Memory training impacts short‐term changes in aging white matter: A Longitudinal Diffusion Tensor Imaging Study

A growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging‐ and training‐related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract‐based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI‐scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10‐week interval. Further, group analysis demonstrated positive effects of training on the short‐term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin‐related processes in WM plasticity. Hum Brain Mapp 33:2390–2406, 2012. © 2011 Wiley Periodicals, Inc.

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

[2]  A. Dale,et al.  Age-related alterations in white matter microstructure measured by diffusion tensor imaging , 2005, Neurobiology of Aging.

[3]  Costanza Papagno,et al.  What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval. , 2011, Brain : a journal of neurology.

[4]  D. Head,et al.  Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. , 2004, Cerebral cortex.

[5]  B. Pakkenberg,et al.  Marked loss of myelinated nerve fibers in the human brain with age , 2003, The Journal of comparative neurology.

[6]  C. Beaulieu The Biological Basis of Diffusion Anisotropy , 2009 .

[7]  M. O’Sullivan,et al.  Activate your online subscription , 2001, Neurology.

[8]  Stephen M. Smith,et al.  Age-related changes in grey and white matter structure throughout adulthood , 2010, NeuroImage.

[9]  Timothy Edward John Behrens,et al.  Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skills , 2007, NeuroImage.

[10]  Peter A. Calabresi,et al.  Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification , 2008, NeuroImage.

[11]  L. Goossens,et al.  Improving memory performance in the aged through mnemonic training: a meta-analytic study. , 1992, Psychology and aging.

[12]  Yasuyuki Taki,et al.  Training of Working Memory Impacts Structural Connectivity , 2010, The Journal of Neuroscience.

[13]  B. Winblad,et al.  An active and socially integrated lifestyle in late life might protect against dementia , 2004, The Lancet Neurology.

[14]  Wang Zhan,et al.  Patterns of age-related water diffusion changes in human brain by concordance and discordance analysis , 2010, Neurobiology of Aging.

[15]  M. Just,et al.  Altering Cortical Connectivity: Remediation-Induced Changes in the White Matter of Poor Readers , 2009, Neuron.

[16]  Lutz Jäncke,et al.  White matter plasticity in the corticospinal tract of musicians: A diffusion tensor imaging study , 2009, NeuroImage.

[17]  Adrian G Barnett,et al.  Regression to the mean: what it is and how to deal with it. , 2004, International journal of epidemiology.

[18]  A. Dale,et al.  Life-span changes of the human brain white matter: diffusion tensor imaging (DTI) and volumetry. , 2010, Cerebral cortex.

[19]  G. Bower Analysis of a mnemonic device , 1970 .

[20]  W. Cleveland,et al.  Locally Weighted Regression: An Approach to Regression Analysis by Local Fitting , 1988 .

[21]  Stefan Skare,et al.  See Blockindiscussions, Blockinstats, Blockinand Blockinauthor Blockinprofiles Blockinfor Blockinthis Blockinpublication Extensive Blockinpiano Blockinpracticing Blockinhas Blockinregionally Specific Blockineffects Blockinon Blockinwhite Blockinmatter Blockindevelopment , 2022 .

[22]  Priti Shah,et al.  Aging, Training, and the Brain: A Review and Future Directions , 2009, Neuropsychology Review.

[23]  Lutz Jäncke,et al.  The plastic human brain. , 2009, Restorative neurology and neuroscience.

[24]  P. Basser Diffusion MRI: From Quantitative Measurement to In vivo Neuroanatomy , 2009 .

[25]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[26]  Stefan Elmer,et al.  Behavioral and Brain Functions , 2009 .

[27]  Arno Villringer,et al.  Dynamic Properties of Human Brain Structure: Learning-Related Changes in Cortical Areas and Associated Fiber Connections , 2010, The Journal of Neuroscience.

[28]  Hauke R. Heekeren,et al.  Age-related differences in white matter microstructure: Region-specific patterns of diffusivity , 2010, NeuroImage.

[29]  R. Fields,et al.  Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. , 2002, Neuron.

[30]  Hans-Jochen Heinze,et al.  Experience-dependent plasticity of white-matter microstructure extends into old age , 2010, Neuropsychologia.

