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Auditory cortical structure predicts superior pitch processing in children with autism
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Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
indicated a reappearance of the myelinated cortical fibers. However, these new fibers lacked directionality observed in the control brains. The analysis of Ki67 antigen, known to be associated with proliferating cells, showed increased number of proliferating cells in the subventricular Zone (SVZ) of the STB mice which followed by a reduction in the LTB mice. We observed blast-induced migration of immature Olig2 expressing oligodendrocytes through the corpus callosum and increased number of Olig2+ cells in the cingulate cortex of LTB mice. Immunostaining for an early neuronal cell marker, Doublecortin, suggests a transient blast-induced increase in the number of neuronal progenitors in the SVZ. The results suggest that the increase in blast-induced activation of the brain neural stem/progenitor cells generates predominantly new oligodendrocytes. This work was supported by NYSTEM contracts C026415 and C026714. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.261 ISDN2014 0315 Digging into the bilingual brain in the elderly Yuriem Fernández García 1,∗ , Lorna 1 , Manuel ˜ García-Pentón 1 , Ileana Quinones Carreiras 1,2 , Jon Andoni Dunabeitia 1 1 Basque Center on Cognition, Brain and Language (BCBL), Donostia, Spain 2 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
A lifelong bilingualism is an interesting condition for investigating structural brain plasticity. It has been shown that dealing with two languages instead of one produces anatomical brain changes (García-Pentón et al., 2014; Klein et al., 2013; Mechelli et al., 2004). However, the precise nature of these structural brain changes associated with bilingualism in normal aging is still under debate (Gold et al., 2013). It has been proposed that because bilinguals monitor two languages on a daily basis, they exhibit an advantage in executive control tasks as compared to monolinguals and that this produces more visible structural brain changes in the elderly (Bialystok et al., 2012). Here, we examine how the age of acquisition (AoA) of the second language (L2) affects grey and white matter (GM/WM) volume in bilingual old adults. Right-handed elderly Spanish-Basque highly proficient bilinguals were tested. MRI data were acquired on a 3-T Magnetom Trio Tim scanner (Siemens AG, Erlangen, Germany). Structural data were analyzed with an optimized voxel-based morphometry (VBM), using the Statistical Parametric Mapping software package (SPM8, Wellcome Trust Centre for Neuroimaging, UK). Data were manually reoriented, segmented into different tissue maps and normalized. Segmentation was performed using the New Segment tool. The DARTEL tool was used to registration. Each resulting normalized and modulated image was smoothed with a Gaussian kernel of 8 mm. Correlation analysis between GM/WM volume and L2 AoA was carried out. Regional differences were reported as significant at p < 0.05, fully corrected for multiple comparisons across space applying topological false discovery rate. We found that GM volume in right-superior frontal and rightinferior frontal (pars triangularis) regions correlated positively with L2 AoA. These results show that the degree of structural reorganization in right frontal regions is modulated by L2 AoA in highly proficient old bilinguals suggesting that late old bilinguals may need a compensatory monitoring/control mechanism for dealing with the two languages.
