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FC14.3 Paired low-frequency transcranial magnetic stimulation (TMS) delivered over homologous primary motor areas induces changes in cortical excitability
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Oral Communications / Clinical Neurophysiology 117 (2006) S49–S111
to the motor cortex for 30 min at a rate of 0.2 Hz. Before and after 30 min intervention, we measured MEPs to a single pulse TMS over the motor cortex. We also studied changes in the MEP size in responses to brainstem stimulation in some subjects. Results: During 30 min repetitive paired TMS, the MEP amplitude enlarged linearly (P < 0.05, repeated measures ANOVA). The MEPs to a single pulse TMS were significantly larger than the control for 5–10 min after the end of intervention (P < 0.05, repeated measures ANOVA). The amplitude of MEPs to brainstem stimulation was not affected by the same paired-pulse TMS. Discussion: After repetitive paired TMS, MEPs to TMS were facilitated similar to the previous report. In contrast, there were no aftereffects on MEPs to brainstem stimulation. These results support the conclusion that repetitive paired TMS at an ISI of 1.5 ms induces a long lasting motor cortical facilitation. doi:10.1016/j.clinph.2006.06.046
FC14.2 Interhemispheric inhibition plays a role in suppressing mirror movements A. Hu¨bers, U. Ziemann Clinic of Neurology, J.W. Goethe-University, Motorcortex Laboratory, Germany Background: Interhemispheric inhibition (IHI) might be important for suppression of mirror movements (MM) during intended unimanual movements. Here, we tested this by applying focal repetitive transcranial magnetic stimulation (rTMS) to one primary motor cortex (M1) to alter IHI and evaluated the consequences on MM. Methods: RTMS (1 Hz, 15 min, 120% resting motor threshold) was delivered in two sessions (A and B) to the hand area of the left M1 (M1stim) of 10 right-handed healthy subjects. Post- and pre-rTMS, MM and IHI were measured according to established protocols (Mayston et al. Ann Neurol 1999;45:583–94; Ferbert et al. J Physiol (Lond) 1992;453:525–46). In session A, MM were assessed in the isometrically contracting left first dorsal interosseus while the right hand (task hand) performed brisk index finger abductions. Accordingly, IHI was measured from M1stim (task M1) to M1non-stim (mirror M1). In session B, task and mirror hand reversed and IHI was measured from M1non-stim to M1stim. RTMS-induced changes (ratios post/pre rTMS) in IHI and MM were related by linear regression analysis. Results: In session A, IHI increased and MM decreased, and there was a significant negative correlation between these changes (r = 0.79, p < 0.01). In session B, IHI and MM decreased, and there was a positive linear correlation between these changes (r = 0.78, p < 0.01). Conclusions: The negative correlation between rTMSinduced changes in IHI and MM in session A strongly
supports the view that IHI acts to suppress MM. The positive correlation between changes in IHI and MM in session B suggests that additional mechanisms contribute to MM. Most likely, unimanual movements are prepared by a bilateral motor command from a premotor area to both M1. RTMS reduces the responsiveness of M1stim to this command and to inhibitory inputs from M1non-stim. This explains the observed decreases in IHI and MM. In summary, data support that interhemispheric inhibition contributes to suppression of mirror activity originating from a bilateral motor command. doi:10.1016/j.clinph.2006.06.047
FC14.3 Paired low-frequency transcranial magnetic stimulation (TMS) delivered over homologous primary motor areas induces changes in cortical excitability V. Rizzo 1, S. Bagnato 1, A. Sant’Angelo 1, F. Morgante 1, C. Mastroeni 1, H.R. Siebner 2, P. Girlanda 1, A. Quartarone 1 1 2
Policlinico Universitario, Neuroscience, Italy Christian-Albrechts-University, Neuroscience, Germany
Background: Plasticity in the human motor cortex can be induced using different intervention paradigms shaped on basis of models of associative long term potentiation (LTP) in experimental animals. A well established paradigm combines low-frequency median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral motor cortex (Stefan et al., 2000, 2002). Objective: In the present study, we used a paired low-frequency TMS delivered over homologous primary motor areas to induce enduring changes in corticospinal excitability. Methods: Ten healthy subjects received 90 TMS paired stimuli at 0.05 Hz through a figure of eight coil over the left (conditioning) and right (test) motor hand area. We used the technique of transcallosal inhibition between the motor cortices to define the optimal interstimulus interval between the two stimuli. The intensity of TMS was above the threshold for inducing short latency interhemispherical inhibition with a single stimulus (equivalent to 115–120% resting motor threshold). Before and after the TMS, we evaluated: (1) MEP, CSP, and short-interval intracortical inhibition and intracortical facilitation (SICI/ICF) by stimulating the right hemisphere, and (2) interhemispherical inhibition (IHI) from the left-to-right hemisphere using a paired-pulse method. These parameters were tested at baseline, immediately, 30 min after and 60 min after the stimulation protocol. Results: After paired low-frequency TMS over both primary motor areas the amplitude of MEPs by stimulating the right hemisphere increased and the IHI from the leftto-right hemisphere was reduced for at least 1 h.
