Toward Neurosubtypes in Autism

Hong, Seok‐Jun; Vogelstein, Joshua T.; Gozzi, Alessandro; Bernhardt, Boris C.; Yeo, B.T. Thomas; Milham, Michael P.; Martino, Adriana Di

doi:10.1016/j.biopsych.2020.03.022

Cited by 121 publications

(92 citation statements)

References 180 publications

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“…Although individuals with ASD show heterogeneity in functional connectivity patterns [117][118][119][120], our sample size was not large enough to examine this factor in the context of inhibitory control in ASD, which may explain why we did not observe recruitment of any alpha-or beta-band networks in the ASD group. Given that people with ASD may utilize alternative networks during inhibition, it would be important for future work to investigate whether adults with ASD demonstrate heterogeneity in the networks they recruit for inhibitory control.…”

Section: Limitationsmentioning

confidence: 87%

Alpha connectivity and inhibitory control in adults with autism spectrum disorder

et al. 2020

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Background Individuals with autism spectrum disorder (ASD) often report difficulties with inhibition in everyday life. During inhibition tasks, adults with ASD show reduced activation of and connectivity between brain areas implicated in inhibition, suggesting impairments in inhibitory control at the neural level. Our study further investigated these differences by using magnetoencephalography (MEG) to examine the frequency band(s) in which functional connectivity underlying response inhibition occurs, as brain functions are frequency specific, and whether connectivity in certain frequency bands differs between adults with and without ASD. Methods We analysed MEG data from 40 adults with ASD (27 males; 26.94 ± 6.08 years old) and 39 control adults (27 males; 27.29 ± 5.94 years old) who performed a Go/No-go task. The task involved two blocks with different proportions of No-go trials: Inhibition (25% No-go) and Vigilance (75% No-go). We compared whole-brain connectivity in the two groups during correct No-go trials in the Inhibition vs. Vigilance blocks between 0 and 400 ms. Results Despite comparable performance on the Go/No-go task, adults with ASD showed reduced connectivity compared to controls in the alpha band (8–14 Hz) in a network with a main hub in the right inferior frontal gyrus. Decreased connectivity in this network predicted more self-reported difficulties on a measure of inhibition in everyday life. Limitations Measures of everyday inhibitory control were not available for all participants, so this relationship between reduced network connectivity and inhibitory control abilities may not be necessarily representative of all adults with ASD or the larger ASD population. Further research with independent samples of adults with ASD, including those with a wider range of cognitive abilities, would be valuable. Conclusions Our findings demonstrate reduced functional brain connectivity during response inhibition in adults with ASD. As alpha-band synchrony has been linked to top-down control mechanisms, we propose that the lack of alpha synchrony observed in our ASD group may reflect difficulties in suppressing task-irrelevant information, interfering with inhibition in real-life situations.

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Section: Limitationsmentioning

confidence: 87%

Alpha connectivity and inhibitory control in adults with autism spectrum disorder

et al. 2020

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“…We additionally explored how alterations in such reward processing among autistic youth might be related to individual variability in implicit social learning and core autism traits. By characterizing the neural underpinnings of core autism symptomatology in girls, these analyses improve our understanding of both sex differences in autism and factors which may contribute to the considerable heterogeneity observed among individuals with autism 42,43 .…”

Section: Introductionmentioning

confidence: 99%

Neural responsivity to social rewards in autistic female youth

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Autism is hypothesized to be in part driven by a reduced sensitivity to the inherently rewarding nature of social stimuli. Previous neuroimaging studies have indicated that autistic males do indeed display reduced neural activity to social rewards, but it is unknown whether this finding extends to autistic females, particularly as behavioral evidence suggests that affected females may not exhibit the same reduction in social motivation as their male peers. We therefore used functional magnetic resonance imaging to examine social reward processing during an instrumental implicit learning task in 154 children and adolescents (ages 8-17): 39 autistic girls, 43 autistic boys, 33 typically developing girls, and 39 typically developing boys. We found that autistic girls displayed increased activity to socially rewarding stimuli, including greater activity in the nucleus accumbens relative to autistic boys, as well as greater activity in lateral frontal cortices and the anterior insula compared with typically developing girls. These results demonstrate for the first time that autistic girls do not exhibit the same reduction in activity within social reward systems as autistic boys. Instead, autistic girls display increased neural activation to such stimuli in areas related to reward processing and salience detection. Our findings indicate that a reduced sensitivity to social rewards, as assessed with a rewarded instrumental implicit learning task, does not generalize to affected female youth and highlight the importance of studying potential sex differences in autism to improve our understanding of the condition and its heterogeneity.

