Patient-Tailored, Connectivity-Based Forecasts of Spreading Brain Atrophy

Neurodegenerative diseases appear to progress by spreading via brain connections. Like Alzheimer’s disease, frontotemporal dementia (FTD) syndromes make compelling test cases for evaluating network‐based spreading models due to their focal and circumscribed atrophy patterns. In this talk, I will describe our recent work (Brown et al, 2019 Neuron) where we evaluated transneuronal degeneration by attempting to predict future atrophy in patients with behavioral variant frontotemporal dementia (bvFTD, n=42) and semantic variant primary progressive aphasia (svPPA, n=30). While evidence for this mode of progression has come from cross‐sectional studies, the critical test was whether network connectivity can predict longitudinal spread of atrophy in individual patients.

[1]  G. Chételat,et al.  Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer's Versus Semantic Dementia. , 2019, Cerebral cortex.

[2]  Maria Luisa Gorno-Tempini,et al.  18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes , 2019, Alzheimer's Research & Therapy.

[3]  J. Trojanowski,et al.  Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo , 2018, Nature Communications.

[4]  Derek H. Oakley,et al.  Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain , 2018, Front. Neurosci..

[5]  Timothy O. Laumann,et al.  Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation , 2018, Neuron.

[6]  Pedro D. Maia,et al.  A method for inferring regional origins of neurodegeneration , 2018, Brain : a journal of neurology.

[7]  Timothy D. Verstynen,et al.  Population-averaged atlas of the macroscale human structural connectome and its network topology , 2018, NeuroImage.

[8]  Nick C Fox,et al.  Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference , 2017, Nature Communications.

[9]  Jesse A. Brown,et al.  Clinicopathological correlations in behavioural variant frontotemporal dementia , 2017, Brain : a journal of neurology.

[10]  G. Chételat,et al.  Distinct influence of specific versus global connectivity on the different Alzheimer’s disease biomarkers , 2017, Brain : a journal of neurology.

[11]  Peter F. Neher,et al.  The challenge of mapping the human connectome based on diffusion tractography , 2017, Nature Communications.

[12]  Keith A. Johnson,et al.  Flortaucipir tau PET imaging in semantic variant primary progressive aphasia , 2017, Journal of Neurology, Neurosurgery, and Psychiatry.

[13]  Luca Passamonti,et al.  [18F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia , 2017, Journal of Neurology, Neurosurgery, and Psychiatry.

[14]  W. Seeley.  Mapping Neurodegenerative Disease Onset and Progression. , 2017, Cold Spring Harbor perspectives in biology.

[15]  Christos Davatzikos,et al.  Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity , 2017, NeuroImage.

[16]  Efstathios D. Gennatas,et al.  Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood , 2017, The Journal of Neuroscience.

[17]  Olivier Piguet,et al.  Disease-specific patterns of cortical and subcortical degeneration in a longitudinal study of Alzheimer's disease and behavioural-variant frontotemporal dementia , 2017, NeuroImage.

[18]  Howard J. Rosen,et al.  Network degeneration and dysfunction in presymptomatic C9ORF72 expansion carriers , 2016, NeuroImage: Clinical.

[19]  Evan M. Gordon,et al.  Individual Variability of the System‐Level Organization of the Human Brain , 2015, Cerebral cortex.

[20]  Maria Luisa Gorno-Tempini,et al.  Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration. , 2016, JAMA neurology.

[21]  M. Polymenidou,et al.  Prion‐like propagation as a pathogenic principle in frontotemporal dementia , 2016, Journal of neurochemistry.

[22]  Yu Zhang,et al.  The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture , 2016, Cerebral cortex.

[23]  R. Sperling,et al.  Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease , 2016, Proceedings of the National Academy of Sciences.

[24]  Jesper Andersson,et al.  A multi-modal parcellation of human cerebral cortex , 2016, Nature.

[25]  Deyu Li,et al.  TDP-43 is intercellularly transmitted across axon terminals , 2015, The Journal of cell biology.

[26]  Allan R. Jones,et al.  Canonical Genetic Signatures of the Adult Human Brain , 2015, Nature Neuroscience.

[27]  Alan C. Evans,et al.  Network structure of brain atrophy in de novo Parkinson's disease , 2015, eLife.

[28]  Richard F. Betzel,et al.  Cooperative and Competitive Spreading Dynamics on the Human Connectome , 2015, Neuron.

[29]  M. Rietschel,et al.  Correlated gene expression supports synchronous activity in brain networks , 2015, Science.

[30]  David K. Yu,et al.  Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography , 2015, Proceedings of the National Academy of Sciences.

[31]  M. Breakspear,et al.  The connectomics of brain disorders , 2015, Nature Reviews Neuroscience.

[32]  Veronica Redaelli,et al.  Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis , 2015, The Lancet Neurology.

[33]  J. Trojanowski,et al.  Spreading of pathology in neurodegenerative diseases: a focus on human studies , 2015, Nature Reviews Neuroscience.

[34]  Michael Weiner,et al.  Network Diffusion Model of Progression Predicts Longitudinal Patterns of Atrophy and Metabolism in Alzheimer's Disease. , 2015, Cell reports.

[35]  D. Leopold,et al.  Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited , 2014, Proceedings of the National Academy of Sciences.

[36]  Alan C. Evans,et al.  Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders , 2014, PLoS Comput. Biol..