Oral Communications / Clinical Neurophysiology 117 (2006) S49–S111
Conclusions: Our data demonstrate that low-frequency associative stimulation over both primary motor areas for 30 min provides a reliable protocol for inducing a sustained increase in excitability in the human corticospinal motor system. doi:10.1016/j.clinph.2006.06.048
FC14.4 Short-latency intracortical inhibition preceding movement: Different time-course of modulation during simple and choice reaction time O. Soto 1, H. Kumru 2, J. Valls-Sole 2 1 2
Clinica Teknon, Spain Hospital Clinic, Neurology, Spain
Background: Motor preparation is associated with excitability changes along the corticospinal tract. In simple reaction time task (SRT), the motor-evoked potentials (MEP) to transcranial magnetic stimulation (TMS) are facilitated before onset of EMG activity (EMGonset), and the short-latency intracortical inhibition (SICI) is reduced preceding the facilitatory changes. We examined the timing of those neural processes in choice reaction time task (CRT). Aim: To identify potential differences in SICI during SRT and CRT paradigms. Patients/Methods: Five subjects were requested to perform a hand pinch in response to a visual stimulus in the context of SRT/CRT paradigms. MEPs were recorded from the first dorsal interosseous. TMS was applied over the contralateral hand area at an intensity of 0.95 active motor threshold for conditioning stimuli and 1.2 resting motor threshold for test stimuli. We obtained sets of responses combining single and paired (interstimulus interval 2.5 ms) stimuli with control and movement trials. Test stimuli were applied at 100, 75, 50 and 25 ms with respect to EMGonset. We used ANOVA to determine the differences between control and test trials. Results: During SRT, significant reduction of SICI with respect to baseline values occurred at 50 ms before EMGonset, while MEP facilitation started 25 ms later. Reduction of SICI occurred significantly later during CRT than during SRT (p < 0.05), while the timing of MEP facilitation was not different between the two conditions (p > 0.05). Discussion: The time course of intracortical excitability changes before EMGonset is different in SRT and CRT. In SRT, with direct stimulus/response mapping, SICI reduction precedes MEP facilitation. In CRT, characterized by uncertain stimulus/response mapping, reduction of SICI and MEP facilitation occur in parallel. Conclusion: The timing of premovement modulation of SICI with respect to MEP facilitation before EMGonset depends on the behavioral context.
