Grammar learning in older adults is linked to white matter microstructure and functional connectivity

Age-related decline in cognitive function has been linked to alterations of white matter and functional brain connectivity. With regard to language, aging has been shown to be associated with impaired syntax processing, but the underlying structural and functional correlates are poorly understood. In the present study, we used an artificial grammar learning (AGL) task to determine the ability to extract grammatical rules from new material in healthy older adults. White matter microstructure and resting-state functional connectivity (FC) of task-relevant brain regions were assessed using multimodal magnetic resonance imaging (MRI). AGL performance correlated positively with fractional anisotropy (FA) underlying left and right Brodmann areas (BA) 44/45 and in tracts originating from left BA 44/45. An inverse relationship was found between task performance and FC of left and right BA 44/45, linking lower performance to stronger inter-hemispheric functional coupling. Our results suggest that white matter microstructure underlying specific prefrontal regions and their functional coupling affect acquisition of syntactic knowledge in the aging brain, offering further insight into mechanisms of functional decline in older adults.

[1]  Justin L. Vincent,et al.  Disruption of Large-Scale Brain Systems in Advanced Aging , 2007, Neuron.

[2]  Karl Magnus Petersson,et al.  Artificial syntactic violations activate Broca's region , 2004 .

[3]  K. Murphy,et al.  Verbal fluency patterns in amnestic mild cognitive impairment are characteristic of Alzheimer's type dementia , 2006, Journal of the International Neuropsychological Society.

[4]  B. Crosson,et al.  Recent developments in functional and structural imaging of aphasia recovery after stroke , 2011, Aphasiology.

[5]  Roberto Cabeza,et al.  The architecture of cross-hemispheric communication in the aging brain: linking behavior to functional and structural connectivity. , 2012, Cerebral cortex.

[6]  Keith M. McGregor,et al.  Impact of changed positive and negative task-related brain activity on word-retrieval in aging , 2012, Neurobiology of Aging.

[7]  A. Friederici.  The brain basis of language processing: from structure to function. , 2011, Physiological reviews.

[8]  T. Flaisch,et al.  Electrical Brain Stimulation Improves Cognitive Performance by Modulating Functional Connectivity and Task-Specific Activation , 2012, The Journal of Neuroscience.

[9]  Mark D'Esposito,et al.  Region-specific changes in prefrontal function with age: a review of PET and fMRI studies on working and episodic memory. , 2005, Brain : a journal of neurology.

[10]  Denise C. Park,et al.  The adaptive brain: aging and neurocognitive scaffolding. , 2009, Annual review of psychology.

[11]  Ian Law,et al.  Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition , 2012, NeuroImage.

[12]  John S. Duncan,et al.  Hemispheric asymmetries in language-related pathways: A combined functional MRI and tractography study , 2006, NeuroImage.

[13]  Robert A. Bornstein,et al.  The Wechsler Memory Scale—Revised , 1990 .

[14]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[15]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[16]  Thomas Elbert,et al.  Age-related changes in neural functional connectivity and its behavioral relevance , 2012, BMC Neuroscience.

[17]  Guy B. Williams,et al.  White Matter Changes and Word Finding Failures with Increasing Age , 2011, PloS one.

[18]  Pierre Perruchet,et al.  Synthetic Grammar Learning : Implicit Rule Abstraction or Explicit Fragmentary Knowledge ? Pierre Perruchet and Chantal Pacteau , 1990 .

[19]  J. Goh.  Functional Dedifferentiation and Altered Connectivity in Older Adults: Neural Accounts of Cognitive Aging. , 2011, Aging and disease.

[20]  Marcus Meinzer,et al.  Neural Signatures of Semantic and Phonemic Fluency in Young and Old Adults , 2009, Journal of Cognitive Neuroscience.

[21]  A. Song,et al.  Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging , 2009, Neuropsychology Review.

[22]  Peter Hagoort,et al.  Topographical functional connectivity pattern in the perisylvian language networks. , 2010, Cerebral cortex.

[23]  Vanessa Taler,et al.  Language performance in Alzheimer's disease and mild cognitive impairment: A comparative review , 2008, Journal of clinical and experimental neuropsychology.

[24]  S. Knecht,et al.  Short-Term Anomia Training and Electrical Brain Stimulation , 2011, Stroke.

[25]  W. Perlstein,et al.  Age-related changes in word retrieval: Role of bilateral frontal and subcortical networks , 2008, Neurobiology of Aging.

[26]  M. Corbetta,et al.  Resting interhemispheric functional magnetic resonance imaging connectivity predicts performance after stroke , 2009, Annals of neurology.

[27]  Pienie Zwitserlood,et al.  Age affects chunk-based, but not rule-based learning in artificial grammar acquisition , 2012, Neurobiology of Aging.

[28]  Allen W. Song,et al.  Measurement of spontaneous signal fluctuations in fMRI: adult age differences in intrinsic functional connectivity , 2009, Brain Structure and Function.

