Atypical functional brain connectivity during rest in autism spectrum disorders

Doyle‐Thomas, Krissy; Lee, Wayne; Foster, Nicholas E.V.; Tryfon, Ana; Ouimet, Tia; Hyde, Krista L.; Evans, Alan C.; Lewis, John D.; Zwaigenbaum, Lonnie; Anagnostou, Evdokia

doi:10.1002/ana.24391

Cited by 71 publications

(78 citation statements)

References 47 publications

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“…Many studies have reported decreased FC between DMN regions in those with ASD (Assaf et al, 2010;Kennedy & Courchesne, 2008;Monk et al, 2009;Weng et al, 2010), although hyperconnectivity within this network has also been reported (Monk et al, 2009;Uddin et al, 2013a). One study found that hypo-or hyperconnectivity of the DMN may be region-specific (Doyle-Thomas et al, 2015). Increased FC in the occipital network is consistent with previous findings of increased local connectivity in primary visual regions (Keown et al, 2013) and increased involvement of extrastriate cortex (Shen et al, 2012) in ASD.…”

Section: Cc-by-nc-nd 40 International License Peer-reviewed) Is the supporting

confidence: 84%

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

Easson

Fatima

McIntosh

2017

Preprint

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Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that is characterized by impairments in social communication and restricted and repetitive behaviours.Neuroimaging studies of individuals with ASD have shown complex patterns of functional connectivity (FC), with no clear consensus on defining brain-behaviour attributes of different subtypes of the disorder. In these studies, "static FC", a metric that considers correlations across the entire time series for a given region, was used. Emerging evidence shows that FC changes over time; this "dynamic FC" can allow for unique detection of the temporal variability of functional connections over time. Here, we used k-means clustering, an unsupervised machine learning algorithm, to characterize two subtypes of ASD based on distinct patterns of static and dynamic FC. A multivariate statistical approach was then implemented to determine optimal relationships between FC patterns and group membership or behaviour. The main objective was to characterize differences in static and dynamic FC between subtypes of ASD defined in a fully data-driven manner, and between subtypes and typically developing individuals. Subtype 2 was defined by increased FC within resting-state networks and decreased FC across networks for static FC, global increases in temporal stability of dynamic FC, and robust relationships between FC and several behaviours, relative to Subtype 1. Further, both ASD subtypes exhibited different patterns of static and dynamic FC compared to controls, particularly within default mode, sensorimotor, and occipital networks. Static and dynamic FC metrics provided both overlapping and unique information about the nature of FC differences between subtypes, and between both subtypes and controls. Our results demonstrate the value of considering FC-based subtypes of ASD to elucidate different relationships between brain and behaviour among individuals with this disorder, and have important clinical implications for catering treatments and behavioural interventions to specific subtypes.

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Section: Cc-by-nc-nd 40 International License Peer-reviewed) Is the supporting

confidence: 84%

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

Easson

Fatima

McIntosh

2017

Preprint

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“…12 Reduced DMN RS connectivity has been observed across age-groups in individuals with ASD, both within the DMN [13][14][15][16] and between the DMN and other regions. [17][18][19][20] In contrast, some studies have reported increased DMN RS connectivity. 13,[20][21][22] Reduced SN RS connectivity has been found in children, adolescents and adults with ASD, affecting connectivity within the SN as well as connectivity between SN key nodes and sensory, prefrontal, and emotion processing regions.…”

Section: Introductionmentioning

confidence: 93%

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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“…Because ASD presents in early childhood and brain connectivity changes with age (Doyle- Thomas et al 2015), the studies were performed serially in developing rats from P18 -P25. These ages would be human equivalent age of 5 to 6 yr (Clancy et al 2007;Workman et al 2013).…”

Section: Altered E/i Balance and Connectivitymentioning

confidence: 99%

“…It is important to note that ASD is an evolving disorder and, like changes in regional brain volume Lange et al 2015), brain connectivity changes with age (Cheng et al 2010;Doyle-Thomas et al 2015). Therefore, it is extremely important that age and developmental stage be accounted for when evaluating functional connectivity in ASD.…”

Section: Aberrant Connectivity In Autismmentioning

confidence: 99%

“…Therefore, it is extremely important that age and developmental stage be accounted for when evaluating functional connectivity in ASD. For example, in a recent study examining age-related changes in default mode network connectivity, children with ASD showed a mixed pattern of increased and decreased connectivity between the posterior cingulate cortex and the default mode network (Doyle- Thomas et al 2015). Importantly, in the children with ASD, connectivity between the posterior cingulate cortex and mPFC was higher than neurotypical controls in the youngest children but then decreased with age.…”

Section: Aberrant Connectivity In Autismmentioning

confidence: 99%

See 1 more Smart Citation

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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Atypical functional brain connectivity during rest in autism spectrum disorders

Abstract: Differences in functional connectivity may suggest the presence of neural atypicalities that impact the development of typical connectivity in ASD. In addition to affecting DMN dynamics, these atypicalities may also impact social-cognitive abilities.

Cited by 71 publications

References 47 publications

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

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

Epilepsy and Autism

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