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P82. Motor network connectivity predicts responsiveness to theta-burst stimulation
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Society Proceedings / Clinical Neurophysiology 126 (2015) e63–e170
Mayberg HS. J Neuropsychiatr Clin Neurosci ;9(3):471–81. Wolkenstein L, Plewnia C. Biol Psychiatr ;73(7):646–51. doi:10.1016/j.clinph.2015.04.214
Huang YZ et al. Theta burst stimulation of the human motor cortex. Neuron 2005;45(2):201–6. Ridding MC, Ziemann U. Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 2010;588(13):2291–304. doi:10.1016/j.clinph.2015.04.215
P82. Motor network connectivity predicts responsiveness to theta-burst stimulation—C. Nettekoven a,b, L.J. Volz a,b, M. Kutscha b, E.-M. Pool a,b, S.B. Eickhoff a,c, G.R. Fink a,b, C. Grefkes a,b (a Institute of Neurosciences and Medicine, Jülich, Germany, b Cologne University Hospital, Department of Neurology, Cologne, Germany, c Institute of Clinical Neuroscience and Medical Psychology, Düsseldorf, Germany) Introduction: Intermittent theta-burst stimulation (iTBS) effectively increases cortical excitability within the human brain (Huang et al., 2005). However, individual after-effects of iTBS vary between subjects, with a large proportion not responding at all in terms of changes in excitability (Ridding and Ziemann, 2010; Hamada et al., 2013). We here investigated whether subjects responding to iTBS show differential changes in resting-state functional connectivity (rsFC) within the cortical motor system compared to subjects with no response and whether the application of multiple iTBS-blocks can alter responsiveness. Methods: We used a sham-stimulation controlled, single-blinded within-subject design to test for iTBS after-effects on (i) motor evoked potentials (MEPs) and (ii) resting-state functional connectivity (rsFC) in 16 healthy, right-handed subjects (m = 7, 27 ± 3 years). iTBS was applied over the left primary motor cortex (M1-iTBS) and over the parieto-occipital vertex (sham-iTBS) in separate sessions. In each stimulation session three iTBS blocks were applied, separated by 15 min. Seed-based whole-brain rsFC was computed for the stimulated M1. Results: Subjects were divided into groups of responders (n = 7) and non-responders (n = 9) according to iTBS-induced changes in MEPs (criterion: increase of at least 10% compared to baseline; Hinder et al., 2014). Increases in MEP-amplitudes following all three M1-iTBS blocks compared to sham-iTBS could exclusively be found for responders. Likewise, rsFC between M1 and premotor areas was significantly higher in responders after all three iTBS blocks (p 6 0.05, cluster-level FWE-corrected), whereas no significant increases could be found for the non-responder group. Dose-dependent increases in MEP-amplitudes and rsFC could also only be found for responders. Importantly, non-responders featured higher levels of pre-interventional rsFC compared to responders (p 6 0.01, cluster-level FWE-corrected). Individual changes in MEPs and rsFC did not correlate. Discussion: Significant iTBS-induced modulations of rsFC and MEP-amplitudes were exclusively found for the responder group, suggesting that responsiveness to iTBS is paralleled by differential changes in motor network connectivity. However, there was no linear correlation between changes in MEP-amplitudes and rsFC. Additional iTBS blocks did not cause a conversion from non-responders to responders, but rather enhanced cortical excitability and rsFC in responders. Furthermore, lower levels of pre-interventional rsFC might contribute to better effectiveness of iTBS. References Hamada M et al. The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 2013;23(7):1593–605. Hinder MR et al. Inter- and intra-individual variability following intermittent theta burst stimulation: implications for rehabilitation and recovery. Brain Stimul 2014;7(3):365–71.