ISDN2014 0316 New research priorities of the National Institute on Drug Abuse (NIDA): Cannabis effects on brain development Da-Yu Wu Division of Basic Neuroscience and Behaviour Research, National Institute on Drug Abuse/NIH, United States Recent epidemiological data on cannabis use among adolescents over the last five-years show significant increases in past-year and past-month (current) use among 8th, 10th and 12th graders. Furthermore, growing evidence suggests that cannabis exposure during prenatal, perinatal, postnatal, childhood, and adolescent periods may have long-lasting effects on brain development into the adulthood. For example, recent human studies suggest that marijuana exposure during adolescence may disrupt neuromodulatory influences of endocannabinoids and cause significant cortical white matter reduction (Ho et al., 2011). Also, heavy cannabis users appear to have reduced amygdala and hippocampal volumes, brain areas important for emotion and memory (Schacht et al., 2012). A study using an animal model found that prenatal exposure to cannabinoid receptor agonists impaired tangential and radial migration of post-mitotic neurons that form the cortical layers (Saez, 2014). Further research is needed to understand whether and how these cannabis–induced alterations of brain development affect subsequent behaviour and brain function into adulthood, and whether they increase the risk of substance use and other mental disorders. Thus, NIDA is interested in supporting research to study the effects of cannabis and cannabinoids (e.g., delta9THC, cannabidiol) on the developing brain. NIDA encourages the exploration of novel concepts and hypotheses of cannabis use and dependence, and the development of enabling research tools and technologies, such as animal behaviour models, iPSC based cellular and molecular studies, genetic and genomic variation studies, as well as brain imaging and genetic/genomic modelling to link brain function with behavioural outcomes. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.263 ISDN2014 0317 Auditory cortical structure predicts superior pitch processing in children with autism Nicholas Foster 1,2,∗ , Ana Tryfon 1,2 , Tia Ouimet 1,2 , Krissy Doyle-Thomas 3 , Evdokia Anagnostou 3 , Alan Evans 4 , Lonnie Zwaigenbaum 5 , Krista Hyde 1,2 , for NeuroDevNet ASD imaging group6 1
International Laboratory for Brain Music and Sound (BRAMS), University of Montreal, Montreal, Canada 2 Faculty of Medicine, McGill University, Montreal, Canada 3 Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada 4 Montreal Neurological Institute, McGill University, Montreal, Canada 5 Glenrose Rehabilitation Hospital, Edmonton, Canada Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by atypical social interaction,
http://dx.doi.org/10.1016/j.ijdevneu.2015.04.262 6
http://www.neurodevnet.ca/research/asd.
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
communication, and sensory perception. In a previous study of ASD adults, we found a correlation between enhanced pitch perception and auditory cortical volume. Here we sought to extend these findings to children with ASD. Subjects were ASD and control children who participated in the NeuroDevNet ASD Project. Groups were matched on age and IQ (>70). In a pitch change direction task, subjects heard two pure tones and had to decide whether the second tone was higher/lower in pitch; difficulty varied by presenting tones at smaller pitch distances or faster temporal rates. Brain structural MRI data were acquired and segmented into gray and white matter using an automatic classification algorithm. Regions of interest in primary (Heschl’s gyrus, HG) and secondary auditory cortex (planum temporale, PT) were defined via thresholded probability maps. Auditory volumes were calculated by summing gray-matter voxels within the regions. A repeated measures model tested group differences in 1) task performance and 2) gray matter volume within each auditory region. ASD individuals performed better than controls overall on the pitch task, but most significantly so at faster temporal rates. Performance on faster temporal rates was positively correlated specifically with left PT volume. These results replicate previous findings in ASD adults in the PT. This region is a hub for processing auditory language and has been shown to be atypical in ASD during language tasks. Our results support the idea that cortical differences in the PT during ASD development can account for enhanced perception of simple auditory sounds, perhaps to the detriment of processing complex material like speech. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.264 ISDN2014 0318 Practicing self-regulation through music: An ERP study comparing child musicians and nonmusicians Kylie Schibli ∗ , Patricia Van Roon, Korey MacDougall, Amedeo D’Angiulli Carleton University, Canada The ability to self-regulate has been associated with schoolreadiness and academic achievement. Research has indicated that young children receiving music instruction perform significantly better on self-regulation tasks. The current study assessed selfregulation ability in twenty children 9–12 years old with and without formal music instruction. Event-related potentials (ERPs) were examined to determine the relationship between music, selfregulation, and brain response. Inhibition control and selective attention was tested using a computerized auditory selective attention task under the go/nogo paradigm. Children were asked to respond to a tone at a specific pitch (go-trial) while ignoring the second tone at a differing pitch (no-go trial). ERPs were recorded as children completed the task. Studies involving a task under the go/no-go paradigm have demonstrated larger amplitude of the N2 component during no-go trials with latency of 280–320 ms in 9–10 year-olds. We found significant increases in amplitude of early ERP components (50–200 ms) for child musicians when compared with nonmusicians, in addition to lower reaction times and improved accuracy for performance. Children also completed the Peabody Picture Vocabulary Test, Fourth Edition (PPVT-IV) to allow us to determine the influence of music learning on verbal comprehension. Family demographics and wellbeing were collected through questionnaires completed by the child’s guardian. Children enrolled in music performed significantly better than children not enrolled on the auditory go/no-go task, however, only
