Accelerated aging and motor control deficits are related to regional deformation of central cerebellar white matter in alcohol use disorder

The World Health Organization estimates a 12‐month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15 years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age‐related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1‐weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248 d) and 128 age‐ and sex‐matched control participants; subsets of these participants completed motor testing. We identified an AUD‐related volume deficit and accelerated aging in the total corpus medullare. Novel deformation‐based surface morphometry revealed regional shrinkage of surfaces adjacent to lobules I‐V, lobule IX, and vermian lobule X. In addition, accelerated aging was detected in the regional surface areas adjacent to lobules I‐V, lobule VI, lobule VIIB, and lobules VIII, IX, and X. Sex differences were not identified for any measure. For both volume‐based and surface‐based analyses, poorer performance in gait and balance, manual dexterity, and grip strength were linked to greater regional white matter structural deficits. Our results suggest that local deformation of the corpus medullare has the potential of identifying structurally and functionally segregated networks affected in AUD.

[1]  A. Wu,et al.  Derivation and properties of a brief health status assessment instrument for use in HIV disease. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[2]  Adolf Pfefferbaum,et al.  Effect of vision, touch and stance on cerebellar vermian-related sway and tremor: a quantitative physiological and MRI study. , 2006, Cerebral cortex.

[3]  H A Skinner,et al.  Reliability of alcohol use indices. The Lifetime Drinking History and the MAST. , 1982, Journal of studies on alcohol.

[4]  Adolf Pfefferbaum,et al.  Disruption of functional connectivity of the default-mode network in alcoholism. , 2011, Cerebral cortex.

[5]  Christopher L. Asplund,et al.  The organization of the human cerebellum estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[6]  Jeannette R. Mahoney,et al.  Neuroimaging of mobility in aging: a targeted review. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[7]  A. Pfefferbaum,et al.  Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study , 2007, Neuropsychopharmacology.

[8]  D. Meyerhoff,et al.  Regional brain volume changes in alcohol‐dependent individuals during early abstinence: associations with relapse following treatment , 2017, Addiction biology.

[9]  S. Torp,et al.  The prevalence of alcoholic cerebellar atrophy A morphometric and histological study of an autopsy material , 1986, Journal of the Neurological Sciences.

[10]  Jerry L. Prince,et al.  Approaching expert results using a hierarchical cerebellum parcellation protocol for multiple inexpert human raters , 2013, NeuroImage.

[11]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[12]  K O Lim,et al.  Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. , 1992, Alcoholism, clinical and experimental research.

[13]  Bente Pakkenberg,et al.  Aging of the human cerebellum: A stereological study , 2003, The Journal of comparative neurology.

[14]  G. Chételat,et al.  Relationship between brain volumetric changes and interim drinking at six months in alcohol-dependent patients. , 2014, Alcoholism, clinical and experimental research.

[15]  David H. Salat,et al.  Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis , 2012, NeuroImage.

[16]  D. Pandya,et al.  The cerebrocerebellar system. , 1997, International review of neurobiology.

[17]  Qingyu Zhao,et al.  The Endoscopogram: A 3D Model Reconstructed from Endoscopic Video Frames , 2016, MICCAI.

[18]  H. Johansen-Berg,et al.  Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. , 2010, Cerebral cortex.

[19]  R. Thoma,et al.  White matter volume in alcohol use disorders: a meta‐analysis , 2013, Addiction biology.

[20]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[21]  Moo K. Chung,et al.  Deformation-based surface morphometry applied to gray matter deformation , 2003, NeuroImage.

[22]  Kayle S. Sawyer,et al.  Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women. , 2016, Alcoholism, clinical and experimental research.

[23]  Lutz Jäncke,et al.  Cerebellar gray and white matter volume and their relation with age and manual motor performance in healthy older adults , 2015, Human brain mapping.

[24]  Ulman Lindenberger,et al.  Trajectories of brain aging in middle-aged and older adults: Regional and individual differences , 2010, NeuroImage.

[25]  F. Eustache,et al.  Integrity of white matter microstructure in alcoholics with and without Korsakoff's syndrome , 2015, Human brain mapping.

[26]  A Graybiel,et al.  Walk on floor eyes closed (WOFEC): a new addition to an ataxia test battery. , 1971, Aerospace medicine.

[27]  Stephen M. Smith,et al.  Permutation inference for the general linear model , 2014, NeuroImage.

[28]  G. M. Halliday,et al.  Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy , 1999, Neuroscience.

[29]  M. Korgaonkar,et al.  Gray Matter Atrophy in the Cerebellum—Evidence of Increased Vulnerability of the Crus and Vermis with Advancing Age , 2017, The Cerebellum.

[30]  C. Harper,et al.  Cerebellar vermis proteome of chronic alcoholic individuals. , 2007, Alcoholism, clinical and experimental research.

[31]  N. Raz,et al.  Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study. , 1998, AJNR. American journal of neuroradiology.

[32]  Gabriel Taubin,et al.  Curve and surface smoothing without shrinkage , 1995, Proceedings of IEEE International Conference on Computer Vision.

[33]  Peng Yuan,et al.  Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms , 2014, NeuroImage.

[34]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[35]  Colin Studholme,et al.  Deformation-based morphometry of brain changes in alcohol dependence and abstinence , 2007, NeuroImage.

[36]  R. Reitan,et al.  Clinical neuropsychology: Current status and applications. , 1974 .

[37]  A. Pfefferbaum,et al.  Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: Comparison of effects in France and the United States , 2014, Human brain mapping.

