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Glenn D Rosen - One of the best experts on this subject based on the ideXlab platform.
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Research report Impaired gap detection in juvenile microgyric rats
2020Co-Authors: Ann M Peiffer, Glenn D Rosen, Jennifer T. Friedman, R. Holly FitchAbstract:Previous research with adult animal models links the presence of cortical neuromigrational anomalies (i.e., Microgyria similar to that found in brains of dyslexics) with rapid auditory processing (RAP) impairments. RAP impairments are in turn found in children with specific language impairment (SLI) and also in individuals with dyslexia. Gap detection, a simple measure of auditory temporal acuity, appears to be impaired in children with SLI but not in dyslexic adults, even though both groups exhibit impaired processing on more complex, rapid auditory tasks. In the current study, juvenile rats with bilateral Microgyria, but not their adult counterparts, exhibited impaired detection of short duration silent gaps in white noise when compared to age-matched sham littermates. Results lend further support to: (1) an association between neuromigrational anomalies and RAP impairments; and (2) the validity of an animal model of RAP impairments associated with language disturbances in humans. Current results also support the view that auditory processing disturbances associated with cortical malformations may be evident early in development at a relatively ‘‘low’’ level (e.g., simple gap detection), but may require ‘‘higher-order’’ auditory discrimination tasks (e.g., tone sequences, phonemic discriminations) to be elicited later in life. D 2004 Elsevier B.V. All rights reserved. Theme: Disorders of the nervous system Topic: Developmental disorders
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effects of test experience and neocortical Microgyria on spatial and non spatial learning in rats
Behavioural Brain Research, 2012Co-Authors: Steven W Threlkeld, Glenn D Rosen, C A Hill, Caitlin E Szalkowski, Dongnhu T Truong, Holly R FitchAbstract: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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low power photomicrograph of a wistar rat brain with bilateral Microgyria arrows
2011Co-Authors: Ann M Peiffer, Holly R Fitch, Jennifer J Thomas, Alexandra Nicole Yurkovic, Glenn D RosenAbstract:Copyright information: Taken from "Brain weight differences associated with induced focal Microgyria"BMC Neuroscience 2003;4():12-12.Published online 24 Jun 2003http://www.ncbi.nlm.nih.gov/pmc/articles/PMC166148.Copyright © 2003 Peiffer et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Note the normal-appearing cortex medial and lateral to the Microgyria. Bar = 800 μm.
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Developmental learning impairments in a rodent model of nodular heterotopia
Journal of Neurodevelopmental Disorders, 2009Co-Authors: Steven W Threlkeld, Glenn D Rosen, Dongnhu T Truong, Courtney A. Hill, Caitlin E. Cleary, R. Holly FitchAbstract:Developmental malformations of neocortex—including Microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (Microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans.
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persistent spatial working memory deficits in rats with bilateral cortical Microgyria
Behavioral and Brain Functions, 2008Co-Authors: Holly R Fitch, Glenn D Rosen, Heather Breslawski, James J ChrobakAbstract:Background: Anomalies of cortical neuronal migration (e.g., Microgyria (MG) and/or ectopias) are associated with a variety of language and cognitive deficits in human populations. In rodents, postnatal focal freezing lesions lead to the formation of cortical Microgyria similar to those seen in human dyslexic brains, and also cause subsequent deficits in rapid auditory processing similar to those reported in human language impaired populations. Thus convergent findings support the ongoing study of disruptions in neuronal migration in rats as a putative model to provide insight on human language disability. Since deficits in working memory using both verbal and non-verbal tasks also characterize dyslexic populations, the present study examined the effects of neonatally induced bilateral cortical Microgyria (MG) on working memory in adult male rats. Methods: A delayed match-to-sample radial water maze task, in which the goal arm was altered among eight locations on a daily basis, was used to assess working memory performance in MG (n = 8) and sham (n = 10) littermates. Results: Over a period of 60 sessions of testing (each session comprising one pre-delay sample trial, and one post-delay test trial), all rats showed learning as evidenced by a significant decrease in overall test errors. However, MG rats made significantly more errors than shams during initial testing, and this memory deficit was still evident after 60 days (12 weeks) of testing. Analyses performed on daily error patterns showed that over the course of testing, MG rats utilized a strategy similar to shams (but with less effectiveness, as indicated by more errors). Conclusion: These results indicate persistent abnormalities in the spatial working memory system in rats with induced disruptions of neocortical neuronal migration.
