Brain Topography

, 24:302 | Cite as

Characterizing Brain Cortical Plasticity and Network Dynamics Across the Age-Span in Health and Disease with TMS-EEG and TMS-fMRI

  • Alvaro Pascual-LeoneEmail author
  • Catarina Freitas
  • Lindsay Oberman
  • Jared C. Horvath
  • Mark Halko
  • Mark Eldaief
  • Shahid Bashir
  • Marine Vernet
  • Mouhshin Shafi
  • Brandon Westover
  • Andrew M. Vahabzadeh-Hagh
  • Alexander Rotenberg
Original Paper


Brain plasticity can be conceptualized as nature’s invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable ‘starting-points’ and different ‘slopes of change’ defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer’s disease.


Cortical brain plasticity Transcranial magnetic stimulation Electroencephalography Functional magnetic resonance imaging Lifespan 



Work on this study was supported by grants from the National Center for Research Resources: Harvard-Thorndike General Clinical Research Center at BIDMC (NCRR MO1 RR01032) and Harvard Clinical and Translational Science Center (UL1 RR025758), NIH grant K24 RR018875, Center for Integration of Medicine and Innovative Technology (CIMIT), Neuronix and Nexstim to APL. CF was supported by a post-doctoral grant from the Foundation for Science and Technology, Portugal (SFRH/BPD/66846/2009), co-funded by the European Social Fund. LO was supported by NIH fellowship F32MH080493 and 1KL2RR025757-01. APL serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision, and is an inventor on patents and patent applications related to noninvasive brain stimulation and the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging.

Conflict of interest



  1. Alexander GE, Furey ML, Grady CL, Pietrini P, Brady DR, Mentis MJ, Schapiro MB (1997) Association of premorbid intellectual function with cerebral metabolism in Alzheimer’s disease: implications for the cognitive reserve hypothesis. Am J Psychiatry 154(2):165–172PubMedGoogle Scholar
  2. Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 93(1):74–104PubMedCrossRefGoogle Scholar
  3. Barnes CA, McNaughton BL (1980) Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence. J Physiol 309:473–485PubMedGoogle Scholar
  4. Battaglia F, Wang HY, Ghilardi MF, Gashi E, Quartarone A, Friedman E et al (2007) Cortical plasticity in Alzheimer’s disease in humans and rodents. Biol Psychiatry 62:1405–1412PubMedCrossRefGoogle Scholar
  5. Bertram L, Tanzi RE (2009) Genome-wide association studies in Alzheimer’s disease. Hum Mol Genet 18(R2):R137–R145PubMedCrossRefGoogle Scholar
  6. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database. Nat Genet 39:17–23PubMedCrossRefGoogle Scholar
  7. Bettus G, Wendling F, Guye M, Valton L, Régis J, Chauvel P, Bartolomei F (2008) Enhanced EEG functional connectivity in mesial temporal lobe epilepsy. Epilepsy Res 81(1):58–68PubMedCrossRefGoogle Scholar
  8. Bliss TV, Collingridge GL, Morris RG (2003) Introduction. Long-term potentiation and structure of the issue. Philos Trans R Soc Lond B Biol Sci 358(1432):607–611PubMedCrossRefGoogle Scholar
  9. Boersma M, Smit DJ, de Bie HM, Van Baal GC, Boomsma DI, de Geus EJ, Delemarre-van de Waal HA, Stam CJ (2011) Network analysis of resting state EEG in the developing young brain: structure comes with maturation. Hum Brain Mapp 32(3):413–425PubMedCrossRefGoogle Scholar
  10. Brans RG, Kahn RS, Schnack HG, van Baal GC, Posthuma D, van Haren NE, Lepage C, Lerch JP, Collins DL, Evans AC, Boomsma DI, Hulshoff Pol HE (2010) Brain plasticity and intellectual ability are influenced by shared genes. J Neurosci 30(16):5519–5524PubMedCrossRefGoogle Scholar
  11. Bray NJ (2008) Gene expression in the etiology of schizophrenia. Schizophr Bull 34(3):412–418PubMedCrossRefGoogle Scholar
