Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry

Arjun Sethi; Edwin Evelyn-Rahr; Nicholas Dowell; Sanjay Jain; Valerie Voon; Hugo D Critchley; Neil A Harrison; Mara Cercignani

doi:10.1016/j.nicl.2017.03.012

Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry

Arjun Sethi, Edwin Evelyn-Rahr, Nicholas Dowell, Sanjay Jain, Valerie Voon, Hugo D Critchley, Neil A Harrison, Mara Cercignani

School of Psychology

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Abstract

In childhood, Attention Deficit Hyperactivity Disorder (ADHD) is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM) neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted) neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT) saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.

© 2017 A. Sethi, E. Evelyn-Rahr, N. Dowell, S. Jain, V. Voon, H. Critchley, N. Harrison, M. Cercignani. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/

Original language	English
Pages (from-to)	8-14
Number of pages	7
Journal	NEUROIMAGE-CLINICAL
Volume	15
DOIs	https://doi.org/10.1016/j.nicl.2017.03.012
Publication status	Published - 30 Mar 2017

Keywords

Adult
Attention Deficit Disorder with Hyperactivity/diagnostic imaging
Basal Ganglia/diagnostic imaging
Brain Mapping/methods
Female
Humans
Iron/metabolism
Magnetic Resonance Imaging/methods
Male
Young Adult

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10.1016/j.nicl.2017.03.012

Magnetization transfer imagingFinal published version, 457 KBLicence: CC BY

https://www.sciencedirect.com/science/article/pii/S2213158217300724?via%3Dihub

Cite this

@article{68410a125ce145fea05a9fd7f21b7926,

title = "Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry",

abstract = "In childhood, Attention Deficit Hyperactivity Disorder (ADHD) is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM) neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted) neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT) saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.{\textcopyright} 2017 A. Sethi, E. Evelyn-Rahr, N. Dowell, S. Jain, V. Voon, H. Critchley, N. Harrison, M. Cercignani. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/ ",

keywords = "Adult, Attention Deficit Disorder with Hyperactivity/diagnostic imaging, Basal Ganglia/diagnostic imaging, Brain Mapping/methods, Female, Humans, Iron/metabolism, Magnetic Resonance Imaging/methods, Male, Young Adult",

author = "Arjun Sethi and Edwin Evelyn-Rahr and Nicholas Dowell and Sanjay Jain and Valerie Voon and Critchley, {Hugo D} and Harrison, {Neil A} and Mara Cercignani",

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language = "English",

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T1 - Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry

AU - Sethi, Arjun

AU - Evelyn-Rahr, Edwin

AU - Dowell, Nicholas

AU - Jain, Sanjay

AU - Voon, Valerie

AU - Critchley, Hugo D

AU - Harrison, Neil A

AU - Cercignani, Mara

PY - 2017/3/30

Y1 - 2017/3/30

N2 - In childhood, Attention Deficit Hyperactivity Disorder (ADHD) is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM) neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted) neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT) saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.© 2017 A. Sethi, E. Evelyn-Rahr, N. Dowell, S. Jain, V. Voon, H. Critchley, N. Harrison, M. Cercignani. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/

AB - In childhood, Attention Deficit Hyperactivity Disorder (ADHD) is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM) neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted) neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT) saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.© 2017 A. Sethi, E. Evelyn-Rahr, N. Dowell, S. Jain, V. Voon, H. Critchley, N. Harrison, M. Cercignani. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/

KW - Adult

KW - Attention Deficit Disorder with Hyperactivity/diagnostic imaging

KW - Basal Ganglia/diagnostic imaging

KW - Brain Mapping/methods

KW - Female

KW - Humans

KW - Iron/metabolism

KW - Magnetic Resonance Imaging/methods

KW - Male

KW - Young Adult

U2 - 10.1016/j.nicl.2017.03.012

DO - 10.1016/j.nicl.2017.03.012

M3 - Article

C2 - 28458999

SN - 2213-1582

VL - 15

SP - 8

EP - 14

JO - NEUROIMAGE-CLINICAL

JF - NEUROIMAGE-CLINICAL

ER -