Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

[1]  L. Bindman,et al.  The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long‐lasting after‐effects , 1964, The Journal of physiology.

[2]  Jacob Cohen.  Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[3]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[4]  P. Lachenbruch.  Statistical Power Analysis for the Behavioral Sciences (2nd ed.) , 1989 .

[5]  C. Marsden,et al.  Corticocortical inhibition in human motor cortex. , 1993, The Journal of physiology.

[6]  P. Rossini,et al.  Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. , 1994, Electroencephalography and clinical neurophysiology.

[7]  K J Ottenbacher,et al.  Why rehabilitation research does not work (as well as we think it should) , 1995, Archives of physical medicine and rehabilitation.

[8]  S. Connelly,et al.  Aging, distraction, and the benefits of predictable location. , 1995, Psychology and aging.

[9]  L Nyberg,et al.  Age differences in episodic memory, semantic memory, and priming: relationships to demographic, intellectual, and biological factors. , 1996, The journals of gerontology. Series B, Psychological sciences and social sciences.

[10]  M. Ridding,et al.  Stimulus/response curves as a method of measuring motor cortical excitability in man. , 1997, Electroencephalography and clinical neurophysiology.

[11]  C. Capaday,et al.  Input-output properties and gain changes in the human corticospinal pathway , 1997, Experimental Brain Research.

[12]  Pedro C. Miranda,et al.  Magnetic stimulation in Alzheimer’s disease , 1997, Journal of Neurology.

[13]  J. Rothwell,et al.  Intracortical inhibition and facilitation in different representations of the human motor cortex. , 1998, Journal of neurophysiology.

[14]  K. Sakai,et al.  Paired‐pulse magnetic stimulation of the human motor cortex: differences among I waves , 1998, The Journal of physiology.

[15]  H. Braak,et al.  Evolution of neuronal changes in the course of Alzheimer's disease. , 1998, Journal of neural transmission. Supplementum.

[16]  K J Werhahn,et al.  Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans , 1999, The Journal of physiology.

[17]  Á. Pascual-Leone,et al.  Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability , 2000, Experimental Brain Research.

[18]  J. Rothwell,et al.  Short latency inhibition of human hand motor cortex by somatosensory input from the hand , 2000, The Journal of physiology.

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

[20]  Robert Chen,et al.  Interactions between two different inhibitory systems in the human motor cortex , 2001, The Journal of physiology.

[21]  H. Siebner,et al.  Age-related decrease in paired-pulse intracortical inhibition in the human primary motor cortex , 2001, Neuroscience Letters.

[22]  Yu,et al.  Changes of Cerebral , 2001 .

[23]  S. Riek,et al.  Reliability of the input–output properties of the cortico-spinal pathway obtained from transcranial magnetic and electrical stimulation , 2001, Journal of Neuroscience Methods.

[24]  J. Rothwell,et al.  Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation , 2002, Neurology.

[25]  B. Christian,et al.  Brain imaging of 18F‐fallypride in normal volunteers: Blood analysis, distribution, test‐retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D‐2/D‐3 receptors , 2002, Synapse.

[26]  M. Nitsche,et al.  Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. , 2002, Brain : a journal of neurology.

[27]  Á. Pascual-Leone,et al.  Transcranial magnetic stimulation in neurology , 2003, The Lancet Neurology.

[28]  H. Möller,et al.  Repetitive Transcranial Magnetic Stimulation , 2003, CNS drugs.

[29]  Paolo Maria Rossini,et al.  Motor cortex excitability in Alzheimer's disease: A transcranial magnetic stimulation study , 2003, Annals of neurology.

[30]  C A Barnes,et al.  Long-term potentiation and the ageing brain. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[31]  T. Miles,et al.  Age and sex differences in human motor cortex input–output characteristics , 2003, The Journal of physiology.

[32]  P. Janicak,et al.  Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression , 2003, Clinical Neurophysiology.

[33]  Mark Hallett,et al.  The electric field induced in the brain by magnetic stimulation: a 3-D finite-element analysis of the effect of tissue heterogeneity and anisotropy , 2003, IEEE Transactions on Biomedical Engineering.

