Predicting brain age with complex networks: From adolescence to adulthood

In recent years, several studies have demonstrated that machine learning and deep learning systems can be very useful to accurately predict brain age. In this work, we propose a novel approach based on complex networks using 1016 T1-weighted MRI brain scans (in the age range 7-64years). We introduce a structural connectivity model of the human brain: MRI scans are divided in rectangular boxes and Pearson's correlation is measured among them in order to obtain a complex network model. Brain connectivity is then characterized through few and easy-to-interpret centrality measures; finally, brain age is predicted by feeding a compact deep neural network. The proposed approach is accurate, robust and computationally efficient, despite the large and heterogeneous dataset used. Age prediction accuracy, in terms of correlation between predicted and actual age r=0.89and Mean Absolute Error MAE =2.19years, compares favorably with results from state-of-the-art approaches. On an independent test set including 262 subjects, whose scans were acquired with different scanners and protocols we found MAE =2.52. The only imaging analysis steps required in the proposed framework are brain extraction and linear registration, hence robust results are obtained with a low computational cost. In addition, the network model provides a novel insight on aging patterns within the brain and specific information about anatomical districts displaying relevant changes with aging.

[1]  Alan C. Evans,et al.  Prediction of brain maturity based on cortical thickness at different spatial resolutions , 2015, NeuroImage.

[2]  R. Marioni,et al.  Brain age and other bodily ‘ages’: implications for neuropsychiatry , 2018, Molecular Psychiatry.

[3]  Michael E. Tipping The Relevance Vector Machine , 1999, NIPS.

[4]  Bernhard Schölkopf,et al.  A tutorial on support vector regression , 2004, Stat. Comput..

[5]  Angela D. Friederici,et al.  The emergence of long-range language network structural covariance and language abilities , 2019, NeuroImage.

[6]  L. Freeman Centrality in social networks conceptual clarification , 1978 .

[7]  O. Witte,et al.  In vivo biomarkers of structural and functional brain development and aging in humans , 2020, Neuroscience & Biobehavioral Reviews.

[8]  Yingchun Zhang,et al.  Development of Brain Structural Networks Over Age 8: A Preliminary Study Based on Diffusion Weighted Imaging , 2020, Frontiers in Aging Neuroscience.

[9]  Daniele Marinazzo,et al.  Information-based methods for neuroimaging: analyzing structure, function and dynamics , 2015 .

[10]  Timothy Ravasi,et al.  From link-prediction in brain connectomes and protein interactomes to the local-community-paradigm in complex networks , 2013, Scientific Reports.

[11]  Y. Ho,et al.  Simple Explanation of the No-Free-Lunch Theorem and Its Implications , 2002 .

[12]  E. Sullivan,et al.  Thalamic structures and associated cognitive functions: Relations with age and aging , 2015, Neuroscience & Biobehavioral Reviews.

[13]  Siegfried Wahl,et al.  Leveraging uncertainty information from deep neural networks for disease detection , 2016, Scientific Reports.

[14]  Noah E. Friedkin,et al.  Theoretical Foundations for Centrality Measures , 1991, American Journal of Sociology.

[15]  Cataldo Guaragnella,et al.  Modelling cognitive loads in schizophrenia by means of new functional dynamic indexes , 2019, NeuroImage.

[16]  Vijay K. Venkatraman,et al.  Neuroanatomical Assessment of Biological Maturity , 2012, Current Biology.

[17]  Mert R. Sabuncu,et al.  The Relevance Voxel Machine (RVoxM): A Self-Tuning Bayesian Model for Informative Image-Based Prediction , 2012, IEEE Transactions on Medical Imaging.

[18]  H. Stefánsson,et al.  Brain age prediction using deep learning uncovers associated sequence variants , 2019, Nature Communications.

[19]  Christopher R Madan,et al.  Predicting age from cortical structure across the lifespan , 2018, bioRxiv.

[20]  Felix D. Schönbrodt,et al.  At what sample size do correlations stabilize , 2013 .