  12. Brignani D, Manganotti P, Rossini PM, Miniussi C (2008) Modulation of cortical oscillatory activity during transcranial magnetic stimulation. Hum Brain Mapp 29(5):603–612PubMedCrossRefGoogle Scholar
  13. Brown RM, Robertson EM, Press DZ (2009) Sequence skill acquisition and off-line learning in normal aging. PLoS One 4(8):e6683PubMedCrossRefGoogle Scholar
  14. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann NY Acad Sci 24:1–38CrossRefGoogle Scholar
  15. Bullmore E, Sporns O (2009) Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 10(4):312CrossRefGoogle Scholar
  16. Cabeza R, Anderson ND, Locantore JK, McIntosh AR (2002) Aging gracefully: compensatory brain activity in high-performing older adults. Neuroimage 17(3):1394–1402PubMedCrossRefGoogle Scholar
  17. Cao C, Slobounov S (2010) Alteration of cortical functional connectivity as a result of traumatic brain injury revealed by graph theory, ICA, and sLORETA analyses of EEG signals. IEEE Trans Neural Syst Rehabil Eng 18(1):11–19PubMedCrossRefGoogle Scholar
  18. Cárdenas-Morales L, Nowak DA, Kammer T, Wolf RC, Schönfeldt-Lecuona C (2010) Mechanisms and applications of theta-burst rTMS on the human motor cortex. Brain Topogr 22(4):294–306PubMedCrossRefGoogle Scholar
  19. Carmeli E, Patish H, Coleman R (2003) The aging hand. J Gerontol A Biol Sci Med Sci 58(2):146–152PubMedCrossRefGoogle Scholar
  20. Castellanos NP, Paúl N, Ordóñez VE, Demuynck O, Bajo R, Campo P, Bilbao A, Ortiz T, del-Pozo F, Maestú F (2010) Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. Brain 133(Pt. 8):2365–2381PubMedGoogle Scholar
  21. Cheeran B, Talelli P, Mori F, Koch G, Suppa A, Edwards M et al (2008) A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J Physiol 586:5717–5725PubMedCrossRefGoogle Scholar
  22. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW et al (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923PubMedCrossRefGoogle Scholar
  23. Curley JP, Jensen CL, Mashoodh R, Champagne FA (2011) Social influences on neurobiology and behavior: epigenetic effects during development. Psychoneuroendocrinology 36(3):352–371PubMedCrossRefGoogle Scholar
  24. Davis SW, Dennis NA, Daselaar SM, Fleck MS, Cabeza R (2008) Que PASA? The posterior-anterior shift in aging. Cereb Cort 18(5):1201–1209CrossRefGoogle Scholar
  25. De Beaumont L, Théoret H, Mongeon D, Messier J, Leclerc S, Tremblay S, Ellemberg D, Lassonde M (2009) Brain function decline in healthy retired athletes who sustained their last sports concussion in early adulthood. Brain 132(Pt. 3):695–708PubMedCrossRefGoogle Scholar
  26. de Haan W, Pijnenburg YA, Strijers RL, van der Made Y, van der Flier WM, Scheltens P, Stam CJ (2009) Functional neural network analysis in frontotemporal dementia and Alzheimer’s disease using EEG and graph theory. BMC Neurosci 10:101PubMedCrossRefGoogle Scholar
  27. Desai P, Nebes R, DeKosky ST, Kamboh MI (2005) Investigation of the effect of brain-derived neurotrophic factor (BDNF) polymorphisms on the risk of late-onset Alzheimer’s disease (AD) and quantitative measures of AD progression. Neurosci Lett 379(3):229–234PubMedCrossRefGoogle Scholar
  28. Douw L, van Dellen E, de Groot M, Heimans JJ, Klein M, Stam CJ, Reijneveld JC (2010) Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients. BMC Neurosci 11:103PubMedCrossRefGoogle Scholar
  29. Driscoll I, Davatzikos C, An Y, Wu X, Shen D, Kraut M, Resnick SM (2009) Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology 72(22):1906–1913PubMedCrossRefGoogle Scholar
  30. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39(1):90–98CrossRefGoogle Scholar