Albert M Galaburda - One of the best experts on this subject based on the ideXlab platform.
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Spectral processing deficits in belt auditory cortex following early postnatal lesions of somatosensory cortex.
Neuroscience, 2008Co-Authors: Nathan C. Higgins, Glenn D Rosen, Albert M Galaburda, Monty A. Escabí, Heather L. ReadAbstract:Abstract Induced or genetically based cortical laminar malformations in somatosensory cortex have been associated with perceptual and acoustic processing deficits in mammals. Perinatal freeze-lesions of developing rat primary somatosensory (S1) cortex induce malformations resembling human Microgyria. Induced Microgyria located in parietal somatosensory cortex have been linked to reduced behavioral detection of rapid sound transitions and altered spectral processing in primary auditory cortex (A1). Here we asked whether belt auditory cortex function would be similarly altered in rats with S1 Microgyria (MG+). Pure-tone acoustic response properties were assessed in A1 and ventral auditory (VAF) cortical fields with Fourier optical imaging and multi-unit recordings. Three changes in spectral response properties were observed in both A1 and VAF in MG+ rats: 1) multi-unit response magnitudes were reduced 2) optical and multi-unit frequency responses were more variable; 3) at high sound levels units responded to a broader range of pure-tone frequencies. Optical and multi-unit pure-tone response magnitudes were both reduced for low sound levels in VAF but not A1. Sound level “tuning” was reduced in VAF but not in A1. Finally, in VAF frequency tuning and spike rates near best frequency were both altered for mid- but not high-frequency recording sites. These data suggest that VAF belt auditory cortex is more vulnerable than A1 to early postnatal induction of Microgyria in neighboring somatosensory cortex.
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Early cortical damage in rat somatosensory cortex alters acoustic feature representation in primary auditory cortex.
Neuroscience, 2007Co-Authors: Monty A. Escabí, Glenn D Rosen, Albert M Galaburda, Nathan C. Higgins, Heather L. ReadAbstract:Early postnatal freeze-lesions to the cortical plate result in malformations resembling human Microgyria. Microgyria in primary somatosensory cortex (S1) of rats are associated with a reduced behavioral detection of rapid auditory transitions and the loss of large cells in the thalamic nucleus projecting to primary auditory cortex (A1). Detection of slow transitions in sound is intact in animals with S1 Microgyria, suggesting dissociation between responding to slow versus rapid transitions and a possible dissociation between levels of auditory processing affected. We hypothesized that neuronal responses in primary auditory cortex (A1) would be differentially reduced for rapid sound repetitions but not for slow sound sequences in animals with S1 Microgyria. We assessed layer IV cortical responses in primary auditory cortex (A1) to single pure-tones and periodic noise bursts (PNB) in rats with and without S1 Microgyria. We found that responses to both types of acoustic stimuli were reduced in magnitude in animals with Microgyria. Furthermore, spectral resolution was degraded in animals with Microgyria. The cortical selectivity and temporal precision were then measured with conventional methods for PNB and tone-stimuli, but no significant changes were observed between microgyric and control animals. Surprisingly, the observed spike rate reduction was similar for rapid and slow temporal modulations of PNB stimuli. These results suggest that acoustic processing in A1 is indeed altered with early perturbations of neighboring cortex. However, the type of deficit does not affect the temporal dynamics of the cortical output. Instead, acoustic processing is altered via a systematic reduction in the driven spike rate output and spectral integration resolution in A1. This study suggests a novel form of plasticity, whereas early postnatal lesions of one sensory cortex can have a functional impact on processing in neighboring sensory cortex.
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Histometric changes and cell death in the thalamus after neonatal neocortical injury in the rat
Neuroscience, 2006Co-Authors: Glenn D Rosen, B. Mesples, M. Hendriks, Albert M GalaburdaAbstract:Freezing injury to the developing cortical plate results in a neocortical malformation resembling four-layered Microgyria. Previous work has demonstrated that following freezing injury to the somatosensory cortex, males (but not females) have more small and fewer large cells in the medial geniculate nucleus. In the first experiment, we examined the effects of induced Microgyria to the somatosensory cortex on neuronal numbers, neuronal size, and nuclear volume of three sensory nuclei: ventrobasal complex, dorsal lateral geniculate nucleus, and medial geniculate nucleus. We found that there was a decrease in neuronal number and nuclear volume in ventrobasal complex of microgyric rats when compared with shams, whereas there were no differences in these variables in the dorsal lateral geniculate nucleus or medial geniculate nucleus. We also found that there were more small and fewer large neurons in both ventrobasal complex and medial geniculate nucleus. In experiment 2, we attempted to determine the role of cell death in the thalamus on these histometric measures. We found that cell death peaked within 24 h of the freezing injury and was concentrated mostly in ventrobasal complex. In addition, there was evidence of greater cell death in males at this age. Taken together, these results support the notion that males are more severely affected by early injury to the cerebral cortex than females.