[34]  G Gainotti,et al.  Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[35]  Faith M. Gunning-Dixon,et al.  Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume , 2004, Neurobiology of Aging.

[36]  R. Echemendia.  Cultural Diversity and Neuropsychology: An Uneasy Relationship in a Time of Change , 2004, Applied neuropsychology.

[37]  D. Bennett,et al.  Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. , 2004, Archives of neurology.

[38]  M. G. Marciani,et al.  Different TMS patterns of intracortical inhibition in early onset Alzheimer dementia and frontotemporal dementia , 2004, Clinical Neurophysiology.

[39]  Stuart Maudsley,et al.  BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders , 2004, Trends in Neurosciences.

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

[41]  Intact Frontal Memory Effect in Older Age and Dementia , 2004, Neuron.

[42]  I. Rektor,et al.  Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients , 2005, Journal of the Neurological Sciences.

[43]  Y. Z. Huang,et al.  Theta‐burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex , 2005, The Journal of physiology.

[44]  D. Delis,et al.  Mental flexibility: age effects on switching. , 2005, Neuropsychology.

[45]  L. Nyberg,et al.  Stability, growth, and decline in adult life span development of declarative memory: cross-sectional and longitudinal data from a population-based study. , 2005, Psychology and aging.

[46]  D. Harvey,et al.  Measures of brain morphology and infarction in the framingham heart study: establishing what is normal , 2005, Neurobiology of Aging.

[47]  J. Rothwell,et al.  Theta Burst Stimulation of the Human Motor Cortex , 2005, Neuron.

[48]  Tianzi Jiang,et al.  Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI , 2006, NeuroImage.

[49]  R. Malinow,et al.  AMPAR Removal Underlies Aβ-Induced Synaptic Depression and Dendritic Spine Loss , 2006, Neuron.

[50]  Sergio P. Rigonatti,et al.  Treatment of major depression with transcranial direct current stimulation. , 2006, Bipolar disorders.

[51]  S. Black,et al.  National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards , 2006, Stroke.

[52]  Carles Falcón,et al.  Repetitive transcranial magnetic stimulation effects on brain function and cognition among elders with memory dysfunction. A randomized sham-controlled study. , 2006, Cerebral cortex.

[53]  David A. Bennett,et al.  Early involvement of small inhibitory cortical interneurons in Alzheimer’s disease , 2006, Acta Neuropathologica.

[54]  J. Lou,et al.  Cortical excitability and age-related volumetric MRI changes , 2006, Clinical Neurophysiology.

[55]  P. A. Tonali,et al.  Effects of aging on motor cortex excitability , 2006, Neuroscience Research.

[56]  J. Rothwell,et al.  The after-effect of human theta burst stimulation is NMDA receptor dependent , 2007, Clinical Neurophysiology.

[57]  Ryan T. Crews,et al.  Reliability of motor-evoked potentials in the ADM muscle of older adults , 2007, Journal of Neuroscience Methods.

[58]  K. Musselman.  Clinical significance testing in rehabilitation research: what, why, and how? , 2007 .

[59]  Juha Silvanto,et al.  Neural adaptation reveals state‐dependent effects of transcranial magnetic stimulation , 2007, The European journal of neuroscience.

[60]  Jason B. Mattingley,et al.  Distance-adjusted motor threshold for transcranial magnetic stimulation , 2007, Clinical Neurophysiology.

[61]  J. Rothwell,et al.  The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex , 2008, The Journal of physiology.

[62]  A. Priori,et al.  Transcranial direct current stimulation improves recognition memory in Alzheimer disease , 2008, Neurology.

[63]  Giacomo Koch,et al.  A common polymorphism in the brain‐derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS , 2008, The Journal of physiology.

[64]  Lynn Hasher,et al.  Age-related differences in cognition: the role of distraction control. , 2008, Neuropsychology.

[65]  C. Miniussi,et al.  Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline , 2008, European journal of neurology.