97
in response to the go note at a higher frequency (2000 Hz), an effect which also corresponded with differences in ERPs between the two groups. Outcomes from this study support the relationship between practicing self-regulation skills through music and children’s levels in executive functioning (i.e. inhibition control and selective attention). Findings from our research may have implications for music training interventions and music training implementation in the school setting, especially as applied to socioeconomically disadvantaged children. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.265 ISDN2014 0319 Lkb1 orients neural precursor division to control expansion and folding of the cerebellar cortex Kaitlyn E. Ryan ∗ , Frances Y. Cheng, Ying Litingtung, Chin Chiang Department of Cell and Developmental Biology, Vanderbilt University, United States Background: Evolution of the mammalian brain has led to a remarkable expansion in both cerebral and cerebellar cortical area. Such expansion is facilitated in part by folding of the cortical surface. In the cerebellum, these folds form during development in a process known as foliation, and the increasing degree of foliation across species correlates with increasing cognitive function and processing capacity. However, the cellular and molecular mechanism governing expansion and folding of the cerebellar cortex remain incompletely understood. Results: During development, granule cell precursors (GCPs) proliferate within a transient germinal layer covering the cerebellar surface known as the external granule layer (EGL). Mice harboring GCP-specific ablation of Lkb1 (Math1-cre; Lkb1fl/− or Lkb1cko mice) had an expanded cerebellar cortex, resulting in a near 40% increase in foliation (15 folds on average in Lkb1cko vs. 10.6 in controls). While previous studies have shown that Hedgehog-driven proliferation in part controls foliation in the mouse, cortical expansion in Lkb1cko was not due to increased GCP proliferation or Hedgehog signaling. Instead, our data indicate that changes in the plane of GCP mitotic division drives Lkb1cko cerebellar cortical expansion. In control animals, the majority of mitotic GCPs divided perpendicular to the cerebellar surface. However, in Lkb1cko animals, orientation of division was randomized, with significantly more cells dividing parallel to the cerebellar surface than controls. These changes were independent of AMPK or mTOR signaling, known downstream substrates of Lkb1. Conclusions: We find that the plane of GCP division is an important determinant of cortical expansion and foliation in the developing cerebellum and identify Lkb1 as a key player in orienting GCP division. GCP-specific loss of Lkb1 increased cerebellar foliation in the absence of changes in Hedgehog signaling or proliferation, elucidating Lkb1 as a novel regulator of the characteristic folding of the cerebellar surface.
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
indicated a reappearance of the myelinated cortical fibers. However, these new fibers lacked directionality observed in the control brains. The analysis of Ki67 antigen, known to be associated with proliferating cells, showed increased number of proliferating cells in the subventricular Zone (SVZ) of the STB mice which followed by a reduction in the LTB mice. We observed blast-induced migration of immature Olig2 expressing oligodendrocytes through the corpus callosum and increased number of Olig2+ cells in the cingulate cortex of LTB mice. Immunostaining for an early neuronal cell marker, Doublecortin, suggests a transient blast-induced increase in the number of neuronal progenitors in the SVZ. The results suggest that the increase in blast-induced activation of the brain neural stem/progenitor cells generates predominantly new oligodendrocytes. This work was supported by NYSTEM contracts C026415 and C026714. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.261 ISDN2014 0315 Digging into the bilingual brain in the elderly Yuriem Fernández García 1,∗ , Lorna 1 , Manuel ˜ García-Pentón 1 , Ileana Quinones Carreiras 1,2 , Jon Andoni Dunabeitia 1 1 Basque Center on Cognition, Brain and Language (BCBL), Donostia, Spain 2 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
A lifelong bilingualism is an interesting condition for investigating structural brain plasticity. It has been shown that dealing with two languages instead of one produces anatomical brain changes (García-Pentón et al., 2014; Klein et al., 2013; Mechelli et al., 2004). However, the precise nature of these structural brain changes associated with bilingualism in normal aging is still under debate (Gold et al., 2013). It has been proposed that because bilinguals monitor two languages on a daily basis, they exhibit an advantage in executive control tasks as compared to monolinguals and that this produces more visible structural brain changes in the elderly (Bialystok et al., 2012). Here, we examine how the age of acquisition (AoA) of the second language (L2) affects grey and white matter (GM/WM) volume in bilingual old adults. Right-handed elderly Spanish-Basque highly proficient bilinguals were tested. MRI data were acquired on a 3-T Magnetom Trio Tim scanner (Siemens AG, Erlangen, Germany). Structural data were analyzed with an optimized voxel-based morphometry (VBM), using the Statistical Parametric Mapping software package (SPM8, Wellcome Trust Centre for Neuroimaging, UK). Data were manually reoriented, segmented into different tissue maps and normalized. Segmentation was performed using the New Segment tool. The DARTEL tool was used to registration. Each resulting normalized and modulated image was smoothed with a Gaussian kernel of 8 mm. Correlation analysis between GM/WM volume and L2 AoA was carried out. Regional differences were reported as significant at p < 0.05, fully corrected for multiple comparisons across space applying topological false discovery rate. We found that GM volume in right-superior frontal and rightinferior frontal (pars triangularis) regions correlated positively with L2 AoA. These results show that the degree of structural reorganization in right frontal regions is modulated by L2 AoA in highly proficient old bilinguals suggesting that late old bilinguals may need a compensatory monitoring/control mechanism for dealing with the two languages.