FC15.1 Reduced blink reflex habituation in patients with early-staged amyotrophic lateral sclerosis J. Gutierrez 1, Z. Lestayo 2, R. Mustelier 2, C. Machado 1 1
Institute of Neurology and Neurosurgery, Department of Clinical Neurophysiology, Cuba 2 Institute of Neurology and Neurosurgery, Department of Neurology, Cuba Background: The assessment of blink reflex habituation (BRH) is a sensitive method to evaluate the influence of suprasegmental structures on brainstem interneurons. BRH could be used as a marker of upper motor neuron (UMN) dysfunction. Previous studies of BRH in patients with amyotrophic lateral sclerosis (ALS) are scarce and contradictory. Objectives: The aim of the present study was to assess the BRH by using paired electrical stimuli in patients with early stages of ALS. Methods: We studied 21 patients with definitive diagnosis of ALS (12: bulbar onset; 9: limb onset), with less than 1 year from symptoms onset and 18-age-matched healthy controls. A typical evoked potential study of the BR was employed. The effects of paired stimulation on R1 and R2 components, with interstimulus intervals (ISI) of 100, 250, 500 and 1000 ms were compared in both groups. BRH was defined as the percentage of change of the amplitude of the test response compared to the conditioning response. {(+) increased; ( ) decreased}. Results: R1 and R2 latencies and R1 amplitude elicited by single stimulation were similar in patients and controls, however the patients showed significantly reduced R2 amplitudes compared to healthy subjects {280 uv (140) vs. 400 uv (81)}. Using an ISI of 250 ms, the amplitude of test R1 was significantly more facilitated in the patients {+35.5% (15.4)} than in the controls {+10.2% (5.2)}, p < 0.05. Conversely, the amplitude of test R2 was significantly less reduced in ALS patients { 15.5% (14.8)} than in healthy volunteers { 71% (24.2)}, p < 0.01. Conclusions: These findings demonstrate that patients with early-staged ALS, have a reduced R2 habituation of the electrically induced blink reflex. These changes could be related to hyperfunction of suprasegmental facilitatory influences on brainstem interneurons. The evaluation of BRH could provide evidence of subclinical UMN involvement, which might help to establish an earlier ALS diagnosis. doi:10.1016/j.clinph.2006.06.050
FC15.2 Reflex and voluntary components of the reaction to pull-test I. Alonso 1, J. Costa 2, J. Casanova 3, J. Valls-Sole 3 1
doi:10.1016/j.clinph.2006.06.049
S67
2 3
Marque´s de Valdecilla, Neurophysiology, Spain Santa Maria University Hospital, Neurology, Portugal Hospital Clinic, Neurology, Spain
Oral Communications / Clinical Neurophysiology 117 (2006) S49–S111
to the motor cortex for 30 min at a rate of 0.2 Hz. Before and after 30 min intervention, we measured MEPs to a single pulse TMS over the motor cortex. We also studied changes in the MEP size in responses to brainstem stimulation in some subjects. Results: During 30 min repetitive paired TMS, the MEP amplitude enlarged linearly (P < 0.05, repeated measures ANOVA). The MEPs to a single pulse TMS were significantly larger than the control for 5–10 min after the end of intervention (P < 0.05, repeated measures ANOVA). The amplitude of MEPs to brainstem stimulation was not affected by the same paired-pulse TMS. Discussion: After repetitive paired TMS, MEPs to TMS were facilitated similar to the previous report. In contrast, there were no aftereffects on MEPs to brainstem stimulation. These results support the conclusion that repetitive paired TMS at an ISI of 1.5 ms induces a long lasting motor cortical facilitation. doi:10.1016/j.clinph.2006.06.046