[31]  Heidi Johansen-Berg,et al.  White matter integrity in the vicinity of Broca's area predicts grammar learning success , 2009, NeuroImage.

[32]  John O. Willis,et al.  Wechsler Abbreviated Scale of Intelligence , 2014 .

[33]  J. H. Howard,et al.  Age‐related differences in multiple measures of white matter integrity: A diffusion tensor imaging study of healthy aging , 2009, Human brain mapping.

[34]  Lutz Jäncke,et al.  The Plasticity of the Superior Longitudinal Fasciculus as a Function of Musical Expertise: A Diffusion Tensor Imaging Study , 2009, Front. Hum. Neurosci..

[35]  Harald Hampel,et al.  Cognitive intervention in Alzheimer disease , 2010, Nature Reviews Neurology.

[36]  Faraz Farzin,et al.  Dynamic Object Representations in Infants with and without Fragile X Syndrome , 2009, Front. Hum. Neurosci..

[37]  M. Witter,et al.  Contributions of Thalamic Nuclei to Declarative Memory Functioning , 2003, Cortex.

[38]  S. Wakana,et al.  MRI Atlas of Human White Matter , 2005 .

[39]  W. Meier-Ruge,et al.  Age‐Related White Matter Atrophy in the Human Brain , 1992, Annals of the New York Academy of Sciences.

[40]  V. Wedeen,et al.  Reduction of eddy‐current‐induced distortion in diffusion MRI using a twice‐refocused spin echo , 2003, Magnetic resonance in medicine.

[41]  Derek K. Jones,et al.  Normal-appearing white matter in ischemic leukoaraiosis: A diffusion tensor MRI study , 2001, Neurology.

[42]  Stephen M. Smith,et al.  Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis , 2002, NeuroImage.

[43]  R. Fields,et al.  Astrocytes Promote Myelination in Response to Electrical Impulses , 2006, Neuron.

[44]  Jennifer L. Mozolic,et al.  Human Neuroscience , 2022 .

[45]  Scott A. Huettel,et al.  Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time , 2004, NeuroImage.

[46]  Heidi Johansen-Berg,et al.  Behavioural relevance of variation in white matter microstructure. , 2010, Current opinion in neurology.

[47]  Nick C. Fox,et al.  Longitudinal and cross-sectional analysis of atrophy in Alzheimer's disease: Cross-validation of BSI, SIENA and SIENAX , 2007, NeuroImage.

[48]  G. Bartzokis Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease , 2004, Neurobiology of Aging.

[49]  L. Minati,et al.  MR Spectroscopy, Functional MRI, and Diffusion-Tensor Imaging in the Aging Brain: A Conceptual Review , 2007, Journal of geriatric psychiatry and neurology.

[50]  Thomas R. Barrick,et al.  White matter structural decline in normal ageing: A prospective longitudinal study using tract-based spatial statistics , 2010, NeuroImage.

[51]  Alexandra J. Fiocco,et al.  Exercising the brain to avoid cognitive decline: examining the evidence , 2010 .

[52]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[53]  Arthur W. Toga,et al.  Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template , 2008, NeuroImage.

[54]  D. Dagenbach,et al.  Recollection Training and Transfer Effects in Older Adults: Successful Use of a Repetition-Lag Procedure , 2005, Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition.

[55]  Bram Stieltjes,et al.  Longitudinal changes in fiber tract integrity in healthy aging and mild cognitive impairment: a DTI follow-up study. , 2010, Journal of Alzheimer's disease : JAD.

[56]  Larry A. Kramer,et al.  Diffusion tensor tractography quantification of the human corpus callosum fiber pathways across the lifespan , 2009, Brain Research.

[57]  A. Pfefferbaum,et al.  MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain , 2010, Neuropsychology Review.

[58]  N. Raz,et al.  Aging white matter and cognition: Differential effects of regional variations in diffusion properties on memory, executive functions, and speed , 2009, Neuropsychologia.

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

[60]  A. Dale,et al.  One-Year Brain Atrophy Evident in Healthy Aging , 2009, The Journal of Neuroscience.