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“…Behaviorally diagnosed on the basis of clinical observations and standardized tools assessing atypical communication, social interaction, and sometimes restricted and repetitive behaviors and interests (APA, 2013), the broad umbrella term of ASD has resulted in a steady increase in autism prevalence (Baio et al, 2018). This increase in diagnostic sensitivity has on the other hand led to an increasing recognition of heterogeneity of diagnosed individuals (Hong et al, 2018;Hong et al, 2020a;Lombardo et al, 2019), and challenges for specificity (Mottron and Bzdok, 2020). This high variability is present at the phenotypic level of behavioral symptoms and at the level of genetic mechanisms previously associated with ASD (Bernard Paulais et al, 2019;Iuculano et al, 2020;Jeste and Geschwind, 2014), and renders the study of autism particularly challenging.…”

Section: Introductionmentioning

confidence: 99%

“…Inconsistent findings have also been attributed to the conventional use of case-control designs in connectomics research in autism, which assume within-group homogeneity (Lenroot and Yeung, 2013;Zabihi et al, 2019). In addition to efforts that attempt to address this heterogeneity by subtyping ASD individuals into more homogeneous groups (Hong et al, 2020a;Lombardo et al, 2019), a nascent literature has emphasized the importance to study inter-individual variability of functional connectivity patterns in ASD compared to TD (Dickie et al, 2018;Hahamy et al, 2015;Nunes et al, 2019). This body of work suggests that such idiosyncrasy may be an important feature of functional connectome organization in ASD, with greater variability in functional topography among ASD individuals relative to TD.…”

Section: Introductionmentioning

confidence: 99%

Functional idiosyncrasy has a shared topography with group-level connectivity alterations in autism

Benkarim

Paquola

Park

et al. 2020

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Autism spectrum disorder (ASD) is commonly understood as a network disorder, yet case-control analyses against typically-developing controls (TD) have yielded somewhat inconsistent patterns of results. The current work was centered on a novel approach to profile functional network idiosyncrasy, the inter-individual variability in the association between functional network organization and brain anatomy, and we tested the hypothesis that idiosyncrasy contributes to connectivity alterations in ASD. Studying functional network idiosyncrasy in a multi-centric dataset with 157 ASD and 172 TD, our approach revealed higher idiosyncrasy in ASD in the default mode, somatomotor and attention networks together with reduced idiosyncrasy in the lateral temporal lobe. Idiosyncrasy was found to increase with age in both ASD and TD, and was significantly correlated with symptom severity in the former group. Association analysis with structural and molecular brain features indicated that patterns of functional network idiosyncrasy were not correlated with ASD-related cortical thickness alterations, but closely with the spatial expression patterns of intracortical ASD risk genes. In line with our main hypothesis, we could demonstrate that idiosyncrasy indeed plays a strong role in the manifestation of connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between the heterogeneity of individuals with an autism diagnosis and group-level functional signatures, and help to consolidate prior research findings on the highly variable nature of the functional connectome in ASD. Our study promotes idiosyncrasy as a potential individualized diagnostic marker of atypical brain network development.

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Toward Neurosubtypes in Autism

Cited by 121 publications

References 180 publications

Alpha connectivity and inhibitory control in adults with autism spectrum disorder

Alpha connectivity and inhibitory control in adults with autism spectrum disorder

Neural responsivity to social rewards in autistic female youth

Functional idiosyncrasy has a shared topography with group-level connectivity alterations in autism

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