FC14.2 Interhemispheric inhibition plays a role in suppressing mirror movements A. Hu¨bers, U. Ziemann Clinic of Neurology, J.W. Goethe-University, Motorcortex Laboratory, Germany Background: Interhemispheric inhibition (IHI) might be important for suppression of mirror movements (MM) during intended unimanual movements. Here, we tested this by applying focal repetitive transcranial magnetic stimulation (rTMS) to one primary motor cortex (M1) to alter IHI and evaluated the consequences on MM. Methods: RTMS (1 Hz, 15 min, 120% resting motor threshold) was delivered in two sessions (A and B) to the hand area of the left M1 (M1stim) of 10 right-handed healthy subjects. Post- and pre-rTMS, MM and IHI were measured according to established protocols (Mayston et al. Ann Neurol 1999;45:583–94; Ferbert et al. J Physiol (Lond) 1992;453:525–46). In session A, MM were assessed in the isometrically contracting left first dorsal interosseus while the right hand (task hand) performed brisk index finger abductions. Accordingly, IHI was measured from M1stim (task M1) to M1non-stim (mirror M1). In session B, task and mirror hand reversed and IHI was measured from M1non-stim to M1stim. RTMS-induced changes (ratios post/pre rTMS) in IHI and MM were related by linear regression analysis. Results: In session A, IHI increased and MM decreased, and there was a significant negative correlation between these changes (r = 0.79, p < 0.01). In session B, IHI and MM decreased, and there was a positive linear correlation between these changes (r = 0.78, p < 0.01). Conclusions: The negative correlation between rTMSinduced changes in IHI and MM in session A strongly
supports the view that IHI acts to suppress MM. The positive correlation between changes in IHI and MM in session B suggests that additional mechanisms contribute to MM. Most likely, unimanual movements are prepared by a bilateral motor command from a premotor area to both M1. RTMS reduces the responsiveness of M1stim to this command and to inhibitory inputs from M1non-stim. This explains the observed decreases in IHI and MM. In summary, data support that interhemispheric inhibition contributes to suppression of mirror activity originating from a bilateral motor command. doi:10.1016/j.clinph.2006.06.047
FC14.3 Paired low-frequency transcranial magnetic stimulation (TMS) delivered over homologous primary motor areas induces changes in cortical excitability V. Rizzo 1, S. Bagnato 1, A. Sant’Angelo 1, F. Morgante 1, C. Mastroeni 1, H.R. Siebner 2, P. Girlanda 1, A. Quartarone 1 1 2
Policlinico Universitario, Neuroscience, Italy Christian-Albrechts-University, Neuroscience, Germany
Background: Plasticity in the human motor cortex can be induced using different intervention paradigms shaped on basis of models of associative long term potentiation (LTP) in experimental animals. A well established paradigm combines low-frequency median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral motor cortex (Stefan et al., 2000, 2002). Objective: In the present study, we used a paired low-frequency TMS delivered over homologous primary motor areas to induce enduring changes in corticospinal excitability. Methods: Ten healthy subjects received 90 TMS paired stimuli at 0.05 Hz through a figure of eight coil over the left (conditioning) and right (test) motor hand area. We used the technique of transcallosal inhibition between the motor cortices to define the optimal interstimulus interval between the two stimuli. The intensity of TMS was above the threshold for inducing short latency interhemispherical inhibition with a single stimulus (equivalent to 115–120% resting motor threshold). Before and after the TMS, we evaluated: (1) MEP, CSP, and short-interval intracortical inhibition and intracortical facilitation (SICI/ICF) by stimulating the right hemisphere, and (2) interhemispherical inhibition (IHI) from the left-to-right hemisphere using a paired-pulse method. These parameters were tested at baseline, immediately, 30 min after and 60 min after the stimulation protocol. Results: After paired low-frequency TMS over both primary motor areas the amplitude of MEPs by stimulating the right hemisphere increased and the IHI from the leftto-right hemisphere was reduced for at least 1 h.
