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Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers

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Abstract

Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus–response (S–R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900–1800 mg). The S–R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R2=0.947–0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference curve, i.e. the maximum and minimum values, the slope, and V50 (the SI at which SP duration is halfway between Min and Max) were 230.8±3.31 ms (x±SEM), −11.51±3.31 ms, 11.56±0.65%, and 49.82±0.65%, respectively. When the curves obtained with the circular coil were compared with those obtained with the figure-of-eight coil, there were differences between V50 (51.69±0.72 vs 47.95±0.82, P<0.001) and SP threshold (31.15 vs 24.77, P<0.01) whereas the other best-fit values did not differ significantly. Oxcarbazepine increased corticomotor threshold from 45.3±5.8% at baseline to 59.4±10.4% (P<0.001). According to the commonly used method, the drug significantly prolonged SP (from 117.6±42.4 ms to 143.5±46.5 ms, P<0.001) and, consequently, enhanced brain inhibition. In contrast, study of the SP curves led to the conclusion that oxcarbazepine does not affect the Max value and slope but significantly increases V50 and SP threshold (from 54.5±4.9% to 59.9±7.2% and from 29.1±6.4% to 34.6±6.8%, respectively, P<0.01). These findings imply that oxcarbazepine does not enhance brain inhibitory mechanisms. Thus, in situations characterized by significant changes in corticomotor threshold the proposed method provides results clearly different from a commonly used approach. It is concluded that S–R curves obtained with a figure-of-eight coil in 5% increments and fitted to a Boltzman function provide an accurate, comprehensive, and clinically applicable method for exploring SP.

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References

  • Ahonen JP, Jehkonen M, Dastidar P, Molnar G, Hakkinen V (1998) Cortical silent period evoked by transcranial magnetic stimulation in ischemic stroke. Electoencephalogr Clin Neurophysiol 109:224–229

    Google Scholar 

  • Boroojerdi B (2002) Pharmacologic influences on TMS effects. J Clin Neurophysiol 19:255–271

    Google Scholar 

  • Cantello R, Gianelli M, Civardi C, Mutani R (1992) Magnetic brain stimulation: the silent period after the motor evoked potential. Neurology 42:1951–1959

    CAS  PubMed  Google Scholar 

  • Carroll TJ, Riek S, Carson RG (2001) Reliability of the input-output properties of the cortico-spinal pathway obtained from transcranial magnetic and electrical stimulation. J Neurosci Methods 112:193–202

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Samii A, Canos M, Wassermann EM, Hallett M (1997) Effects of phenytoin on cortical excitability in humans. Neurology 49:881–883

    Google Scholar 

  • Christopoulos A (1998) Assessing the distribution of parameters in models of ligand-receptor interaction: to log or not to log. Trends Pharm Sci 19:351–357

    Google Scholar 

  • Cincotta M, Borgheresi A, Lori S, Fabbri M, Zaccara G (1998) Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation. Electoencephalogr Clin Neurophysiol 107:1–7

    Google Scholar 

  • Daniel WW (1987) Biostatistics: a foundation for analysis in the health sciences, 4th edn. Wiley, New York, pp 152–154

  • Davey NJ, Romaiguere P, Maskill DW, Ellaway PH (1994) Suppression of voluntary motor activity revealed using transcranial magnetic stimulation of the motor cortex in man. J Physiol 477:223–235

    PubMed  Google Scholar 

  • Devanne H, Lavoie BA, Capaday C (1997) Input-output properties and gain changes in the human corticospinal pathway. Exp Brain Res 114:329–338

    CAS  PubMed  Google Scholar 

  • Fritz C, Braune HJ, Pylatiuk C, Pohl M (1997) Silent period following transcranial magnetic stimulation: a study of intra- and inter-examiner reliability. Electroencephalogr Clin Neurophysiol 105:235–240

    Google Scholar 

  • Hallett M (1995) Transcranial magnetic stimulation: negative effects. Adv Neurol 67:107–113

    Google Scholar 

  • Haug BA, Schonle PW, Knobloch C, Kohne M (1992) Silent period measurement revives as a valuable diagnostic tool with transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 85:158–160

    Article  CAS  PubMed  Google Scholar 

  • Ho K, Nithi K, Mills K (1998) Co variation between human intrinsic hand muscles of the silent periods and compound muscle action potentials evoked by magnetic brain stimulation: evidence for common inhibitory connections. Exp Brain Res 122:433–440

    Google Scholar 

  • Inghilleri M, Berardelli A, Cruccu G, Manfredi M (1993) Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction. J Physiol 466:521–534

    CAS  PubMed  Google Scholar 

  • Kukowski B, Haug B (1992) Quantitative evaluation of the silent period evoked by transcranial magnetic stimulation during sustained muscle contraction in normal man and in patients with stroke. Electromyogr Clin Neurophysiol 32:373–378

    Google Scholar 

  • Maccabee PJ, Amassian VE, Ziemann U et al. (2000) Cortical Silent Period. In: Levin K, Luders H (eds) Comprehensive clinical neurophysiology. WB Saunders, Philadelphia, pp 335–336

  • Mathis J, de Quervain D, Hess CW (1998) Dependence of the transcranially induced silent period on the “instruction set” and the individual reaction time. Electoencephalogr Clin Neurophysiol 109:426–435

    Google Scholar 

  • McLean MJ, Schmutz M, Wamil A et al. (1994) Oxcarbazepine: mechanisms of action. Epilepsia 35:5–9.