[37]  Frederik Maes,et al.  Assessing age-related gray matter decline with voxel-based morphometry depends significantly on segmentation and normalization procedures , 2014, Front. Aging Neurosci..

[38]  E. Bullmore,et al.  The hubs of the human connectome are generally implicated in the anatomy of brain disorders , 2014, Brain : a journal of neurology.

[39]  V. Lee,et al.  Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases , 2014, Nature Medicine.

[40]  O. Sporns,et al.  Network hubs in the human brain , 2013, Trends in Cognitive Sciences.

[41]  B. Miller,et al.  Anterior temporal lobe degeneration produces widespread network-driven dysfunction. , 2013, Brain : a journal of neurology.

[42]  Li Xiong,et al.  VBM with viscous fluid registration of gray matter segments in SPM , 2013, Front. Aging Neurosci..

[43]  D. Barr,et al.  Random effects structure for confirmatory hypothesis testing: Keep it maximal. , 2013, Journal of memory and language.

[44]  Gerard R. Ridgway,et al.  Symmetric Diffeomorphic Modeling of Longitudinal Structural MRI , 2013, Front. Neurosci..

[45]  Simon B. Eickhoff,et al.  An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data , 2013, NeuroImage.

[46]  G. Chételat,et al.  Region-Specific Hierarchy between Atrophy, Hypometabolism, and β-Amyloid (Aβ) Load in Alzheimer's Disease Dementia , 2012, The Journal of Neuroscience.

[47]  Nick C Fox,et al.  Clinical and biomarker changes in dominantly inherited Alzheimer's disease. , 2012, The New England journal of medicine.

[48]  Matthew L Senjem,et al.  Shapes of the trajectories of 5 major biomarkers of Alzheimer disease. , 2012, Archives of neurology.

[49]  Efstathios D. Gennatas,et al.  Predicting Regional Neurodegeneration from the Healthy Brain Functional Connectome , 2012, Neuron.

[50]  Naruhiko Sahara,et al.  Propagation of Tau Pathology in a Model of Early Alzheimer's Disease , 2012, Neuron.

[51]  Menno P. Witter,et al.  Trans-Synaptic Spread of Tau Pathology In Vivo , 2012, PloS one.

[52]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[53]  Nick C Fox,et al.  Rates of hemispheric and lobar atrophy in the language variants of frontotemporal lobar degeneration. , 2012, Journal of Alzheimer's disease : JAD.

[54]  Timothy O. Laumann,et al.  Functional Network Organization of the Human Brain , 2011, Neuron.

[55]  Nick C Fox,et al.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. , 2011, Brain : a journal of neurology.

[56]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[57]  Olaf Sporns,et al.  Weight-conserving characterization of complex functional brain networks , 2011, NeuroImage.

[58]  B. Miller,et al.  Classification of primary progressive aphasia and its variants , 2011, Neurology.

[59]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[60]  Markus Tolnay,et al.  The propagation of prion-like protein inclusions in neurodegenerative diseases , 2010, Trends in Neurosciences.

[61]  Eran Perlson,et al.  Retrograde axonal transport: pathways to cell death? , 2010, Trends in Neurosciences.

[62]  M. Diamond,et al.  Prion-like mechanisms in neurodegenerative diseases , 2010, Nature Reviews Neuroscience.

[63]  C. Jack,et al.  Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade , 2010, The Lancet Neurology.

[64]  Matthew L Senjem,et al.  Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study. , 2009, Brain : a journal of neurology.

[65]  B. Biswal,et al.  The resting brain: unconstrained yet reliable. , 2009, Cerebral cortex.

[66]  B. Miller,et al.  Neurodegenerative Diseases Target Large-Scale Human Brain Networks , 2009, Neuron.

[67]  J. Ashburner,et al.  Atrophy progression in semantic dementia with asymmetric temporal involvement: A tensor-based morphometry study , 2009, Neurobiology of Aging.

[68]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[69]  Jean-Loup Guillaume,et al.  Fast unfolding of communities in large networks , 2008, 0803.0476.

[70]  Maria Luisa Gorno-Tempini,et al.  Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia. , 2008, Archives of neurology.

[71]  Geoffrey E. Hinton,et al.  Visualizing Data using t-SNE , 2008 .

[72]  E. Todeva.  Networks , 2007 .

[73]  Alan Y. Chiang,et al.  Generalized Additive Models: An Introduction With R , 2007, Technometrics.

[74]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[75]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[76]  S. Wood.  Generalized Additive Models: An Introduction with R , 2006 .

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

[78]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[79]  B. L. Miller,et al.  The natural history of temporal variant frontotemporal dementia , 2005, Neurology.

[80]  R. Ribchester,et al.  The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves , 2005, BMC Neuroscience.

[81]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[82]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[83]  Karalyn Patterson,et al.  Left/right asymmetry of atrophy in semantic dementia , 2003, Neurology.

[84]  J. Hodges,et al.  Staging disease severity in pathologically confirmed cases of frontotemporal dementia , 2003, Neurology.

[85]  B L Miller,et al.  Patterns of brain atrophy in frontotemporal dementia and semantic dementia , 2002, Neurology.

[86]  M N Rossor,et al.  Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease , 2001, Annals of neurology.

[87]  J. Hodges,et al.  Semantic dementia: clinical, radiological and pathological perspectives , 2000, Journal of Neurology.

[88]  Gerald L. Russell,et al.  The temporal variant of frontotemporal dementia. , 1997, Brain : a journal of neurology.