[66]  Yaakov Stern,et al.  The Impact of Age-Related Changes on Working Memory Functional Activity , 2009, Brain Imaging and Behavior.

[67]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[68]  A. Mitchell,et al.  Rate of progression of mild cognitive impairment to dementia – meta‐analysis of 41 robust inception cohort studies , 2009, Acta psychiatrica Scandinavica.

[69]  P. Jezzard,et al.  Neurochemical Effects of Theta Burst Stimulation as Assessed by Magnetic Resonance Spectroscopy , 2009, Journal of neurophysiology.

[70]  Ethan R. Buch,et al.  Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation , 2009, Proceedings of the National Academy of Sciences.

[71]  P. Matthews,et al.  Polarity-Sensitive Modulation of Cortical Neurotransmitters by Transcranial Stimulation , 2009, The Journal of Neuroscience.

[72]  S. Rossi,et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research , 2009, Clinical Neurophysiology.

[73]  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.

[74]  Klaus Funke,et al.  Theta burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex , 2009, Experimental Brain Research.

[75]  Jonathan Bentwich,et al.  Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study , 2011, Journal of Neural Transmission.

[76]  Rosalind J. Sadleir,et al.  Transcranial direct current stimulation (tDCS) in a realistic head model , 2010, NeuroImage.

[77]  Brian C. Clark,et al.  Older adults exhibit more intracortical inhibition and less intracortical facilitation than young adults , 2010, Experimental Gerontology.

[78]  C. Miniussi,et al.  Improved language performance in Alzheimer disease following brain stimulation , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[79]  T. Salthouse.  Influence of age on practice effects in longitudinal neurocognitive change. , 2010, Neuropsychology.

[80]  E. M. Khedr,et al.  The relationship between motor cortex excitability and severity of Alzheimer's disease: A transcranial magnetic stimulation study , 2011, Neurophysiologie Clinique/Clinical Neurophysiology.

[81]  G. Hammond,et al.  Short-interval intracortical inhibition and manual dexterity in healthy aging , 2011, Neuroscience Research.

[82]  Denise C. Park,et al.  Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[83]  Margot J. Taylor,et al.  A Developmental Framework of Brain and Cognition from Infancy to Old Age , 2011, Brain Topography.

[84]  Manuela Pennisi,et al.  Motor cortex hyperexcitability in subcortical ischemic vascular dementia. , 2011, Archives of gerontology and geriatrics.

[85]  Hongkeun Kim,et al.  Neural activity that predicts subsequent memory and forgetting: A meta-analysis of 74 fMRI studies , 2011, NeuroImage.

[86]  John C. Rothwell,et al.  The theoretical model of theta burst form of repetitive transcranial magnetic stimulation , 2011, Clinical Neurophysiology.

[87]  E. Khedr,et al.  Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia , 2011, Journal of Neurology.

[88]  G. Cumming.  Understanding the New Statistics: Effect Sizes, Confidence Intervals, and Meta-Analysis , 2011 .

[89]  Cleofé Peña-Gómez,et al.  Changes in Cortical Plasticity Across the Lifespan , 2011, Front. Ag. Neurosci..

[90]  K. Funke,et al.  Modulation of cortical inhibition by rTMS – findings obtained from animal models , 2011, The Journal of physiology.

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

[92]  Masashi Hamada,et al.  Cerebellar modulation of human associative plasticity , 2012, The Journal of physiology.

[93]  A. Meyer-Lindenberg,et al.  Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? , 2012, Neurobiology of Aging.

[94]  L. Cipolotti,et al.  Enhancing memory performance with rTMS in healthy subjects and individuals with Mild Cognitive Impairment: the role of the right dorsolateral prefrontal cortex , 2012, Front. Hum. Neurosci..

[95]  F. Fregni,et al.  Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease , 2012, Brain Stimulation.

[96]  J. Rabey,et al.  Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: a randomized, double-blind study , 2013, Journal of Neural Transmission.

