Executive performance is related to regional gray matter volume in healthy older individuals

Individual differences in executive functioning and brain morphology are considerable. In this study, we investigated their interrelation in a large sample of healthy older individuals. Digit span, trail‐making, and Stroop tasks were used to assess different executive subfunctions in 367 nondemented community‐dwelling individuals (50–81 years). Task performance was analyzed relative to brain structure using voxel‐based morphometry, corrected for age and sex. Improved task performance was associated with increased local gray matter volume in task‐specific patterns that showed partial, but not complete overlap with known task‐specific functional imaging patterns. While all three tasks showed associations with prefrontal gray matter volume as expected for executive functioning, the strongest overlap between the three tasks was found in insular cortex, suggesting that it has a previously underestimated role for executive functions. The association between the insular cortex and executive functioning was corroborated using stereological region‐of‐interest measurement of insular volume in a subgroup of 93 subjects. Quantitatively, the volume of the single most strongly related region explained 2.4 ± 1.1% of the variance in executive performance over and above the variance explained by age, which amounted to 7.4 ± 4.1%. The age‐independent peak associations between executive performance and gray matter described here occurred in regions that were also strongly affected by age‐related gray matter atrophy, consistent with the hypothesis that age‐related regional brain volume loss and age‐related cognitive changes are linked. Hum Brain Mapp 34:3333–3346, 2013. © 2012 Wiley Periodicals, Inc.

[1]  B. Turetsky,et al.  Sex differences in aging of the human frontal and temporal lobes , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  Karl J. Friston,et al.  A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory. , 1994, Brain : a journal of neurology.

[3]  F. Flynn,et al.  Anatomy of the insula functional and clinical correlates , 1999 .

[4]  A. Dale,et al.  Thinning of the cerebral cortex in aging. , 2004, Cerebral cortex.

[5]  O. Selnes.  A Compendium of Neuropsychological Tests , 1991, Neurology.

[6]  R. Passingham.  The frontal lobes and voluntary action , 1993 .

[7]  P. Skudlarski,et al.  An event-related functional MRI study of the stroop color word interference task. , 2000, Cerebral cortex.

[8]  Dorothee P. Auer,et al.  Neural networks of response shifting: Influence of task speed and stimulus material , 2006, Brain Research.

[9]  Colin M. Macleod.  Half a century of research on the Stroop effect: an integrative review. , 1991, Psychological bulletin.

[10]  M. D’Esposito,et al.  Functional MRI studies of spatial and nonspatial working memory. , 1998, Brain research. Cognitive brain research.

[11]  Sterling C. Johnson,et al.  The Relationship Between Gray Matter Morphometry and Neuropsychological Performance in a Large Sample of Cognitively Healthy Adults , 2007, Brain Imaging and Behavior.

[12]  M J Puddephat,et al.  The benefit of stereology for quantitative radiology. , 2000, The British journal of radiology.

[13]  Richard S. J. Frackowiak,et al.  The neural correlates of the verbal component of working memory , 1993, Nature.

[14]  Fred L. Bookstein,et al.  “Voxel-Based Morphometry” Should Not Be Used with Imperfectly Registered Images , 2001, NeuroImage.

[15]  Steven Laureys,et al.  Exploring the unity and diversity of the neural substrates of executive functioning , 2005, Human brain mapping.

[16]  G. Breithardt,et al.  Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy. , 2008, European heart journal.

[17]  D. V. Essen,et al.  Surface-Based and Probabilistic Atlases of Primate Cerebral Cortex , 2007, Neuron.

[18]  Bogdan Draganski,et al.  Training-induced structural changes in the adult human brain , 2008, Behavioural Brain Research.

[19]  Aysenil Belger,et al.  Emotional priming effects during Stroop task performance , 2009, NeuroImage.

[20]  E. Luders,et al.  Voxel-Based Morphometry , 2015 .

[21]  G. Glover,et al.  Error‐related brain activation during a Go/NoGo response inhibition task , 2001, Human brain mapping.

[22]  K. Kiehl,et al.  A supramodal limbic‐paralimbic‐neocortical network supports goal‐directed stimulus processing , 2005, Human brain mapping.