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Unilateral induced neocortical malformation and the formation of ipsilateral and contralateral barrel fields
Neuroscience, 2001Co-Authors: Glenn D Rosen, H Windzio, Albert M GalaburdaAbstract:Freezing lesions to the developing cortical plate of rodents results in a focal malformation resembling human 4- layered Microgyria, and this malformation has been shown to result in local and widespread disruptions of neuronal architecture, connectivity, and physiology. Because we had previously demonstrated that Microgyria caused disruptions in callosal connections, we hypothesized that freeze lesions to the postero-medial barrel sub-field (PMBSF) in one hemi- sphere would affect the organization of this barrel field contralaterally. We placed freeze lesions in the presumptive PMBSF of neonatal rats and, in adulthood, assessed the architecture of the ipsilateral and contralateral barrel fields. Malformations in the PMBSF resulted in a substantial decrease in the number of barrels as identified by cytochrome oxidase activity. More importantly, we found an increase in the total area of the contralateral PMBSF, although there was no difference in individual barrel cross-sectional areas, indicating an increase in the area of inter-barrel septae. This increase in the septal area of the contralateral PMBSF is consistent with changes in callosal and/or thalamic connectivity in the contralateral hemisphere. These results are another example of both local and widespread disruption of connectional architecture following induction of focal Microgyria. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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Single cause, polymorphic neuronal migration disorders: an animal model
Developmental Medicine & Child Neurology, 2000Co-Authors: Glenn D Rosen, Albert M GalaburdaAbstract:Injury to the developing cortical plate can result in a variety of neuronal migration disorders. The results are reported of experimental research aimed at determining whether these different types of neocortical malformations are the consequence of comparable injury of varying intensity. Freezing probes were placed on the skulls of 44 newborn rats (age equivalent to 4 to 5 months of gestation in humans) and induced either one or two freezing injuries of durations ranging from 2 to 20 seconds. A variety of cortical malformations including minor laminar dysplasias, molecular layer ectopias, Microgyria, and porencephalic cysts were seen in the brains of these animals when they were examined on postnatal day (P)2, P21, and P60. The severity of the malformation was directly related to the strength (number of hits and duration) of the freezing injury. These results suggest that a single etiologic event of varying severity during neuronal migration to the neocortex can induce widely disparate malformations of the cortex.
Holly R Fitch - One of the best experts on this subject based on the ideXlab platform.
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effects of test experience and neocortical Microgyria on spatial and non spatial learning in rats
Behavioural Brain Research, 2012Co-Authors: Steven W Threlkeld, Glenn D Rosen, C A Hill, Caitlin E Szalkowski, Dongnhu T Truong, Holly R FitchAbstract: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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low power photomicrograph of a wistar rat brain with bilateral Microgyria arrows
2011Co-Authors: Ann M Peiffer, Holly R Fitch, Jennifer J Thomas, Alexandra Nicole Yurkovic, Glenn D RosenAbstract:Copyright information: Taken from "Brain weight differences associated with induced focal Microgyria"BMC Neuroscience 2003;4():12-12.Published online 24 Jun 2003http://www.ncbi.nlm.nih.gov/pmc/articles/PMC166148.Copyright © 2003 Peiffer et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Note the normal-appearing cortex medial and lateral to the Microgyria. Bar = 800 μm.
