Functional and structural syntax networks in aging

Language abilities are known to deteriorate in aging, possibly related to decreased functional and structural connectivity within specialized brain networks. Here, we investigated syntactic ability in healthy young and older adults using a comprehensive assessment of behavioral performance, task-independent functional (FC) and structural brain connectivity (SC). Seed-based FC originating from left pars opercularis (part of Broca's area) known to support syntactic processes was assessed using resting-state functional magnetic resonance imaging, and SC using fractional anisotropy from diffusion weighted imaging, in the dorsally located superior longitudinal and the ventrally located uncinate fasciculi (SLF, UF) and forceps minor. Young compared to older adults exhibited superior syntactic performance and stronger FC within the mainly left-lateralized syntax network, which was beneficial for performance. In contrast, in older adults, FC within the mainly left-lateralized syntax network was reduced and did not correlate with performance; inter-hemispheric FC to right inferior frontal and angular gyri was detrimental for performance. In both groups, performance was positively correlated with inter-hemispheric SC. For intra-hemispheric SC, performance correlated with structural integrity of SLF in young adults and with integrity of UF in older adults. Our data show that reduced syntactic ability in older adults is associated with decreased FC within dedicated syntax networks. Moreover, young adults showed an association of syntactic ability with structural integrity of the dorsal tract, while older adults rely more on ventral fibers. In sum, our study provided novel insight into the relationship between connectivity and syntactic performance in young and older adults. In addition to elucidating age-related changes in syntax networks and their behavioral relevance, our results contribute to a better understanding of age-related changes in functional and structural brain organization in general, an important prerequisite for developing novel strategies to counteract age-related cognitive decline.

[1]  David Caplan,et al.  Task-dependent and task-independent neurovascular responses to syntactic processing , 2008, Cortex.

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

[3]  S. Kemper Syntactic complexity and elderly adults' prose recall. , 1987, Experimental aging research.

[4]  Ina Bornkessel-Schlesewsky,et al.  Setting the frame: the human brain activates a basic low-frequency network for language processing. , 2010, Cerebral cortex.

[5]  J. Morris,et al.  Functional deactivations: Change with age and dementia of the Alzheimer type , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[7]  Linda Geerligs,et al.  Reduced specificity of functional connectivity in the aging brain during task performance , 2014, Human brain mapping.

[8]  Robert Lindenberg,et al.  Grammar learning in older adults is linked to white matter microstructure and functional connectivity , 2012, NeuroImage.

[9]  Robert Lindenberg,et al.  Same Modulation but Different Starting Points: Performance Modulates Age Differences in Inferior Frontal Cortex Activity during Word-Retrieval , 2012, PloS one.

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

[11]  Randy L. Gollub,et al.  Reproducibility of quantitative tractography methods applied to cerebral white matter , 2007, NeuroImage.

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

[13]  Angela D. Friederici,et al.  Maturation of the Language Network: From Inter- to Intrahemispheric Connectivities , 2011, PloS one.

[14]  Angela D. Friederici,et al.  Linking ordering in Broca's area to storage in left temporo-parietal regions: The case of sentence processing , 2012, NeuroImage.

[15]  B. Day,et al.  Interhemispheric inhibition of the human motor cortex. , 1992, The Journal of physiology.

[16]  William D. Marslen-Wilson,et al.  Is left fronto-temporal connectivity essential for syntax? Effective connectivity, tractography and performance in left-hemisphere damaged patients , 2011, NeuroImage.

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

[18]  S. M. Daselaar,et al.  Resting-state functional connectivity of ventral parietal regions associated with attention reorienting and episodic recollection , 2013, Front. Hum. Neurosci..

[19]  L. Pantoni,et al.  Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients , 2010, Neurology.

[20]  Lorraine K. Tyler,et al.  Dynamic Processing in the Human Language System: Synergy between the Arcuate Fascicle and Extreme Capsule , 2011, The Journal of Neuroscience.

[21]  M. Petrides,et al.  Broca’s region: linking human brain functional connectivity data and non‐human primate tracing anatomy studies , 2010, The European journal of neuroscience.

[22]  S. Kemper,et al.  Limitations on Syntactic Processing , 2002 .

[23]  Benjamin J. Shannon,et al.  Coherent spontaneous activity identifies a hippocampal-parietal memory network. , 2006, Journal of neurophysiology.

[24]  A. Friederici,et al.  Comprehension in aphasia: A cross-linguistic study , 1987, Brain and Language.

[25]  Gordon Kindlmann,et al.  Cross-Subject Comparison of Local Diffusion MRI Parameters , 2013 .

[26]  Angela D. Friederici,et al.  Who did what to whom? The neural basis of argument hierarchies during language comprehension , 2005, NeuroImage.

[27]  Bernard Mazoyer,et al.  Meta-analyzing left hemisphere language areas: Phonology, semantics, and sentence processing , 2006, NeuroImage.

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

[29]  Faith M. Gunning-Dixon,et al.  Aging of cerebral white matter: a review of MRI findings , 2009, International journal of geriatric psychiatry.

[30]  N. Volkow,et al.  Resting Functional Connectivity of Language Networks: Characterization and Reproducibility , 2011, Molecular Psychiatry.

