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Durable effect of very low-frequency repetitive transcranial magnetic stimulation for modulating cortico-spinal neuron excitability
International Congress Series 1278 (2005) 272 – 275
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Durable effect of very low-frequency repetitive transcranial magnetic stimulation for modulating cortico-spinal neuron excitability Michiko Ikeguchia, Tetsuo Tougeb,*, Ryuji Kajic, Kazushi Deguchid, Iwao Sasakid, Masago Tsukaguchid, Hiroaki Takeuchie, Shigeki Kuriyamad a
Division of Neurology, National Hospital Organization, Takamatsu Higashi Hospital, Kagawa, Japan b Health Sciences, School of Nursing, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan c Department of Clinical Neuroscience, Tokushima University School of Medicine, Tokushima, Japan d Third Department of Internal Medicine, Faculty of Medicine, Kagawa University, Japan e Kagawa University, Japan
Abstract. Objective: We studied the durable effects of 0.2 Hz-rTMS on the cortico-spinal neuron excitabilities by recording the motor-evoked potentials (MEPs) or Hoffman-reflex (H-reflex) before and after rTMS. Methods: We employed a figure-of-eight coil for stimulating the primary motor (M1) or premotor cortex (PMC) or a round coil held over the vertex with subthreshold stimulus intensity (90% resting motor threshold). rTMS consisted of six blocks of 30 pulses (total 180 pulses). Changes in the MEP or H-reflex amplitudes in the forearm muscles following rTMS were expressed as the test/control (t/c) ratio. Results: In comparison to sham stimulation, rTMS to PMC induced a significant reduction of t/c ratios of MEP amplitudes ( Pb0.05). rTMS using a round coil significantly reduced t/c ratios of MEP amplitudes ( Pb0.05) without affecting H-reflex amplitudes. Conclusions: We therefore conclude that 0.2 Hz-rTMS appears to have inhibitory effects on the
Abbreviations: M1, the primary motor cortex; PMC, the premotor cortex; MEPs, motor-evoked potentials; H-reflex, Hoffman reflex; RMT, resting motor threshold; (t/c) ratio, test/control ratio subthreshold; rTMS, The intensity of rTMS was 90% of RMT; suprathreshold rTMS, 110% of RMT. * Corresponding author. Tel.: +81 87 891 2156; fax: +81 87 891 2158. E-mail address: [email protected] (T. Touge). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.11.189
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cortico-spinal neurons for an extended period, and the inhibitory action of rTMS on MEP sizes is attributable to a cortical mechanism. D 2004 Elsevier B.V. All rights reserved. Keywords: rTMS; Low frequency; Costicospinal neuron excitability; Motor-evoked potentials; Hoffman reflex
1. Introduction The effects of very low-frequency rTMS with different stimulating intensities, different coil shapes and different stimulating positions on cortico-spinal neuron excitabilities remains to be studied. To examine the effects of low-frequency rTMS on cortico-spinal neuron excitabilities, we studied the changes in MEPs or H-reflex after 0.2 Hz-rTMS under the different stimulating conditions. 2. Subjects Thirty-eight right-handed normal subjects including 19 males and 19 females (mean ageFS.D.=27.9F5.7 years ranging from 20 to 42 years) were examined. All subjects gave informed consent to participate in this study. The protocol was approved by the local ethics committee in our institution. 3. Methods 3.1. rTMS with different stimulating intensities A 13-cm-diameter round coil connected to a magnetic stimulator was held over the vertex with counterclockwise electric currents in the coil. This coil placement implies that rTMS mainly stimulated the left M1. The coil was fixed at the hot spot to induce MEPs in the right FDI. The intensity was 90% of RMT (subthreshold rTMS) in 10 subjects or 110% of RMT (suprathreshold rTMS) in 8 subjects. Sham stimulation was also performed as a control run in 7 subjects; a round coil not connected to a magnetic stimulator was horizontally placed over the scalp. The vertically held coil connected with a magnetic stimulator made clicking sounds similar to those for the test rTMS. To avoid over-heating of coils, rTMS consisting of six blocks of 30 stimuli (total 180 pulses) were delivered to subjects with intervals between blocks ranging 1–3 min. 3.2. Focal rTMS We used a figure-of-eight coil connected to a magnetic stimulator for focal subthreshold rTMS. The coil position to stimulate M1 in eight subjects was the optimal point (hot spot) to induce MEPs in the right FDI muscle, which was probed by shifting the stimulus position manually from the point 2 cm anterior to and 7 cm left of the vertex. For stimulation of the PMC in six subjects, the coil was set 2.5 cm anterior to the hot spot. 3.3. Simultaneous recording of H-reflex and MEPs H-reflex and MEPs in the right FCR muscle were simultaneously recorded before, immediately after, 10 and 20 min after subthreshold 0.2 Hz-rTMS in five subjects. rTMS consisted of six blocks of 30 pulses through a round coil. To induce H-reflex in the FCR
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M. Ikeguchi et al. / International Congress Series 1278 (2005) 272–275
Fig. 1. Time courses of the test/control (t/c) ratios of MEP amplitudes after focal 0.2 Hz-rTMS. (A). A solid line indicates the mean t/c ratios for subthreshold rTMS, a dotted line indicates those for suprathreshold rTMS and a thin line shows those for sham stimulation. (B). A solid line indicates the mean t/c ratios for rTMS to M1, a dotted line indicates those for rTMS to PMC. Vertical bars indicate S.E. After three blocks of rTMS: 3b; after six blocks of rTMS: 6b; 5–30 min after rTMS: 5–30 m.
