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P 83. Effects of quadripulse stimulation over medial frontal cortex on human visuomotor sequence learning
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
Objectives: The aim of our study was to investigate the effect of a triple TBS session on the cortical excitability compared to a controlstimulation. By combining TBS with functional magnetic resonance imaging (fMRI) measurements we sought to reveal stimulation effects on cortical connectivity. Methods: 15 healthy subjects received three stimulations according to the iTBS-protocol (600 pulses per stimulation, (Huang et al., 2005)). iTBS sessions were applied in a serial fashion spaced by intervals of 15 min. Two different stimulation sites were tested at different days: primary motor cortex (M1) and the parieto-occipital cortex (control). Stimulation after-effects on cortical excitability were tested via stimulus–response curves. In separate stimulation sessions, the iTBS effects on fMRI-connectivity were tested for two conditions: (i) resting-state measurements and (ii) during thumb movements. The following motor areas were included in the network analysis: M1, supplementary motor area (SMA), dorsal and ventral premotor cortex (dPMC, vPMC), anterior intraparietal cortex, putamen, thalamus and cerebellum. Results: We found a dose-dependent effect of iTBS on the height of the stimulus–response-curve with significantly higher MEPs after applying iTBS over M1 compared to the control-stimulation. The connectivity-analyses revealed that after M1 stimulation with 1800 pulses the effective connectivity of the ipsilateral dPMC to the stimulated M1 was significantly enhanced while the control-stimulation had no differential effect on cortical connectivity (p < 0.05). Conclusions: Our results suggest that the after-effects of iTBS are dose-dependent. Furthermore, our data show that iTBS of M1 leads to a higher integration of the stimulated area with premotor areas. References Huang YZ et al. Theta burst stimulation of the human motor cortex. Neuron 2005;45:201–6. Hamda M et al. The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 2012. doi:10.1093/cercor/bhs147. Thickbroom GW. Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models. Exp Brain Res 2007;180:583–93. Volz LJ et al. “Dose-dependence” of changes in cortical protein expression determined for intermittent and continuous theta-burst TMS in the rat. FENS Abstr 2010;5:192. Gamboa OL et al. Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation. Exp Brain Res 2010;204:181–7. Gamboa OL et al. Impact of interneuron networks in driving human motor cortical plasticity. Brain Stimul 2011;4:145–51. doi:10.1016/j.clinph.2013.04.160
P 83. Effects of quadripulse stimulation over medial frontal cortex on human visuomotor sequence learning—T. Shimizu a, R. Hanajima a, R. Tsutsumi a, Y. Shirota a, N. Tanaka a, Y. Terao a, Y. Ugawa b (a University of Tokyo, Department of Neurology, Tokyo, Japan, b Fukushima Medical University, Department of Neurology, Fukushima, Japan) Introduction: Motor learning is important to perform skillful movements automatically in daily life. The medial frontal cortices, cerebellum and basal ganglia are activated in the motor learning processes. Especially, the pre-supplementary motor area (pre-SMA) is considered to play important roles in learning new visuomotor sequence movements. A functional MRI study revealed that preSMA was activated during learning of a new sequence with button press tasks (Hikosaka et al., 1996). To learn new motor sequence, neural plastic change should occur in the pre-SMA. Non-invasive brain stimulation (NIBS) such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) can induce plasticity-like effects on human brain structures. The
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motor learning performances could be modulated by stimulation over some relevant area for this process. The medial frontal cortices have not been a main target of motor learning process studies. Objectives: To study whether plastic changes in the medial frontal cortices can modulate human visuomotor sequence learning using quadripulse stimulation (QPS), a new patterned rTMS technique. Materials and methods: Seven healthy volunteers participated. We applied QPS or sham stimulation over left pre-SMA for 30 min. QPS consisted of repeated trains of four monophasic TMS pulses separated by inter-stimulus intervals of 5 ms (QPS-5) or 50 ms (QPS50) with an inter-train interval of 5 s. QPS-5 was reported to induce LTP in stimulated cortex, and QPS-50 Ltd. After QPS, each subject performed the 2 10 task, which is similar to the visuomotor sequential task reported by Hikosaka et al. Participants asked to press 2 illuminated buttons from 16 buttons in the correct order which he must learn by trial-and-error. A total of 10 pairs were presented in a