Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder

Bradley S. Peterson; Ariana Zargarian; Jarod B. Peterson; Suzanne Goh; Siddhant Sawardekar; Steven C.R. Williams; David J. Lythgoe; Fernando O. Zelaya; Ravi Bansal

doi:10.1016/j.biopsych.2018.11.026

Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder

Bradley S. Peterson, Ariana Zargarian, Jarod B. Peterson, Suzanne Goh, Siddhant Sawardekar, Steven C.R. Williams, David J. Lythgoe, Fernando O. Zelaya, Ravi Bansal

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Abstract

Background Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with Autism Spectrum Disorder (ASD). Methods We acquired pulsed arterial spin labeling MRI data in 44 generally high functioning ASD simplex participants and 66 typically developing (TD) controls with comparable mean full-scale IQ’s. We compared rCBF values voxel-wise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with NAA (N-acetylaspartate) metabolite levels. Results We detected significantly higher rCBF values throughout frontal white matter and subcortical gray in ASD participants. rCBF correlated positively with socialization deficits in regions where ASD hyperperfusion was greatest. rCBF declined with increasing IQ in the TD group, a correlation that was absent in ASD participants because their rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with NAA metabolite levels throughout frontal white matter, with greater rCBF accompanying lower and increasingly abnormal NAA levels relative to TD controls. Conclusions These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning, and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.

Original language	English
Journal	Biological psychiatry
Early online date	21 Dec 2018
DOIs	https://doi.org/10.1016/j.biopsych.2018.11.026
Publication status	E-pub ahead of print - 21 Dec 2018

Keywords

Autism
Magnetic Resonance Imaging
Arterial Spin Labeling
white matter
glia
cerebral blood flow

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10.1016/j.biopsych.2018.11.026

Hyperperfusion of Frontal White_PETERSON_Firstonline21December2018_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 9.8 MBLicence: CC BY-NC-ND

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@article{8eabc7c8f1764ec185b33a4c80c12df0,

title = "Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder",

abstract = "Background Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with Autism Spectrum Disorder (ASD). Methods We acquired pulsed arterial spin labeling MRI data in 44 generally high functioning ASD simplex participants and 66 typically developing (TD) controls with comparable mean full-scale IQ{\textquoteright}s. We compared rCBF values voxel-wise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with NAA (N-acetylaspartate) metabolite levels. Results We detected significantly higher rCBF values throughout frontal white matter and subcortical gray in ASD participants. rCBF correlated positively with socialization deficits in regions where ASD hyperperfusion was greatest. rCBF declined with increasing IQ in the TD group, a correlation that was absent in ASD participants because their rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with NAA metabolite levels throughout frontal white matter, with greater rCBF accompanying lower and increasingly abnormal NAA levels relative to TD controls. Conclusions These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning, and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.",

keywords = "Autism, Magnetic Resonance Imaging, Arterial Spin Labeling, white matter, glia, cerebral blood flow",

author = "Peterson, {Bradley S.} and Ariana Zargarian and Peterson, {Jarod B.} and Suzanne Goh and Siddhant Sawardekar and Williams, {Steven C.R.} and Lythgoe, {David J.} and Zelaya, {Fernando O.} and Ravi Bansal",

year = "2018",

month = dec,

day = "21",

doi = "10.1016/j.biopsych.2018.11.026",

language = "English",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

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TY - JOUR

T1 - Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder

AU - Peterson, Bradley S.

AU - Zargarian, Ariana

AU - Peterson, Jarod B.

AU - Goh, Suzanne

AU - Sawardekar, Siddhant

AU - Williams, Steven C.R.

AU - Lythgoe, David J.

AU - Zelaya, Fernando O.

AU - Bansal, Ravi

PY - 2018/12/21

Y1 - 2018/12/21

N2 - Background Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with Autism Spectrum Disorder (ASD). Methods We acquired pulsed arterial spin labeling MRI data in 44 generally high functioning ASD simplex participants and 66 typically developing (TD) controls with comparable mean full-scale IQ’s. We compared rCBF values voxel-wise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with NAA (N-acetylaspartate) metabolite levels. Results We detected significantly higher rCBF values throughout frontal white matter and subcortical gray in ASD participants. rCBF correlated positively with socialization deficits in regions where ASD hyperperfusion was greatest. rCBF declined with increasing IQ in the TD group, a correlation that was absent in ASD participants because their rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with NAA metabolite levels throughout frontal white matter, with greater rCBF accompanying lower and increasingly abnormal NAA levels relative to TD controls. Conclusions These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning, and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.

AB - Background Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with Autism Spectrum Disorder (ASD). Methods We acquired pulsed arterial spin labeling MRI data in 44 generally high functioning ASD simplex participants and 66 typically developing (TD) controls with comparable mean full-scale IQ’s. We compared rCBF values voxel-wise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with NAA (N-acetylaspartate) metabolite levels. Results We detected significantly higher rCBF values throughout frontal white matter and subcortical gray in ASD participants. rCBF correlated positively with socialization deficits in regions where ASD hyperperfusion was greatest. rCBF declined with increasing IQ in the TD group, a correlation that was absent in ASD participants because their rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with NAA metabolite levels throughout frontal white matter, with greater rCBF accompanying lower and increasingly abnormal NAA levels relative to TD controls. Conclusions These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning, and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.

KW - Autism

KW - Magnetic Resonance Imaging

KW - Arterial Spin Labeling

KW - white matter

KW - glia

KW - cerebral blood flow

U2 - 10.1016/j.biopsych.2018.11.026

DO - 10.1016/j.biopsych.2018.11.026

M3 - Article

SN - 0006-3223

JO - Biological psychiatry

JF - Biological psychiatry

ER -

Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder

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