Optimization of the transcranial magnetic stimulation protocol by defining a reliable estimate for corticospinal excitability

Koen Cuypers, Herbert Thijs, Raf L J Meesen, Koen Cuypers, Herbert Thijs, Raf L J Meesen

Abstract

The goal of this study was to optimize the transcranial magnetic stimulation (TMS) protocol for acquiring a reliable estimate of corticospinal excitability (CSE) using single-pulse TMS. Moreover, the minimal number of stimuli required to obtain a reliable estimate of CSE was investigated. In addition, the effect of two frequently used stimulation intensities [110% relative to the resting motor threshold (rMT) and 120% rMT] and gender was evaluated. Thirty-six healthy young subjects (18 males and 18 females) participated in a double-blind crossover procedure. They received 2 blocks of 40 consecutive TMS stimuli at either 110% rMT or 120% rMT in a randomized order. Based upon our data, we advise that at least 30 consecutive stimuli are required to obtain the most reliable estimate for CSE. Stimulation intensity and gender had no significant influence on CSE estimation. In addition, our results revealed that for subjects with a higher rMT, fewer consecutive stimuli were required to reach a stable estimate of CSE. The current findings can be used to optimize the design of similar TMS experiments.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Data for subject 36 (a)…
Figure 1. Data for subject 36 (a) and 34 (b) is illustrated.
The Y-axis shows the MEP amplitude (mV), while the number of TMS stimuli (n) is shown on the X-axis. White dots represent the individual (raw) MEPs, whereas the black dots represent the average of consecutive MEPs (). Dashed lines represent the 95% confidence interval (CI), which is based upon all 40 stimuli. The upper panel (a) illustrates data that was included in the statistical analysis (slope estimate: 0.007; p = 0.355). For this particular subject, 8 consecutive stimuli were sufficient to enter the CI. The lower panel (b) shows data that has been excluded due to a significant change in slope over time (slope estimate: 0.062; p<0.001).
Figure 2. Results for gender (a) and…
Figure 2. Results for gender (a) and intensity (b) based upon the raw data are illustrated.
The Y-axis shows probability of inclusion in the 95% CI, while the number of TMS stimuli (n) is shown on the X-axis. The upper panel (a) illustrates the probability of inclusion in the 95% CI for females (white dots) and males rMT (black dots). The lower panel (b) illustrates the probability of inclusion in the 95% CI for the stimulation intensity of 110% rMT (white dots) and 120% rMT (black dots).

