Skip to main content
SpringerLink
Log in

Correlation between cortical plasticity, motor learning and BDNF genotype in healthy subjects

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

There is good evidence that synaptic plasticity in human motor cortex is involved in behavioural motor learning; in addition, it is now possible to probe mechanisms of synaptic plasticity using a variety of transcranial brain-stimulation protocols. Interactions between these protocols suggest that they both utilise common mechanisms. The aim of the present experiments was to test how well responsiveness to brain-stimulation protocols and behavioural motor learning correlate with each other in a sample of 21 healthy volunteers. We also examined whether any of these measures were influenced by the presence of a Val66Met polymorphism in the BDNF gene since this is another factor that has been suggested to be able to predict response to tests of synaptic plasticity. In 3 different experimental sessions, volunteers underwent 5-Hz rTMS, intermittent theta-burst stimulation (iTBS) and a motor learning task. Blood samples were collected from each subject for BDNF genotyping. As expected, both 5-Hz rTMS and iTBS significantly facilitated MEPs. Similarly, as expected, kinematic variables of finger movement significantly improved during the motor learning task. Although there was a significant correlation between the effect of iTBS and 5-Hz rTMS, there was no relationship in each subject between the amount of TMS-induced plasticity and the increase in kinematic variables during motor learning. Val66Val and Val66Met carriers did not differ in their response to any of the protocols. The present results emphasise that although some TMS measures of cortical plasticity may correlate with each other, they may not always relate directly to measures of behavioural learning. Similarly, presence of the Val66Met BDNF polymorphism also does not reliably predict responsiveness in small groups of individuals. Individual success in behavioural learning is unlikely to be closely related to any single measure of synaptic plasticity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Agostino R, Iezzi E, Dinapoli L, Gilio F, Conte A, Mari F, Berardelli A (2007) Effects of 5 Hz subthreshold magnetic stimulation of primary motor cortex on fast finger movements in normal subjects. Exp Brain Res 180:105–111

    Article  PubMed  CAS  Google Scholar 

  • Agostino R, Iezzi E, Dinapoli L, Suppa A, Conte A, Berardelli A (2008) Effects of intermittent theta -burst stimulation on practice-related changes in fast finger movements in healthy subjects. Eur J Neurosci 28:822–888

    Article  PubMed  Google Scholar 

  • Balkowiec A, Katz DM (2002) Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons. J Neurosci 22:10399–10407

    PubMed  CAS  Google Scholar 

  • Baraduc P, Lang N, Rothwell JC, Wolpert DM (2004) Consolidation of dynamic motor learning is not disrupted by rTMS of primary motor cortex. Curr Biol 14:252–256

    PubMed  CAS  Google Scholar 

  • Berardelli A, Inghilleri M, Rothwell JC, Romeo S, Currà A, Gilio F, Modugno N, Manfredi M (1998) Facilitation of muscle evoked responses after repetitive cortical stimulation in man. Exp Brain Res 122:79–84

    Article  PubMed  CAS  Google Scholar 

  • Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  • Bliss TV, Lømo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356

    PubMed  CAS  Google Scholar 

  • Carmignoto G, Pizzorusso T, Tia S, Vicini S (1997) Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory synaptic transmission in the rat visual cortex. J Physiol 498:153–164

    PubMed  CAS  Google Scholar 

  • Castro-Alamancos MA, Connors BW (1996) Short-term synaptic enhancement and long-term potentiation in neocortex. Proc Natl Acad Sci USA 93:1335–1339

    Article  PubMed  CAS  Google Scholar 

  • Cheeran B, Talelli P, Mori F, Koch G, Suppa A, Edwards M, Houlden H, Bhatia K, Greenwood R, Rothwell JC (2008) A common polymorphism in the brain-derived neurotrophic factor gene modulates human cortical plasticity and the response to rTMS. J Physiol 586:5717–5725

    Article  PubMed  CAS  Google Scholar 

  • Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS (2006) Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behaviour. Science 314:140–143