[23]  A. Gorman,et al.  Stroop Interference as a Function of Percentage of Congruent Items , 1986 .

[24]  Guy B. Williams,et al.  Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. , 2003, Brain : a journal of neurology.

[25]  Anand R. Kumar,et al.  Executive function and MRI prefrontal volumes among healthy older adults. , 2008, Neuropsychology.

[26]  A. Kaufman,et al.  Analysis of WAIS-R factor patterns by sex and race. , 1991, Journal of clinical psychology.

[27]  R. Henson,et al.  Frontal lobes and human memory: insights from functional neuroimaging. , 2001, Brain : a journal of neurology.

[28]  L. Pessoa,et al.  Neural Correlates of Perceptual Choice and Decision Making during Fear–Disgust Discrimination , 2007, The Journal of Neuroscience.

[29]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[30]  J. Fuster.  The Prefrontal Cortex—An Update Time Is of the Essence , 2001, Neuron.

[31]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[32]  S. Graham,et al.  An fMRI study of the Trail Making Test , 2005, Neuropsychologia.

[33]  P. Maeder,et al.  Strokes restricted to the insular cortex , 2002, Neurology.

[34]  M. García-Fiñana,et al.  Sulcal variability, stereological measurement and asymmetry of Broca's area on MR images , 2007, Journal of anatomy.

[35]  A. Anderson,et al.  An fMRI study of stroop word-color interference: evidence for cingulate subregions subserving multiple distributed attentional systems , 1999, Biological Psychiatry.

[36]  M. Baulac,et al.  Functional anatomy of the insula: new insights from imaging , 2003, Surgical and Radiologic Anatomy.

[37]  David C. Van Essen,et al.  Lost in localization — But found with foci?! , 2009, NeuroImage.

[38]  Gregory McCarthy,et al.  Dynamic and strategic aspects of executive processing , 2004, Brain Research.

[39]  Xun Liu,et al.  Common and distinct neural substrates of attentional control in an integrated Simon and spatial Stroop task as assessed by event-related fMRI , 2004, NeuroImage.

[40]  M. Corbetta,et al.  Selective and divided attention during visual discriminations of shape, color, and speed: functional anatomy by positron emission tomography , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  D. Stuss,et al.  Cognitive neuroscience. , 1993, Current opinion in neurobiology.

[42]  J. Ridley.  Studies of Interference in Serial Verbal Reactions , 2001 .

[43]  S. Gerhand.  THE PREFRONTAL CORTEX—EXECUTIVE AND COGNITIVE FUNCTIONS. , 1999 .

[44]  J. Gabrieli,et al.  Insights into the ageing mind: a view from cognitive neuroscience , 2004, Nature Reviews Neuroscience.

[45]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[46]  S. Petersen,et al.  Role of the anterior insula in task-level control and focal attention , 2010, Brain Structure and Function.

[47]  Leslie G. Ungerleider,et al.  ‘What’ and ‘where’ in the human brain , 1994, Current Opinion in Neurobiology.

[48]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[49]  Sterling C. Johnson,et al.  White Matter in Aging and Cognition: A Cross-Sectional Study of Microstructure in Adults Aged Eighteen to Eighty-Three , 2010, Developmental neuropsychology.

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

[51]  N. Dronkers.  A new brain region for coordinating speech articulation , 1996, Nature.

[52]  Bennett A. Landman,et al.  Statistical parametric mapping of brain morphology: Sensitivity is dramatically increased by using brain-extracted images as inputs , 2006, NeuroImage.

[53]  Y. Suchy,et al.  Executive Functioning: Overview, Assessment, and Research Issues for Non-Neuropsychologists , 2009, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[54]  G. Douaud,et al.  Brain Morphometry and Cognitive Performance in Detoxified Alcohol-Dependents with Preserved Psychosocial Functioning , 2007, Neuropsychopharmacology.

[55]  N. Roberts,et al.  Voxel‐based morphometry of temporal lobe epilepsy: An introduction and review of the literature , 2008, Epilepsia.

