Local Functional Overconnectivity in Posterior Brain Regions Is Associated with Symptom Severity in Autism Spectrum Disorders

Keown, Christopher L.; Shih, Patricia; Nair, Aarti; Peterson, Nick; Mulvey, Mark E.; Müller, Ralph‐Axel

doi:10.1016/j.celrep.2013.10.003

Cited by 250 publications

(222 citation statements)

References 45 publications

(57 reference statements)

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“…They are in line with earlier results of population-based studies on adolescents and adults, indicating that RS connectivity correlates with both autistic traits [49][50][51][52] and ASD symptom severity scores in clinical samples. 14,53,54 However, our results extend the latter findings as they show the relationship within twin pairs, where most genetic and environmental confounders are controlled for. Indeed, twins with higher autistic traits showed increased within-SN connectivity compared to their co-twins.…”

Section: Discussioncontrasting

confidence: 39%

Alterations in resting state connectivity along the autism trait continuum: a twin study

et al. 2017

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Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD. Using a within-twin pair design (N = 150 twins; 8-23 years), we examined altered RS connectivity between core regions of the DMN and SN in relation to autistic trait severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing typical development, ASD or other neurodevelopmental conditions. Connectivity between core regions of the SN was stronger in twins with higher autistic traits compared to their co-twins. This effect was significant both in the total sample and in MZ twins alone, highlighting the effect of non-shared environmental factors on the link between SN-connectivity and autistic traits. While this link was strongest in children, we did not identify differences between age groups for the SN. In contrast, connectivity between core hubs of the DMN was negatively correlated with autistic traits in adolescents and showed a similar trend in adults but not in children. The results support hypotheses of age-dependent altered RS connectivity in ASD, making altered SN and DMN connectivity promising candidate biomarkers for ASD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.160 INTRODUCTION Altered patterns of brain connectivity have been suggested as a key neurobiological correlate of the behavioral characteristics of autism spectrum disorder (ASD). However, as findings are inconsistent, the precise brain connectivity characteristics of ASD remain unclear. A large number of resting-state (RS) functional magnetic resonance imaging (MRI) brain connectivity studies have shown a complex pattern of both hypo-and hyper-connectivity in ASD.1-3 Notably, a large multi-site classification study including ASD and typically developing individuals (N = 252, 6-36 years) showed that of the top 100 biomarkers of brain connectivity achieving together 90.8% accuracy, 45% were related to hyperconnectivity and the remaining 55% to hypo-connectivity. 4 It is likely that the observed inconsistencies in classical brain connectivity investigations are limited by methodological issues, such as insufficient control for head motion or the inclusion of global signal regression which can modulate or even invert the direction of functional connectivity differences. [5][6][7] Moreover, gender has recently been shown to modulate the direction of connectivity differences in ASD. 8 In contrast, another study found default mode network (DMN) hypo-connectivity in both genders.

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Section: Discussioncontrasting

confidence: 39%

Alterations in resting state connectivity along the autism trait continuum: a twin study

et al. 2017

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“…More recent fMRI studies using connectivity measures derived from resting state measures report both under- (Dinstein et al, 2011) and over-connectivity (Keown et al, 2013;Supekar et al, 2013) or normal patterns (Tyszka et al, 2014). However, a recent article by (Hahamy et al, 2015) suggested that there are marked individual differences (or idiosyncrasies) shown by whole-brain analyses of connectivity, with ASD participants showing substantially more deviation from group-averaged patterns of inter-hemispheric connectivity.…”

Section: Aberrant Cortical Connectivity In Asdmentioning

confidence: 97%

Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling

Kessler

Seymour

Rippon

2016

Neuroscience & Biobehavioral Reviews

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Please cite this article as: Kessler, K., Seymour, R.A., Rippon, G., Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10. 1016/j.neubiorev.2016.10.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Abstract:Although atypical social behaviour remains a key characterisation of ASD, the presence of sensory and perceptual abnormalities has been given a more central role in recent classification changes. An understanding of the origins of such aberrations could thus prove a fruitful focus for ASD research. Early neurocognitive models of ASD suggested that the study of high frequency activity in the brain as a measure of cortical connectivity might provide the key to understanding the neural correlates of sensory and perceptual deviations in ASD. As our review shows, the findings from subsequent research have been inconsistent, with a lack of agreement about the nature of any high frequency disturbances in ASD brains.Based on the application of new techniques using more sophisticated measures of brain synchronisation, direction of information flow, and invoking the coupling between high and low frequency bands, we propose a framework which could reconcile apparently conflicting findings in this area and would be consistent both with emerging neurocognitive models of autism and with the heterogeneity of the condition.

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“…Reports have been published revealing reduced long-range, distant brain connectivity during both task-specific (Besag 2004;Koshino et al 2005Koshino et al , 2008Kana et al 2006;Just et al 2007) and restingstate paradigms Weng et al 2010). Likewise, a number of studies have shown reduced short-range, local connectivity (Besag 2004;Koshino et al 2005Koshino et al , 2008Just et al 2007;Kana et al 2011). Results from yet other studies have shown increased connectivity, both long range (Ben Bashat et al 2007;Cheng et al 2010;Supekar et al 2013) and short range (Weng et al 2010;Anderson et al 2011;Keown et al 2013;Khan et al 2013;Lewis et al 2013). …”

Section: Aberrant Connectivity In Autismmentioning

confidence: 97%

Epilepsy and Autism

Buckley

Holmes

2016

Cold Spring Harb Perspect Med

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Epilepsy and autistic spectrum disorder frequently coexist in the same individual. Electroencephalogram (EEG) epileptiform activity is also present at a substantially higher rate in children with autism than normally developing children. As with epilepsy, there are a multitude of genetic and environmental factors that can result in autistic spectrum disorder. There is growing consensus from both animal and clinical studies that autism is a disorder of aberrant connectivity. As measured with functional magnetic resonance imaging (MRI) and EEG, the brain in autistic spectrum disorder may be under-or overconnected or have a mixture of over-and underconnectivity. In the case of comorbid epilepsy and autism, an imbalance of the excitatory/inhibitory (E/I) ratio in selected regions of the brain may drive overconnectivity. Understanding the mechanism by which altered connectivity in individuals with comorbid epilepsy and autistic spectrum disorder results in the behaviors specific to the autistic spectrum disorder remains a challenge.

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Local Functional Overconnectivity in Posterior Brain Regions Is Associated with Symptom Severity in Autism Spectrum Disorders

Cited by 250 publications

References 45 publications

Alterations in resting state connectivity along the autism trait continuum: a twin study

Alterations in resting state connectivity along the autism trait continuum: a twin study

Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling

Epilepsy and Autism

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