    Article  PubMed  CAS  Google Scholar 

  • Cooke SF, Bliss TV (2006) Plasticity in the human central nervous system. Brain 129:1659–1673

    Article  PubMed  CAS  Google Scholar 

  • Delvendahl I, Jung NH, Mainberger F, Kuhnke NG, Cronjaeger M, Mall V (2010) Occlusion of bidirectional plasticity by preceding low-frequency stimulation in the human motor cortex. Clin Neurophysiol 121:594–602

    Article  PubMed  Google Scholar 

  • Di Lazzaro V, Pilato F, Dileone M, Profice P, Oliviero A, Mazzone P, Insola A, Ranieri F, Meglio M, Tonali PA, Rothwell JC (2008) The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. J Physiol 586:3871–3879

    Article  PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Profice P, Pilato F, Capone F, Ranieri F, Pasqualetti P, Colosimo C, Pravatà E, Cianfoni A, Dileone M (2010) Motor cortex plasticity predicts recovery in acute stroke. Cereb Cortex 20:1523–1528

    Article  PubMed  Google Scholar 

  • Dileone M, Profice P, Pilato F, Alfieri P, Cesarini L, Mercuri E, Leoni C, Tartaglia M, Di Iorio R, Zampino G, Di Lazzaro V (2010) Enhanced human brain associative plasticity in Costello syndrome. J Physiol 588:3445–3456

    Article  PubMed  CAS  Google Scholar 

  • Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269

    Article  PubMed  CAS  Google Scholar 

  • Gilio F, Conte A, Vanacore N, Frasca V, Inghilleri M, Berardelli A (2007) Excitatory and inhibitory after-effects after repetitive magnetic transcranial stimulation in normal subjects. Exp Brain Res 176:588–593

    Article  PubMed  CAS  Google Scholar 

  • Hartmann M, Heumann R, Lessmann V (2001) Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses. EMBO J 20:5887–5897

    Article  PubMed  CAS  Google Scholar 

  • He X, Yang F, Xie Z, Lu B (2000) Intracellular Ca2+ and Ca2+/calmodulin-dependent kinase II mediate acute potentiation of neurotransmitter release by neurotrophin-3. J Cell Biol 149:783–792

    Article  PubMed  CAS  Google Scholar 

  • Heide G, Witte OW, Ziemann U (2006) Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation. Exp Brain Res 171:26–34

    Article  PubMed  CAS  Google Scholar 

  • Houdayer E, Degardin A, Cassim F, Bocquillon P, Derambure P, Devanne H (2008) The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway. Exp Brain Res 187:207–217

    Article  PubMed  CAS  Google Scholar 

  • Huang YZ, Rothwell JC (2004) The effect of short-duration bursts of high frequency, low-intensity transcranial magnetic stimulation on the human motor cortex. Clin Neurophysiol 115:1069–1075

    Article  PubMed  Google Scholar 

  • Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206

    Article  PubMed  CAS  Google Scholar 

  • Huang YZ, Chen RS, Rothwell JC, Wen HY (2007) The after-effect of human theta burst stimulation is NMDA receptor dependent. Clin Neurophysiol 118:1028–1032

    Article  PubMed  CAS  Google Scholar 

  • 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 18:563–570

    Article  PubMed  Google Scholar 

  • Iezzi E, Suppa A, Conte A, Agostino R, Nardella A, Berardelli A (2010) Theta-burst stimulation over primary motor cortex degrades early motor learning. Eur Neurosci 31:585–592

    Article  Google Scholar 

  • Inghilleri M, Conte A, Frasca V, Gilio F, Lorenzano C, Berardelli A (2005) Synaptic potentiation induced by rTMS: effect of lidocaine infusion. Exp Brain Res 163:114–117

    Article  PubMed  CAS  Google Scholar 

  • Jung P, Ziemann U (2009) Homeostatic and nonhomeostatic modulation of learning in human motor cortex. J Neurosci 29:5597–5604