[61]  Shu-Wei Sun,et al.  Selective vulnerability of cerebral white matter in a murine model of multiple sclerosis detected using diffusion tensor imaging , 2007, Neurobiology of Disease.

[62]  Denis Le Bihan,et al.  Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature Reviews Neuroscience.

[63]  B. Stankoff,et al.  Induction of myelination in the central nervous system by electrical activity. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[64]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[65]  Atle Bjørnerud,et al.  Error-related negativity is mediated by fractional anisotropy in the posterior cingulate gyrus--a study combining diffusion tensor imaging and electrophysiology in healthy adults. , 2009, Cerebral cortex.

[66]  Luis Concha,et al.  In Vivo Diffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy , 2010, The Journal of Neuroscience.

[67]  Anders M. Dale,et al.  Six-month atrophy in MTL structures is associated with subsequent memory decline in elderly controls , 2010, NeuroImage.

[68]  Willie F. Tobin,et al.  Rapid formation and selective stabilization of synapses for enduring motor memories , 2009, Nature.

[69]  James J. Pekar,et al.  Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease , 2009, NeuroImage.

[70]  K. Lim,et al.  Age‐related decline in brain white matter anisotropy measured with spatially corrected echo‐planar diffusion tensor imaging , 2000, Magnetic resonance in medicine.

[71]  Andreas Engvig,et al.  Effects of memory training on cortical thickness in the elderly , 2010, NeuroImage.

[72]  Roberto Cabeza,et al.  Assessing the effects of age on long white matter tracts using diffusion tensor tractography , 2009, NeuroImage.

[73]  Luc Goossens,et al.  Improving memory performance in the aged through mnemonic training: a meta-analytic study. , 1992, Psychology and aging.

[74]  P. Matthews,et al.  Normalized Accurate Measurement of Longitudinal Brain Change , 2001, Journal of computer assisted tomography.

[75]  Klaus Oberauer,et al.  The contributions of encoding, retention, and recall to the Hebb effect , 2009, Memory.

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

[77]  Lutz Jäncke,et al.  Structural neuroplasticity in the sensorimotor network of professional female ballet dancers , 2009, Human brain mapping.

[78]  Volkmar Glauche,et al.  Ventral and dorsal pathways for language , 2008, Proceedings of the National Academy of Sciences.

[79]  Naftali Raz,et al.  Pattern of normal age-related regional differences in white matter microstructure is modified by vascular risk , 2009, Brain Research.

[80]  Reinhold Kliegl,et al.  On the locus and process of magnification of age differences during mnemonic training. , 1990 .

[81]  Nathalie Tzourio-Mazoyer,et al.  New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. , 2005, Brain : a journal of neurology.

[82]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[83]  Heidi Johansen-Berg,et al.  The rate of visuomotor adaptation correlates with cerebellar white‐matter microstructure , 2009, Human brain mapping.

[84]  David H. Miller,et al.  Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation , 2008, Magnetic resonance in medicine.

[85]  R. Fields,et al.  White matter in learning, cognition and psychiatric disorders , 2008, Trends in Neurosciences.

[86]  C. Wheeler-Kingshott,et al.  About “axial” and “radial” diffusivities , 2009, Magnetic resonance in medicine.

[87]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[88]  A. Pfefferbaum,et al.  Increased brain white matter diffusivity in normal adult aging: Relationship to anisotropy and partial voluming , 2003, Magnetic resonance in medicine.

[89]  A. Dale,et al.  Building memories: remembering and forgetting of verbal experiences as predicted by brain activity. , 1998, Science.

[90]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[91]  R. Morris,et al.  Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline , 2009, Journal of Neurology, Neurosurgery & Psychiatry.

[92]  Timothy Edward John Behrens,et al.  Training induces changes in white matter architecture , 2009, Nature Neuroscience.

[93]  Jun Yoshino,et al.  Demyelination increases radial diffusivity in corpus callosum of mouse brain , 2005, NeuroImage.

[94]  Edith V. Sullivan,et al.  Frontal circuitry degradation marks healthy adult aging: Evidence from diffusion tensor imaging , 2005, NeuroImage.

[95]  D. Pandya,et al.  Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. , 2007, Brain : a journal of neurology.

[96]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.