[21]  Douglas G Altman,et al.  Correlation in restricted ranges of data , 2011, BMJ : British Medical Journal.

[22]  Wiepke Cahn,et al.  Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study. , 2016, The American journal of psychiatry.

[23]  Stefan Klöppel,et al.  Estimating the age of healthy subjects from T1-weighted MRI scans using kernel methods: Exploring the influence of various parameters , 2010, NeuroImage.

[24]  Giovanni Montana,et al.  Predicting brain age with deep learning from raw imaging data results in a reliable and heritable biomarker , 2016, NeuroImage.

[25]  H. Zou,et al.  Regularization and variable selection via the elastic net , 2005 .

[26]  Jared A. Nielsen,et al.  Multisite functional connectivity MRI classification of autism: ABIDE results , 2013, Front. Hum. Neurosci..

[27]  Emiliano Santarnecchi,et al.  Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging , 2019, NeuroImage.

[28]  Ben Glocker,et al.  Neighbourhood approximation using randomized forests , 2013, Medical Image Anal..

[29]  Evgeny Putin,et al.  Deep biomarkers of human aging: Application of deep neural networks to biomarker development , 2016, Aging.

[30]  Changsong Zhou,et al.  Hierarchical organization unveiled by functional connectivity in complex brain networks. , 2006, Physical review letters.

[31]  Eileen Luders,et al.  Brain maturation: Predicting individual BrainAGE in children and adolescents using structural MRI , 2012, NeuroImage.

[32]  Nassir Navab,et al.  Learning with multi-site fMRI graph data , 2014, 2014 48th Asilomar Conference on Signals, Systems and Computers.

[33]  D. M. Whitacre,et al.  Reviews of Environmental Contamination and Toxicology , 2016 .

[34]  Mert R. Sabuncu,et al.  Deep neural networks and kernel regression achieve comparable accuracies for functional connectivity prediction of behavior and demographics , 2020, NeuroImage.

[35]  Dennis S. Charney,et al.  Neurobiology of Mental Illness , 2004 .

[36]  Nicola Amoroso,et al.  Deep Learning and Multiplex Networks for Accurate Modeling of Brain Age , 2019, Front. Aging Neurosci..

[37]  Sabina Sonia Tangaro,et al.  Complex networks reveal early MRI markers of Parkinson's disease , 2018, Medical Image Anal..

[38]  Osamu Abe,et al.  Aging in the CNS: Comparison of gray/white matter volume and diffusion tensor data , 2008, Neurobiology of Aging.

[39]  Gareth Ball,et al.  Modelling neuroanatomical variation during childhood and adolescence with neighbourhood-preserving embedding , 2017, Scientific Reports.

[40]  R. N. Spreng,et al.  Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest , 2016, Neurobiology of Aging.

[41]  Arno Klein,et al.  Brain age prediction: Cortical and subcortical shape covariation in the developing human brain , 2019, NeuroImage.

[42]  Tamás D. Gedeon,et al.  Data Mining of Inputs: Analysing Magnitude and Functional Measures , 1997, Int. J. Neural Syst..

[43]  B. Koopmans,et al.  Integrating all-optical switching with spintronics , 2018, Nature Communications.

[44]  J. Moriguti,et al.  (Pre)diabetes, brain aging, and cognition. , 2009, Biochimica et biophysica acta.

[45]  Christine L. Tardif,et al.  MR‐based age‐related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan , 2019, Human brain mapping.

[46]  Toshihiko Wakabayashi,et al.  Reorganization of brain networks and its association with general cognitive performance over the adult lifespan , 2019, Scientific Reports.

[47]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[48]  Jing Hua,et al.  Age estimation using cortical surface pattern combining thickness with curvatures , 2013, Medical & Biological Engineering & Computing.

[49]  K. Walhovd,et al.  Structural Brain Changes in Aging: Courses, Causes and Cognitive Consequences , 2010, Reviews in the neurosciences.

[50]  Geraldo F. Busatto,et al.  Age-related gray matter volume changes in the brain during non-elderly adulthood , 2011, Neurobiology of Aging.