[97]  F. Fregni,et al.  Neurobiological Effects of Transcranial Direct Current Stimulation: A Review , 2012, Front. Psychiatry.

[98]  Shin Ah Kim,et al.  Effects of five daily high-frequency rTMS on Stroop task performance in aging individuals , 2012, Neuroscience Research.

[99]  Adam J. Woods,et al.  Transcranial direct current stimulation in pediatric brain: A computational modeling study , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[100]  Vincent Hok,et al.  Rosiglitazone enhances learning, place cell activity, and synaptic plasticity in middle-aged rats , 2012, Neurobiology of Aging.

[101]  Patrick S. R. Davidson,et al.  Paired-pulse afferent modulation of TMS responses reveals a selective decrease in short latency afferent inhibition with age , 2012, Neurobiology of Aging.

[102]  C. Caltagirone,et al.  Impaired LTP- but not LTD-like cortical plasticity in Alzheimer's disease patients. , 2012, Journal of Alzheimer's disease : JAD.

[103]  H. Arrighi,et al.  Rate of Conversion from Prodromal Alzheimer's Disease to Alzheimer's Dementia: A Systematic Review of the Literature , 2013, Dementia and Geriatric Cognitive Disorders Extra.

[104]  Á. Pascual-Leone,et al.  Differential Pharmacological Effects on Brain Reactivity and Plasticity in Alzheimer’s Disease , 2013, Front. Psychiatry.

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

[106]  C. Harada,et al.  Normal cognitive aging. , 2013, Clinics in geriatric medicine.

[107]  Adam J. Woods,et al.  Dosage Considerations for Transcranial Direct Current Stimulation in Children: A Computational Modeling Study , 2013, PloS one.

[108]  Charlotte J Stagg,et al.  Widespread Modulation of Cerebral Perfusion Induced during and after Transcranial Direct Current Stimulation Applied to the Left Dorsolateral Prefrontal Cortex , 2013, The Journal of Neuroscience.

[109]  T. Flaisch,et al.  Anodal Transcranial Direct Current Stimulation Temporarily Reverses Age-Associated Cognitive Decline and Functional Brain Activity Changes , 2013, The Journal of Neuroscience.

[110]  Alexander Opitz,et al.  Physiological observations validate finite element models for estimating subject-specific electric field distributions induced by transcranial magnetic stimulation of the human motor cortex , 2013, NeuroImage.

[111]  M. Rajah,et al.  Association between prefrontal activity and volume change in prefrontal and medial temporal lobes in aging and dementia: A review , 2013, Ageing Research Reviews.

[112]  David S Knopman,et al.  Classification and epidemiology of MCI. , 2013, Clinics in geriatric medicine.

[113]  J. Rothwell,et al.  The role of interneuron networks in driving human motor cortical plasticity. , 2013, Cerebral cortex.

[114]  Elzbieta Jankowska,et al.  Evidence for long‐lasting subcortical facilitation by transcranial direct current stimulation in the cat , 2013, The Journal of physiology.

[115]  M. Nitsche,et al.  Partially non‐linear stimulation intensity‐dependent effects of direct current stimulation on motor cortex excitability in humans , 2013, The Journal of physiology.

[116]  Á. Pascual-Leone,et al.  Changes in plasticity across the lifespan: cause of disease and target for intervention. , 2013, Progress in brain research.

[117]  M. Nitsche,et al.  Comparing Cortical Plasticity Induced by Conventional and High-Definition 4 × 1 Ring tDCS: A Neurophysiological Study , 2013, Brain Stimulation.

[118]  Y. Kim,et al.  Long-term effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults , 2014, Neuroreport.

[119]  Mark Hallett,et al.  Efficient and Reliable Characterization of the Corticospinal System Using Transcranial Magnetic Stimulation , 2014, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[120]  F. Tremblay,et al.  Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults , 2014, Front. Aging Neurosci..

[121]  J. Semmler,et al.  ACCEPTED VERSION , 2017 .

[122]  Peng Wen,et al.  Assessment of electric field distribution in anisotropic cortical and subcortical regions under the influence of tDCS , 2014, Bioelectromagnetics.