Oral Communications / Clinical Neurophysiology 117 (2006) S49–S111
Conclusions: Our data demonstrate that low-frequency associative stimulation over both primary motor areas for 30 min provides a reliable protocol for inducing a sustained increase in excitability in the human corticospinal motor system. doi:10.1016/j.clinph.2006.06.048
FC14.4 Short-latency intracortical inhibition preceding movement: Different time-course of modulation during simple and choice reaction time O. Soto 1, H. Kumru 2, J. Valls-Sole 2 1 2
Clinica Teknon, Spain Hospital Clinic, Neurology, Spain
Background: Motor preparation is associated with excitability changes along the corticospinal tract. In simple reaction time task (SRT), the motor-evoked potentials (MEP) to transcranial magnetic stimulation (TMS) are facilitated before onset of EMG activity (EMGonset), and the short-latency intracortical inhibition (SICI) is reduced preceding the facilitatory changes. We examined the timing of those neural processes in choice reaction time task (CRT). Aim: To identify potential differences in SICI during SRT and CRT paradigms. Patients/Methods: Five subjects were requested to perform a hand pinch in response to a visual stimulus in the context of SRT/CRT paradigms. MEPs were recorded from the first dorsal interosseous. TMS was applied over the contralateral hand area at an intensity of 0.95 active motor threshold for conditioning stimuli and 1.2 resting motor threshold for test stimuli. We obtained sets of responses combining single and paired (interstimulus interval 2.5 ms) stimuli with control and movement trials. Test stimuli were applied at 100, 75, 50 and 25 ms with respect to EMGonset. We used ANOVA to determine the differences between control and test trials. Results: During SRT, significant reduction of SICI with respect to baseline values occurred at 50 ms before EMGonset, while MEP facilitation started 25 ms later. Reduction of SICI occurred significantly later during CRT than during SRT (p < 0.05), while the timing of MEP facilitation was not different between the two conditions (p > 0.05). Discussion: The time course of intracortical excitability changes before EMGonset is different in SRT and CRT. In SRT, with direct stimulus/response mapping, SICI reduction precedes MEP facilitation. In CRT, characterized by uncertain stimulus/response mapping, reduction of SICI and MEP facilitation occur in parallel. Conclusion: The timing of premovement modulation of SICI with respect to MEP facilitation before EMGonset depends on the behavioral context.
FC15.1 Reduced blink reflex habituation in patients with early-staged amyotrophic lateral sclerosis J. Gutierrez 1, Z. Lestayo 2, R. Mustelier 2, C. Machado 1 1
Institute of Neurology and Neurosurgery, Department of Clinical Neurophysiology, Cuba 2 Institute of Neurology and Neurosurgery, Department of Neurology, Cuba Background: The assessment of blink reflex habituation (BRH) is a sensitive method to evaluate the influence of suprasegmental structures on brainstem interneurons. BRH could be used as a marker of upper motor neuron (UMN) dysfunction. Previous studies of BRH in patients with amyotrophic lateral sclerosis (ALS) are scarce and contradictory. Objectives: The aim of the present study was to assess the BRH by using paired electrical stimuli in patients with early stages of ALS. Methods: We studied 21 patients with definitive diagnosis of ALS (12: bulbar onset; 9: limb onset), with less than 1 year from symptoms onset and 18-age-matched healthy controls. A typical evoked potential study of the BR was employed. The effects of paired stimulation on R1 and R2 components, with interstimulus intervals (ISI) of 100, 250, 500 and 1000 ms were compared in both groups. BRH was defined as the percentage of change of the amplitude of the test response compared to the conditioning response. {(+) increased; ( ) decreased}. Results: R1 and R2 latencies and R1 amplitude elicited by single stimulation were similar in patients and controls, however the patients showed significantly reduced R2 amplitudes compared to healthy subjects {280 uv (140) vs. 400 uv (81)}. Using an ISI of 250 ms, the amplitude of test R1 was significantly more facilitated in the patients {+35.5% (15.4)} than in the controls {+10.2% (5.2)}, p < 0.05. Conversely, the amplitude of test R2 was significantly less reduced in ALS patients { 15.5% (14.8)} than in healthy volunteers { 71% (24.2)}, p < 0.01. Conclusions: These findings demonstrate that patients with early-staged ALS, have a reduced R2 habituation of the electrically induced blink reflex. These changes could be related to hyperfunction of suprasegmental facilitatory influences on brainstem interneurons. The evaluation of BRH could provide evidence of subclinical UMN involvement, which might help to establish an earlier ALS diagnosis. doi:10.1016/j.clinph.2006.06.050
FC15.2 Reflex and voluntary components of the reaction to pull-test I. Alonso 1, J. Costa 2, J. Casanova 3, J. Valls-Sole 3 1
doi:10.1016/j.clinph.2006.06.049
S67
2 3
Marque´s de Valdecilla, Neurophysiology, Spain Santa Maria University Hospital, Neurology, Portugal Hospital Clinic, Neurology, Spain