Experimental Brain Research

, Volume 175, Issue 2, pp 246–255 | Cite as

The neural response to transcranial magnetic stimulation of the human motor cortex. II. Thalamocortical contributions

  • Ysbrand D. Van Der WerfEmail author
  • Abbas F. Sadikot
  • Antonio P. Strafella
  • Tomáš Paus
Research Article


Beta oscillations (15–30 Hz) constitute an important electrophysiological signal recorded in the resting state over the human precentral gyrus. The brain circuitry involved in generating the beta oscillations is not well understood but appears to involve both cortical and subcortical structures. We have shown that single pulses of transcranial magnetic stimulation (TMS) applied over the primary motor cortex consistently elicit a brief beta oscillation. Reducing the local cortical excitability using low-frequency repetitive TMS does not change the amplitude of the induced beta oscillation (Van Der Werf and Paus in Exp Brain Res DOI 10.1007/s00221-006-0551-2). Here, we investigated the possible involvement of the thalamus in the cortically expressed beta response to single-pulse TMS. We included eight patients with Parkinson’s disease who had undergone unilateral surgical lesioning of the ventrolateral nucleus of the thalamus. We administered 50 single pulses of TMS, at an intensity of 120% of resting motor threshold, over the left and right primary motor cortex and, at the same time, recorded the electroencephalogram (EEG) using a 60-electrode cap. We were able to perform analyses on seven EEG data sets and found that stimulation of the unoperated hemisphere (with thalamus) resulted in higher amplitudes of the single-trial induced beta oscillations than in the operated hemisphere (with thalamotomy). The beta oscillation obtained in response to pulses applied over the unoperated hemisphere was also higher than that obtained in healthy controls. We suggest that (1) the beta oscillatory response to pulses of TMS applied over the primary motor cortex is higher in Parkinson’s disease patients, (2) thalamotomy serves to reduce the abnormally high TMS-induced beta oscillations, and (3) the motor thalamus facilitates the cortically generated oscillation, through cortico-subcortico-cortical feedback loops.