[51]  Nicola Amoroso,et al.  Extensive Evaluation of Morphological Statistical Harmonization for Brain Age Prediction , 2020, Brain sciences.

[52]  Zachary C. Lipton,et al.  Estimating brain age based on a uniform healthy population with deep learning and structural magnetic resonance imaging , 2020, Neurobiology of Aging.

[53]  Stuart J. Ritchie,et al.  Brain age predicts mortality , 2017, Molecular Psychiatry.

[54]  Danielle S. Bassett,et al.  Multi-scale brain networks , 2016, NeuroImage.

[55]  Daniel Durstewitz,et al.  Deep neural networks in psychiatry , 2019, Molecular Psychiatry.

[56]  Christos Davatzikos,et al.  Imaging patterns of brain development and their relationship to cognition. , 2015, Cerebral cortex.

[57]  Natalie M. Zahr,et al.  The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity , 2018, Front. Aging Neurosci..

[58]  Tammy Riklin-Raviv,et al.  Ensemble of expert deep neural networks for spatio‐temporal denoising of contrast‐enhanced MRI sequences , 2017, Medical Image Anal..

[59]  Danilo Bzdok,et al.  Deep learning for brains?: Different linear and nonlinear scaling in UK Biobank brain images vs. machine-learning datasets , 2019, bioRxiv.

[60]  Brian B. Avants,et al.  N4ITK: Improved N3 Bias Correction , 2010, IEEE Transactions on Medical Imaging.

[61]  Andrea Vedaldi,et al.  Accurate brain age prediction with lightweight deep neural networks , 2019, bioRxiv.

[62]  Khader M. Hasan,et al.  Development and validation of a brain maturation index using longitudinal neuroanatomical scans , 2015, NeuroImage.

[63]  Jessica S. Damoiseaux,et al.  Effects of aging on functional and structural brain connectivity , 2017, NeuroImage.

[64]  Kyung-Ah Sohn,et al.  Biological Brain Age Prediction Using Cortical Thickness Data: A Large Scale Cohort Study , 2018, Front. Aging Neurosci..

[65]  Christian Gaser,et al.  Ten Years of BrainAGE as a Neuroimaging Biomarker of Brain Aging: What Insights Have We Gained? , 2019, Front. Neurol..

[66]  Nicola Amoroso,et al.  A novel approach to brain connectivity reveals early structural changes in Alzheimer’s disease , 2018, Physiological measurement.

[67]  Arno Klein,et al.  Brain age prediction: Cortical and subcortical shape covariation in the developing human brain , 2019, NeuroImage.

[68]  Daniel P. Kennedy,et al.  The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism , 2013, Molecular Psychiatry.

[69]  R. Tibshirani Regression Shrinkage and Selection via the Lasso , 1996 .

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

[71]  Jonathan D. Power,et al.  Prediction of Individual Brain Maturity Using fMRI , 2010, Science.

[72]  Nicola Amoroso,et al.  Multiplex Networks for Early Diagnosis of Alzheimer's Disease , 2018, Front. Aging Neurosci..

[73]  J. Cole,et al.  Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers , 2017, Trends in Neurosciences.

[74]  Islem Rekik,et al.  Morphological Brain Age Prediction using Multi-View Brain Networks Derived from Cortical Morphology in Healthy and Disordered Participants , 2019, Scientific Reports.

[75]  Nathan D. Cahill,et al.  The predictive power of structural MRI in Autism diagnosis , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[76]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[77]  M. Mukaka,et al.  Statistics corner: A guide to appropriate use of correlation coefficient in medical research. , 2012, Malawi medical journal : the journal of Medical Association of Malawi.

[78]  C. Jack,et al.  Alzheimer's Disease Neuroimaging Initiative , 2008 .

[79]  Ke Li,et al.  Predicting Brain Age of Healthy Adults Based on Structural MRI Parcellation Using Convolutional Neural Networks , 2020, Frontiers in Neurology.

[80]  Andy Liaw,et al.  Classification and Regression by randomForest , 2007 .