[56]  M. Mesulam,et al.  Insula of the old world monkey. Architectonics in the insulo‐orbito‐temporal component of the paralimbic brain , 1982, The Journal of comparative neurology.

[57]  Guy B. Williams,et al.  Impact of inconsistent resolution on VBM studies , 2008, NeuroImage.

[58]  Karl J. Friston,et al.  Why Voxel-Based Morphometry Should Be Used , 2001, NeuroImage.

[59]  D. Stuss,et al.  Principles of frontal lobe function , 2002 .

[60]  F. Collette,et al.  Brain imaging of the central executive component of working memory , 2002, Neuroscience & Biobehavioral Reviews.

[61]  T. Salthouse,et al.  Effects of increased processing demands on age differences in working memory. , 1990, Psychology and aging.

[62]  Nikolaus Weiskopf,et al.  A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging , 2009, NeuroImage.

[63]  Karl J. Friston,et al.  Distributional Assumptions in Voxel-Based Morphometry , 2002, NeuroImage.

[64]  David Shum,et al.  Construct validity of eight tests of attention : comparison of normal and closed head injured samples , 1990 .

[65]  Jens C. Pruessner,et al.  Regional Frontal Cortical Volumes Decrease Differentially in Aging: An MRI Study to Compare Volumetric Approaches and Voxel-Based Morphometry , 2002, NeuroImage.

[66]  Karl J. Friston,et al.  Voxel-Based Morphometry , 2015 .

[67]  C Büchel,et al.  Brain regions involved in articulation , 1999, The Lancet.

[68]  E. Glisky.  Changes in Cognitive Function in Human Aging , 2007 .

[69]  Jan Kassubek,et al.  Executive dysfunction in early stages of Huntington's disease is associated with striatal and insular atrophy: A neuropsychological and voxel-based morphometric study , 2005, Journal of the Neurological Sciences.

[70]  Ivanei E. Bramati,et al.  The cerebral correlates of set-shifting: an fMRI study of the trail making test. , 2002, Arquivos de neuro-psiquiatria.

[71]  M. Mesulam,et al.  Insula of the old world monkey. III: Efferent cortical output and comments on function , 1982, The Journal of comparative neurology.

[72]  Gene E. Alexander,et al.  Age-related networks of regional covariance in MRI gray matter: Reproducible multivariate patterns in healthy aging , 2010, NeuroImage.

[73]  C. Büchel,et al.  Temporal and Spatial Dynamics of Brain Structure Changes during Extensive Learning , 2006, The Journal of Neuroscience.

[74]  Bruce G. Pollock,et al.  Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study , 2012, Neurobiology of Aging.

[75]  Alan C. Evans,et al.  A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time. , 2004, Cerebral cortex.

[76]  Christian Gaser,et al.  Magnetic resonance-based morphometry: a window into structural plasticity of the brain , 2006, Current opinion in neurology.

[77]  David C. Van Essen,et al.  Application of Information Technology: An Integrated Software Suite for Surface-based Analyses of Cerebral Cortex , 2001, J. Am. Medical Informatics Assoc..

[78]  David R. Riddle,et al.  Brain aging : models, methods, and mechanisms , 2007 .

[79]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[80]  Carl Ludy,et al.  Clinical and anatomical correlates of apraxia of speech , 2006, Brain and Language.

[81]  C. Price.  The anatomy of language: contributions from functional neuroimaging , 2000, Journal of anatomy.

[82]  Robert T Knight.  Neuroscience. Neural networks debunk phrenology. , 2007, Science.

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

[84]  Adrian M. Owen,et al.  The role of the lateral frontal cortex in mnemonic processing: the contribution of functional neuroimaging , 2000, Experimental Brain Research.

[85]  R. Knight.  Neural Networks Debunk Phrenology , 2007, Science.

[86]  Neil Roberts,et al.  Effects of sex and age on regional prefrontal brain volume in two human cohorts , 2007, The European journal of neuroscience.

[87]  A. Baddeley.  Fractionating the central executive. , 2002 .

[88]  Stefan Knecht,et al.  Can the Language-dominant Hemisphere Be Predicted by Brain Anatomy? , 2011, Journal of Cognitive Neuroscience.