Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder

Bedford, Saashi A.; Park, Min Tae M.; Devenyi, Gabriel A.; Tullo, Stephanie; Germann, Jürgen; Patel, Raihaan; Anagnostou, Evdokia; Baron‐Cohen, Simon; Bullmore, Edward T.; Chura, Lindsay R.; Craig, Michael C.; Ecker, Christine; Floris, Dorothea L.; Holt, Rosemary; Lenroot, Rhoshel; Lerch, Jason P.; Lombardo, Michael; Murphy, Declan; Raznahan, Armin; Ruigrok, Amber; Smith, Elizabeth G.; Spencer, Michael D.; Suckling, John; Taylor, Margot J.; Thurm, Audrey; Lai, Meng‐Chuan; Chakravarty, M. Mallar

doi:10.1038/s41380-019-0420-6

Cited by 159 publications

(216 citation statements)

References 96 publications

(146 reference statements)

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“…Recent work from our group, Bedford et al (2019), and others (Ducharme et al, 2016) mean age = 66.9 ± 6.3, 58 males and 87 females). In addition, a unique contribution of this manuscript is the complementary analyses of microstructure and surface-based morphometry measures of the striatum, globus pallidus, and thalamus in order to achieve a multi-dimensional normative baseline across several indices related to microstructure and morphology.…”

Section: Introductionmentioning

confidence: 58%

“…Furthermore, we sought to examine a potential factor related to the different age trajectories reported in the literature; the effect of quality control (QC) and segmentation accuracy. Recent work from our group, Bedford et al (2019), and others (Ducharme et al, 2016) demonstrate that varying levels of QC alter cortical thickness age trajectories radically. When implementing strict QC criteria, both studies report previously observed higher order trajectories were mostly replaced by linear effects.…”

Section: Introductionmentioning

confidence: 80%

“…Images with motion artifacts were discarded following the QC procedure implemented by our group, as described in Bedford et al (2019), and can be found on our GitHub page, https://github.com/CobraLab/ documentation/wiki/Motion-Quality-Control-Manual. Images with motion artifacts were discarded following the QC procedure implemented by our group, as described in Bedford et al (2019), and can be found on our GitHub page, https://github.com/CobraLab/ documentation/wiki/Motion-Quality-Control-Manual.…”

Section: Quality Controlmentioning

confidence: 99%

“…All images were visually inspected by one rater (ST) for artifacts. Images with motion artifacts were discarded following the QC procedure implemented by our group, as described in Bedford et al (2019), and can be found on our GitHub page, https://github.com/CobraLab/ documentation/wiki/Motion-Quality-Control-Manual. All segmentations were quality controlled by visual inspection, such that all labels that were not deemed accurate were excluded from the statistical analyses, following the QC procedure implemented by our group (https://github.com/CobraLab/documentation/wiki/MAGeT-Brain-Quality-Control-(QC)-Guide).…”

Section: Quality Controlmentioning

confidence: 99%

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MR‐based age‐related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan

Tullo

Patel

Devenyi

et al. 2019

Human Brain Mapping

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While numerous studies have used magnetic resonance imaging (MRI) to elucidate normative age‐related trajectories in subcortical structures across the human lifespan, there exists substantial heterogeneity among different studies. Here, we investigated the normative relationships between age and morphology (i.e., volume and shape), and microstructure (using the T1‐weighted/T2‐weighted [T1w/T2w] signal ratio as a putative index of myelin and microstructure) of the striatum, globus pallidus, and thalamus across the adult lifespan using a dataset carefully quality controlled, yielding a final sample of 178 for the morphological analyses, and 162 for the T1w/T2w analyses from an initial dataset of 253 healthy subjects, aged 18–83. In accordance with previous cross‐sectional studies of adults, we observed age‐related volume decrease that followed a quadratic relationship between age and bilateral striatal and thalamic volumes, and a linear relationship in the globus pallidus. Our shape indices consistently demonstrated age‐related posterior and medial areal contraction bilaterally across all three structures. Beyond morphology, we observed a quadratic inverted U‐shaped relationship between T1w/T2w signal ratio and age, with a peak value occurring in middle age (at around 50 years old). After permutation testing, the Akaike information criterion determined age relationships remained significant for the bilateral globus pallidus and thalamus, for both the volumetric and T1w/T2w analyses. Our findings serve to strengthen and expand upon previous volumetric analyses by providing a normative baseline of morphology and microstructure of these structures to which future studies investigating patients with various disorders can be compared.

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Section: Introductionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 80%

Section: Quality Controlmentioning

confidence: 99%

Section: Quality Controlmentioning

confidence: 99%

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MR‐based age‐related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan

Tullo

Patel

Devenyi

et al. 2019

Human Brain Mapping

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“…Thus, one potential explanation for the male-specific reduction of H in vMPFC could have to do with early developmental and androgen-sensitive upregulation of genes that play central roles in excitatory postsynaptic potentials, and thus ultimately affecting downstream E:I imbalance. Such effects may be sex-differential and thus less critical in human females, serving an important basis of sexdifferential human brain development 43 and explaining the sex-based heterogeneity and qualitative sex differences of autism neurobiology in human 10,44 .…”

Section: Discussionmentioning

confidence: 99%

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Trakoshis

Martínez‐Cañada

Rocchi

et al. 2020

Preprint

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Imbalance between neurophysiological excitation versus inhibition (E:I) has been theorized as a core pathophysiological mechanism of autism. However, a majority of the evidence behind the E:I theory comes from animal models of rare genetic mutations that account for only a small fraction of the autistic population. Scale-free metrics of neural time-series data could represent biomarkers for E:I imbalance and could enable a greater understanding of how E:I imbalance affects different types of autistic individuals and how such mechanisms relate to behavior. Here we show that a measure of scale-free dynamics, the Hurst exponent (H), measured in-vivo in resting state fMRI (rsfMRI) data, is a surrogate marker of E:I imbalance and differentially affects autistic males versus females. In-silico modeling of local field potentials (LFP) from recurrent networks of interacting excitatory and inhibitory neurons shows that increasing the E:I ratio by specifically enhancing excitation attenuates H and flattens the 1/f slope. These in-silico predictions are confirmed in-vivo with chemogenetic manipulations to enhance excitation of prefrontal cortex in mice. In humans, social brain areas such as ventromedial prefrontal cortex (vMPFC), show decreased H specifically in autistic males but not females. However, continuous variation in vMPFC H correlates with ability to behaviorally camouflage social-communicative difficulties in autistic females but not males. This work provides insight into how in-vivo neuroimaging readouts can be utilized to understand E:I imbalance in human clinical populations. E:I imbalance in social brain circuitry may differentially affect autistic males versus females and may help explain sexrelated differences in compensatory phenomena.

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The Necessity to Identify Subtypes of Autism Spectrum Disorder

Harris

2019

JAMA Psychiatry

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Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder

Cited by 159 publications

References 96 publications

MR‐based age‐related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan

MR‐based age‐related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

The Necessity to Identify Subtypes of Autism Spectrum Disorder

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