    Article  PubMed  CAS  Google Scholar 

  • Kim DH, Jahng TA (2004) Continuous brain-derived neurotrophic factor infusion after methylprednisolone treatment in severe spinal cord injury. J Korean Med Sci 19:113–122

    Article  PubMed  CAS  Google Scholar 

  • 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 9:735–737

    Article  PubMed  CAS  Google Scholar 

  • Levine ES, Dreyfus CF, Black IB, Plummer MR (1995) Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Proc Natl Acad Sci USA 92:8074–8077

    Article  PubMed  CAS  Google Scholar 

  • Li YX, Zhang Y, Lester HA, Schuman EM, Davidson N (1998) Enhancement of neurotransmitter release induced by brain-derived neurotrophic factor in cultured hippocampal neurons. J Neurosci 18:10231–10240

    PubMed  CAS  Google Scholar 

  • Liepert J, Terborg C, Weiller C (1999) Motor plasticity induced by synchronized thumb and foot movements. Exp Brain Res 125:435–439

    Article  PubMed  CAS  Google Scholar 

  • Ljubisavljevic M (2006) Transcranial magnetic stimulation and the motor learning-associated cortical plasticity. Exp Brain Res 173:215–222

    Article  PubMed  Google Scholar 

  • Lohof AM, Ip NY, Poo MM (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363:350–353

    Article  PubMed  CAS  Google Scholar 

  • 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 20:1254–1262

    Article  PubMed  Google Scholar 

  • Muellbacher W, Ziemann U, Boroojerdi B, Cohen L, Hallett M (2001) Role of the human motor cortex in rapid motor learning. Exp Brain Res 136:431–438

    Article  PubMed  CAS  Google Scholar 

  • Muellbacher W, Ziemann U, Wissel J, Dang N, Kofler M, Facchini S, Boroojerdi B, Poewe W, Hallett M (2002) Early consolidation in human primary motor cortex. Nature 415:640–644

    Article  PubMed  CAS  Google Scholar 

  • Nakamura K, Enomoto H, Hanajima R, Hamada M, Shimizu E, Kawamura Y, Sasaki T, Matsuzawa D, Sutoh C, Shirota Y, Terao Y, Ugawa Y (2011) Quadri-pulse stimulation induced LTP/LTD was not affected by Val66Met polymorphism in the brain-derived neurotrophic factor gene. Neurosci Lett 487:264–267

    Article  PubMed  CAS  Google Scholar 

  • Numakawa T, Takei N, Yamagishi S, Sakai N, Hatanaka H (1999) Neurotrophin-elicited short-term glutamate release from cultured cerebellar granule neurons. Brain Res 842:431–438

    Article  PubMed  CAS  Google Scholar 

  • Numakawa T, Matsumoto T, Adachi N, Yokomaku D, Kojima M, Takei N, Hatanaka H (2001) Brain-derived neurotrophic factor triggers a rapid glutamate release via the neuronal glutamate transporter in cultured cerebellar neurons. J Neurosci Res 66:96–108

    Article  PubMed  CAS  Google Scholar 

  • Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M (1994) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117:847–858

    Article  PubMed  Google Scholar 

  • Pascual-Leone A, Nguyet D, Cohen LG, Brasil-Neto JP, Cammarota A, Hallett M (1995) Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills. J Neurophysiol 74:1037–1045

    PubMed  CAS  Google Scholar 

  • Plewnia C, Lotze M, Gerloff C (2003) Disinhibition of the contralateral motorcortex by low-frequency rTMS. Neuroreport 14:609–612

    Article  PubMed  Google Scholar 

  • Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2:24–32

    Article  PubMed  CAS  Google Scholar 

  • Richardson AG, Overduin SA, Valero-Cabre’ A, Padoa-Schioppa C, Pascual-Leone A, Bizzi E, Press DZ (2006) Disruption of primary motor cortex before learning impairs memory of movement dynamics. J Neurosci 26:12466–12470

    Article  PubMed  CAS  Google Scholar 

  • Ridding MC, Ziemann U (2010) Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 588:2291–2304

