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      Co-localisation of abnormal brain structure and function in specific language impairment

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          Abstract

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          Highlights

          ► Compared brain structure and function in SLI, unaffected siblings, and typical peers. ► More grey matter in SLI in the left inferior frontal cortex. ► Less grey matter in SLI in the right caudate nucleus and superior temporal cortex bilaterally. ► Functional activation was examined with an auditory covert naming task. ► Functionally, SLI had reduced activation of the left inferior frontal cortex and the superior temporal cortex bilaterally.

          Abstract

          We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing.

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          Most cited references43

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          A forkhead-domain gene is mutated in a severe speech and language disorder.

          Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity. Although studies of twins consistently indicate that a significant genetic component is involved, most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait. Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval. Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language.
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            Regional differences in synaptogenesis in human cerebral cortex.

            The formation of synaptic contacts in human cerebral cortex was compared in two cortical regions: auditory cortex (Heschl's gyrus) and prefrontal cortex (middle frontal gyrus). Synapse formation in both cortical regions begins in the fetus, before conceptual age 27 weeks. Synaptic density increases more rapidly in auditory cortex, where the maximum is reached near postnatal age 3 months. Maximum synaptic density in middle frontal gyrus is not reached until after age 15 months. Synaptogenesis occurs concurrently with dendritic and axonal growth and with myelination of the subcortical white matter. A phase of net synapse elimination occurs late in childhood, earlier in auditory cortex, where it has ended by age 12 years, than in prefrontal cortex, where it extends to midadolescence. Synaptogenesis and synapse elimination in humans appear to be heterochronous in different cortical regions and, in that respect, appears to differ from the rhesus monkey, where they are concurrent. In other respects, including overproduction of synaptic contacts in infancy, persistence of high levels of synaptic density to late childhood or adolescence, the absolute values of maximum and adult synaptic density, and layer specific differences, findings in the human resemble those in rhesus monkeys.
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              Beyond Bonferroni: Less conservative analyses for conservation genetics

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                Author and article information

                Journal
                Brain Lang
                Brain Lang
                Brain and Language
                Academic Press
                0093-934X
                1090-2155
                March 2012
                March 2012
                : 120
                : 3-4
                : 310-320
                Affiliations
                [a ]Department of Experimental Psychology, University of Oxford, South Parks Road Oxford OX1 3UD, United Kingdom
                [b ]MRC Institute of Hearing Research, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom
                [c ]FMRIB Centre, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, United Kingdom
                Author notes
                [* ]Corresponding author at: Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford OX1 3UD, United Kingdom. kate.watkins@ 123456psy.ox.ac.uk
                Article
                YBRLN3914
                10.1016/j.bandl.2011.10.006
                3315677
                22137677
                ad27109c-b41a-44cb-88ca-dae9c5ff66e4
                © 2012 Elsevier Inc.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 24 October 2011
                Categories
                Article

                Neurosciences
                functional magnetic resonance imaging,developmental disorders,lateralisation,voxel-based morphometry,language specialisation

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