Research reportImpaired two-tone processing at rapid rates in male rats with induced microgyria
Introduction
Evidence suggests that humans with developmental language disabilities, including specific language impairment (SLI) and developmental dyslexia, may exhibit a fundamental dysfunction in the ability to process brief auditory stimuli followed in rapid succession by other acoustic information (i.e., auditory temporal processing [14], [18], [19]). Moreover, postmortem analysis of dyslexic brains has revealed neocortical malformations, including molecular layer ectopias and microgyria [6], [8], [11]. Malformations similar in appearance to microgyria can be induced in rats via focal freezing lesions of the cortical plate on the first day (P1) of life [12], [17]. This animal model allows for assessment of a posited relationship between neocortical malformations and defects in rapid auditory processing. Specifically, Fitch and colleagues [4], [5], [10] trained adult male rats with bilateral microgyric lesions and sham rats to perform a go/no-go auditory discrimination task in a modified operant conditioning apparatus. The rats were to perform a target identification of two-tone stimuli with total stimulus durations reduced from 540 to 249 ms over a period of 24 days of testing (6 days at each of 4 stimulus durations). Results demonstrated that all adult male rats were able to discriminate at the longer stimulus durations, but at the ‘short’ 249 ms condition, the microgyric subjects were significantly impaired compared to sham subjects. This deficit is strikingly similar to those observed in some individuals with developmental language disabilities. Hence our results may provide a critical bridge for relating developmental cortical anomalies (e.g., cerebrocortical microgyria) and impaired rapid auditory processing.
Our original procedure [4], [5], [10], however, contained a potential confound between stimulus duration and learning. Specifically, by beginning with the longest stimulus duration and continuing to the shortest, stimulus-duration-specific group differences could have been affected by (or interact with) experiential learning. In the current study, therefore, we assessed auditory processing of two-tone stimuli with the same 4 stimulus durations (540, 390, 300 and 249 ms), but two-tone stimuli of different durations were randomly presented within each day of testing.
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Subjects
Twenty-four male Wistar rats, (12 sham/12 lesion) from 6 litters were used in the current experiment. On P1, male pups were randomly designated to receive either sham or bilateral freezing lesion surgery balanced within each litter. Focal necrotic lesions were induced based on a modification of the technique employed by Dvorák and associates [1], [2] and explained in detail elsewhere [12], [17]. Pups were anesthetized and a midline incision was made over the skull. A 2 mm diameter, stainless
Results
Histological verification of post mortem data confirmed that all subjects classified as microgyric exhibited microgyria located bilaterally in SM-I cortex. No cortical anomalies were found in sham subjects.
A multi-variate ANOVA was used to analyze response latencies for the 24 subjects. Treatment was a between-subject variable with 2 levels (sham, lesion); Response Type was a within-subject variable with 2 levels (hit, false alarm); Stimulus Duration was a within-subject variable with 4 levels
Discussion
In the current study we found that microgyric and sham male rats are equally able to process two-tone stimuli with ‘long’ stimulus durations of 540 ms to 332 ms, while microgyric (but not sham) rats, are impaired at processing stimuli presented at the ‘short’ stimulus duration of 249 ms.
Importantly, these results expand upon the previously reported findings obtained from microgyric and sham adult male rats tested in our modified operant conditioning apparatus [4], [5], [10]. The current results
Acknowledgements
Dr. Paula Tallal is a co-founder of Scientific Learning Corporation. This research was supported by a grant from the March of Dimes to RHF and by HD20806 and a grant from the New England Branch of the International Dyslexia Association to GDR. The authors thank Victor Denenberg for his input to this manuscript and research.
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