Disrupted topological organization of structural networks revealed by probabilistic diffusion tractography in Tourette syndrome children

Tourette syndrome (TS) is a childhood‐onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole‐brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug‐naive TS children and 41 age‐ and gender‐matched healthy children. The WM networks were constructed by estimating inter‐regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small‐world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network‐based statistical (NBS) analysis, primarily composed of the parieto‐occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis. Hum Brain Mapp 38:3988–4008, 2017. © 2017 Wiley Periodicals, Inc.

[1]  T. Prescott,et al.  The brainstem reticular formation is a small-world, not scale-free, network , 2006, Proceedings of the Royal Society B: Biological Sciences.

[2]  Irene Neuner,et al.  Microstructure assessment of grey matter nuclei in adult tourette patients by diffusion tensor imaging , 2011, Neuroscience Letters.

[3]  Diane Swick,et al.  Are the neural correlates of stopping and not going identical? Quantitative meta-analysis of two response inhibition tasks , 2011, NeuroImage.

[4]  P. Thiran,et al.  Mapping Human Whole-Brain Structural Networks with Diffusion MRI , 2007, PloS one.

[5]  S. Petersen,et al.  Multivariate pattern classification of pediatric Tourette syndrome using functional connectivity MRI , 2016, Developmental science.

[6]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[7]  H. Benali,et al.  Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. , 2012, Brain : a journal of neurology.

[8]  Huiguang He,et al.  Structural Abnormalities in Early Tourette Syndrome Children: A Combined Voxel-Based Morphometry and Tract-Based Spatial Statistics Study , 2013, PloS one.

[9]  Michael Weiner,et al.  Automated MRI-based classification of primary progressive aphasia variants , 2009, NeuroImage.

[10]  Disrupted cortical network as a vulnerability marker for obsessive–compulsive disorder , 2014, Brain Structure and Function.

[11]  G. S. Golden,et al.  The effect of central nervous system stimulants on tourette syndrome , 1977, Annals of neurology.

[12]  A. Toga,et al.  Thinning of sensorimotor cortices in children with Tourette syndrome , 2008, Nature Neuroscience.

[13]  Andrew Zalesky,et al.  Connectomic Disturbances in Attention-Deficit/Hyperactivity Disorder: A Whole-Brain Tractography Analysis , 2014, Biological Psychiatry.

[14]  E. S. B. van Oort,et al.  An investigation into the functional and structural connectivity of the Default Mode Network , 2014, NeuroImage.

[15]  Andreas Horn,et al.  The structural–functional connectome and the default mode network of the human brain , 2014, NeuroImage.

[16]  Yun Peng,et al.  A diagnosis model for early Tourette syndrome children based on brain structural network characteristics , 2016, SPIE Medical Imaging.

[17]  Yong He,et al.  Abnormal baseline brain activity in drug-naïve patients with Tourette syndrome: a resting-state fMRI study , 2014, Front. Hum. Neurosci..

[18]  Lester Melie-García,et al.  Studying the human brain anatomical network via diffusion-weighted MRI and Graph Theory , 2008, NeuroImage.

[19]  Huiguang He,et al.  Combining Disrupted and Discriminative Topological Properties of Functional Connectivity Networks as Neuroimaging Biomarkers for Accurate Diagnosis of Early Tourette Syndrome Children , 2018, Molecular Neurobiology.

[20]  Jan Kassubek,et al.  Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry , 2006, British Journal of Psychiatry.

[21]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[22]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[23]  M Hallett,et al.  Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. , 2006, Brain : a journal of neurology.

[24]  Haiqing Yang,et al.  Disrupted brain connectivity networks in acute ischemic stroke patients , 2017, Brain Imaging and Behavior.

[25]  K. Müller-Vahl,et al.  Tourette's syndrome. , 2009, Current topics in behavioral neurosciences.

[26]  Huiguang He,et al.  Combining tract‐ and atlas‐based analysis reveals microstructural abnormalities in early Tourette syndrome children , 2016, Human brain mapping.

[27]  M. Jorge Cardoso,et al.  Consensus between Pipelines in Structural Brain Networks , 2014, PloS one.

[28]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[29]  Edward T. Bullmore,et al.  Network-based statistic: Identifying differences in brain networks , 2010, NeuroImage.

[30]  R. Stieglitz,et al.  Reliabilität und Validität der Wender-Utah-Rating-Scale-Kurzform , 2003, Der Nervenarzt.

[31]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[32]  J. Mink.  The Basal Ganglia and involuntary movements: impaired inhibition of competing motor patterns. , 2003, Archives of neurology.

[33]  R. Kahn,et al.  Aberrant Frontal and Temporal Complex Network Structure in Schizophrenia: A Graph Theoretical Analysis , 2010, The Journal of Neuroscience.

[34]  D. Cohen,et al.  The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. , 1989, Journal of the American Academy of Child and Adolescent Psychiatry.

