Integrated analysis of gray and white matter alterations in attention-deficit/hyperactivity disorder.
Magnetic resonance imaging (MRI) is able to provide detailed insights into the structural organization of the brain, e.g., by means of mapping brain anatomy and white matter microstructure. Understanding interrelations between MRI modalities, rather than mapping modalities in isolation, will contribute to unraveling the complex neural mechanisms associated with neuropsychiatric disorders as deficits detected across modalities suggest common underlying mechanisms. Here, we conduct a multimodal analysis of structural MRI modalities in the context of attention-deficit/hyperactivity disorder (ADHD).



Gray matter volume, cortical thickness, surface areal expansion estimates, and white matter diffusion indices of 129 participants with ADHD and 204 participants without ADHD were entered into a linked independent component analysis. This data-driven analysis decomposes the data into multimodal independent components reflecting common inter-subject variation across imaging modalities.



ADHD severity was related to two multimodal components. The first component revealed smaller prefrontal volumes in participants with more symptoms, co-occurring with abnormal white matter indices in prefrontal cortex. The second component demonstrated decreased orbitofrontal volume as well as abnormalities in insula, occipital, and somato-sensory areas in participants with more ADHD symptoms.



Our results replicate and extend previous unimodal structural MRI findings by demonstrating that prefrontal, parietal, and occipital areas, as well as fronto-striatal and fronto-limbic systems are implicated in ADHD. By including multiple modalities, sensitivity for between-participant effects is increased, as shared variance across modalities is modeled. The convergence of modality-specific findings in our results suggests that different aspects of brain structure share underlying pathophysiology and brings us closer to a biological characterization of ADHD.
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Department of Cognitive Neuroscience, Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands. Electronic address: w.francx@donders.ru.nl.
Winke
W
Francx
Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.
Alberto
A
Llera
Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.
Maarten
M
Mennes
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Department of Cognitive Neuroscience, Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.
Marcel P
MP
Zwiers
Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, USA; K.G. Jebsen Centre for Psychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
Stephen V
SV
Faraone
VU University Amsterdam, Department of Clinical Neuropsychology, Amsterdam, The Netherlands.
Jaap
J
Oosterlaan
VU University Amsterdam, Department of Clinical Neuropsychology, Amsterdam, The Netherlands.
Dirk
D
Heslenfeld
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Pieter J
PJ
Hoekstra
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Catharina A
CA
Hartman
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Department of Human Genetics, Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Nijmegen, The Netherlands.
Barbara
B
Franke
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Department of Cognitive Neuroscience, Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
Jan K
JK
Buitelaar
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Department of Cognitive Neuroscience, Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands; Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom.
Christian F
CF
Beckmann
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
ADHD; Gray matter; Multimodal analysis; Structural MRI; White matter