  31. Esser SK, Huber R, Massimini M, Peterson MJ, Ferrarelli F, Tononi G (2006) A direct demonstration of cortical LTP in humans: a combined TMS/EEG study. Brain Res Bull 69(1):86–94PubMedCrossRefGoogle Scholar
  32. Fehér A, Juhász A, Rimanóczy A, Kálmán J, Janka Z (2009) Association between BDNF Val66Met polymorphism and Alzheimer disease, dementia with Lewy bodies, and Pick disease. Alzheimer Dis Assoc Disord 23(3):224–228PubMedCrossRefGoogle Scholar
  33. Fingelkurts AA, Fingelkurts AA, Rytsälä H, Suominen K, Isometsä E, Kähkönen S (2007) Impaired functional connectivity at EEG alpha and theta frequency bands in major depression. Hum Brain Mapp 28(3):247–261PubMedCrossRefGoogle Scholar
  34. Fjell AM, Walhoyd KB (2010) Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neurosci 21(3):187–221PubMedCrossRefGoogle Scholar
  35. Fjell AM, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Walhovd KB (2009) High consistency of regional cortical thinning in aging across multiple samples. Cereb Cortex 19(9):2001–2012PubMedCrossRefGoogle Scholar
  36. Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL (2005) Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 64(6):1032–1039PubMedCrossRefGoogle Scholar
  37. Fratiglioni L, Wang HX (2007) Brain reserve hypothesis in dementia. J Alzheimers Dis 12(1):11–22PubMedGoogle Scholar
  38. Freitas C, Perez J, Knobel M, Tormos JM, Oberman L, Eldaief M, Bashir S, Vernet M, Peña-Gómez C, Pascual-Leone A (2011a) Changes in cortical plasticity across the lifespan. Front Aging Neurosci 3:5PubMedGoogle Scholar
  39. Freitas C, Mondragón-Llorca H, Pascual-Leone A (2011b) Noninvasive brain stimulation in Alzheimer’s disease: Systematic review and perspectives for the future. Exp Gerontol 46(8):611–627PubMedGoogle Scholar
  40. Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG, Lu B (2010) Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66(2):198–204PubMedCrossRefGoogle Scholar
  41. Fuggetta G, Rizzo S, Pobric G, Lavidor M, Walsh V (2009) Functional representation of living and nonliving domains across the cerebral hemispheres: a combined event-related potential/transcranial magnetic stimulation study. J Cogn Neurosci 21(2):403–414PubMedCrossRefGoogle Scholar
  42. Gazzaley A, D’Esposito M (2007) Top-down modulation and normal aging. In: DeLeon MJ, Snider DA, Federoff H (eds) Imaging and the Aging Brain. Ann NY Acad Sci, New York, pp 67–83Google Scholar
  43. Gladstone DJ, Black SE, Hakim AM (2002) Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions. Stroke 33(8):2123–2136PubMedCrossRefGoogle Scholar
  44. Gogolla N, Galimberti I, Deguchi Y, Caroni P (2009) Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus. Neuron 62(4):510–525PubMedCrossRefGoogle Scholar
  45. Grady CL, Protzner AB, Kovacevic N, Strother SC, Afshin-Pour B, Wojtowicz M, Anderson JA, Churchill N, McIntosh AR (2010) A multivariate analysis of age-related differences in default mode and task-positive networks across multiple cognitive domains. Cereb Cortex 20(6):1432–1447PubMedCrossRefGoogle Scholar
  46. Griskova I, Ruksenas O, Dapsys K, Herpertz S, Höppner J (2007) The effects of 10 Hz repetitive transcranial magnetic stimulation on resting EEG power spectrum in healthy subjects. Neurosci Lett 419(2):162–167PubMedCrossRefGoogle Scholar
  47. Grossheinrich N, Rau A, Pogarell O, Hennig-Fast K, Reinl M, Karch S, Dieler A, Leicht G, Mulert C, Sterr A, Padberg F (2009) Theta burst stimulation of the prefrontal cortex: safety and impact on cognition, mood, and resting electroencephalogram. Biol Psychiatry 65(9):778–784PubMedCrossRefGoogle Scholar
  48. Halko M, Eldaief MC, Horvath JC, Pascual-Leone A (2010) Combining transcranial magnetic stimulation and fMRI to examine the default mode network. J Vis Exp 46. doi: 10.3791/2271