fixed order for completion. As a behavioural outcome, we counted the number of errors to complete 20 successful trials to assess the performance accuracy, and measured movement time (MT): the time from the first button release to the second button press, and the button press reaction time (BP-RT): the time from stimulus onset to the first button press to assess the performance speed. Results: The number of errors was larger in QPS-5 compared to sham stimulation, whereas it did not differ between QPS-50 and sham conditions. Neither MT nor BP-RT differed significantly among any stimulation conditions. Conclusion: QPS-5 over pre-SMA reduced the motor learning performances. Several possible mechanisms can explain this finding: QPS5 may induce LTP of inhibitory neurons, BCM curve may shift from the curve of M1 in pre-SMA, metaplasticity may occur after QPS, inverse BCM for pre-SMA or others. References Hikosaka O, Sakai K, Miyauchi S, Takino R, Sasaki Y, Pütz B. Activation of human presupplementary motor area in learning of sequential procedures: a functional MRI study. J Neurophysiol 1996;76(1):617–21. doi:10.1016/j.clinph.2013.04.161
P 84. High-frequency neuronavigated cerebellar repetitive Transcranial Magnetic stimulation (rTMS) increases human pharyngeal motor cortex excitability—D. Vasant, S. Mistry, V. Jayasekeran, E. Michou, S. Hamdy (University of Manchester, Gastrointestinal Centre, Manchester, United Kingdom) Introduction: Animal studies, human brain imaging and more recently Transcranial Magnetic Stimulation (TMS) suggest a role for the cerebellum in human swallowing. Moreover, paired-pulse cerebellar-cortical TMS delivered in rapid succession (50–200 ms intervals) facilitates pharyngeal motor cortex excitability (Jayasekeran et al., 2011). Objectives: The aim of this study was to determine if longer trains of rTMS can induce long-lasting changes in pharyngeal cortical excitability that may prove to be therapeutically useful for dysphagia after stroke. Materials and methods: In 17 healthy adults (6 female, age range 18–61 yrs), anatomical MR brain scans were acquired. Thereafter participants were intubated with an intraluminal catheter to record pharyngeal electromyography and underwent TMS cortical mapping with neuronavigation to co-localise pharyngeal motor representation bilaterally, hand motor cortex and the cerebellar site which evoked the largest pharyngeal motor response. Subjects were then randomised to receive one of 5 neuronavigated cerebellar rTMS interventions (Sham, 1 Hz, 5 Hz, 10 Hz and 20 Hz, at least 1 week apart) to the
Objectives: The aim of our study was to investigate the effect of a triple TBS session on the cortical excitability compared to a controlstimulation. By combining TBS with functional magnetic resonance imaging (fMRI) measurements we sought to reveal stimulation effects on cortical connectivity. Methods: 15 healthy subjects received three stimulations according to the iTBS-protocol (600 pulses per stimulation, (Huang et al., 2005)). iTBS sessions were applied in a serial fashion spaced by intervals of 15 min. Two different stimulation sites were tested at different days: primary motor cortex (M1) and the parieto-occipital cortex (control). Stimulation after-effects on cortical excitability were tested via stimulus–response curves. In separate stimulation sessions, the iTBS effects on fMRI-connectivity were tested for two conditions: (i) resting-state measurements and (ii) during thumb movements. The following motor areas were included in the network analysis: M1, supplementary motor area (SMA), dorsal and ventral premotor cortex (dPMC, vPMC), anterior intraparietal cortex, putamen, thalamus and cerebellum. Results: We found a dose-dependent effect of iTBS on the height of the stimulus–response-curve with significantly higher MEPs after applying iTBS over M1 compared to the control-stimulation. The connectivity-analyses revealed that after M1 stimulation with 1800 pulses the effective connectivity of the ipsilateral dPMC to the stimulated M1 was significantly enhanced while the control-stimulation had no differential effect on cortical connectivity (p < 0.05). Conclusions: Our results suggest that the after-effects of iTBS are dose-dependent. Furthermore, our data show that iTBS of M1 leads to a higher integration of the stimulated area with premotor areas. References Huang YZ et al. Theta burst stimulation of the human motor cortex. Neuron 2005;45:201–6. Hamda M et al. The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 2012. doi:10.1093/cercor/bhs147. Thickbroom GW. Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models. Exp Brain Res 2007;180:583–93. Volz LJ et al. “Dose-dependence” of changes in cortical protein expression determined for intermittent and continuous theta-burst TMS in the rat. FENS Abstr 2010;5:192. Gamboa OL et al. Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation. Exp Brain Res 2010;204:181–7. Gamboa OL et al. Impact of interneuron networks in driving human motor cortical plasticity. Brain Stimul 2011;4:145–51. doi:10.1016/j.clinph.2013.04.160
