS that were truncated. Our evidence indicates that motor map expansion following repeated experimental seizures is associated with reduced segregation between cortical movement representations that is not entirely due to reduced cortical inhibition but may contribute to interictal motor deficits in some individuals with epilepsy.