[29]  A. Anwander,et al.  Connectivity-Based Parcellation of Broca's Area. , 2006, Cerebral cortex.

[30]  J. Henry,et al.  Verbal fluency performance in dementia of the Alzheimer’s type: a meta-analysis , 2004, Neuropsychologia.

[31]  Meredith A. Shafto,et al.  Preserving Syntactic Processing across the Adult Life Span: The Modulation of the Frontotemporal Language System in the Context of Age-Related Atrophy , 2009, Cerebral cortex.

[32]  Karl J. Friston,et al.  Ten simple rules for dynamic causal modeling , 2010, NeuroImage.

[33]  A. Wingfield,et al.  Language and the aging brain: patterns of neural compensation revealed by functional brain imaging. , 2006, Journal of neurophysiology.

[34]  Richard W Briggs,et al.  Left and right basal ganglia and frontal activity during language generation: Contributions to lexical, semantic, and phonological processes , 2003, Journal of the International Neuropsychological Society.

[35]  U. Ziemann,et al.  Hemispheric asymmetry of transcallosal inhibition in man. , 1995, Experimental brain research.

[36]  Loraine K. Obler,et al.  Bilateral brain regions associated with naming in older adults , 2010, Brain and Language.

[37]  Fenna H Poletiek,et al.  Implicit learning of a recursive rule in an artificial grammar. , 2002, Acta psychologica.

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

[39]  R. Gur,et al.  Leftward asymmetry in relative fiber density of the arcuate fasciculus , 2005, Neuroreport.

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

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

[42]  Jennifer S. W. Campbell,et al.  Dissociating the Human Language Pathways with High Angular Resolution Diffusion Fiber Tractography , 2008, The Journal of Neuroscience.

[43]  Joan Y. Chiao,et al.  An Event-related fMRI Study of Artificial Grammar Learning in a Balanced Chunk Strength Design , 2004, Journal of Cognitive Neuroscience.

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

[45]  P. Hagoort,et al.  The inferior frontal cortex in artificial syntax processing: An rTMS study , 2008, Brain Research.

[46]  R. Cabeza,et al.  Que PASA? The posterior-anterior shift in aging. , 2008, Cerebral cortex.

[47]  Rachael D. Seidler,et al.  Age Differences in Interhemispheric Interactions: Callosal Structure, Physiological Function, and Behavior , 2011, Front. Neurosci..

[48]  Guillén Fernández,et al.  Neural correlates of artificial syntactic structure classification , 2006, NeuroImage.

[49]  R. Cabeza.  Hemispheric asymmetry reduction in older adults: the HAROLD model. , 2002, Psychology and aging.

[50]  A. Wingfield,et al.  Neural processing during older adults' comprehension of spoken sentences: age differences in resource allocation and connectivity. , 2010, Cerebral cortex.

[51]  Siu Cheung Li,et al.  Cross-level unification: A computational exploration of the link between deterioration of neurotrans , 1999 .

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

[53]  Johannes Pantel,et al.  Syntactic Comprehension Deficits in Alzheimer's Disease , 2000, Brain and Language.

[54]  Martin Ystad,et al.  Subcortical functional connectivity and verbal episodic memory in healthy elderly—A resting state fMRI study , 2010, NeuroImage.

[55]  Carl F. Kaestle,et al.  Adult Literacy and Education in America: Four Studies Based on the National Adult Literacy Survey. , 2001 .

[56]  U. Ziemann,et al.  Hemispheric asymmetry of transcallosalinhibition in man , 2004, Experimental Brain Research.

[57]  Derek K. Jones,et al.  Perisylvian language networks of the human brain , 2005, Annals of neurology.

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

[59]  Stefan Knecht,et al.  Electrical Stimulation of Broca's Area Enhances Implicit Learning of an Artificial Grammar , 2010, Journal of Cognitive Neuroscience.

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

[61]  Pienie Zwitserlood,et al.  Syntactic structure and artificial grammar learning: The learnability of embedded hierarchical structures , 2008, Cognition.

[62]  A. Thiel,et al.  Direct Demonstration of Transcallosal Disinhibition in Language Networks , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[63]  Thierry Meulemans,et al.  Does the artificial grammar learning paradigm involve the acquisition of complex information , 1997 .

[64]  A. Reber.  Implicit learning of artificial grammars , 1967 .

[65]  Pierre Perruchet,et al.  Synthetic grammar learning: Implicit rule abstraction or explicit fragmentary knowledge? Journal of , 1990 .

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

[67]  Xi-Nian Zuo,et al.  Resting-State Functional Connectivity Indexes Reading Competence in Children and Adults , 2011, The Journal of Neuroscience.

[68]  Angela D. Friederici,et al.  Pathways to language: fiber tracts in the human brain , 2009, Trends in Cognitive Sciences.

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