  49. Hashimoto R, Hirata Y, Asada T, Yamashita F, Nemoto K, Mori T, Moriguchi Y, Kunugi H, Arima K, Ohnishi T (2009) Effect of the brain-derived neurotrophic factor and the apolipoprotein E polymorphisms on disease progression in preclinical Alzheimer’s disease. Genes Brain Behav 8(1):43–52PubMedCrossRefGoogle Scholar
  50. Horvath JC, Perez JM, Forrow L, Fregni F, Pascual-Leone A (2011) Transcranial magnetic stimulation: a historical review and future prognosis of therapeutically relevant ethical concerns. J Med Ethics 37(3):137–143PubMedCrossRefGoogle Scholar
  51. Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206PubMedCrossRefGoogle Scholar
  52. Huang YZ, Rothwell JC, Edwards MJ, Chen RS (2008) Effect of physiological activity on an NMDA-dependent form of cortical plasticity in human. Cereb Cortex 18(3):563–570PubMedCrossRefGoogle Scholar
  53. Inghilleri M, Conte A, Frasca V, Scaldaferri N, Gilio F, Santini M et al (2006) Altered response to rTMS in patients with Alzheimer’s disease. Clin Neurophysiol 117:103–109PubMedCrossRefGoogle Scholar
  54. Ishikawa S, Matsunaga K, Nakanishi R, Kawahira K, Murayama N, Tsuji S, Huang YZ, Rothwell JC (2007) Effects of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials. Clin Neurophysiol 118(5):1033–1043PubMedCrossRefGoogle Scholar
  55. Ives JR, Rotenberg A, Poma R, Thut G, Pascual-Leone A (2006) Electroencephalographic recording during transcranial magnetic stimulation in humans and animals. Clin Neurophysiol 117(8):1870–1875PubMedCrossRefGoogle Scholar
  56. Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27–29PubMedCrossRefGoogle Scholar
  57. Jelles B, Scheltens P, van der Flier WM, Jonkman EJ, da Silva FH, Stam CJ (2008) Global dynamical analysis of the EEG in Alzheimer’s disease: frequency-specific changes in functional interactions. Clin Neurophysiol 119(4):837–841PubMedCrossRefGoogle Scholar
  58. Jing H, Takigawa M (2000) Observation of EEG coherence after repetitive transcranial magnetic stimulation. Clin Neurophysiol 111:1620–1631PubMedCrossRefGoogle Scholar
  59. Jolles DD, Kleibeuker SW, Rombouts SA, Crone EA (2010) Developmental differences in prefrontal activation during working memory maintenance and manipulation for different memory loads. Dev Sci 14(4):713–724PubMedCrossRefGoogle Scholar
  60. Julkunen P, Jauhiainen AM, Westeren-Punnonen S, Pirinen E, Soininen H, Kononen M et al (2008) Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer’s disease: a pilot study. J Neurosci Methods 172:270–276PubMedCrossRefGoogle Scholar
  61. Julkunen P, Jauhiainen AM, Könönen M, Pääkkönen A, Karhu J, Soininen H (2011) Combining transcranial magnetic stimulation and electroencephalography may contribute to assess the severity of Alzheimer’s disease. Int J Alzheimers Dis: 654794Google Scholar
  62. Kaminski M, Ding M, Truccolo WA, Bressler SL (2001) Evaluating causal relations in neural systems: granger causality, directed transfer function and statistical assessment of significance. Biol Cybern 85:145–157PubMedCrossRefGoogle Scholar
  63. Kelly KM, Nadon NL, Morrison JH, Thibault O, Barnes CA, Blalock EM (2006) The neurobiology of aging. Epilepsy Res 68(Suppl 1):S5–S20PubMedCrossRefGoogle Scholar
  64. Kemppainen NM, Aalto S, Karrasch M, Någren K, Savisto N, Oikonen V, Viitanen M, Parkkola R, Rinne JO (2008) Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol 63(1):112–118PubMedCrossRefGoogle Scholar
  65. Kleim JA, Chan S, Pringle E, Schallert K, Procaccio V, Jimenez R, Cramer SC (2006) BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci 9(6):735–737PubMedCrossRefGoogle Scholar
  66. Kobayashi M, Pascual-Leone A (2003) Transcranial magnetic stimulation in neurology. Lancet Neurol 2:145–156PubMedCrossRefGoogle Scholar