Primary motor cortex Oscillations Excitability Plasticity Parkinson’s disease 


  1. Atkinson JD, Collins DL, Bertrand G, Peters TM, Pike GB, Sadikot AF (2002) Optimal location of thalamotomy lesions for tremor associated with Parkinson disease: a probabilistic analysis based on postoperative magnetic resonance imaging and an integrated digital atlas. J Neurosurg 96:854–866PubMedCrossRefGoogle Scholar
  2. Avoli M, Gloor P, Kostopoulos G, Naquet R (1990) Generalized epilepsy. Neurobiological approaches. Birkhaüser, Boston, USAGoogle Scholar
  3. Bevan MD, Magill PJ, Terman D, Bolam JP, Wilson CJ (2002) Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network. Trends Neurosci 25:525–531PubMedCrossRefGoogle Scholar
  4. Brown P (2003) Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson’s Disease. Mov Disord 18:357–363PubMedCrossRefGoogle Scholar
  5. Brown P, Williams D (2005) Basal ganglia local field potential activity: character and functional significance in the human. Clin Neurophysiol 116:2510–2519PubMedCrossRefGoogle Scholar
  6. Brown P, Oliviero A, Mazzone P, Insola A, Tonali P, Di Lazzaro V (2001) Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J Neurosci 21:1033–1038PubMedGoogle Scholar
  7. Cassidy M, Mazzone P, Oliviero A, Insola A, Tonali P, Di Lazzaro V, Brown P (2002) Movement-related changes in synchronization in the human basal ganglia. Brain 125:1235–1246PubMedCrossRefGoogle Scholar
  8. Colebatch JG, Dieber MP, Passingham RE, Friston KJ, Frackowiak RS (1991) Regional cerebral blood flow during voluntary arm and hand movements in human subjects. J Neurophysiol 65:1392–1401PubMedGoogle Scholar
  9. Collins DL, Neelin P, Peters TM, Evans AC (1994) Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comp Assist Tomogr 18:192–205CrossRefGoogle Scholar
  10. Deschênes M, Veinante P, Zhang ZW (1998) The organization of corticothalamic projections: reciprocity versus parity. Brain Res Rev 28:286–308PubMedCrossRefGoogle Scholar
  11. Dettmers C, Fink GR, Lemon RN, Stephan KM, Passingham RE, Silbersweig D, Holmes D, Ridding MC, Brooks DJ, Frakowiak RS (1995) Relation between cerebral activity and force in motor areas of the brain. J Neurophysiol 74:802–815PubMedGoogle Scholar
  12. Doyle LMF, Kühn AA, Hariz M, Kupsch A, Schnieder G-H, Brown P (2005a) Levodopa-induced modulation of subthalamic beta oscillations during self-paced movements in patients with Parkinson’s disease. Eur J Neurosci 21:1403–1412CrossRefGoogle Scholar
  13. Doyle LMF, Yarrow K, Brown P (2005b) Lateralization of event-related beta desynchronization in the EEG during pre-cued reaction time tasks. Clin Neurophysiol 116:1879–1888CrossRefGoogle Scholar
  14. Duval C, Panisset M, Bertrand G, Sadikot AF (2000) Evidence that ventrolateral thalamotomy may eliminate the supraspinal component of both pathological and physiological tremors. Exp Brain Res 132:216–222PubMedCrossRefGoogle Scholar
  15. Foffani G, Bianchi AM, Baselli G, Priori A (2005) Movement-related frequency modulation of beta oscillatory activity in the human subthalamic nucleus. J Physiol 568:699–711PubMedCrossRefGoogle Scholar
  16. Fogelson N, Williams D, Tijssen M, Van Bruggen, Speelman H, Brown P (2006) Different functional loops between cerebral cortex and the subthalamic area in Parkinson’s disease. Cerebral Cortex 16:64–75PubMedCrossRefGoogle Scholar
  17. Grafton ST, Woods RP, Mazziota JC (1993) Within-arm somatotopy in human motor areas determined by positron emission tomography imaging of cerebral blood flow. Exp Brain Res 95:172–176PubMedCrossRefGoogle Scholar
  18. Hari R, Salmelin R (1997) Human cortical oscillations: a neuromagnetic view through the skull. Trends Neurosci 20:44–49PubMedCrossRefGoogle Scholar
  19. Ilinsky IA, Kultas-Ilinsky K, Rosina A, Haddy M (1987) Quantitative evaluation of crossed and uncrossed projections from basal ganglia and cerebellum to the cat thalamus. Neuroscience 21:207–227PubMedCrossRefGoogle Scholar
  20. Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE, Brooks DJ (1995) Self-initiated versus externally triggered movements: I. An investigation using measurement of cerebral blood flow with PET and movement-related potentials in normal and Parkinson’s disease subjects. Brain 118:913–933PubMedCrossRefGoogle Scholar