[35]  V. Menon,et al.  Development of Large-Scale Functional Brain Networks in Children , 2009, NeuroImage.

[36]  Alan C. Evans,et al.  Somatosensory–motor bodily representation cortical thinning in Tourette: Effects of tic severity, age and gender , 2010, Cortex.

[37]  K. Shin,et al.  Regional differences in acute corticosterone-induced dendritic remodeling in the rat brain and their behavioral consequences , 2014, BMC Neuroscience.

[38]  Aixia Guo,et al.  Gene Selection for Cancer Classification using Support Vector Machines , 2014 .

[39]  Jason Weston,et al.  Gene Selection for Cancer Classification using Support Vector Machines , 2002, Machine Learning.

[40]  Irene Neuner,et al.  Imaging the where and when of tic generation and resting state networks in adult Tourette patients , 2014, Front. Hum. Neurosci..

[41]  F. Schneider,et al.  Altered motor network activation and functional connectivity in adult tourette's syndrome , 2011, Human brain mapping.

[42]  Nancy Kanwisher,et al.  Spurious group differences due to head motion in a diffusion MRI study , 2013, NeuroImage.

[43]  Dinggang Shen,et al.  Inter-modality relationship constrained multi-modality multi-task feature selection for Alzheimer's Disease and mild cognitive impairment identification , 2014, NeuroImage.

[44]  M. Chakravarty,et al.  Enlargement of thalamic nuclei in Tourette syndrome. , 2010, Archives of general psychiatry.

[45]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[46]  M. Wittfoth,et al.  Lateral frontal cortex volume reduction in Tourette syndrome revealed by VBM , 2012, BMC Neuroscience.

[47]  A. Cavanna.  The Precuneus and Consciousness , 2007, CNS Spectrums.

[48]  Alexander Münchau,et al.  Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome☆☆☆ , 2013, NeuroImage: Clinical.

[49]  Pamela Guevara,et al.  Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome , 2014, Brain : a journal of neurology.

[50]  M. P. van den Heuvel,et al.  Impaired Structural Motor Connectome in Amyotrophic Lateral Sclerosis , 2011, PloS one.

[51]  Frank Schneider,et al.  White-matter abnormalities in Tourette syndrome extend beyond motor pathways , 2010, NeuroImage.

[52]  Paul J. Laurienti,et al.  The Ubiquity of Small-World Networks , 2011, Brain Connect..

[53]  Yan-Fang Chen,et al.  Chinese Classification of Mental Disorders (CCMD-3): Towards Integration in International Classification , 2002, Psychopathology.

[54]  Reinhard Dengler,et al.  Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging , 2009, BMC Neuroscience.

[55]  Christian Beste,et al.  Neural correlates of altered sensorimotor gating in boys with Tourette Syndrome: A combined EMG/fMRI study , 2016, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[56]  M. Behen,et al.  Microstructural abnormalities of striatum and thalamus in children with Tourette syndrome , 2008, Movement disorders : official journal of the Movement Disorder Society.

[57]  Jun Liu,et al.  Morphologic features of the amygdala and hippocampus in children and adults with Tourette syndrome. , 2007, Archives of general psychiatry.

[58]  Yun Peng,et al.  Diffusion tractography and graph theory analysis reveal the disrupted rich-club organization of white matter structural networks in early Tourette Syndrome children , 2017, Medical Imaging.

[59]  Jian Huang,et al.  Involvement of left inferior frontal gyrus in sentence-level semantic integration , 2009, NeuroImage.

[60]  P. Camfield,et al.  Peer problems in Tourette's disorder. , 1991, Pediatrics.

[61]  Delong Zhang,et al.  Widespread Increase of Functional Connectivity in Parkinson’s Disease with Tremor: A Resting-State fMRI Study , 2015, Front. Aging Neurosci..

[62]  Alan C. Evans,et al.  Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography. , 2009, Cerebral cortex.

[63]  Paul M. Thompson,et al.  Support Vector Machine Classification of Major Depressive Disorder Using Diffusion-Weighted Neuroimaging and Graph Theory , 2015, Front. Psychiatry.

[64]  Yong He,et al.  Diffusion Tensor Tractography Reveals Abnormal Topological Organization in Structural Cortical Networks in Alzheimer's Disease , 2010, The Journal of Neuroscience.

[65]  Yasheng Chen,et al.  Diffusion tensor imaging based network analysis detects alterations of neuroconnectivity in patients with clinically early relapsing‐remitting multiple sclerosis , 2013, Human brain mapping.

[66]  P. Wender,et al.  [Reliability and validity of the Wender-Utah-Rating-Scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder]. , 2003, Der Nervenarzt.

[67]  WestonJason,et al.  Gene Selection for Cancer Classification using Support Vector Machines , 2002 .

[68]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[69]  Kaustubh Supekar,et al.  Development of Large-Scale Functional Brain Networks in Children , 2009, NeuroImage.