[123]  Á. Pascual-Leone,et al.  Task-dependent Activity and Connectivity Predict Episodic Memory Network-based Responses to Brain Stimulation in Healthy Aging , 2014, Brain Stimulation.

[124]  Roy H. Hamilton,et al.  Space, time, and causality in the human brain , 2014, NeuroImage.

[125]  Alvaro Pascual-Leone,et al.  Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants , 2014, Clinical Neurophysiology.

[126]  Marco Bozzali,et al.  Dopaminergic Modulation of Cortical Plasticity in Alzheimer’s Disease Patients , 2014, Neuropsychopharmacology.

[127]  C. Miniussi,et al.  Transcranial Direct Current Stimulation over Right Dorsolateral Prefrontal Cortex Enhances Error Awareness in Older Age , 2014, The Journal of Neuroscience.

[128]  S. Thompson-Schill,et al.  Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: A tDCS‐fMRI study , 2014, Human brain mapping.

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

[130]  M. Marcolin,et al.  Transcranial Magnetic Stimulation to Address Mild Cognitive Impairment in the Elderly: A Randomized Controlled Study , 2015, Behavioural neurology.

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

[132]  Dennis J. L. G. Schutter,et al.  Efficacy and Time Course of Theta Burst Stimulation in Healthy Humans , 2015, Brain Stimulation.

[133]  Charles DeCarli,et al.  Cognitive correlates of white matter lesion load and brain atrophy , 2015, Neurology.

[134]  Theodore P. Zanto,et al.  Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer's disease: a systematic review and meta-analysis , 2015, Neurobiology of Aging.

[135]  Pascale Piolino,et al.  Intermittent theta burst stimulation over left BA10 enhances virtual reality-based prospective memory in healthy aged subjects , 2015, Neurobiology of Aging.

[136]  S. Rossi,et al.  Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee , 2015, Clinical Neurophysiology.

[137]  A. Flöel,et al.  Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS , 2015, Front. Cell. Neurosci..

[138]  M. Ridding,et al.  Inter- and intra-subject variability of motor cortex plasticity following continuous theta-burst stimulation , 2015, Neuroscience.

[139]  M. Nitsche,et al.  Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016 , 2016, Brain Stimulation.

[140]  J. Rabey,et al.  Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: clinical experience , 2016, Journal of Neural Transmission.

[141]  Á. Pascual-Leone,et al.  Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation , 2016, Clinical Neurophysiology.

[142]  M. McLaren,et al.  Transcranial Direct Current Stimulation Use in the Treatment of Neuropsychiatric Disorders: A Brief Review. , 2016, Psychiatric annals.

[143]  F. Pichiorri,et al.  Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer’s Disease: Results from a 4-year Prospective Cohort Study , 2016, Front. Aging Neurosci..

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

[145]  C. Caltagirone,et al.  Long‐term potentiation–like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset , 2016, Annals of neurology.

[146]  Changes in cerebral glucose metabolism after 3 weeks of noninvasive electrical stimulation of mild cognitive impairment patients , 2016, Alzheimer's Research & Therapy.

[147]  P. Fitzgerald,et al.  Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis , 2016, Neuroscience & Biobehavioral Reviews.

[148]  Alexander Opitz,et al.  Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates , 2016, Scientific Reports.

[149]  B. Mulsant,et al.  A meta-analysis of the effects of aging on motor cortex neurophysiology assessed by transcranial magnetic stimulation , 2016, Clinical Neurophysiology.

[150]  M. Kiernan,et al.  Threshold tracking transcranial magnetic stimulation: Effects of age and gender on motor cortical function , 2016, Clinical Neurophysiology.

[151]  Munish Chauhan,et al.  Changing head model extent affects finite element predictions of transcranial direct current stimulation distributions , 2016, Journal of neural engineering.

[152]  Patrick H. Khader,et al.  At-home tDCS of the left dorsolateral prefrontal cortex improves visual short-term memory in mild vascular dementia , 2016, Journal of the Neurological Sciences.