  21. Jasper HH, Andrews HL (1936) Human brain rhythms I. Recording Techniques and preliminary results. J Gen Psychol 14:98–126CrossRefGoogle Scholar
  22. Jasper HH, Andrews HL (1938) Electroencephalography III. Normal differentiation of occipital and precentral regions in man. Arch Neurol Psychiat 39:96–115Google Scholar
  23. Jasper HH, Penfield W (1949) Electrocorticograms in man: effect of voluntary movement upon the electrical activity of the precentral gyrus. Arch f Psych Zeitschr 183:163–174CrossRefGoogle Scholar
  24. Jenkins IH, Brooks DJ, Nixon PD, Frackowiak RS, Passingham RE (1994) Motor sequence learning: a study with positron emission tomography. J Neurosci 14:3775–3790PubMedGoogle Scholar
  25. Kühn AA, Williams D, Kupsch A, Limousin P, Hariz M, Schneider G-H, Yarrow K, Brown P (2004) Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance. Brain 127:735–746PubMedCrossRefGoogle Scholar
  26. Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO (2002) Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s disease. Brain 125:1196–1209PubMedCrossRefGoogle Scholar
  27. Llinás RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA 96:15222–15227PubMedCrossRefGoogle Scholar
  28. Lopes da Silva F (1991) Neural mechanisms underlying brain waves: from neural membranes to networks. Electroencephalogr Clin Neurophysiol 79:81–93PubMedCrossRefGoogle Scholar
  29. Matelli M, Rizzolatti G, Bettinardi V, Gilardi MC, Perani D, Rizzo G, Fazio F (1993) Activation of precentral and mesial motor areas during the execution of elementary proximal and distal arm movements: a PET study. NeuroReport 4:1295–1298PubMedCrossRefGoogle Scholar
  30. Marsden CD, Obeso JA (1994) The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson’s disease. Brain 117:877–897PubMedCrossRefGoogle Scholar
  31. Marsden JF, Ashby P, Limousin-Dowsey P, Rothwell JC, Brown P (2000) Coherence between cerebellar thalamus, cortex and muscle in man. Cerebellar thalamus interactions. Brain 123:1459–1470PubMedCrossRefGoogle Scholar
  32. Marsden JF, Limousin-Dowsey P, Ashby P, Pollak P, Brown P (2001) Subthalamic nucleus, sensorimotor cortex and muscle interrelationships in Parkinson’s Disease. Brain 124:378–388PubMedCrossRefGoogle Scholar
  33. Neuper C, Pfurtscheller G (2001) Evidence for distinct beta resonance frequencies in human EEG related to specific sensorimotor cortical areas. Clin Neurophysiol 112:2084–2097PubMedCrossRefGoogle Scholar
  34. Niedermeyer E (1999) The normal EEG of the waking adult. In: Niedermeyer E, Lopes da Silva F (eds) Electroencephalography. Basic principles, clinical applications and related fields, 4th edn. Williams and Wilkins, Baltimore, pp 149–173Google Scholar
  35. Ohye C (2000) Use of selective thalamotomy for various kinds of movement disorder, based on basic studies. Stereotact Funct Neurosurg 75:54–65PubMedCrossRefGoogle Scholar
  36. Paradiso G, Cunic D, Saint-Cyr JA, Hoque T, Lozano AM, Lang AE, Chen R (2004) Involvement of human thalamus in the preparation of self-paced movement. Brain 127:2717–2731PubMedCrossRefGoogle Scholar
  37. Paus T (2002) Combination of transcranial magnetic stimulation with brain imaging. In: Mazziotta J, Toga A (eds) Brain mapping: the methods, 2nd edn. Academic, San Diego, pp 691–705Google Scholar
  38. Paus T (2003) Principles of functional neuroimaging. In: Schiffer RB, Rao SM, Fogel BS (eds) Neuropsychiatry, 2 edn. Lippincott, Williams and Wilkins, pp 63–90Google Scholar
  39. Paus T, Petrides M, Evans AC, Meyer E (1993) Role of the human anterior cingulate cortex in the control of occulomotor, manual, and speech responses: a positron emission tomography study. J Neurophysiol 70:453–469PubMedGoogle Scholar
  40. Paus T, Jech R, Thompson CJ, Comeau R, Peters T, Evans AC (1997) Transcranial magnetic stimulation during positron emission tomography: a new method of studying connectivity of the human cerebral cortex. J Neurosci 17:3178–3184PubMedGoogle Scholar
  41. Paus T, Sipila PK, Strafella AP (2001) Synchronization of neuronal activity in the human sensorimotor cortex by transcranial magnetic stimulation: a combined TMS/EEG study. J Neurophysiol 86:1983–1990PubMedGoogle Scholar