  67. Koch W, Teipel S, Mueller S, Buerger K, Bokde ALW, Hampel H, Coates U, Reiser M, Meindl T (2010) Effects of aging on default mode network activity in resting state fMRI: does the method of analysis matter. Neuroimage 15(1):280–287CrossRefGoogle Scholar
  68. Kramer MA, Eden UT, Cash SS, Kolaczyk ED (2009) Network inference with confidence from multivariate time series. Phys Rev E Stat Nonlin Soft Matter Phys 79:061916PubMedCrossRefGoogle Scholar
  69. Larkin W, Read J (2008) Childhood trauma and psychosis: evidence, pathways, and implications. J Postgrad Med 54(4):287–293PubMedCrossRefGoogle Scholar
  70. Larson J, Wong D, Lynch G (1986) Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res 368(2):347–350PubMedCrossRefGoogle Scholar
  71. Leistedt SJ, Coumans N, Dumont M, Lanquart JP, Stam CJ, Linkowski P (2009) Altered sleep brain functional connectivity in acutely depressed patients. Hum Brain Mapp 30(7):2207–2219PubMedCrossRefGoogle Scholar
  72. Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429(6994):883–891PubMedCrossRefGoogle Scholar
  73. Luft AR, Kaelin-Lang A, Hauser TK, Cohen LG, Thakor NV, Hanley DF (2001) Transcranial magnetic stimulation in the rat. Exp Brain Res 140(1):112–121PubMedCrossRefGoogle Scholar
  74. Luft AR, Kaelin-Lang A, Hauser TK, Buitrago MM, Thakor NV, Hanley DF, Cohen LG (2002) Modulation of rodent cortical motor excitability by somatosensory input. Exp Brain Res 142(4):562–569PubMedCrossRefGoogle Scholar
  75. Matsushita S, Arai H, Matsui T, Yuzuriha T, Urakami K, Masaki T, Higuchi S (2005) Brain-derived neurotrophic factor gene polymorphisms and Alzheimer’s disease. J Neural Transm 112(5):703–711PubMedCrossRefGoogle Scholar
  76. McHughen SA, Rodriguez PF, Kleim JA, Kleim ED, Marchal Crespo L, Procaccio V, Cramer SC (2010) BDNF val66met polymorphism influences motor system function in the human brain. Cereb Cortex 20(5):1254–1262PubMedCrossRefGoogle Scholar
  77. Medkour T, Walden AT, Burgess AP, Strelets VB (2010) Brain connectivity in positive and negative syndrome schizophrenia. Neurosci 169(4):1779–1788CrossRefGoogle Scholar
  78. Micheloyannis S, Pachou E, Stam CJ, Breakspear M, Bitsios P, Vourkas M, Erimaki S, Zervakis M (2006) Small-world networks and disturbed functional connectivity in schizophrenia. Schizophr Res 87:60–66PubMedCrossRefGoogle Scholar
  79. Micheloyannis S, Vourkas M, Tsirka V, Karakonstantaki E, Kanatsouli K, Stam CJ (2009) The influence of ageing on complex brain networks: a graph theoretical analysis. Hum Brain Mapp 30(1):200–208PubMedCrossRefGoogle Scholar
  80. Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321(5886):218–223PubMedCrossRefGoogle Scholar
  81. Murias M, Webb SJ, Greenson J, Dawson G (2007) Resting state cortical connectivity reflected in EEG coherence in individuals with autism. Biol Psychiatry 62(3):270–273PubMedCrossRefGoogle Scholar
  82. Oberman L, Ifert-Miller F, Najib U, Bashir S, Woollacott I, Gonzalez-Heydrich J, Picker J, Rotenberg A, Pascual-Leone A (2010) Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile x syndrome and autism spectrum disorder. Front Synaptic Neurosci 2:26Google Scholar
  83. Oberman L, Edwards D, Eldaief M, Pascual-Leone A (2011) Safety of theta burst transcranial magnetic stimulation: A systematic review of the literature. J Clin Neurophysiol, [Epub ahead of print]Google Scholar
  84. Okamura H, Jing H, Takigawa M (2001) EEG modification induced by repetitive transcranial magnetic stimulation. J Clin Neurophysiol 18(4):318–325PubMedCrossRefGoogle Scholar