muscle, the right median nerve was stimulated at the elbow. The H-reflex and MEPs were adjusted to show similar amplitudes for each subject. 3.4. MEPs recordings and data analysis A round coil was fixed at the hot spot to induce MEPs in the right FDI. Nine MEPs were collected: twice before, and once immediately after three and six blocks of rTMS. They were also recorded every 5 min for 30 min after rTMS. Mean peak-to-peak amplitudes of nine MEPs obtained at each recording time point were expressed as t/c ratio: each nine MEP amplitude after rTMS/meaned 18 MEP amplitudes twice measured before rTMS. Statistic analysis was performed using two-way repeated-measures ANOVA with paired Student’s t-test. 4. Results Repeated-measures ANOVA showed that 0.2 Hz-rTMS with subthreshold intensity significantly reduced t/c ratios ( Pb0.05) than sham stimulation (paired Student’s ttestafter 6 blocks, 5, 15 min after rTMS: Pb0.05) (Fig. 1A). Focal 0.2 Hz-rTMS to PMC
Fig. 2. Time courses of the t/c ratios of MEP or H-reflex amplitudes after 0.2 Hz-rTMS. A solid line indicates the mean t/c ratios for MEPs and a dotted line shows those for H-reflex. Vertical bars indicate S.E. After six blocks of rTMS: 6b; 10–20 min after rTMS: 10–20 m.
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significantly decreased t/c ratios compared with sham stimulation (paired Student’s t-test after six blocks: Pb0.01) (Fig. 1B). 0.2 Hz-rTMS did not significantly affect H-reflex, while MEP sizes were significantly decreased by rTMS compared with H-reflex (paired Student’s t-test: Pb0.05) (Fig. 2). There was no significant differences between rTMS with subthreshold and suprathreshold intensity, or between rTMS to the M1 and the PMC. 5. Discussion The present study showed that 0.2 Hz-rTMS with either coil reduced cortico-spinal neuron excitabilities for an extended period after rTMS. Previous studies showed that 1 Hz-rTMS to M1 reduced cortico-spinal neuron excitabilities during a short period after rTMS [1,3–5]. A recent study demonstrated that 1 Hz-rTMS to PMC with a stimulus intensity below active motor threshold decreased MEP amplitudes, while similar stimulation to M1 showed no effects on MEPs [2]. According to these findings, the authors postulated that rTMS to PMC extended inhibitory effects on cortico-spinal neurons through interneurons innervated from PMC to M1. Also, because those of Hreflex amplitudes did not significantly change after 0.2 Hz-rTMS, we suggest that the inhibitory effects of 0.2 Hz-rTMS are attributable to the cortical mechanism. 6. Conclusion 0.2 Hz-rTMS reduced cortico-spinal neuron excitabilities in the same manner as 1 HzrTMS. There are no significant differences between the effects of 0.2 Hz-rTMS using a round coil and a figure-of-eight coil on MEPs. Since 0.2 Hz-rTMS did not significantly affect H-reflex, the effects of 0.2 Hz-rTMS are predominantly ascribed to changes of cortical neuron activities. We need further studies to elucidate the effects of changing stimulus intensity and stimulus position on cortical neuron activities. References [1] R. Chen, et al., Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation, Neurology 48 (1997) 1398 – 1403. [2] W. Gerschlager, H.R. Siebner, J.C. Rothwell, Decreased cortico-spinal excitability after subthreshold 1 Hz rTMS over F, Rizzo V, Siebner HR, Rothwell JC. Effects on the right motor hand-area excitability produced by low-frequency rTMS o lateral premotor cortex, Neurology 57 (2001) 449 – 455. [3] F. Maeda, et al., Modulation of cortico-spinal excitability by repetitive transcranial magnetic stimulation, Clin. Neurophysiol. 111 (2000) 800 – 805. [4] W. Muellbacher, et al., Effects of low-frequency transcranial magnetic stimulation on motor exicitability and basic motor behavior, Clin. Neurophysiol. 111 (2000) 1002 – 1007. [5] T. Touge, et al., Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses? Clin. Neurophysiol. 112 (2001) 2138 – 2145.