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persistent spatial working memory deficits in rats with bilateral cortical Microgyria
Behavioral and Brain Functions, 2008Co-Authors: Holly R Fitch, Glenn D Rosen, Heather Breslawski, James J ChrobakAbstract:Background: Anomalies of cortical neuronal migration (e.g., Microgyria (MG) and/or ectopias) are associated with a variety of language and cognitive deficits in human populations. In rodents, postnatal focal freezing lesions lead to the formation of cortical Microgyria similar to those seen in human dyslexic brains, and also cause subsequent deficits in rapid auditory processing similar to those reported in human language impaired populations. Thus convergent findings support the ongoing study of disruptions in neuronal migration in rats as a putative model to provide insight on human language disability. Since deficits in working memory using both verbal and non-verbal tasks also characterize dyslexic populations, the present study examined the effects of neonatally induced bilateral cortical Microgyria (MG) on working memory in adult male rats. Methods: A delayed match-to-sample radial water maze task, in which the goal arm was altered among eight locations on a daily basis, was used to assess working memory performance in MG (n = 8) and sham (n = 10) littermates. Results: Over a period of 60 sessions of testing (each session comprising one pre-delay sample trial, and one post-delay test trial), all rats showed learning as evidenced by a significant decrease in overall test errors. However, MG rats made significantly more errors than shams during initial testing, and this memory deficit was still evident after 60 days (12 weeks) of testing. Analyses performed on daily error patterns showed that over the course of testing, MG rats utilized a strategy similar to shams (but with less effectiveness, as indicated by more errors). Conclusion: These results indicate persistent abnormalities in the spatial working memory system in rats with induced disruptions of neocortical neuronal migration.
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use of a modified prepulse inhibition paradigm to assess complex auditory discrimination in rodents
Brain Research Bulletin, 2008Co-Authors: Holly R Fitch, Steven W Threlkeld, Melissa M Mcclure, Ann M PeifferAbstract:Abstract Prepulse inhibition (PPI; also termed startle reduction or reflex modification, see Ref. [H.S. Hoffman, J.R. Ison, Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input, Psychol. Rev. 87 (1980) 175–189]) provides an efficient and accurate method to assess both simple and complex acoustic discrimination in rodents [J.R. Ison, G.R. Hammond, Modification of the startle reflex in the rat by changes in the auditory and visual environments, J. Comp. Physiol. Psychol. 75 (1971) 435–452]. Assessment of acoustic processing using PPI is less time consuming than operant conditioning paradigms, allows for the testing of many subjects simultaneously, and largely eliminates confounds due to motivation and attention [M. Clark, G. Rosen, P. Tallal, R.H. Fitch, Impaired processing of complex auditory stimuli in rats with induced cerebrocortical Microgyria, J. Cog. Neurosci. 12 (2000) 828–839]. Moreover, PPI procedures allow for data acquisition from the first day of testing, and can be used on rats as young as P14–15 [J.T. Friedman, A. Peiffer, M. Clark, A. Benasich, R.H. Fitch, Age and experience related improvements in gap detection in the rat, Dev. Brain Res. 152 (2004) 83–91; M. McClure, S. Threlkeld, G. Rosen, R.H. Fitch, Rapid auditory processing and learning deficits in rats with P1 versus P7 neonatal hypoxic-ischemic injury, Behav. Brain Res. 172 (2006) 114–121; S.W. Threlkeld, M.M. McClure, G.D. Rosen, R.H. Fitch, Developmental timeframes for the induction of Microgyria and rapid auditory processing deficits in the rat, Brain Res. 1109 (2006) 22–31]. For these and additional reasons, the PPI paradigm has more recently been adapted to the assessment of complex acoustic discrimination (tone sequences and FM sweeps), and applied to the study of normally developing as well as neuropathologically affected rodent populations. The purpose of the current review is to provide a background on the PPI paradigm, and to summarize what has been learned more recently using modified versions of PPI with rodent models.
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developmental timeframes for induction of Microgyria and rapid auditory processing deficits in the rat
Brain Research, 2006Co-Authors: Steven W Threlkeld, Glenn D Rosen, Melissa M Mcclure, Holly R FitchAbstract:Abstract Induction of a focal freeze lesion to the skullcap of a 1-day-old rat pup leads to the formation of Microgyria similar to those identified postmortem in human dyslexics. Rats with Microgyria exhibit rapid auditory processing deficits similar to those seen in language-impaired (LI) children, and infants at risk for LI and these effects are particularly marked in juvenile as compared to adult subjects. In the current study, a startle response paradigm was used to investigate gap detection in juvenile and adult rats that received bilateral freezing lesions or sham surgery on postnatal day (P) 1, 3 or 5. Microgyria were confirmed in P1 and 3 lesion rats, but not in the P5 lesion group. We found a significant reduction in brain weight and neocortical volume in P1 and 3 lesioned brains relative to shams. Juvenile (P27–39) behavioral data indicated significant rapid auditory processing deficits in all three lesion groups as compared to sham subjects, while adult (P60+) data revealed a persistent disparity only between P1-lesioned rats and shams. Combined results suggest that generalized pathology affecting neocortical development is responsible for the presence of rapid auditory processing deficits, rather than factors specific to the formation of Microgyria per se. Finally, results show that the window for the induction of rapid auditory processing deficits through disruption of neurodevelopment appears to extend beyond the endpoint for cortical neuronal migration, although, the persistent deficits exhibited by P1 lesion subjects suggest a secondary neurodevelopmental window at the time of cortical neuromigration representing a peak period of vulnerability.