[153]  J. Stephens,et al.  Older Adults Improve on Everyday Tasks after Working Memory Training and Neurostimulation , 2016, Brain Stimulation.

[154]  Á. Pascual-Leone,et al.  The effects of exercise on cognitive function and brain plasticity - a feasibility trial. , 2017, Restorative neurology and neuroscience.

[155]  P. Reddy,et al.  Therapeutics of Neurotransmitters in Alzheimer's Disease. , 2017, Journal of Alzheimer's disease : JAD.

[156]  Andrew T. Drysdale,et al.  Resting-state connectivity biomarkers define neurophysiological subtypes of depression , 2016, Nature Medicine.

[157]  Junwu Zhao,et al.  Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer's disease patients , 2016, Oncotarget.

[158]  P. Damier,et al.  Repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease , 2017, Neurophysiologie Clinique/Clinical Neurophysiology.

[159]  A. Woods,et al.  Efficacy of transcranial direct current stimulation over primary motor cortex (anode) and contralateral supraorbital area (cathode) on clinical pain severity and mobility performance in persons with knee osteoarthritis: An experimenter- and participant-blinded, randomized, sham-controlled pilot clin , 2017, Brain Stimulation.

[160]  Alexander Thomas Sack,et al.  Interindividual Variability and Intraindividual Reliability of Intermittent Theta Burst Stimulation-induced Neuroplasticity Mechanisms in the Healthy Brain , 2017, Journal of Cognitive Neuroscience.

[161]  Adam J. Woods,et al.  Frontal Structural Neural Correlates of Working Memory Performance in Older Adults , 2017, Front. Aging Neurosci..

[162]  Emiliano Santarnecchi,et al.  Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease. , 2016, Current Alzheimer research.

[163]  A. Ibáñez,et al.  Non-Invasive Brain Stimulation: A New Strategy in Mild Cognitive Impairment? , 2017, Front. Aging Neurosci..

[164]  Á. Pascual-Leone,et al.  Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects , 2017, Clinical Neurophysiology.

[165]  Alessandra Flammini,et al.  Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia , 2017, Neurology.

[166]  L. Parra,et al.  Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation , 2017, Brain Stimulation.

[167]  S. Meunier,et al.  The reliability of commonly used electrophysiology measures , 2017, Brain Stimulation.

[168]  Á. Pascual-Leone,et al.  Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits. , 2016, Journal of Alzheimer's disease : JAD.

[169]  Michael Schär,et al.  Imaging of current flow in the human head during transcranial electrical therapy , 2017, Brain Stimulation.

[170]  J. Rabey,et al.  Quantitative EEG After Brain Stimulation and Cognitive Training in Alzheimer Disease , 2017, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[171]  Á. Pascual-Leone,et al.  Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer’s Disease , 2017, Front. Aging Neurosci..

[172]  Á. Pascual-Leone,et al.  Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites , 2017, Biological Psychiatry.

[173]  Á. Pascual-Leone,et al.  Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression , 2018, Brain Stimulation.

[174]  M. McLaren,et al.  The effects of medication use in transcranial direct current stimulation: A brief review , 2018, Brain Stimulation.

[175]  G. Gioia,et al.  National Institute of Neurological Disorders and Stroke and Department of Defense Sport-Related Concussion Common Data Elements Version 1.0 Recommendations. , 2018, Journal of neurotrauma.

[176]  Michael Marsiske,et al.  Augmenting cognitive training in older adults (The ACT Study): Design and Methods of a Phase III tDCS and cognitive training trial. , 2018, Contemporary clinical trials.

[177]  A. Woods,et al.  Effect of transcranial direct current stimulation combined with cognitive training on cognitive functioning in older adults with HIV: A pilot study , 2019, Applied neuropsychology. Adult.

[178]  J. Bongaarts,et al.  United Nations Department of Economic and Social Affairs, Population Division World Family Planning 2020: Highlights, United Nations Publications, 2020. 46 p. , 2020 .