P 83. Effects of quadripulse stimulation over medial frontal cortex on human visuomotor sequence learning—T. Shimizu a, R. Hanajima a, R. Tsutsumi a, Y. Shirota a, N. Tanaka a, Y. Terao a, Y. Ugawa b (a University of Tokyo, Department of Neurology, Tokyo, Japan, b Fukushima Medical University, Department of Neurology, Fukushima, Japan) Introduction: Motor learning is important to perform skillful movements automatically in daily life. The medial frontal cortices, cerebellum and basal ganglia are activated in the motor learning processes. Especially, the pre-supplementary motor area (pre-SMA) is considered to play important roles in learning new visuomotor sequence movements. A functional MRI study revealed that preSMA was activated during learning of a new sequence with button press tasks (Hikosaka et al., 1996). To learn new motor sequence, neural plastic change should occur in the pre-SMA. Non-invasive brain stimulation (NIBS) such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) can induce plasticity-like effects on human brain structures. The
e105
motor learning performances could be modulated by stimulation over some relevant area for this process. The medial frontal cortices have not been a main target of motor learning process studies. Objectives: To study whether plastic changes in the medial frontal cortices can modulate human visuomotor sequence learning using quadripulse stimulation (QPS), a new patterned rTMS technique. Materials and methods: Seven healthy volunteers participated. We applied QPS or sham stimulation over left pre-SMA for 30 min. QPS consisted of repeated trains of four monophasic TMS pulses separated by inter-stimulus intervals of 5 ms (QPS-5) or 50 ms (QPS50) with an inter-train interval of 5 s. QPS-5 was reported to induce LTP in stimulated cortex, and QPS-50 Ltd. After QPS, each subject performed the 2 10 task, which is similar to the visuomotor sequential task reported by Hikosaka et al. Participants asked to press 2 illuminated buttons from 16 buttons in the correct order which he must learn by trial-and-error. A total of 10 pairs were presented in a fixed order for completion. As a behavioural outcome, we counted the number of errors to complete 20 successful trials to assess the performance accuracy, and measured movement time (MT): the time from the first button release to the second button press, and the button press reaction time (BP-RT): the time from stimulus onset to the first button press to assess the performance speed. Results: The number of errors was larger in QPS-5 compared to sham stimulation, whereas it did not differ between QPS-50 and sham conditions. Neither MT nor BP-RT differed significantly among any stimulation conditions. Conclusion: QPS-5 over pre-SMA reduced the motor learning performances. Several possible mechanisms can explain this finding: QPS5 may induce LTP of inhibitory neurons, BCM curve may shift from the curve of M1 in pre-SMA, metaplasticity may occur after QPS, inverse BCM for pre-SMA or others. References Hikosaka O, Sakai K, Miyauchi S, Takino R, Sasaki Y, Pütz B. Activation of human presupplementary motor area in learning of sequential procedures: a functional MRI study. J Neurophysiol 1996;76(1):617–21. doi:10.1016/j.clinph.2013.04.161
P 84. High-frequency neuronavigated cerebellar repetitive Transcranial Magnetic stimulation (rTMS) increases human pharyngeal motor cortex excitability—D. Vasant, S. Mistry, V. Jayasekeran, E. Michou, S. Hamdy (University of Manchester, Gastrointestinal Centre, Manchester, United Kingdom) Introduction: Animal studies, human brain imaging and more recently Transcranial Magnetic Stimulation (TMS) suggest a role for the cerebellum in human swallowing. Moreover, paired-pulse cerebellar-cortical TMS delivered in rapid succession (50–200 ms intervals) facilitates pharyngeal motor cortex excitability (Jayasekeran et al., 2011). Objectives: The aim of this study was to determine if longer trains of rTMS can induce long-lasting changes in pharyngeal cortical excitability that may prove to be therapeutically useful for dysphagia after stroke. Materials and methods: In 17 healthy adults (6 female, age range 18–61 yrs), anatomical MR brain scans were acquired. Thereafter participants were intubated with an intraluminal catheter to record pharyngeal electromyography and underwent TMS cortical mapping with neuronavigation to co-localise pharyngeal motor representation bilaterally, hand motor cortex and the cerebellar site which evoked the largest pharyngeal motor response. Subjects were then randomised to receive one of 5 neuronavigated cerebellar rTMS interventions (Sham, 1 Hz, 5 Hz, 10 Hz and 20 Hz, at least 1 week apart) to the