  85. Oliviero A, Strens LH, Di Lazzaro V, Tonali PA, Brown P (2003) Persistent effects of high frequency repetitive TMS on the coupling between motor areas in the human. Exp Brain Res 49:107–113Google Scholar
  86. Park DC, Gutchess AH (2002) Aging, cognition, and culture: a neuroscientific perspective. Neurosci Biobehav Rev 26(7):859–867PubMedCrossRefGoogle Scholar
  87. Park DC, Reuter-Lorenz P (2009) The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol 60:173–196PubMedCrossRefGoogle Scholar
  88. Pascual-Leone A, Amedi A, Fregni F, Merabet LB (2005) The plastic human brain cortex. Annu Rev of Neurosci 28:377–401CrossRefGoogle Scholar
  89. Pearson-Fuhrhop KM, Kleim JA, Cramer SC (2009) Brain plasticity and genetic factors. Top Stroke Rehabil 16(4):282–299PubMedCrossRefGoogle Scholar
  90. Pivac N, Nikolac M, Nedic G, Mustapic M, Borovecki F, Hajnsek S et al (2010) Brain derived neurotrophic factor Val66Met polymorphism and psychotic symptoms in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 35(2):356–362PubMedCrossRefGoogle Scholar
  91. Raz N, Rodrigue KM, Head D, Kennedy KM, Acker JD (2004) Differential aging of the medial temporal lobe—a study of five-year change. Neurol 62(3):433–438Google Scholar
  92. Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Dahle C, Gerstorf D, Acker JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15(11):1676–1689PubMedCrossRefGoogle Scholar
  93. Read J, van Os J, Morrison AP, Ross CA (2005) Childhood trauma, psychosis, and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatr Scand 112(5):330–350PubMedCrossRefGoogle Scholar
  94. Reuter-Lorenz PA, Park DC (2010) Human neuroscience and the aging mind: a new look at old problems. J Gerontol B Pschol Sci Soc Sci 65(4):405–415Google Scholar
  95. Roe CM, Xiong C, Miller JP, Morris JC (2007) Education and Alzheimers disease without dementia: support for the cognitive reserve hypothesis. Neurology 68(3):223–228PubMedCrossRefGoogle Scholar
  96. Roman F, Staubli U, Lynch G (1987) Evidence for synaptic potentiation in a cortical network during learning. Brain Res 418(2):221–226PubMedCrossRefGoogle Scholar
  97. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69(3):143–179PubMedCrossRefGoogle Scholar
  98. Rotenberg A, Muller PA, Vahabzadeh-Hagh AM, Navarro X, López-Vales R, Pascual-Leone A, Jensen F (2010) Lateralization of forelimb motor evoked potentials by transcranial magnetic stimulation in rats. Clin Neurophysiol 121(1):104–108PubMedCrossRefGoogle Scholar
  99. Saarela MS, Lehtimaki T, Rinne JO, Huhtala H, Rontu R, Hervonen A, Roytta M, Ahonen JP, Mattila KM (2006) No association between the brain-derived neurotrophic factor 196G>A or 270C>T polymorphisms and Alzheimer’s or Parkinson’s disease. Folia Neuropathol 44(1):12–16PubMedGoogle Scholar
  100. Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RSR, Busa E, Morris JC, Dale AM, Fischi B (2004) Thinning of the cerebral cortex in aging. Cereb Cortex 14(7):721–730PubMedCrossRefGoogle Scholar
  101. Salat DH, Tuch DS, Greve DN, Van Der Kouwe AJW, Hevelone ND, Zaleta AK, Rosen BR, Fischl B, Corkin S, Rosas HD, Dale AM (2005) Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging 26(8):1215–1227PubMedCrossRefGoogle Scholar
  102. Sambataro F, Murty VP, Callicott JH, Tan HY, Das S, Weinberger DR, Mattay VS (2010) Age-related alterations in default mode network: impact on working memory performance. Neurobiol Aging 31(5):839–852PubMedCrossRefGoogle Scholar
  103. Sameshima K, Baccala LA (1999) Using partial directed coherence to describe neuronal ensemble interactions. J Neurosci Methods 94:93–103PubMedCrossRefGoogle Scholar
  104. Scahill RI, Frost C, Jenkins R, Whitwell JL, Rossor MN, Fox NC (2003) A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol 60(7):989–994PubMedCrossRefGoogle Scholar