ISDN2014 0316 New research priorities of the National Institute on Drug Abuse (NIDA): Cannabis effects on brain development Da-Yu Wu Division of Basic Neuroscience and Behaviour Research, National Institute on Drug Abuse/NIH, United States Recent epidemiological data on cannabis use among adolescents over the last five-years show significant increases in past-year and past-month (current) use among 8th, 10th and 12th graders. Furthermore, growing evidence suggests that cannabis exposure during prenatal, perinatal, postnatal, childhood, and adolescent periods may have long-lasting effects on brain development into the adulthood. For example, recent human studies suggest that marijuana exposure during adolescence may disrupt neuromodulatory influences of endocannabinoids and cause significant cortical white matter reduction (Ho et al., 2011). Also, heavy cannabis users appear to have reduced amygdala and hippocampal volumes, brain areas important for emotion and memory (Schacht et al., 2012). A study using an animal model found that prenatal exposure to cannabinoid receptor agonists impaired tangential and radial migration of post-mitotic neurons that form the cortical layers (Saez, 2014). Further research is needed to understand whether and how these cannabis–induced alterations of brain development affect subsequent behaviour and brain function into adulthood, and whether they increase the risk of substance use and other mental disorders. Thus, NIDA is interested in supporting research to study the effects of cannabis and cannabinoids (e.g., delta9THC, cannabidiol) on the developing brain. NIDA encourages the exploration of novel concepts and hypotheses of cannabis use and dependence, and the development of enabling research tools and technologies, such as animal behaviour models, iPSC based cellular and molecular studies, genetic and genomic variation studies, as well as brain imaging and genetic/genomic modelling to link brain function with behavioural outcomes. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.263 ISDN2014 0317 Auditory cortical structure predicts superior pitch processing in children with autism Nicholas Foster 1,2,∗ , Ana Tryfon 1,2 , Tia Ouimet 1,2 , Krissy Doyle-Thomas 3 , Evdokia Anagnostou 3 , Alan Evans 4 , Lonnie Zwaigenbaum 5 , Krista Hyde 1,2 , for NeuroDevNet ASD imaging group6 1
International Laboratory for Brain Music and Sound (BRAMS), University of Montreal, Montreal, Canada 2 Faculty of Medicine, McGill University, Montreal, Canada 3 Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada 4 Montreal Neurological Institute, McGill University, Montreal, Canada 5 Glenrose Rehabilitation Hospital, Edmonton, Canada Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by atypical social interaction,
http://dx.doi.org/10.1016/j.ijdevneu.2015.04.262 6
http://www.neurodevnet.ca/research/asd.