Ann M Peiffer - One of the best experts on this subject based on the ideXlab platform.
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Research report Impaired gap detection in juvenile microgyric rats
2020Co-Authors: Ann M Peiffer, Glenn D Rosen, Jennifer T. Friedman, R. Holly FitchAbstract:Previous research with adult animal models links the presence of cortical neuromigrational anomalies (i.e., Microgyria similar to that found in brains of dyslexics) with rapid auditory processing (RAP) impairments. RAP impairments are in turn found in children with specific language impairment (SLI) and also in individuals with dyslexia. Gap detection, a simple measure of auditory temporal acuity, appears to be impaired in children with SLI but not in dyslexic adults, even though both groups exhibit impaired processing on more complex, rapid auditory tasks. In the current study, juvenile rats with bilateral Microgyria, but not their adult counterparts, exhibited impaired detection of short duration silent gaps in white noise when compared to age-matched sham littermates. Results lend further support to: (1) an association between neuromigrational anomalies and RAP impairments; and (2) the validity of an animal model of RAP impairments associated with language disturbances in humans. Current results also support the view that auditory processing disturbances associated with cortical malformations may be evident early in development at a relatively ‘‘low’’ level (e.g., simple gap detection), but may require ‘‘higher-order’’ auditory discrimination tasks (e.g., tone sequences, phonemic discriminations) to be elicited later in life. D 2004 Elsevier B.V. All rights reserved. Theme: Disorders of the nervous system Topic: Developmental disorders
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low power photomicrograph of a wistar rat brain with bilateral Microgyria arrows
2011Co-Authors: Ann M Peiffer, Holly R Fitch, Jennifer J Thomas, Alexandra Nicole Yurkovic, Glenn D RosenAbstract:Copyright information: Taken from "Brain weight differences associated with induced focal Microgyria"BMC Neuroscience 2003;4():12-12.Published online 24 Jun 2003http://www.ncbi.nlm.nih.gov/pmc/articles/PMC166148.Copyright © 2003 Peiffer et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Note the normal-appearing cortex medial and lateral to the Microgyria. Bar = 800 μm.
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use of a modified prepulse inhibition paradigm to assess complex auditory discrimination in rodents
Brain Research Bulletin, 2008Co-Authors: Holly R Fitch, Steven W Threlkeld, Melissa M Mcclure, Ann M PeifferAbstract:Abstract Prepulse inhibition (PPI; also termed startle reduction or reflex modification, see Ref. [H.S. Hoffman, J.R. Ison, Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input, Psychol. Rev. 87 (1980) 175–189]) provides an efficient and accurate method to assess both simple and complex acoustic discrimination in rodents [J.R. Ison, G.R. Hammond, Modification of the startle reflex in the rat by changes in the auditory and visual environments, J. Comp. Physiol. Psychol. 75 (1971) 435–452]. Assessment of acoustic processing using PPI is less time consuming than operant conditioning paradigms, allows for the testing of many subjects simultaneously, and largely eliminates confounds due to motivation and attention [M. Clark, G. Rosen, P. Tallal, R.H. Fitch, Impaired processing of complex auditory stimuli in rats with induced cerebrocortical Microgyria, J. Cog. Neurosci. 12 (2000) 828–839]. Moreover, PPI procedures allow for data acquisition from the first day of testing, and can be used on rats as young as P14–15 [J.T. Friedman, A. Peiffer, M. Clark, A. Benasich, R.H. Fitch, Age and experience related improvements in gap detection in the rat, Dev. Brain Res. 152 (2004) 83–91; M. McClure, S. Threlkeld, G. Rosen, R.H. Fitch, Rapid auditory processing and learning deficits in rats with P1 versus P7 neonatal hypoxic-ischemic injury, Behav. Brain Res. 172 (2006) 114–121; S.W. Threlkeld, M.M. McClure, G.D. Rosen, R.H. Fitch, Developmental timeframes for the induction of Microgyria and rapid auditory processing deficits in the rat, Brain Res. 1109 (2006) 22–31]. For these and additional reasons, the PPI paradigm has more recently been adapted to the assessment of complex acoustic discrimination (tone sequences and FM sweeps), and applied to the study of normally developing as well as neuropathologically affected rodent populations. The purpose of the current review is to provide a background on the PPI paradigm, and to summarize what has been learned more recently using modified versions of PPI with rodent models.