  105. Scarmeas N, Stern Y (2003) Cognitive reserve and lifestyle. J Clin Exp Neuropsychol 25(5):625–633PubMedCrossRefGoogle Scholar
  106. Schindler K, Nyffeler T, Wiest R, Hauf M, Mathis J, Hess ChW et al (2008) Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere. Neurosci Lett 436:31–34PubMedCrossRefGoogle Scholar
  107. Schlag MG, Hopf R, Redl H (2001) Serial recording of sensory, corticomotor, and brainstem-derived motor evoked potentials in the rat. Somatosens Mot Res 18(2):106–116PubMedCrossRefGoogle Scholar
  108. Schutter DJ, van Honk J, d’Alfonso AA, Postma A, de Haan EH (2001) Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood. Neuroreport 12(3):445–447PubMedCrossRefGoogle Scholar
  109. Sponheim SR, McGuire KA, Kang SS, Davenport ND, Aviyente S, Bernat EM, Lim KO (2011) Evidence of disrupted functional connectivity in the brain after combat-related blast injury. Neuroimage 54(Suppl 1):S21–S29PubMedCrossRefGoogle Scholar
  110. Stagg CJ, Wylezinska M, Matthews PM, Johansen-Berg H, Jezzard P, Rothwell JC, Bestmann S (2009) Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. J Neurophysiol 101(6):2872–2877PubMedCrossRefGoogle Scholar
  111. Stam CJ, van Dijk BW (2002) Synchronization likelihood: an unbiased measure of generalized synchronization in multivariate data sets. Physica D: Nonlinear Phenomena 163(3):236–251CrossRefGoogle Scholar
  112. Stam CJ, Jones BF, Nolte G, Breakspear M, Scheltens P (2007) Small-world networks and functional connectivity in Alzheimer’s disease. Eur J Clin Invest 32(Suppl 1):79–83Google Scholar
  113. Stern Y (2003) The concept of cognitive reserve: a catalyst for research. J Clin Exp Neuropsychol 25(5):589–593PubMedCrossRefGoogle Scholar
  114. Stern Y (2009) Cognitive reserve. Neuropsychologia 47(10):2015–2028PubMedCrossRefGoogle Scholar
  115. Stern Y, Alexander GE, Prohovnik I, Mayeux R (1992) Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer’s disease. Ann Neurol 32(3):371–375PubMedCrossRefGoogle Scholar
  116. Strens LH, Oliviero A, Bloem BR, Gerschlager W, Rothwell JC, Brown P (2002) The effects of subthreshold 1 Hz repetitive TMS on cortico-cortical and interhemispheric coherence. Clin Neurophysiol 113:1279–1285PubMedCrossRefGoogle Scholar
  117. Teipel SJ, Bokde AL, Meindl T, Amaro E Jr, Soldner J, Reiser MF, Herpertz SC, Möller HJ, Hampel H (2010) White matter microstructure underlying default mode network connectivity in the human brain. Neuroimage 49(3):2021–2032PubMedCrossRefGoogle Scholar
  118. Thompson PM, Hayashi KM, Dutton RA, Chiang MC, Leow AD, Sowell ER, DeZubicaray G, Becker JT, Lopez OL, Aizenstein HJ, Toga AW (2007) Tracking Alzheimer’s disease. In: DeLeon MJ, Snider DA, Federoff H (eds) Imaging and the aging brain. Ann NY Acad Sci, New York, pp 183–214Google Scholar
  119. Thut G, Pascual-Leone A (2010) A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr 22:219–232PubMedCrossRefGoogle Scholar
  120. Thut G, Ives JR, Kampmann F, Pastor MA, Pascual-Leone A (2005) A new device and protocol for combining TMS and online recordings of EEG and evoked potentials. J Neurosci Methods 141:207–217PubMedCrossRefGoogle Scholar
  121. Tokay T, Holl N, Kirschstein T, Zschorlich V, Köhling R (2009) High-frequency magnetic stimulation induces long-term potentiation in rat hippocampal slices. Neurosci Lett 461(2):150–154PubMedCrossRefGoogle Scholar
  122. Toro R, Chupin M, Garnero L, Leonard G, Perron M, Pike B, Pitiot A, Richer L, Veillette S, Pausova Z, Paus T (2009) Brain volumes and Val66Met polymorphism of the BDNF gene: local or global effects? Brain Struct Funct 213(6):501–509PubMedCrossRefGoogle Scholar