References

    1. Kiers L, Cros D, Chiappa KH, Fang J (1993) Variability of motor potentials evoked by transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 89: 415–423.
    1. Roy Choudhury K, Boyle L, Burke M, Lombard W, Ryan S, et al. (2011) Intra subject variation and correlation of motor potentials evoked by transcranial magnetic stimulation. Ir J Med Sci 180: 873–880.
    1. Magistris MR, Rosler KM, Truffert A, Myers JP (1998) Transcranial stimulation excites virtually all motor neurons supplying the target muscle. A demonstration and a method improving the study of motor evoked potentials. Brain 121 (Pt 3): 437–450.
    1. Rosler KM, Petrow E, Mathis J, Aranyi Z, Hess CW, et al. (2002) Effect of discharge desynchronization on the size of motor evoked potentials: an analysis. Clin Neurophysiol 113: 1680–1687.
    1. Pitcher JB, Ogston KM, Miles TS (2003) Age and sex differences in human motor cortex input-output characteristics. J Physiol 546: 605–613.
    1. Ellaway PH, Davey NJ, Maskill DW, Rawlinson SR, Lewis HS, et al. (1998) Variability in the amplitude of skeletal muscle responses to magnetic stimulation of the motor cortex in man. Electroencephalogr Clin Neurophysiol 109: 104–113.
    1. Funase K, Miles TS, Gooden BR (1999) Trial-to-trial fluctuations in H-reflexes and motor evoked potentials in human wrist flexor. Neurosci Lett 271: 25–28.
    1. Darling WG, Wolf SL, Butler AJ (2006) Variability of motor potentials evoked by transcranial magnetic stimulation depends on muscle activation. Exp Brain Res 174: 376–385.
    1. Mars RB, Bestmann S, Rothwell JC, Haggard P (2007) Effects of motor preparation and spatial attention on corticospinal excitability in a delayed-response paradigm. Exp Brain Res 182: 125–129.
    1. Nielsen JF (1996) Logarithmic distribution of amplitudes of compound muscle action potentials evoked by transcranial magnetic stimulation. J Clin Neurophysiol 13: 423–434.
    1. Brasil-Neto JP, Cohen LG, Panizza M, Nilsson J, Roth BJ, et al. (1992) Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity. J Clin Neurophysiol 9: 132–136.
    1. Meyer BU, Britton TC, Kloten H, Steinmetz H, Benecke R (1991) Coil placement in magnetic brain stimulation related to skull and brain anatomy. Electroencephalogr Clin Neurophysiol 81: 38–46.
    1. Lewis GN, Signal N, Taylor D (2013) Reliability of lower limb motor evoked potentials in stroke and healthy populations: How many responses are needed? Clin Neurophysiol.
    1. Levin O, Cuypers K, Netz Y, Thijs H, Nuttin B, et al. (2011) Age-related differences in human corticospinal excitability during simple reaction time. Neurosci Lett 487: 53–57.
    1. Mantovani A, Rossi S, Bassi BD, Simpson HB, Fallon BA, et al... (2013) Modulation of motor cortex excitability in obsessive-compulsive disorder: An exploratory study on the relations of neurophysiology measures with clinical outcome. Psychiatry Res.
    1. Veniero D, Bortoletto M, Miniussi C (2012) Cortical modulation of short-latency TMS-evoked potentials. Front Hum Neurosci 6: 352.
    1. Fujiyama H, Hinder MR, Schmidt MW, Tandonnet C, Garry MI, et al. (2012) Age-related differences in corticomotor excitability and inhibitory processes during a visuomotor RT task. J Cogn Neurosci 24: 1253–1263.
    1. Meesen RL, Cuypers K, Rothwell JC, Swinnen SP, Levin O (2011) The effect of long-term TENS on persistent neuroplastic changes in the human cerebral cortex. Hum Brain Mapp 32: 872–882.
    1. Vaalto S, Saisanen L, Kononen M, Julkunen P, Hukkanen T, et al. (2011) Corticospinal output and cortical excitation-inhibition balance in distal hand muscle representations in nonprimary motor area. Hum Brain Mapp 32: 1692–1703.
    1. Smith MJ, Adams LF, Schmidt PJ, Rubinow DR, Wassermann EM (2002) Effects of ovarian hormones on human cortical excitability. Ann Neurol 51: 599–603.
    1. Wassermann EM (2002) Variation in the response to transcranial magnetic brain stimulation in the general population. Clin Neurophysiol 113: 1165–1171.
    1. Smith MJ, Keel JC, Greenberg BD, Adams LF, Schmidt PJ, et al. (1999) Menstrual cycle effects on cortical excitability. Neurology 53: 2069–2072.
    1. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9: 97–113.
    1. Wassermann EM (1998) Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996. Electroencephalogr Clin Neurophysiol 108: 1–16.
    1. Liang KY, Zeger SL (1986) Longitudinal data analysis using generalized linear models. Biometrika 73: 13–22.
    1. Zeger SL, Liang KY (1986) Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42: 121–130.
    1. Christie A, Fling B, Crews RT, Mulwitz LA, Kamen G (2007) Reliability of motor-evoked potentials in the ADM muscle of older adults. J Neurosci Methods 164: 320–324.
    1. Cuypers K, Leenus DJ, Van Wijmeersch B, Thijs H, Levin O, et al... (2013) Anodal tDCS increases corticospinal output and projection strength in multiple sclerosis. Neurosci Lett.
    1. Nitsche MA, Seeber A, Frommann K, Klein CC, Rochford C, et al. (2005) Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex. J Physiol 568: 291–303.
    1. Smith AE, Sale MV, Higgins RD, Wittert GA, Pitcher JB (2011) Male human motor cortex stimulus-response characteristics are not altered by aging. J Appl Physiol 110: 206–212.
    1. Kokate TG, Svensson BE, Rogawski MA (1994) Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 270: 1223–1229.
    1. Lan NC, Gee KW (1994) Neuroactive steroid actions at the GABAA receptor. Horm Behav 28: 537–544.
    1. Sahota P, Prabhakar S, Lal V, Khurana D, Das CP, et al. (2005) Transcranial magnetic stimulation: role in the evaluation of disability in multiple sclerosis. Neurol India 53: 197–201 discussion 201.
    1. Pennisi G, Alagona G, Rapisarda G, Nicoletti F, Costanzo E, et al. (2002) Transcranial magnetic stimulation after pure motor stroke. Clin Neurophysiol 113: 1536–1543.
    1. Ferreri F, Pauri F, Pasqualetti P, Fini R, Dal Forno G, et al. (2003) Motor cortex excitability in Alzheimer's disease: a transcranial magnetic stimulation study. Ann Neurol 53: 102–108.
    1. Julkunen P, Saisanen L, Danner N, Niskanen E, Hukkanen T, et al. (2009) Comparison of navigated and non-navigated transcranial magnetic stimulation for motor cortex mapping, motor threshold and motor evoked potentials. Neuroimage 44: 790–795.
    1. Jung NH, Delvendahl I, Kuhnke NG, Hauschke D, Stolle S, et al. (2010) Navigated transcranial magnetic stimulation does not decrease the variability of motor-evoked potentials. Brain Stimul 3: 87–94.
    1. Magistris MR, Rosler KM, Truffert A, Landis T, Hess CW (1999) A clinical study of motor evoked potentials using a triple stimulation technique. Brain 122 (Pt 2): 265–279.
    1. Grupe DW, Nitschke JB (2013) Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nat Rev Neurosci 14: 488–501.
    1. Hess CW, Mills KR, Murray NM (1987) Responses in small hand muscles from magnetic stimulation of the human brain. J Physiol 388: 397–419.
    1. Buccolieri A, Abbruzzese G, Rothwell JC (2004) Relaxation from a voluntary contraction is preceded by increased excitability of motor cortical inhibitory circuits. J Physiol 558: 685–695.
    1. Taylor JL, Gandevia SC (2001) Transcranial magnetic stimulation and human muscle fatigue. Muscle Nerve 24: 18–29.

Source: PubMed

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