    Article  PubMed  CAS  Google Scholar 

  • Sherwood NT, Lo DC (1999) Long-term enhancement of central synaptic transmission by chronic brain-derived neurotrophic factor treatment. J Neurosci 19:7025–7036

    PubMed  CAS  Google Scholar 

  • Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J (2000) Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123:572–584

    Article  PubMed  Google Scholar 

  • Stoop R, Poo MM (1996) Synaptic modulation by neurotrophic factors: differential and synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor. J Neurosci 16:3256–3264

    PubMed  CAS  Google Scholar 

  • Suppa A, Bologna M, Gilio F, Lorenzano C, Rothwell JC, Berardelli A (2008) Preconditioning repetitive transcranial magnetic stimulation of premotor cortex can reduce but not enhance short-term facilitation of primary motor cortex. J Neurophysiol 99:564–570

    Article  PubMed  CAS  Google Scholar 

  • Takei N, Sasaoka K, Inoue K, Takahashi M, Endo Y, Hatanaka H (1997) Brain-derived neurotrophic factor increases the stimulation-evoked release of glutamate and the levels of exocytosis-associated proteins in cultured cortical neurons from embryonic rats. J Neurochem 68:370–375

    Article  PubMed  CAS  Google Scholar 

  • Takei N, Numakawa T, Kozaki S, Sakai N, Endo Y, Takahashi M, Hatanaka H (1998) Brain-derived neurotrophic factor induces rapid and transient release of glutamate through the non-exocytotic pathway from cortical neurons. J Biol Chem 273:27620–27624

    Article  PubMed  CAS  Google Scholar 

  • Tanaka J, Horiike Y, Matsuzaki M, Miyazaki T, Ellis-Davies GC, Kasai H (2008) Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319:1683–1687

    Article  PubMed  CAS  Google Scholar 

  • Teo JT, Swayne OB, Rothwell JC (2007) Further evidence for NMDA dependence of the after-effects of human theta burst stimulation. Clin Neurophysiol 118:1649–1651

    Article  PubMed  CAS  Google Scholar 

  • Yang F, He X, Feng L, Mizuno K, Liu XW, Russell J, Xiong WC, Lu B (2001) PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. Nat Neurosci 4:19–28

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Poo MM (2002) Localized synaptic potentiation by BDNF requires local protein synthesis in the developing axon. Neuron 36:675–688

    Article  PubMed  CAS  Google Scholar 

  • Ziemann U, Paulus W, Nitsche MA, Pascual-Leone A, Byblow WD, Berardelli A, Siebner HR, Classen J, Cohen LG, Rothwell JC (2008) Consensus: motor cortex plasticity protocols. Brain Stimul 1:164–182

    Article  PubMed  Google Scholar 

  • Zucker RS (1989) Short-term synaptic plasticity. Ann Rev Neurosci 12:13–31

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

There are no funding sources and potential conflicts of interest from each author that relate to the research covered in the article submitted.

Author information

Authors and Affiliations

  1. Department of Neurology and Psychiatry, “Sapienza”, University of Rome, Viale dell’Università, 30, 00185, Rome, Italy

    P. Li Voti, A. Conte, A. Suppa, M. Bologna & Alfredo Berardelli

  2. Neuromed Institute, I.R.C.C.S., Pozzilli (IS), Italy

    P. Li Voti, A. Conte, A. Suppa, E. Iezzi, M. Bologna & Alfredo Berardelli

  3. Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

    M. S. Aniello & G. Defazio

  4. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, UK

    J. C. Rothwell

Authors
  1. P. Li Voti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Suppa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Iezzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Bologna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. S. Aniello
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Defazio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. C. Rothwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alfredo Berardelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfredo Berardelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li Voti, P., Conte, A., Suppa, A. et al. Correlation between cortical plasticity, motor learning and BDNF genotype in healthy subjects. Exp Brain Res 212, 91–99 (2011). https://doi.org/10.1007/s00221-011-2700-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-011-2700-5

Keywords

Search

Navigation