[70]  Tore Wentzel-Larsen,et al.  Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[71]  Corinna Cortes,et al.  Support-Vector Networks , 1995, Machine Learning.

[72]  K. Worsley,et al.  Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. , 2009, Brain : a journal of neurology.

[73]  Huiguang He,et al.  Accurate prediction of AD patients using cortical thickness networks , 2012, Machine Vision and Applications.

[74]  Olaf Sporns,et al.  Small worlds inside big brains , 2006, Proceedings of the National Academy of Sciences.

[75]  R. Tsien,et al.  Specificity and Stability in Topology of Protein Networks , 2022 .

[76]  P. Haggard,et al.  The neural correlates of tic inhibition in Gilles de la Tourette syndrome , 2014, Neuropsychologia.

[77]  Xiaoqi Huang,et al.  Disrupted Brain Connectivity Networks in Drug-Naive, First-Episode Major Depressive Disorder , 2011, Biological Psychiatry.

[78]  Yong He,et al.  Altered Topological Organization of White Matter Structural Networks in Patients with Neuromyelitis Optica , 2012, PloS one.

[79]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[80]  PM0.1 particles from aircraft may increase risk of vascular disease , 2013, BMJ.

[81]  Shouliang Qi,et al.  Structural Brain Network: What is the Effect of LiFE Optimization of Whole Brain Tractography? , 2016, Front. Comput. Neurosci..

[82]  Yun Peng,et al.  Multi-modal multiple kernel learning for accurate identification of Tourette syndrome children , 2017, Pattern Recognit..

[83]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[84]  Huiguang He,et al.  Classification of ADHD children through multimodal magnetic resonance imaging , 2012, Front. Syst. Neurosci..

[85]  Heping Zhang,et al.  Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. , 2003, Archives of general psychiatry.

[86]  Olaf Sporns,et al.  The Human Connectome: A Structural Description of the Human Brain , 2005, PLoS Comput. Biol..

[87]  J C Gore,et al.  Regional brain and ventricular volumes in Tourette syndrome. , 2001, Archives of general psychiatry.

[88]  Ryan J. Felling,et al.  Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation , 2011, The Journal of Neuroscience.

[89]  N. Sousa,et al.  The Bounds Of Education In The Human Brain Connectome , 2015, Scientific Reports.

[90]  S. Petersen,et al.  Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity , 2008, Brain : a journal of neurology.

[91]  N. Bodammer,et al.  Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms , 2014, BMC Neuroscience.

[92]  D. Wolpert,et al.  Maintaining internal representations: the role of the human superior parietal lobe , 1998, Nature Neuroscience.

[93]  D. Shen,et al.  Identification of infants at high‐risk for autism spectrum disorder using multiparameter multiscale white matter connectivity networks , 2015, Human brain mapping.

[94]  Mircea Ariel Schoenfeld,et al.  Differentiation of idiopathic Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and healthy controls using magnetization transfer imaging , 2004, NeuroImage.

[95]  W. Goodman,et al.  Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[96]  Yun Peng,et al.  Multi-threshold white matter structural networks fusion for accurate diagnosis of Tourette syndrome children , 2017, Medical Imaging.

[97]  Michael D. Greicius,et al.  Development of functional and structural connectivity within the default mode network in young children , 2010, NeuroImage.

[98]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[99]  R. Schultz,et al.  Visual-motor integration functioning in children with Tourette syndrome. , 1998, Neuropsychology.

[100]  Tore Wentzel-Larsen,et al.  Altered interhemispheric connectivity in individuals with Tourette's disorder. , 2004, The American journal of psychiatry.

[101]  R. Seitz,et al.  Diversity of the inferior frontal gyrus—A meta-analysis of neuroimaging studies , 2011, Behavioural Brain Research.

[102]  Yong He,et al.  Probabilistic Diffusion Tractography and Graph Theory Analysis Reveal Abnormal White Matter Structural Connectivity Networks in Drug-Naive Boys with Attention Deficit/Hyperactivity Disorder , 2013, The Journal of Neuroscience.

[103]  Suiping Wang,et al.  Large Scale Brain Functional Networks Support Sentence Comprehension: Evidence from Both Explicit and Implicit Language Tasks , 2013, PloS one.

[104]  Daoqiang Zhang,et al.  Integration of Network Topological and Connectivity Properties for Neuroimaging Classification , 2014, IEEE Transactions on Biomedical Engineering.

[105]  Yong He,et al.  Diffusion tensor tractography reveals disrupted topological efficiency in white matter structural networks in multiple sclerosis. , 2011, Cerebral cortex.

[106]  D. Mikulis,et al.  Scale and pattern of atrophy in the chronic stages of moderate-severe TBI , 2014, Frontiers in Human Neuroscience.

[107]  Alan C. Evans,et al.  Age- and Gender-Related Differences in the Cortical Anatomical Network , 2009, The Journal of Neuroscience.