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
communication, and sensory perception. In a previous study of ASD adults, we found a correlation between enhanced pitch perception and auditory cortical volume. Here we sought to extend these findings to children with ASD. Subjects were ASD and control children who participated in the NeuroDevNet ASD Project. Groups were matched on age and IQ (>70). In a pitch change direction task, subjects heard two pure tones and had to decide whether the second tone was higher/lower in pitch; difficulty varied by presenting tones at smaller pitch distances or faster temporal rates. Brain structural MRI data were acquired and segmented into gray and white matter using an automatic classification algorithm. Regions of interest in primary (Heschl’s gyrus, HG) and secondary auditory cortex (planum temporale, PT) were defined via thresholded probability maps. Auditory volumes were calculated by summing gray-matter voxels within the regions. A repeated measures model tested group differences in 1) task performance and 2) gray matter volume within each auditory region. ASD individuals performed better than controls overall on the pitch task, but most significantly so at faster temporal rates. Performance on faster temporal rates was positively correlated specifically with left PT volume. These results replicate previous findings in ASD adults in the PT. This region is a hub for processing auditory language and has been shown to be atypical in ASD during language tasks. Our results support the idea that cortical differences in the PT during ASD development can account for enhanced perception of simple auditory sounds, perhaps to the detriment of processing complex material like speech. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.264 ISDN2014 0318 Practicing self-regulation through music: An ERP study comparing child musicians and nonmusicians Kylie Schibli ∗ , Patricia Van Roon, Korey MacDougall, Amedeo D’Angiulli Carleton University, Canada The ability to self-regulate has been associated with schoolreadiness and academic achievement. Research has indicated that young children receiving music instruction perform significantly better on self-regulation tasks. The current study assessed selfregulation ability in twenty children 9–12 years old with and without formal music instruction. Event-related potentials (ERPs) were examined to determine the relationship between music, selfregulation, and brain response. Inhibition control and selective attention was tested using a computerized auditory selective attention task under the go/nogo paradigm. Children were asked to respond to a tone at a specific pitch (go-trial) while ignoring the second tone at a differing pitch (no-go trial). ERPs were recorded as children completed the task. Studies involving a task under the go/no-go paradigm have demonstrated larger amplitude of the N2 component during no-go trials with latency of 280–320 ms in 9–10 year-olds. We found significant increases in amplitude of early ERP components (50–200 ms) for child musicians when compared with nonmusicians, in addition to lower reaction times and improved accuracy for performance. Children also completed the Peabody Picture Vocabulary Test, Fourth Edition (PPVT-IV) to allow us to determine the influence of music learning on verbal comprehension. Family demographics and wellbeing were collected through questionnaires completed by the child’s guardian. Children enrolled in music performed significantly better than children not enrolled on the auditory go/no-go task, however, only
97
in response to the go note at a higher frequency (2000 Hz), an effect which also corresponded with differences in ERPs between the two groups. Outcomes from this study support the relationship between practicing self-regulation skills through music and children’s levels in executive functioning (i.e. inhibition control and selective attention). Findings from our research may have implications for music training interventions and music training implementation in the school setting, especially as applied to socioeconomically disadvantaged children. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.265 ISDN2014 0319 Lkb1 orients neural precursor division to control expansion and folding of the cerebellar cortex Kaitlyn E. Ryan ∗ , Frances Y. Cheng, Ying Litingtung, Chin Chiang Department of Cell and Developmental Biology, Vanderbilt University, United States Background: Evolution of the mammalian brain has led to a remarkable expansion in both cerebral and cerebellar cortical area. Such expansion is facilitated in part by folding of the cortical surface. In the cerebellum, these folds form during development in a process known as foliation, and the increasing degree of foliation across species correlates with increasing cognitive function and processing capacity. However, the cellular and molecular mechanism governing expansion and folding of the cerebellar cortex remain incompletely understood. Results: During development, granule cell precursors (GCPs) proliferate within a transient germinal layer covering the cerebellar surface known as the external granule layer (EGL). Mice harboring GCP-specific ablation of Lkb1 (Math1-cre; Lkb1fl/− or Lkb1cko mice) had an expanded cerebellar cortex, resulting in a near 40% increase in foliation (15 folds on average in Lkb1cko vs. 10.6 in controls). While previous studies have shown that Hedgehog-driven proliferation in part controls foliation in the mouse, cortical expansion in Lkb1cko was not due to increased GCP proliferation or Hedgehog signaling. Instead, our data indicate that changes in the plane of GCP mitotic division drives Lkb1cko cerebellar cortical expansion. In control animals, the majority of mitotic GCPs divided perpendicular to the cerebellar surface. However, in Lkb1cko animals, orientation of division was randomized, with significantly more cells dividing parallel to the cerebellar surface than controls. These changes were independent of AMPK or mTOR signaling, known downstream substrates of Lkb1. Conclusions: We find that the plane of GCP division is an important determinant of cortical expansion and foliation in the developing cerebellum and identify Lkb1 as a key player in orienting GCP division. GCP-specific loss of Lkb1 increased cerebellar foliation in the absence of changes in Hedgehog signaling or proliferation, elucidating Lkb1 as a novel regulator of the characteristic folding of the cerebellar surface.