  42. Pfurtscheller G, Woertz M, Supp G, Lopes da Silva FH (2003) Early onset of post-movement beta electroencephalogram synchronization in the supplementary motor area during self-paced finger movement in man. Neurosci Lett 339:111–114PubMedCrossRefGoogle Scholar
  43. Pierantozzi M, Palmieria MG, Mazzone P, Marciania MG, Rossini PM, Stefani A, Giacomini P, Peppe A, Stanzione P (2002) Deep brain stimulation of both subthalamic nucleus and internal globus pallidus restores intracortical inhibition in Parkinson’s disease paralleling apomorphine effects: a paired magnetic stimulation study. Clin Neurophysiol 113:108–113PubMedCrossRefGoogle Scholar
  44. Priori A, Foffani G, Pesenti A, Bianchi A, Chiesa V, Baselli G, Caputo E, Tamma F, Rampini P, Egidi M, Locatelli Barbieri S, Scarlato G (2002) Neurol Sci 23:S101–S102PubMedCrossRefGoogle Scholar
  45. Priori A, Foffani G, Pesenti A, Tamma F, Bianchi AM, Pellegrini M, Locatelli M, Moxon KA, Villani RM (2004) Exp Neurol 189:369–379PubMedCrossRefGoogle Scholar
  46. Rouiller EM, Liang F, Babalian A, Moret V, Wiesendanger M (1994) Cerebellothalamocortical and pallidothalamocortical projections to the primary and supplementary motor cortical areas: a multiple tracing study in macaque monkeys. J Comp Neurol 345:185–213PubMedCrossRefGoogle Scholar
  47. Sarnthein J, Morel A, Von Stein A, Jeanmonod D (2003) Thalamic theta field potentials and EEG: high thalamocortical coherence in patients with neurogenic pain, epilepsy and movement disorders. Thalamus Related Syst 2:231–238Google Scholar
  48. Schaltenbrand G, Wahren W (1977) Atlas of stereotaxy of the human brain. Thieme, StuttgartGoogle Scholar
  49. Schlaug G, Knorr U, Seitz R (1994) Inter-subject variability of cerebral activations in acquiring motor skill: a study with positron emission tomography. Exp Brain Res 98:523–534PubMedCrossRefGoogle Scholar
  50. Siebner HR, Rossmeier C, Mentschel C, Peinemann A, Conrad B (2000) Short-term motor improvement after sub-threshold 5-Hz repetitive tanscranial magnetic stimulation of the primary motor hand area in Parkinson’s disease. J Neurol Sci 178:91–94PubMedCrossRefGoogle Scholar
  51. Soikkeli R, Partanen J, Soininen H, Pääkkönen A, Riekkinen P Sr (1991) Slowing of EEG in Parkinson’s disease. Electroencephalogr Clin Neurophysiol 79:159–165PubMedCrossRefGoogle Scholar
  52. Steriade M (1999) Cellular substrates of brain rhythms. In: Niedermeyer E, Lopes da Silva F (eds) Electroencephalography. Basic principles, clinical applications and related fields, 4th edn. Williams and Wilkins, Baltimore, pp 28–75Google Scholar
  53. St-Jean P, Sadikot AF, Collins L, Clonda D, Kasrai R, Evans AC, Peters TM (1998) Automated atlas integration and interactive three-dimensional visualization tools for planning and guidance in functional neurosurgery. IEEE Trans Med Imaging 17:672–680PubMedCrossRefGoogle Scholar
  54. Talairach J, Tournoux P (1988) Co-planar stereotactic atlas of the human brain: dimensional proportional system: an approach to cerebral imaging. Thieme, Stuttgart, GermanyGoogle Scholar
  55. Van Der Werf YD, Paus T (2006) The neural response to transcranial magnetic stimulation of the human motor cortex. I. Intracortical and cortico-cortical contributions. DOI 10.1007/s00221-006-0551-2Google Scholar
  56. Virtanen J, Ruohonen J, Naatanen R, Ilmoniemi RJ (1999) Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation. Med Biol Eng Comput 37:332–326CrossRefGoogle Scholar
  57. Williams D, Tijssen M, Van Bruggen G, Bosch A, Insola A, Di Lazzaro V, Mazzone P, Oliviero A, Quartarone A, Speelman H, Brown P (2002). Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans. Brain 125:1558–1569PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ysbrand D. Van Der Werf
    • 1
    • 3
    Email author
  • Abbas F. Sadikot
    • 1
  • Antonio P. Strafella
    • 1
  • Tomáš Paus
    • 1
    • 2
  1. 1.Montreal Neurological InstituteMcGill UniversityMontrealCanada
  2. 2.Brain & Body CentreUniversity of NottinghamNottinghamUK
  3. 3.Department of Clinical NeurophysiologyVrije Universiteit Medical CentreAmsterdamThe Netherlands

Personalised recommendations