Age-dependent effects of brain stimulation on network centrality

ABSTRACT Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task‐related imaging paradigms. Resting‐state (rs‐) fMRI, that is independent of age‐related differences in performance, is well suited to investigate age‐associated differential neural tDCS effects. Three “online” tDCS conditions (anodal, cathodal, sham) were compared in a cross‐over, within‐subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph‐based rs‐fMRI data analysis approach (eigenvector centrality mapping) and complementary seed‐based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed‐based analyses revealed that these opposing patterns of tDCS‐induced centrality modulation originated from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults.

[1]  C. Miniussi,et al.  Transcranial Electrical Stimulation , 2016, The Neuroscientist.

[2]  Walter Paulus,et al.  Transcranial direct current stimulation over the primary motor cortex during fMRI , 2011, NeuroImage.

[3]  Marian E. Berryhill,et al.  The strategy and motivational influences on the beneficial effect of neurostimulation: A tDCS and fNIRS study , 2015, NeuroImage.

[4]  Satoshi Tanaka,et al.  Inter-subject Variability in Electric Fields of Motor Cortical tDCS , 2015, Brain Stimulation.

[5]  Rafael Polanía,et al.  Transcranial Direct Current Stimulation: Modulation of Brain Pathways and Potential Clinical Applications , 2015 .

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

[7]  P. Rossini,et al.  Consensus paper: Combining transcranial stimulation with neuroimaging , 2009, Brain Stimulation.

[8]  N. Wenderoth,et al.  A technical guide to tDCS, and related non-invasive brain stimulation tools , 2016, Clinical Neurophysiology.

[9]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[10]  G. Frisoni,et al.  Resting state fMRI in Alzheimer's disease: beyond the default mode network , 2012, Neurobiology of Aging.

[11]  O. Sporns,et al.  Network centrality in the human functional connectome. , 2012, Cerebral cortex.

[12]  M. Nitsche,et al.  Physiological Basis of Transcranial Direct Current Stimulation , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[13]  Arno Villringer,et al.  Dynamic modulation of intrinsic functional connectivity by transcranial direct current stimulation. , 2012, Journal of neurophysiology.

[14]  Walter Paulus,et al.  Induction of Late LTP-Like Plasticity in the Human Motor Cortex by Repeated Non-Invasive Brain Stimulation , 2013, Brain Stimulation.

[15]  D. Antonenko,et al.  Neuronal and behavioral effects of multi-day brain stimulation and memory training , 2018, Neurobiology of Aging.

[16]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[17]  Dost Öngür,et al.  Anticorrelations in resting state networks without global signal regression , 2012, NeuroImage.

[18]  A. Antal,et al.  Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients , 2007, Brain Research Bulletin.

[19]  Debora Brignani,et al.  Combining Transcranial Electrical Stimulation With Electroencephalography , 2012, Clinical EEG and neuroscience.

[20]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[21]  Marian E. Berryhill,et al.  Task demands, tDCS intensity, and the COMT val158met polymorphism impact tDCS-linked working memory training gains , 2017, Scientific Reports.

[22]  Walter Paulus,et al.  Introducing graph theory to track for neuroplastic alterations in the resting human brain: A transcranial direct current stimulation study , 2011, NeuroImage.

[23]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[24]  Axel Thielscher,et al.  Modeling the effects of noninvasive transcranial brain stimulation at the biophysical, network, and cognitive level. , 2015, Progress in brain research.

[25]  Xiao Luo,et al.  Intrinsic functional connectivity alterations in cognitively intact elderly APOE ε4 carriers measured by eigenvector centrality mapping are related to cognition and CSF biomarkers: a preliminary study , 2016, Brain Imaging and Behavior.

[26]  Alberto Priori,et al.  Transcranial Direct Current Stimulation and Cognition in the Elderly , 2014 .

[27]  R. Turner,et al.  Eigenvector Centrality Mapping for Analyzing Connectivity Patterns in fMRI Data of the Human Brain , 2010, PloS one.

[28]  Thomas T. Liu,et al.  A component based noise correction method (CompCor) for BOLD and perfusion based fMRI , 2007, NeuroImage.

[29]  David Bartrés-Faz,et al.  Reorganization of brain networks in aging: a review of functional connectivity studies , 2015, Front. Psychol..

[30]  H. Johansen-Berg,et al.  Modulation of GABA and resting state functional connectivity by transcranial direct current stimulation , 2015, eLife.

[31]  Jeffery J. Summers,et al.  Does transcranial direct current stimulation enhance cognitive and motor functions in the ageing brain? A systematic review and meta- analysis , 2016, Ageing Research Reviews.

[32]  Roi Cohen Kadosh,et al.  Not all brains are created equal: the relevance of individual differences in responsiveness to transcranial electrical stimulation , 2014, Front. Syst. Neurosci..

[33]  D. Watson,et al.  Development and validation of brief measures of positive and negative affect: the PANAS scales. , 1988, Journal of personality and social psychology.

[34]  B. Ittermann,et al.  tDCS-Induced Modulation of GABA Levels and Resting-State Functional Connectivity in Older Adults , 2017, The Journal of Neuroscience.

[35]  Anqi Qiu,et al.  A posterior-to-anterior shift of brain functional dynamics in aging , 2017, Brain Structure and Function.

[36]  Agnes Flöel,et al.  Can transcranial direct current stimulation counteract age-associated functional impairment? , 2016, Neuroscience & Biobehavioral Reviews.

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

[38]  Carlo Caltagirone,et al.  Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia , 2016, Journal of Cognitive Neuroscience.

