Fitch R Holy, Alexander Michelle L, Threlkeld Steven W
1Department of Psychology/Behavioral Neuroscience, University of Connecticut Storrs, CT, USA.
Front Syst Neurosci. 2013 Oct 21;7:58. doi: 10.3389/fnsys.2013.00058.
Most researchers in the field of neural plasticity are familiar with the "Kennard Principle," which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood). As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents) aspects of human sensory processing that may correlate-both developmentally and functionally-with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic (HI) injuries (similar to those seen in premature infants and term infants with birth complications) led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human "term," but only transient deficits (undetectable in adulthood) when induced in a "preterm" window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing (RAP) outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations). Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in human populations.
神经可塑性领域的大多数研究人员都熟悉“肯纳德原则”,该原则认为脑损伤时的年龄与随后缺陷的严重程度之间存在正相关关系(成年后趋于平稳)。例如,接受左半球切除术的儿童可以恢复看似正常的语言能力,而左颞叶和/或额叶皮层亚区域受到局灶性损伤的成年人可能会遭受严重且永久性的语言丧失。在此,我们展示了关于大鼠模型中早期脑损伤的影响的数据,该影响是类型和时间的函数,通过在时间要求上有所不同的听觉辨别任务来测量长期行为结果。创建这些任务是为了在啮齿动物中模拟人类感觉处理的各个方面,这些方面在发育和功能上可能与典型和非典型语言相关。我们发现,在活跃的神经元迁移期间对大鼠皮质板进行双侧局灶性损伤,导致的听觉结果比皮质迁移完成后诱导的类似损伤更差。相反,单侧缺氧缺血性(HI)损伤(类似于早产和足月产有并发症的婴儿所见的损伤)在与人类“足月”相当的神经发育阶段诱导时会导致永久性听觉处理缺陷,但在“早产”期诱导时只会导致短暂性缺陷(成年后无法检测到)。趋同的证据表明,无论早期神经发育的破坏何时发生或如何发生,当它们引发延伸至皮层下结构(即较低级的感觉处理站)的发育改变时,其后果可能对快速听觉处理(RAP)结果特别有害。综合研究结果对早期脑损伤以及基因/环境破坏后的行为结果研究具有启示意义,并且与我们对人类群体中发育性语言障碍潜在神经危险因素的理解相关。