www.ics-elsevier.com
Durable effect of very low-frequency repetitive transcranial magnetic stimulation for modulating cortico-spinal neuron excitability Michiko Ikeguchia, Tetsuo Tougeb,*, Ryuji Kajic, Kazushi Deguchid, Iwao Sasakid, Masago Tsukaguchid, Hiroaki Takeuchie, Shigeki Kuriyamad a
Division of Neurology, National Hospital Organization, Takamatsu Higashi Hospital, Kagawa, Japan b Health Sciences, School of Nursing, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan c Department of Clinical Neuroscience, Tokushima University School of Medicine, Tokushima, Japan d Third Department of Internal Medicine, Faculty of Medicine, Kagawa University, Japan e Kagawa University, Japan
Abstract. Objective: We studied the durable effects of 0.2 Hz-rTMS on the cortico-spinal neuron excitabilities by recording the motor-evoked potentials (MEPs) or Hoffman-reflex (H-reflex) before and after rTMS. Methods: We employed a figure-of-eight coil for stimulating the primary motor (M1) or premotor cortex (PMC) or a round coil held over the vertex with subthreshold stimulus intensity (90% resting motor threshold). rTMS consisted of six blocks of 30 pulses (total 180 pulses). Changes in the MEP or H-reflex amplitudes in the forearm muscles following rTMS were expressed as the test/control (t/c) ratio. Results: In comparison to sham stimulation, rTMS to PMC induced a significant reduction of t/c ratios of MEP amplitudes ( Pb0.05). rTMS using a round coil significantly reduced t/c ratios of MEP amplitudes ( Pb0.05) without affecting H-reflex amplitudes. Conclusions: We therefore conclude that 0.2 Hz-rTMS appears to have inhibitory effects on the
Abbreviations: M1, the primary motor cortex; PMC, the premotor cortex; MEPs, motor-evoked potentials; H-reflex, Hoffman reflex; RMT, resting motor threshold; (t/c) ratio, test/control ratio subthreshold; rTMS, The intensity of rTMS was 90% of RMT; suprathreshold rTMS, 110% of RMT. * Corresponding author. Tel.: +81 87 891 2156; fax: +81 87 891 2158. E-mail address: [email protected] (T. Touge). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.11.189
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cortico-spinal neurons for an extended period, and the inhibitory action of rTMS on MEP sizes is attributable to a cortical mechanism. D 2004 Elsevier B.V. All rights reserved. Keywords: rTMS; Low frequency; Costicospinal neuron excitability; Motor-evoked potentials; Hoffman reflex
1. Introduction The effects of very low-frequency rTMS with different stimulating intensities, different coil shapes and different stimulating positions on cortico-spinal neuron excitabilities remains to be studied. To examine the effects of low-frequency rTMS on cortico-spinal neuron excitabilities, we studied the changes in MEPs or H-reflex after 0.2 Hz-rTMS under the different stimulating conditions. 2. Subjects Thirty-eight right-handed normal subjects including 19 males and 19 females (mean ageFS.D.=27.9F5.7 years ranging from 20 to 42 years) were examined. All subjects gave informed consent to participate in this study. The protocol was approved by the local ethics committee in our institution. 3. Methods 3.1. rTMS with different stimulating intensities A 13-cm-diameter round coil connected to a magnetic stimulator was held over the vertex with counterclockwise electric currents in the coil. This coil placement implies that rTMS mainly stimulated the left M1. The coil was fixed at the hot spot to induce MEPs in the right FDI. The intensity was 90% of RMT (subthreshold rTMS) in 10 subjects or 110% of RMT (suprathreshold rTMS) in 8 subjects. Sham stimulation was also performed as a control run in 7 subjects; a round coil not connected to a magnetic stimulator was horizontally placed over the scalp. The vertically held coil connected with a magnetic stimulator made clicking sounds similar to those for the test rTMS. To avoid over-heating of coils, rTMS consisting of six blocks of 30 stimuli (total 180 pulses) were delivered to subjects with intervals between blocks ranging 1–3 min. 3.2. Focal rTMS We used a figure-of-eight coil connected to a magnetic stimulator for focal subthreshold rTMS. The coil position to stimulate M1 in eight subjects was the optimal point (hot spot) to induce MEPs in the right FDI muscle, which was probed by shifting the stimulus position manually from the point 2 cm anterior to and 7 cm left of the vertex. For stimulation of the PMC in six subjects, the coil was set 2.5 cm anterior to the hot spot. 3.3. Simultaneous recording of H-reflex and MEPs H-reflex and MEPs in the right FCR muscle were simultaneously recorded before, immediately after, 10 and 20 min after subthreshold 0.2 Hz-rTMS in five subjects. rTMS consisted of six blocks of 30 pulses through a round coil. To induce H-reflex in the FCR
274
M. Ikeguchi et al. / International Congress Series 1278 (2005) 272–275
Fig. 1. Time courses of the test/control (t/c) ratios of MEP amplitudes after focal 0.2 Hz-rTMS. (A). A solid line indicates the mean t/c ratios for subthreshold rTMS, a dotted line indicates those for suprathreshold rTMS and a thin line shows those for sham stimulation. (B). A solid line indicates the mean t/c ratios for rTMS to M1, a dotted line indicates those for rTMS to PMC. Vertical bars indicate S.E. After three blocks of rTMS: 3b; after six blocks of rTMS: 6b; 5–30 min after rTMS: 5–30 m.
