Impaired two-tone processing at rapid rates in male rats with induced microgyria

doi:10.1016/S0006-8993(00)02447-1

Brain Research

Volume 871, Issue 1, 14 July 2000, Pages 94-97

https://doi.org/10.1016/S0006-8993(00)02447-1 Get rights and content

Abstract

We previously reported that adult male rats with bilateral induced microgyria exhibit deficits in rapid auditory processing, which appear similar to auditory processing deficits seen in individuals with developmental language disabilities. The current study was designed to further elaborate that finding using an improved paradigm in which stimulus duration was uncoupled from testing experience and learning effects. Specifically, two-tone stimuli with durations of 540, 390, 332 and 249 ms were all presented within a single test session in a modified operant conditioning paradigm. Subjects were tested over a period of 12 days using this variable-stimulus format. Results confirmed microgyric male rats were impaired only in processing two-tone stimuli presented at rapid rates (i.e., 249 ms duration). Thus the current results support the previously observed link between focal malformations and deficits in rapid auditory processing.

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.

Section snippets

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.

References (19)

P.S. Goldman et al.
Prenatal removal of frontal association cortex in the fetal rhesus monkey: anatomical and functional consequences in postnatal life
Brain Res.
(1978)
M.A. Reed
Speech perception and the discrimination of brief auditory cues in reading disabled children
J. Exp. Child Psychol.
(1989)
P. Tallal
Auditory temporal perception, phonics, and reading disabilities in children
Brain Lang.
(1980)
K. Dvorák et al.
Migration of neuroblasts through partial necrosis of the cerebral cortex in newborn rats; contribution to the problems of morphological development and developmental period of cerebral microgyria. Histological and autoradiographical study
Acta Neuropathol. (Berl.)
(1977)
K. Dvorák et al.
Experimentally induced focal microgyria and status verrucosus deformis in rats; pathogenesis and interrelation. Histological and autoradiographical study
Acta Neuropathol. (Berl.)
(1978)
R.H. Fitch et al.
Left hemisphere specialization for auditory temporal processing in rats
Ann. NY Acad. Sci.
(1993)
R.H. Fitch et al.
Effects of sex and MK-801 on auditory-processing deficits associated with developmental microgyric lesions in rats
Behav. Neurosci.
(1997)
R.H. Fitch et al.
Induced microgyria and auditory temporal processing in rats: a model for language impairment?
Cereb. Cortex
(1994)
A.M. Galaburda et al.
Cytoarchitectonic abnormalities in developmental dyslexia: a case study
Ann. Neurol.
(1979)

There are more references available in the full text version of this article.

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Rodent models of MCD further support a link between cortical malformations, anomalous subcortical anatomy, and rapid auditory processing (RAP) deficits. Male rats with injury-induced cerebrocortical microgyria (comparable in structure to those found in dyslexic individuals studied by Galaburda et al.) also showed impairments in RAP [45–47]. Subsequent examination of neuronal size in the MGN of male rats with injury-induced microgyria revealed not only smaller neurons in general, but a shift in the distribution of neuronal sizes toward the left (smaller neurons) compared to sham controls [48–50].
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Neocortical neuronal migration anomalies such as microgyria and heterotopia have been associated with developmental language learning impairments in humans, and rapid auditory processing deficits in rodent models. Similar processing impairments have been suggested to play a causal role in human language impairment. Recent data from our group has shown spatial working memory deficits associated with neocortical microgyria in rats. Similar deficits have also been identified in humans with language learning impairments. To further explore the extent of learning deficits associated with cortical neuronal migration anomalies, we evaluated the effects of neocortical microgyria and test order experience using spatial (Morris water maze) and non-spatial water maze learning paradigms. Two independent groups were employed (G1 or G2) incorporating both microgyria and sham conditions. G1 received spatial testing for five days followed by non-spatial testing, while the reverse order was followed for G2. Initial analysis, including both test groups and both maze conditions, revealed a main effect of treatment, with microgyric rats performing significantly worse than shams. Overall analysis also revealed a task by order interaction, indicating that each group performed better on the second task as compared to the first, regardless of which task was presented first. Independent analyses of each task revealed a significant effect of treatment (microgyria worse than sham) only for the spatial water maze condition. Results indicate that prior maze experience (regardless of task type) leads to better subsequent performance. Results suggest that behavioral abnormalities associated with microgyria extend beyond auditory and working memory deficits seen in previous studies, to include spatial but not non-spatial learning impairments and that non-specific test experience may improve behavioral performance.
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Aspects of the response that encode the faster elements of speech differed between males and females while slower elements, specifically the F0, did not. As is discussed below, our findings are in agreement with selective sex differences observed for click-evoked and tone-evoked responses (Hoormann et al., 1992) as well as behavioral and cognitive processing differences in humans (Burman et al., 2008; Cahill, 2006; Camarata and Woodcock, 2006) and animals (Clark et al., 2000a,b; Fitch et al., 1993b; Herman et al., 1997). Moreover, our results parallel differences in the encoding of the fast elements of speech that is seen in the subcortical encoding of speech in good and poor readers (Banai et al., 2009).
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A dissimilarity between males and females was seen in the neural response to the components of the speech stimulus that change rapidly over time; but not in the slower changing, lower frequency information in the stimulus. We demonstrate that, in agreement with the click-evoked brainstem response, females have earlier peaks relative to males in the subcomponents of the response representing the onset of the speech sound. In contrast, the response peaks comprising the frequency-following response, which encode the fundamental frequency (F₀) of the stimulus, as well as the spectral amplitude of the response to the F₀, is not affected by sex. Notably, the higher-frequency elements of the speech syllable are encoded differently between males and females, with females having greater representation of spectrotemporal information for frequencies above the F₀.
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Specifically, rodent models of cortical developmental disruption (microgyria, ectopia, or heterotopia in neocortex) have consistently revealed rapid auditory processing impairments in male subjects, similar to those identified in language-impaired populations (Peiffer et al., 2004b, 2002a; Rosen et al., 1999). That is, studies have repeatedly shown specific deficits in processing rapid and/or complex acoustic stimuli as a consequence of perinatal disruption to neuronal migration in male rats and mice (Threlkeld et al., 2006, 2007; Peiffer et al., 2004a,b, 2002a; Clark et al., 2000b; Fitch et al., 1994) and these results parallel a higher incidence of neurodevelopmental disabilities in human males as compared to females (Rutter et al., 2003; Liederman et al., 2005). Convergent data thus indicate a link between perinatal cortical pathology (particularly involving neuronal migration), and subsequent auditory processing impairments (which may in turn contribute to language disruption in humans).
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Research reportImpaired two-tone processing at rapid rates in male rats with induced microgyria

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Acknowledgements

Brain Res.

J. Exp. Child Psychol.

Brain Lang.

Migration of neuroblasts through partial necrosis of the cerebral cortex in newborn rats; contribution to the problems of morphological development and developmental period of cerebral microgyria. Histological and autoradiographical study

Acta Neuropathol. (Berl.)

Experimentally induced focal microgyria and status verrucosus deformis in rats; pathogenesis and interrelation. Histological and autoradiographical study

Acta Neuropathol. (Berl.)

Left hemisphere specialization for auditory temporal processing in rats

Ann. NY Acad. Sci.

Effects of sex and MK-801 on auditory-processing deficits associated with developmental microgyric lesions in rats

Behav. Neurosci.

Induced microgyria and auditory temporal processing in rats: a model for language impairment?

Cereb. Cortex

Cytoarchitectonic abnormalities in developmental dyslexia: a case study

Ann. Neurol.

Research report
Impaired two-tone processing at rapid rates in male rats with induced microgyria