[38]  J. Kril,et al.  A quantitative histological study of the cerebellar vermis in alcoholic patients. , 1987, Brain : a journal of neurology.

[39]  J. Kril,et al.  Human alcohol-related neuropathology , 2013, Acta Neuropathologica.

[40]  Yong Tang,et al.  Myelinated nerve fibres in the subcortical white matter of cerebral hemispheres are preserved in alcoholic subjects , 2004, Brain Research.

[41]  A. Pfefferbaum,et al.  Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders , 2017, Neuropharmacology.

[42]  B. Graubard,et al.  Trends in Alcohol Consumption Among Older Americans: National Health Interview Surveys, 1997 to 2014 , 2017, Alcoholism, clinical and experimental research.

[43]  P. Strick,et al.  Cerebellar Loops with Motor Cortex and Prefrontal Cortex of a Nonhuman Primate , 2003, The Journal of Neuroscience.

[44]  J. O’Brien,et al.  Volumetric Differences in Cerebellar Lobes in Individuals from Multiplex Alcohol Dependence Families and Controls: Their Relationship to Externalizing and Internalizing Disorders and Working Memory , 2015, The Cerebellum.

[45]  E. Sullivan,et al.  Compensatory recruitment of neural resources in chronic alcoholism. , 2014, Handbook of clinical neurology.

[46]  M. Nissen,et al.  Assessing treatment effects: A neuropsychological battery. , 1986 .

[47]  Jeremy D. Schmahmann,et al.  Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke , 2016, NeuroImage: Clinical.

[48]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[49]  Qingyu Zhao,et al.  Surface Registration in the Presence of Missing Patches and Topology Change , 2015, MIUA.

[50]  Stefan Gazdzinski,et al.  Cerebral white matter recovery in abstinent alcoholics--a multimodality magnetic resonance study. , 2010, Brain : a journal of neurology.

[51]  Daniel H. Mathalon,et al.  Correction for head size in brain-imaging measurements , 1993, Psychiatry Research: Neuroimaging.

[52]  J. Kril,et al.  Neuropathology of alcoholism. , 2014, Handbook of clinical neurology.

[53]  Pierrick Coupé,et al.  An Optimized Blockwise Nonlocal Means Denoising Filter for 3-D Magnetic Resonance Images , 2008, IEEE Transactions on Medical Imaging.

[54]  Sydney Katz.  Assessing Self‐maintenance: Activities of Daily Living, Mobility, and Instrumental Activities of Daily Living , 1983, Journal of the American Geriatrics Society.

[55]  Jeremy D. Schmahmann,et al.  Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies , 2009, NeuroImage.

[56]  Kilian M. Pohl,et al.  Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection. , 2018, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[57]  P. Goldman-Rakic,et al.  Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. Variability in locations of areas 9 and 46 and relationship to the Talairach Coordinate System. , 1995, Cerebral cortex.

[58]  William E. Lorensen,et al.  Marching cubes: A high resolution 3D surface construction algorithm , 1987, SIGGRAPH.

[59]  C. Studholme,et al.  Brain Morphology at Entry into Treatment for Alcohol Dependence Is Related to Relapse Propensity , 2011, Biological Psychiatry.

[60]  K. Mann,et al.  Rapid partial regeneration of brain volume during the first 14 days of abstinence from alcohol. , 2013, Alcoholism, clinical and experimental research.

[61]  F. Eustache,et al.  Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism , 2016, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[62]  R. Moos,et al.  Global assessment of functioning (GAF) ratings: determinants and role as predictors of one-year treatment outcomes. , 2000, Journal of Clinical Psychology.

[63]  Edith V. Sullivan,et al.  Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study , 2003, NeuroImage.

[64]  Aaron Carass,et al.  Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease , 2016, NeuroImage.

[65]  W. Thompson,et al.  The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise , 2018, JAMA psychiatry.

[66]  P. Langlais,et al.  Neuropathology of thiamine deficiency: an update on the comparative analysis of human disorders and experimental models , 1996, Metabolic Brain Disease.

[67]  Guido Gerig,et al.  Unbiased diffeomorphic atlas construction for computational anatomy , 2004, NeuroImage.

[68]  L. Jäncke,et al.  Brain structural trajectories over the adult lifespan , 2012, Human brain mapping.

[69]  Jeremy D. Schmahmann,et al.  Functional Topography of the Human Cerebellum , 2016 .

[70]  K. Hutchison,et al.  Brain‐derived neurotrophic factor genotype is associated with brain gray and white matter tissue volumes recovery in abstinent alcohol‐dependent individuals , 2013, Genes, brain, and behavior.

[71]  E. Sullivan,et al.  Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. , 1991, Brain : a journal of neurology.

[72]  W. Ilg,et al.  Lesion-Symptom Mapping of the Human Cerebellum , 2008, The Cerebellum.

[73]  Satrajit S. Ghosh,et al.  Functional gradients of the cerebellum , 2018, bioRxiv.

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

[75]  S. Crowe,et al.  Characterization of cerebellar ataxia in chronic alcoholics using the International Cooperative Ataxia Rating Scale (ICARS). , 2012, Alcoholism, clinical and experimental research.

[76]  R. Adams,et al.  The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition , 1989 .

[77]  J. Desmond,et al.  Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: relation to ataxia. , 2000, Neuropsychology.

[78]  Michael W. L. Chee,et al.  Skull stripping using graph cuts , 2010, NeuroImage.

[79]  A. Pfefferbaum,et al.  Remapping the brain to compensate for impairment in recovering alcoholics. , 2013, Cerebral cortex.