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Changes in prefrontal axons may disrupt the network in autism.

ABSTRACT: Neural communication is disrupted in autism by unknown mechanisms. Here, we examined whether in autism there are changes in axons, which are the conduit for neural communication. We investigated single axons and their ultrastructure in the white matter of postmortem human brain tissue below the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and lateral prefrontal cortex (LPFC), which are associated with attention, social interactions, and emotions, and have been consistently implicated in the pathology of autism. Area-specific changes below ACC (area 32) included a decrease in the largest axons that communicate over long distances. In addition, below ACC there was overexpression of the growth-associated protein 43 kDa accompanied by excessive number of thin axons that link neighboring areas. In OFC (area 11), axons had decreased myelin thickness. Axon features below LPFC (area 46) appeared to be unaffected, but the altered white matter composition below ACC and OFC changed the relationships among all prefrontal areas examined, and could indirectly affect LPFC function. These findings provide a mechanism for disconnection of long-distance pathways, excessive connections between neighboring areas, and inefficiency in pathways for emotions, and may help explain why individuals with autism do not adequately shift attention, engage in repetitive behavior, and avoid social interactions. These changes below specific prefrontal areas appear to be linked through a cascade of developmental events affecting axon growth and guidance, and suggest targeting the associated signaling pathways for therapeutic interventions in autism.

SUBMITTER: Zikopoulos B

PROVIDER: S-EPMC3073590 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Changes in prefrontal axons may disrupt the network in autism.

Zikopoulos Basilis B Barbas Helen H

The Journal of neuroscience : the official journal of the Society for Neuroscience 20101101 44

Neural communication is disrupted in autism by unknown mechanisms. Here, we examined whether in autism there are changes in axons, which are the conduit for neural communication. We investigated single axons and their ultrastructure in the white matter of postmortem human brain tissue below the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and lateral prefrontal cortex (LPFC), which are associated with attention, social interactions, and emotions, and have been consistently implic ...[more]

PMID: 21048117

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Project description:BackgroundDisrupted cortical connectivity is thought to underlie the complex cognitive and behavior profile observed in individuals with autism spectrum disorder (ASD). Previous neuroimaging research has identified patterns of both functional hypo- and hyper-connectivity in individuals with ASD. A recent theory attempting to reconcile conflicting results in the literature proposes that hyper-connectivity of brain networks may be more characteristic of young children with ASD, while hypo-connectivity may be more prevalent in adolescents and adults with the disorder when compared to typical development (TD) (Uddin etal., 2013). Previous work has examined only young children, mixed groups of children and adolescents, or adult cohorts in separate studies, leaving open the question of developmental influences on functional brain connectivity in ASD.MethodsThe current study tests this developmental hypothesis by examining within- and between-network resting state functional connectivity in a large sample of 26 children, 28 adolescents, and 18 adults with ASD and age- and IQ-matchedTD individuals for the first time using an entirely data-driven approach. Independent component analyses (ICA) and dual regression was applied to data from three age cohorts to examine the effects of participant age on patterns of within-networkwhole-brain functional connectivity in individuals with ASD compared with TD individuals. Between-network connectivity differences were examined for each age cohort by comparing correlations between ICA components across groups.ResultsWe find that in the youngest cohort (age 11 and under), children with ASD exhibit hyper-connectivity within large-scale brain networks as well as decreased between-network connectivity compared with age-matchedTD children. In contrast, adolescents with ASD (age 11-18) do not differ from TD adolescents in within-network connectivity, yet show decreased between-network connectivity compared with TD adolescents. Adults with ASD show no within- or between-network differences in functional network connectivity compared with neurotypical age-matched individuals.ConclusionsCharacterizing within- and between-network functional connectivity in age-stratified cohorts of individuals with ASD and TD individuals demonstrates that functional connectivity atypicalities in the disorder are not uniform across the lifespan. These results demonstrate how explicitly characterizing participant age and adopting a developmental perspective can lead to a more nuanced understanding of atypicalities of functional brain connectivity in autism.

Project description:Trans-saccadic memory consists of keeping track of objects' locations and features across saccades; pre-saccadic information is remembered and compared with post-saccadic information. It has been shown to have limited resources and involve attention with respect to the selection of objects and features. In support, a previous study showed that recognition of distinct post-saccadic objects in the visual scene is impaired when pre-saccadic objects are relevant and thus already encoded in memory (Poth, Herwig, Schneider, 2015). Here, we investigated the inverse (i.e. how the memory of pre-saccadic objects is affected by abrupt but irrelevant changes in the post-saccadic visual scene). We also modulated the amount of attention to the relevant pre-saccadic object by having participants either make a saccade to it or elsewhere and observed that pre-saccadic attentional facilitation affected how much post-saccadic changes disrupted trans-saccadic memory of pre-saccadic objects. Participants identified a flashed symbol (d, b, p, or q, among distracters), at one of six placeholders (figures "8") arranged in circle around fixation while planning a saccade to one of them. They reported the identity of the symbol after the saccade. We changed the post-saccadic scene in Experiment one by removing the entire scene, only the placeholder where the pre-saccadic symbol was presented, or all other placeholders except this one. We observed reduced identification performance when only the saccade-target placeholder disappeared after the saccade. In Experiment two, we changed one placeholder location (inward/outward shift or rotation re. saccade vector) after the saccade and observed that identification performance decreased with increased shift/rotation of the saccade-target placeholder. We conclude that pre-saccadic memory is disrupted by abrupt attention-capturing post-saccadic changes of visual scene, particularly when these changes involve the object prioritized by being the goal of a saccade. These findings support the notion that limited trans-saccadic memory resources are disrupted when object correspondence at saccadic goal is broken through removal or location change.

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Changes in prefrontal axons may disrupt the network in autism.

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Changes in prefrontal axons may disrupt the network in autism.

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