[39]  Frederik Barkhof,et al.  Brain network alterations in Alzheimer's disease measured by eigenvector centrality in fMRI are related to cognition and CSF biomarkers , 2013, Alzheimer's & Dementia.

[40]  Robert Lindenberg,et al.  Differential Effects of Dual and Unihemispheric Motor Cortex Stimulation in Older Adults , 2013, The Journal of Neuroscience.

[41]  Frederik Barkhof,et al.  Fast Eigenvector Centrality Mapping of Voxel-Wise Connectivity in Functional Magnetic Resonance Imaging: Implementation, Validation, and Interpretation , 2012, Brain Connect..

[42]  Arno Villringer,et al.  Imperceptible Somatosensory Stimulation Alters Sensorimotor Background Rhythm and Connectivity , 2015, The Journal of Neuroscience.

[43]  N. Maurits,et al.  A Brain-Wide Study of Age-Related Changes in Functional Connectivity. , 2015, Cerebral cortex.

[44]  Arno Villringer,et al.  FMRI for the assessment of functional connectivity , 2012 .

[45]  M. Nitsche,et al.  Studying and modifying brain function with non-invasive brain stimulation , 2018, Nature Neuroscience.

[46]  Martin Klein,et al.  Altered eigenvector centrality is related to local resting‐state network functional connectivity in patients with longstanding type 1 diabetes mellitus , 2017, Human brain mapping.

[47]  Andrew K. Martin,et al.  Effects of Transcranial Direct Current Stimulation on Neural Networks in Young and Older Adults , 2017, Journal of Cognitive Neuroscience.

[48]  R. Lindenberg,et al.  Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms , 2015, Alzheimer's & Dementia.

[49]  Arno Villringer,et al.  Sustained Effects of Acupuncture Stimulation Investigated with Centrality Mapping Analysis , 2016, Front. Hum. Neurosci..

[50]  Phillip Bonacich,et al.  Some unique properties of eigenvector centrality , 2007, Soc. Networks.

[51]  Andrew J. Saykin,et al.  The Relationship between fMRI Activation and Cerebral Atrophy: Comparison of Normal Aging and Alzheimer Disease , 2000, NeuroImage.

[52]  A. Datta,et al.  Effect of aging on current flow due to transcranial direct current stimulation , 2017, Brain Stimulation.

[53]  Axel Thielscher,et al.  Field modeling for transcranial magnetic stimulation: A useful tool to understand the physiological effects of TMS? , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[54]  J. Whitwell,et al.  Alzheimer's disease neuroimaging , 2018, Current opinion in neurology.

[55]  A. Thielscher,et al.  Where does TMS Stimulate the Motor Cortex? Combining Electrophysiological Measurements and Realistic Field Estimates to Reveal the Affected Cortex Position , 2016, Cerebral cortex.

[56]  Frederik Barkhof,et al.  The Association of Glucose Metabolism and Eigenvector Centrality in Alzheimer's Disease , 2016, Brain Connect..

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

[58]  Clifford R. Jack,et al.  A robust biomarker of large-scale network failure in Alzheimer's disease , 2017, Alzheimer's & dementia.

[59]  Farzad Towhidkhah,et al.  Computational human head models of tDCS: Influence of brain atrophy on current density distribution , 2018, Brain Stimulation.

[60]  C. Stagg,et al.  tDCS and Magnetic Resonance Imaging , 2016, Transcranial Direct Current Stimulation in Neuropsychiatric Disorders.

[61]  David T. Jones,et al.  Age-related changes in the default mode network are more advanced in Alzheimer disease , 2011, Neurology.

[62]  Robert Lindenberg,et al.  Neural correlates of unihemispheric and bihemispheric motor cortex stimulation in healthy young adults , 2016, NeuroImage.

[63]  D. Reato,et al.  Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad , 2009, Brain Stimulation.

[64]  G. Busatto,et al.  Resting-state functional connectivity in normal brain aging , 2013, Neuroscience & Biobehavioral Reviews.

[65]  Alexander Opitz,et al.  Electric field calculations in brain stimulation based on finite elements: An optimized processing pipeline for the generation and usage of accurate individual head models , 2013, Human brain mapping.

[66]  Nadia Bolognini,et al.  Multimodal Association of tDCS with Electroencephalography , 2016 .

[67]  Alexander Opitz,et al.  Determinants of the electric field during transcranial direct current stimulation , 2015, NeuroImage.

[68]  M. Nitsche,et al.  Effects of Transcranial Electrical Stimulation on Cognition , 2012, Clinical EEG and neuroscience.

[70]  Axel Thielscher,et al.  On the importance of electrode parameters for shaping electric field patterns generated by tDCS , 2015, NeuroImage.

[71]  Frederik Barkhof,et al.  Increased default-mode network centrality in cognitively impaired multiple sclerosis patients , 2017, Neurology.

[72]  Robert Lindenberg,et al.  Transcranial direct current stimulation and simultaneous functional magnetic resonance imaging. , 2014, Journal of visualized experiments : JoVE.

[73]  Daniel S. Margulies,et al.  Long-term effects of motor training on resting-state networks and underlying brain structure , 2011, NeuroImage.

[74]  Marian E. Berryhill,et al.  Longitudinal tDCS: Consistency across Working Memory Training Studies , 2017 .

[75]  Hartwig R. Siebner,et al.  Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives , 2016, NeuroImage.

[76]  C. Im,et al.  Inconsistent outcomes of transcranial direct current stimulation may originate from anatomical differences among individuals: Electric field simulation using individual MRI data , 2014, Neuroscience Letters.

[77]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.