Hotchkiss Brain Institute, Calgary, Alberta, Canada.
Hotchkiss Brain Institute, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
Neuroscience. 2020 Nov 21;449:134-146. doi: 10.1016/j.neuroscience.2020.09.002. Epub 2020 Sep 8.
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.
在癫痫患者中,观察到运动皮层的功能组织发生改变和发作间期运动缺陷。虽然大鼠的癫痫发作导致更多的皮质区域专门用于使用短持续时间皮质内微刺激(ICMS)评估的简单皮质前肢运动代表(运动图),但癫痫发作对长持续时间 ICMS 产生的复杂运动的影响尚不清楚。此外,运动图表达与运动障碍之间的关系尚不清楚。我们在大鼠中使用长持续时间的 ICMS 来检验以下假设:反复的癫痫发作活动(皮质点燃)增加了多个前肢运动被刺激所引起的重叠皮质代表的程度。皮质点燃(n=7)显著扩大了(100%)前肢运动图,其特征是复杂和简单运动代表区域的比例均增加,与假点燃对照(n=5)相比,重叠前肢代表区显著增加(285%)。在第二个实验中,在急性皮质应用苯二氮䓬(n=6)以减少皮质内抑制或生理盐水对照(n=10)下,使用长持续时间的 ICMS 得出运动图。苯二氮䓬也显著扩大了前肢运动图(108%),但没有增加代表性重叠。此外,在苯二氮䓬大鼠中,扩大的地图区域引发了与长持续时间(但不是短持续时间(n=5))ICMS 截断的不同质的前肢运动。我们的证据表明,反复实验性癫痫发作后运动图的扩大与皮质运动代表之间的分离减少有关,这不仅是由于皮质抑制减少,但可能导致某些癫痫患者发作间期运动缺陷。