[31]  A. Friederici,et al.  Memory or aging? That's the question: An electrophysiological perspective on language , 2002 .

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

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

[34]  Bernard Mazoyer,et al.  What is right-hemisphere contribution to phonological, lexico-semantic, and sentence processing? Insights from a meta-analysis , 2011, NeuroImage.

[35]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[36]  Alfred Anwander,et al.  Segregating the core computational faculty of human language from working memory , 2009, Proceedings of the National Academy of Sciences.

[37]  P. Skudlarski,et al.  Brain Connectivity Related to Working Memory Performance , 2006, The Journal of Neuroscience.

[38]  A. Friederici,et al.  The role of the posterior superior temporal cortex in sentence comprehension , 2009, Neuroreport.

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

[40]  Martin I Sereno,et al.  The relation between connection length and degree of connectivity in young adults: a DTI analysis. , 2009, Cerebral cortex.

[41]  B. Miller,et al.  Neural Correlates of Syntactic Processing in the Nonfluent Variant of Primary Progressive Aphasia , 2010, The Journal of Neuroscience.

[42]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[43]  Marcus E. Raichle,et al.  The Restless Brain , 2011, Brain Connect..

[44]  A. Anwander,et al.  The brain differentiates human and non-human grammars: Functional localization and structural connectivity , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Angela D. Friederici,et al.  Differential Age Effects on Semantic and Syntactic Priming , 1998 .

[46]  M. Fox,et al.  Frontiers in Systems Neuroscience Systems Neuroscience , 2022 .

[47]  M. V. D. Heuvel,et al.  Exploring the brain network: A review on resting-state fMRI functional connectivity , 2010, European Neuropsychopharmacology.

[48]  Rachael D. Seidler,et al.  Frontiers in Systems Neuroscience Systems Neuroscience , 2022 .

[49]  William W. Graves,et al.  Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. , 2009, Cerebral cortex.

[50]  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.

[51]  R. N. Spreng,et al.  Default network modulation and large-scale network interactivity in healthy young and old adults. , 2012, Cerebral cortex.

[52]  Bharat B. Biswal,et al.  Competition between functional brain networks mediates behavioral variability , 2008, NeuroImage.

[53]  Scott T. Grafton,et al.  Structural Organization of the Corpus Callosum Predicts the Extent and Impact of Cortical Activity in the Nondominant Hemisphere , 2008, The Journal of Neuroscience.

[54]  Loraine K. Obler,et al.  Auditory comprehension and aging: Decline in syntactic processing , 1991, Applied Psycholinguistics.

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

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

[57]  C. Miniussi,et al.  Naming Ability Changes in Physiological and Pathological Aging , 2012, Front. Neurosci..

[58]  William D. Marslen-Wilson,et al.  Reorganization of syntactic processing following left-hemisphere brain damage : does right-hemisphere activity preserve function ? , 2010 .

[59]  Michelle Hampson,et al.  Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance. , 2010, Magnetic resonance imaging.

[60]  C. Grady The cognitive neuroscience of ageing , 2012, Nature Reviews Neuroscience.

[61]  Marcus Meinzer,et al.  The impact of aging on neural systems for language , 2013 .

[62]  Thomas E. Nichols,et al.  Handbook of Functional MRI Data Analysis: Index , 2011 .

[63]  Stefan Klöppel,et al.  Combining Functional and Anatomical Connectivity Reveals Brain Networks for Auditory Language Comprehension , 2022 .

[64]  Alfred Anwander,et al.  Neuroanatomical prerequisites for language functions in the maturing brain. , 2011, Cerebral cortex.

[65]  Cornelius Weiller,et al.  How the ventral pathway got lost – And what its recovery might mean , 2011, Brain and Language.

[66]  Melina R. Uncapher,et al.  Posterior parietal cortex and episodic retrieval: convergent and divergent effects of attention and memory. , 2009, Learning & memory.

[67]  Meredith A. Shafto,et al.  Aging and Language Production , 2004, Current directions in psychological science.

[68]  Sharlene D. Newman,et al.  The effect of semantic relatedness on syntactic analysis: An fMRI study , 2010, Brain and Language.

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

[70]  A. Friederici The Time Course of Syntactic Activation During Language Processing: A Model Based on Neuropsychological and Neurophysiological Data , 1995, Brain and Language.

[71]  Yong He,et al.  Discrete Neuroanatomical Networks Are Associated with Specific Cognitive Abilities in Old Age , 2011, The Journal of Neuroscience.

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

[73]  A. Turken,et al.  The Neural Architecture of the Language Comprehension Network: Converging Evidence from Lesion and Connectivity Analyses , 2011, Front. Syst. Neurosci..

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

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

[76]  Emmanuel A Stamatakis,et al.  Functional organization of the neural language system: dorsal and ventral pathways are critical for syntax. , 2013, Cerebral cortex.

[77]  A. Friederici The cortical language circuit: from auditory perception to sentence comprehension , 2012, Trends in Cognitive Sciences.

[78]  Susumu Mori,et al.  MRI Atlas of Human White Matter 2nd Edition , 2010 .

[79]  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.

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