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Impaired gap detection in juvenile microgyric rats.
Developmental Brain Research, 2004Co-Authors: Ann M Peiffer, Glenn D Rosen, Jennifer T. Friedman, R. Holly FitchAbstract:Abstract Previous research with adult animal models links the presence of cortical neuromigrational anomalies (i.e., Microgyria similar to that found in brains of dyslexics) with rapid auditory processing (RAP) impairments. RAP impairments are in turn found in children with specific language impairment (SLI) and also in individuals with dyslexia. Gap detection, a simple measure of auditory temporal acuity, appears to be impaired in children with SLI but not in dyslexic adults, even though both groups exhibit impaired processing on more complex, rapid auditory tasks. In the current study, juvenile rats with bilateral Microgyria, but not their adult counterparts, exhibited impaired detection of short duration silent gaps in white noise when compared to age-matched sham littermates. Results lend further support to: (1) an association between neuromigrational anomalies and RAP impairments; and (2) the validity of an animal model of RAP impairments associated with language disturbances in humans. Current results also support the view that auditory processing disturbances associated with cortical malformations may be evident early in development at a relatively “low” level (e.g., simple gap detection), but may require “higher-order” auditory discrimination tasks (e.g., tone sequences, phonemic discriminations) to be elicited later in life.
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severity of focal Microgyria and associated rapid auditory processing deficits
Neuroreport, 2004Co-Authors: Ann M Peiffer, Glenn D Rosen, Melissa M Mcclure, Steven W Threlkeld, Holly R FitchAbstract:Data from rodent models of induced Microgyria suggest that bilateral damage leads to more severe rapid auditory processing de¢cits than unilateral damage. It is unclear whether this re£ects the degree, or bilateral/unilateral nature, of damage. The current study evaluates the eiects of microgyric severity by assessing rats with single- vs double-pair bilateral focal microgyric lesions, using auditory discrimination and MGN measures. Behavioral data show a signi¢cant auditory processing de¢cit on rapid processing tasks for microgyric as compared to control subjects, and also reveal more severe de¢cits for double- than for single-pair bilateral microgyrics. Greater disruptions are also seen in the MGN of double-pair compared to single-pair bilateral microgyric subjects. NeuroReport 15:1923^1926 � c 2004 Lippincott Williams & Wilkins.
Steven W Threlkeld - One of the best experts on this subject based on the ideXlab platform.
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effects of test experience and neocortical Microgyria on spatial and non spatial learning in rats
Behavioural Brain Research, 2012Co-Authors: Steven W Threlkeld, Glenn D Rosen, C A Hill, Caitlin E Szalkowski, Dongnhu T Truong, Holly R FitchAbstract: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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Developmental learning impairments in a rodent model of nodular heterotopia
Journal of Neurodevelopmental Disorders, 2009Co-Authors: Steven W Threlkeld, Glenn D Rosen, Dongnhu T Truong, Courtney A. Hill, Caitlin E. Cleary, R. Holly FitchAbstract:Developmental malformations of neocortex—including Microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (Microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans.
