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      Is Open Access

      From early markers to neuro-developmental mechanisms of autism

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          Highlights

          • Studies of infants at-risk could reveal the developmental origin of autism.

          • Behavioral and brain markers differentiate infants that develop autism symptoms from controls, during the first year of life.

          • Little evidence for decreased social orienting or social motivation.

          • Some evidence for multiple developmental pathways to autism.

          Abstract

          A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the “social brain”. Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions.

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          Most cited references138

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          Neocortical excitation/inhibition balance in information processing and social dysfunction.

          Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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            Executive function and the frontal lobes: a meta-analytic review.

            Currently, there is debate among scholars regarding how to operationalize and measure executive functions. These functions generally are referred to as "supervisory" cognitive processes because they involve higher level organization and execution of complex thoughts and behavior. Although conceptualizations vary regarding what mental processes actually constitute the "executive function" construct, there has been a historical linkage of these "higher-level" processes with the frontal lobes. In fact, many investigators have used the term "frontal functions" synonymously with "executive functions" despite evidence that contradicts this synonymous usage. The current review provides a critical analysis of lesion and neuroimaging studies using three popular executive function measures (Wisconsin Card Sorting Test, Phonemic Verbal Fluency, and Stroop Color Word Interference Test) in order to examine the validity of the executive function construct in terms of its relation to activation and damage to the frontal lobes. Empirical lesion data are examined via meta-analysis procedures along with formula derivatives. Results reveal mixed evidence that does not support a one-to-one relationship between executive functions and frontal lobe activity. The paper concludes with a discussion of the implications of construing the validity of these neuropsychological tests in anatomical, rather than cognitive and behavioral, terms.
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              Autism spectrum disorders: developmental disconnection syndromes.

              Autism is a common and heterogeneous childhood neurodevelopmental disorder. Analogous to broad syndromes such as mental retardation, autism has many etiologies and should be considered not as a single disorder but, rather, as 'the autisms'. However, recent genetic findings, coupled with emerging anatomical and functional imaging studies, suggest a potential unifying model in which higher-order association areas of the brain that normally connect to the frontal lobe are partially disconnected during development. This concept of developmental disconnection can accommodate the specific neurobehavioral features that are observed in autism, their emergence during development, and the heterogeneity of autism etiology, behaviors and cognition.
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                Author and article information

                Contributors
                Journal
                Dev Rev
                Dev Rev
                Developmental Review
                Academic Press
                0273-2297
                1 September 2014
                September 2014
                : 34
                : 3
                : 189-207
                Affiliations
                [a ]Centre for Brain and Cognitive Development, Birkbeck College, University of London, United Kingdom
                [b ]Biostatistics Department, Institute of Psychiatry, King’s College London, United Kingdom
                [c ]Psychology Department, Institute of Psychiatry, King’s College London, United Kingdom
                Author notes
                [* ]Corresponding author. Address: Centre for Brain and Cognitive Development, Birkbeck College, Malet Street, WC1E 7HX London, United Kingdom. t.gliga@ 123456bbk.ac.uk
                Article
                S0273-2297(14)00024-0
                10.1016/j.dr.2014.05.003
                4119302
                25187673
                89aeb6a8-4d7e-4cbd-ae61-c92af819cb81
                © 2014 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

                History
                : 14 July 2013
                : 19 May 2014
                Categories
                Article

                infants,autism,the “social brain”,sensory processing

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