muscle, the right median nerve was stimulated at the elbow. The H-reflex and MEPs were adjusted to show similar amplitudes for each subject. 3.4. MEPs recordings and data analysis A round coil was fixed at the hot spot to induce MEPs in the right FDI. Nine MEPs were collected: twice before, and once immediately after three and six blocks of rTMS. They were also recorded every 5 min for 30 min after rTMS. Mean peak-to-peak amplitudes of nine MEPs obtained at each recording time point were expressed as t/c ratio: each nine MEP amplitude after rTMS/meaned 18 MEP amplitudes twice measured before rTMS. Statistic analysis was performed using two-way repeated-measures ANOVA with paired Student’s t-test. 4. Results Repeated-measures ANOVA showed that 0.2 Hz-rTMS with subthreshold intensity significantly reduced t/c ratios ( Pb0.05) than sham stimulation (paired Student’s ttestafter 6 blocks, 5, 15 min after rTMS: Pb0.05) (Fig. 1A). Focal 0.2 Hz-rTMS to PMC
Fig. 2. Time courses of the t/c ratios of MEP or H-reflex amplitudes after 0.2 Hz-rTMS. A solid line indicates the mean t/c ratios for MEPs and a dotted line shows those for H-reflex. Vertical bars indicate S.E. After six blocks of rTMS: 6b; 10–20 min after rTMS: 10–20 m.
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significantly decreased t/c ratios compared with sham stimulation (paired Student’s t-test after six blocks: Pb0.01) (Fig. 1B). 0.2 Hz-rTMS did not significantly affect H-reflex, while MEP sizes were significantly decreased by rTMS compared with H-reflex (paired Student’s t-test: Pb0.05) (Fig. 2). There was no significant differences between rTMS with subthreshold and suprathreshold intensity, or between rTMS to the M1 and the PMC. 5. Discussion The present study showed that 0.2 Hz-rTMS with either coil reduced cortico-spinal neuron excitabilities for an extended period after rTMS. Previous studies showed that 1 Hz-rTMS to M1 reduced cortico-spinal neuron excitabilities during a short period after rTMS [1,3–5]. A recent study demonstrated that 1 Hz-rTMS to PMC with a stimulus intensity below active motor threshold decreased MEP amplitudes, while similar stimulation to M1 showed no effects on MEPs [2]. According to these findings, the authors postulated that rTMS to PMC extended inhibitory effects on cortico-spinal neurons through interneurons innervated from PMC to M1. Also, because those of Hreflex amplitudes did not significantly change after 0.2 Hz-rTMS, we suggest that the inhibitory effects of 0.2 Hz-rTMS are attributable to the cortical mechanism. 6. Conclusion 0.2 Hz-rTMS reduced cortico-spinal neuron excitabilities in the same manner as 1 HzrTMS. There are no significant differences between the effects of 0.2 Hz-rTMS using a round coil and a figure-of-eight coil on MEPs. Since 0.2 Hz-rTMS did not significantly affect H-reflex, the effects of 0.2 Hz-rTMS are predominantly ascribed to changes of cortical neuron activities. We need further studies to elucidate the effects of changing stimulus intensity and stimulus position on cortical neuron activities. References [1] R. Chen, et al., Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation, Neurology 48 (1997) 1398 – 1403. [2] W. Gerschlager, H.R. Siebner, J.C. Rothwell, Decreased cortico-spinal excitability after subthreshold 1 Hz rTMS over F, Rizzo V, Siebner HR, Rothwell JC. Effects on the right motor hand-area excitability produced by low-frequency rTMS o lateral premotor cortex, Neurology 57 (2001) 449 – 455. [3] F. Maeda, et al., Modulation of cortico-spinal excitability by repetitive transcranial magnetic stimulation, Clin. Neurophysiol. 111 (2000) 800 – 805. [4] W. Muellbacher, et al., Effects of low-frequency transcranial magnetic stimulation on motor exicitability and basic motor behavior, Clin. Neurophysiol. 111 (2000) 1002 – 1007. [5] T. Touge, et al., Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses? Clin. Neurophysiol. 112 (2001) 2138 – 2145.