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use of a modified prepulse inhibition paradigm to assess complex auditory discrimination in rodents
Brain Research Bulletin, 2008Co-Authors: Holly R Fitch, Steven W Threlkeld, Melissa M Mcclure, Ann M PeifferAbstract:Abstract Prepulse inhibition (PPI; also termed startle reduction or reflex modification, see Ref. [H.S. Hoffman, J.R. Ison, Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input, Psychol. Rev. 87 (1980) 175–189]) provides an efficient and accurate method to assess both simple and complex acoustic discrimination in rodents [J.R. Ison, G.R. Hammond, Modification of the startle reflex in the rat by changes in the auditory and visual environments, J. Comp. Physiol. Psychol. 75 (1971) 435–452]. Assessment of acoustic processing using PPI is less time consuming than operant conditioning paradigms, allows for the testing of many subjects simultaneously, and largely eliminates confounds due to motivation and attention [M. Clark, G. Rosen, P. Tallal, R.H. Fitch, Impaired processing of complex auditory stimuli in rats with induced cerebrocortical Microgyria, J. Cog. Neurosci. 12 (2000) 828–839]. Moreover, PPI procedures allow for data acquisition from the first day of testing, and can be used on rats as young as P14–15 [J.T. Friedman, A. Peiffer, M. Clark, A. Benasich, R.H. Fitch, Age and experience related improvements in gap detection in the rat, Dev. Brain Res. 152 (2004) 83–91; M. McClure, S. Threlkeld, G. Rosen, R.H. Fitch, Rapid auditory processing and learning deficits in rats with P1 versus P7 neonatal hypoxic-ischemic injury, Behav. Brain Res. 172 (2006) 114–121; S.W. Threlkeld, M.M. McClure, G.D. Rosen, R.H. Fitch, Developmental timeframes for the induction of Microgyria and rapid auditory processing deficits in the rat, Brain Res. 1109 (2006) 22–31]. For these and additional reasons, the PPI paradigm has more recently been adapted to the assessment of complex acoustic discrimination (tone sequences and FM sweeps), and applied to the study of normally developing as well as neuropathologically affected rodent populations. The purpose of the current review is to provide a background on the PPI paradigm, and to summarize what has been learned more recently using modified versions of PPI with rodent models.
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Age at Developmental Cortical Injury Differentially Alters Corpus Callosum Volume in the Rat
BMC Neuroscience, 2007Co-Authors: Steven W Threlkeld, Glenn D Rosen, R. Holly FitchAbstract:Background Freezing lesions to developing rat cortex induced between postnatal day (P) one and three (P1 – 3) lead to malformations similar to human Microgyria, and further correspond to reductions in brain weight and cortical volume. In contrast, comparable lesions on P5 do not produce microgyric malformations, nor the changes in brain weight seen with Microgyria. However, injury occurring at all three ages does lead to rapid auditory processing deficits as measured in the juvenile period. Interestingly, these deficits persist into adulthood only in the P1 lesion case [1]. Given prior evidence that early focal cortical lesions induce abnormalities in cortical morphology and connectivity [1, 2, 3, 4], we hypothesized that the differential behavioral effects of focal cortical lesions on P1, P3 or P5 may be associated with underlying neuroanatomical changes that are sensitive to timing of injury. Clinical studies indicate that humans with perinatal brain injury often show regional reductions in corpus callosum size and abnormal symmetry, which frequently correspond to learning impairments [5, 6, 7]. Therefore, in the current study the brains of P1, 3 or 5 lesion rats, previously evaluated for brain weight, and cortical volume changes and auditory processing impairments (P21-90), were further analyzed for changes in corpus callosum volume.
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developmental timeframes for induction of Microgyria and rapid auditory processing deficits in the rat
Brain Research, 2006Co-Authors: Steven W Threlkeld, Glenn D Rosen, Melissa M Mcclure, Holly R FitchAbstract:Abstract Induction of a focal freeze lesion to the skullcap of a 1-day-old rat pup leads to the formation of Microgyria similar to those identified postmortem in human dyslexics. Rats with Microgyria exhibit rapid auditory processing deficits similar to those seen in language-impaired (LI) children, and infants at risk for LI and these effects are particularly marked in juvenile as compared to adult subjects. In the current study, a startle response paradigm was used to investigate gap detection in juvenile and adult rats that received bilateral freezing lesions or sham surgery on postnatal day (P) 1, 3 or 5. Microgyria were confirmed in P1 and 3 lesion rats, but not in the P5 lesion group. We found a significant reduction in brain weight and neocortical volume in P1 and 3 lesioned brains relative to shams. Juvenile (P27–39) behavioral data indicated significant rapid auditory processing deficits in all three lesion groups as compared to sham subjects, while adult (P60+) data revealed a persistent disparity only between P1-lesioned rats and shams. Combined results suggest that generalized pathology affecting neocortical development is responsible for the presence of rapid auditory processing deficits, rather than factors specific to the formation of Microgyria per se. Finally, results show that the window for the induction of rapid auditory processing deficits through disruption of neurodevelopment appears to extend beyond the endpoint for cortical neuronal migration, although, the persistent deficits exhibited by P1 lesion subjects suggest a secondary neurodevelopmental window at the time of cortical neuromigration representing a peak period of vulnerability.