    Google Scholar 

  • Mills KR, Boniface SJ, Schubert M (1992) Magnetic brain stimulation with a double coil: the importance of coil orientation. Electoencephalogr Clin Neurophysiol 85:17–21

    Google Scholar 

  • Mills KR (1999) Measurement of the silent period. In: Mills KR (ed) Magnetic stimulation of the human nervous system. Oxford University Press, Oxford, p 177

  • Mills KR, Nithi KA (1997) Corticomotor threshold to magnetic stimulation: normal values and repeatability. Muscle Nerve 20:570–576

    Google Scholar 

  • Motulsky HJ (1999) Introducing curve fitting and non-linear regression. In: Analyzing data with Graph Pad Prism. Graph Pad Software Inc, San Diego, CA, pp 157–241

  • Orth M, Rothwell JC (2004) The cortical silent period: intrinsic variability and relation to the waveform of the transcranial magnetic stimulation pulse. Clin Neurophysiol 115:1076–1082

    Article  CAS  PubMed  Google Scholar 

  • Parada A, Soares-da-Silva P (2002) The novel anticonvulsant BIA 2–093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbazepine and oxcarbazepine. Neurochem Int 40:435–440

    Google Scholar 

  • Reid AE, Chiappa KH, Cross D (2002) Motor threshold, facilitation and the silent period in cortical magnetic stimulation. In: Pascual-Leone A, Davey NJ, Rothwell J, Wassermann EM, Puri BK (eds) Handbook of transcranial magnetic stimulation. Arnold, London, pp 103–108

  • Schnitzler A, Benecke R (1994) The silent period after transcranial magnetic stimulation is of exclusive cortical origin: evidence from isolated cortical ischemic lesions in man. Neurosci Lett 180:41–45

    Article  CAS  PubMed  Google Scholar 

  • Triggs WJ, Macdonell RA, Cros D, Chiappa KH, Shahani BT, Day BJ (1992) Motor inhibition and excitation are independent effects of magnetic cortical stimulation. Ann Neurol 32:345–351

    Google Scholar 

  • Uncini A, Treviso M, Di Muzio A, Simone P, Pullman S (1993) Physiological basis of voluntary activity inhibition induced by transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 89:211–220

    Google Scholar 

  • Uozumi T, Ito Y, Tsuji S, Murai Y (1992) Inhibitory period following motor potentials evoked by magnetic cortical stimulation. Electroencephalogr Clin Neurophysiol 85:273–279

    Google Scholar 

  • Valls-Solle J, Pascual-Leone A, Brasil-Neto JP, Cammarota A, McShane L, Hallett M (1994) Abnormal facilitation of the response to transcranial magnetic stimulation in patients with Parkinson’s disease. Neurology 44:735–741

    Google Scholar 

  • Van der Kamp W, Zwinderman AH, Ferrari MD, van Dijk JG (1996) Cortical excitability and response variability of transcranial magnetic stimulation. J Clin Neurophysiol 13:164–171

    Google Scholar 

  • Waldmeier PC, Baumann PA, Wicki P et al. (1995) Similar potency of carbamazepine, oxcarbazepine, and lamotrigine in inhibiting the release of glutamate and other neurotransmitters. Neurology 45:1907–1913

    Google Scholar 

  • Wassermann E, Pascual-Leone A, Valls-Sole J, Toro C, Cohen LG, Hallett M (1993) Topography of the inhibitory and excitatory responses to transcranial magnetic stimulation in a hand muscle. Electroencephalogr Clin Neurophysiol 89:424–433

    Google Scholar 

  • Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol 517:591–597

    CAS  PubMed  Google Scholar 

  • Wilson SA, Lockwood RJ, Thickbroom GW, Mastaglia FL (1993) The muscle silent period following transcranial magnetic cortical stimulation. J Neurol Sci 114:216–222

    Google Scholar 

  • Ziemann U, Lonnecker S, Steinhoff BJ, Paulus W (1996) The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res 109:127–135

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to V. K. Kimiskidis.

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Presented in part at the meeting of the EFNS, Helsinki, September 2003

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Kimiskidis, V.K., Papagiannopoulos, S., Sotirakoglou, K. et al. Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers. Exp Brain Res 163, 21–31 (2005). https://doi.org/10.1007/s00221-004-2134-4

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  • DOI: https://doi.org/10.1007/s00221-004-2134-4

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