  123. Tsai SJ, Hong CJ, Liu HC, Liu TY, Liou YJ (2006) The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer’s disease in a chinese population. Dement Geriatr Cogn Disord 21(3):139–143PubMedCrossRefGoogle Scholar
  124. Vahabzadeh-Hagh AM, Muller PA, Pascual-Leone A, Jensen FE, Rotenberg A (2010) Measures of cortical inhibition by paired-pulse transcranial magnetic stimulation in anesthetized rats. J Neurophysiol 105(2):615–624PubMedCrossRefGoogle Scholar
  125. Valero-Cabre A, Payne BR, Pascual-Leone A (2007) Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex. Exp Brain Res 176(4):603–615PubMedCrossRefGoogle Scholar
  126. van Dellen E, Douw L, Baayen JC, Heimans JJ, Ponten SC, Vandertop WP, Velis DN, Stam CJ, Reijneveld JC (2009) Long-term effects of temporal lobe epilepsy on local neural networks: a graph theoretical analysis of corticography recordings. PLoS One 4(11):e8081PubMedCrossRefGoogle Scholar
  127. Van Der Werf YD, Paus T (2006) The neural response to transcranial magnetic stimulation of the human motor cortex: intracortical and cortico-cortical contributions. Exp Brain Res 175(2):231–245CrossRefGoogle Scholar
  128. Volkers KM, Scherder EJ (2011) Impoverished environment, cognition, aging and dementia. Rev Neurosci 22(3):259–266PubMedCrossRefGoogle Scholar
  129. Voss MW, Nagamatsu LS, Liu-Ambrose T, Kramer AF (2011) Exercise, brain, and cognition across the lifespan. J Appl Physiol (Epub ahead of print)Google Scholar
  130. Wagner T, Valero-Cabre A, Pascual-Leone A (2007) Noninvasive human brain stimulation. Annu Rev Biomed Eng 9:527–565PubMedCrossRefGoogle Scholar
  131. Walhovd KB, Fjell AM, Reinvang I, Lundervold A, Dale AM, Eilertsen DE, Quinn BT, Salat D, Makris N, Fischl B (2005) Effects of age on volumes of cortex, white matter and subcortical structures. Neurobiol Aging 26(9):1261–1270PubMedCrossRefGoogle Scholar
  132. Walhovd KB, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Fjell AM (2009) Consistent neuroanatomical age-related volume differences across multiple samples. Neurobiol Aging. doi: 10.1016/j.neurobiolaging
  133. Wang L, Li Y, Metzak P, He Y, Woodward TS (2010) Age-related changes in topological patterns of large-scale brain functional networks during memory encoding and recognition. Neuroimage 50(3):862–872PubMedCrossRefGoogle Scholar
  134. Wolk DA, Dickerson BC (2010) Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional-executive network function in Alzheimer’s disease. Proc Natl Acad Sci USA 107:10256–10261PubMedCrossRefGoogle Scholar
  135. Woo J (2011) Nutritional strategies for successful aging. Med Clin North Am 95(3):477–493PubMedCrossRefGoogle Scholar
  136. Zandieh S, Hopf R, Redl H, Schlag MG (2003) The effects of ketamine/xylazine anesthesia on sensory and motor evoked potentials in the rat. Spinal Cord 41(1):16–22PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Alvaro Pascual-Leone
    • 1
    • 4
    Email author
  • Catarina Freitas
    • 1
  • Lindsay Oberman
    • 1
  • Jared C. Horvath
    • 1
  • Mark Halko
    • 1
  • Mark Eldaief
    • 1
  • Shahid Bashir
    • 1
  • Marine Vernet
    • 1
  • Mouhshin Shafi
    • 1
    • 2
  • Brandon Westover
    • 1
    • 2
  • Andrew M. Vahabzadeh-Hagh
    • 1
    • 3
  • Alexander Rotenberg
    • 3
  1. 1.Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of NeurologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  2. 2.Department of NeurologyMassachusetts General Hospital; Partner’s Neurology Program, Harvard Medical SchoolBostonUSA
  3. 3.Department of NeurologyChildren’s Hospital, Boston, Harvard Medical SchoolBostonUSA
  4. 4.Institut Universitari de Neurorehabilitació GuttmannUniversidad Autónoma de BarcelonaBarcelonaSpain

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