Abstract
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.
Highlights
The profound plasticity of the developing brain affords an adaptive and often advantageous quality that is no longer prominent in adulthood
The remaining sections of this review further address this issue of a “neural substrate” for language disability, and our efforts to examine the relative impact of timing of “disruption of brain development” on behavioral outcomes relevant to the language domain (RAP) using rodent models
A RAT MODEL OF CORTICAL NEURONAL MIGRATION ANOMALIES AND rapid auditory processing (RAP) OUTCOMES To further examine the underlying neurodevelopmental events that may contribute to functional RAP deficits, we investigated silent gap detection capabilities in juvenile and adult rats that received bilateral freezing lesions or sham surgery on P1, 3 or 5 (Threlkeld et al, 2006), following on the procedure described earlier that leads to cortical microgyria when performed on P1
Summary
The profound plasticity of the developing brain affords an adaptive and often advantageous quality that is no longer prominent in adulthood (though recent research shows that the adult brain retains a greater level of plasticity than once thought). ANIMAL MODELS OF RAPID AUDITORY PROCESSING DEFICITS Initial efforts in developing an animal model for RAP deficits focused on evidence that induction of a focal freeze lesion to cortex of a 1-day-old rat pup (performed through the skull cap, which is very thin at this age) would lead to the subsequent formation of a microgyrus—a focal region of cortex characterized by anomalous cortical layers ( indicative of abnormalities in migration; see Figure 2) Microgyri induced in this manner were found to be remarkably histologically similar to the microgyria identified by Galaburda et al (1985) in postmortem human dyslexic brains (Dvorák and Feit, 1977; Humphreys et al, 1991; Rosen et al, 1992). This conundrum represents a huge issue in human clinical language disability research, and clearly highlights one reason that animal research is crucial to a complete understanding of the mechanisms at play in the complex process of emergent developmental disorders of language
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