P145. Transcranial biphasic quadro-pulse stimulation with one but not two full-sine cycles induces long-term depression-like corticomotor plasticity—N.H. Jung a, B. Gleich b, A. Kalb a, K. Limburg a, N. Gattinger b, J. Fritsch a, H.R. Siebner c, V. Mall a (a Technische Universität München, Department of Pediatrics, München, Germany, b Zentral Institut für Medizintechnik at Technische Universität München, München, Germany, c Copenhagen University Hospital Hvidovre, Danish Research Centre for Magnetic Resonance (DRCMR), Hvidovre, Denmark) Question: Neuronal plasticity in form of long-term potentiation (LTP) and long-term depression (LTD) is considered to be the neurophysiological mechanism of learning and memory. There is growing evidence that the induction of LTD-like effects plays a crucial role in mediating therapeutic effects of transcranial magnetic stimulation (TMS). We previously demonstrated that biphasic transcranial quadro-pulse stimulation (QPS) consisting of two-full sine cycles is slightly more effective than with one full-sine cycle in induction of LTP-like effects in human primary motor cortex. Here, we aimed to study the effectiveness of QPS with one and two full-sine cycles in induction of LTD-like effects of synaptic plasticity. Methods: We investigated healthy volunteers (n = 7 per protocol) with quadro-pulse stimulation consisting of one (QPS-1) and two (QPS-2) full-sine cycles (duration: 160 ls, respectively) separated by an inter-stimulus interval of 50 ms and an inter-burst interval of 200 ms with a total amount of 1440 pulses. Resting motor threshold (rMT), and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1 mV (SI1mV) were measured before (Pre) intervention, directly after (Post1), after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4). Results: We found a significant decrease of MEP amplitudes after QPS-1 but not after QPS-2 at all time points lasting for 1 h (Post 1– 4). No significant changes in rMT were observed. Conclusion: QPS with one full-sine-cycle induces LTD-like changes in human primary motor cortex at interstimulus intervals of 50 ms. Using two-full sine cycles – previously demonstrating to be more effective in induction of LTP-like plasticity at interstimulus intervals of 5 ms – did not lead to changes in corticomotor excitability. These divergence in the capability to induce corticomotor plasticity suggests different underlying neurophysiological mechanisms. The results may be of interest when applying QPS or other patterned stimulation protocols therapeutically. doi:10.1016/j.clinph.2015.04.216
P146. Comparison of alpha-entrainment with oscillatory and noisy low-voltage stimulation—A. Jooß a, L. Haberbosch a, M. Scholz b, S. Brandt a, S. Schmidt a (a Charité – Universitätsmedizin Berlin, Vision & Motor Research Group, Dept. Neurology, Berlin, Germany, b Technical University Berlin, Neural Information Processing Group, Berlin, Germany) Introduction: Non-invasive brain stimulation is an emerging field in clinical neurology. Frequency- and noise specific stimulation can induce specific oscillatory activity patterns that are associated with
Society Proceedings / Clinical Neurophysiology 126 (2015) e63–e170
Mayberg HS. J Neuropsychiatr Clin Neurosci ;9(3):471–81. Wolkenstein L, Plewnia C. Biol Psychiatr ;73(7):646–51. doi:10.1016/j.clinph.2015.04.214
Huang YZ et al. Theta burst stimulation of the human motor cortex. Neuron 2005;45(2):201–6. Ridding MC, Ziemann U. Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 2010;588(13):2291–304. doi:10.1016/j.clinph.2015.04.215
P82. Motor network connectivity predicts responsiveness to theta-burst stimulation—C. Nettekoven a,b, L.J. Volz a,b, M. Kutscha b, E.-M. Pool a,b, S.B. Eickhoff a,c, G.R. Fink a,b, C. Grefkes a,b (a Institute of Neurosciences and Medicine, Jülich, Germany, b Cologne University Hospital, Department of Neurology, Cologne, Germany, c Institute of Clinical Neuroscience and Medical Psychology, Düsseldorf, Germany) Introduction: Intermittent theta-burst stimulation (iTBS) effectively increases cortical excitability within the human brain (Huang et al., 2005). However, individual after-effects of iTBS vary between subjects, with a large proportion not responding at all in terms of changes in excitability (Ridding and Ziemann, 2010; Hamada et al., 2013). We here investigated whether subjects responding to iTBS show differential changes in resting-state functional connectivity (rsFC) within the cortical motor system compared to subjects with no response and whether the application of multiple iTBS-blocks can alter responsiveness. Methods: We used a sham-stimulation controlled, single-blinded within-subject design to test for iTBS after-effects on (i) motor evoked potentials (MEPs) and (ii) resting-state functional connectivity (rsFC) in 16 healthy, right-handed subjects (m = 7, 27 ± 3 years). iTBS was applied over the left primary motor cortex (M1-iTBS) and over the parieto-occipital vertex (sham-iTBS) in separate sessions. In each stimulation session three iTBS blocks were applied, separated by 15 min. Seed-based whole-brain rsFC was computed for the stimulated M1. Results: Subjects were divided into groups of responders (n = 7) and non-responders (n = 9) according to iTBS-induced changes in MEPs (criterion: increase of at least 10% compared to baseline; Hinder et al., 2014). Increases in MEP-amplitudes following all three M1-iTBS blocks compared to sham-iTBS could exclusively be found for responders. Likewise, rsFC between M1 and premotor areas was significantly higher in responders after all three iTBS blocks (p 6 0.05, cluster-level FWE-corrected), whereas no significant increases could be found for the non-responder group. Dose-dependent increases in MEP-amplitudes and rsFC could also only be found for responders. Importantly, non-responders featured higher levels of pre-interventional rsFC compared to responders (p 6 0.01, cluster-level FWE-corrected). Individual changes in MEPs and rsFC did not correlate. Discussion: Significant iTBS-induced modulations of rsFC and MEP-amplitudes were exclusively found for the responder group, suggesting that responsiveness to iTBS is paralleled by differential changes in motor network connectivity. However, there was no linear correlation between changes in MEP-amplitudes and rsFC. Additional iTBS blocks did not cause a conversion from non-responders to responders, but rather enhanced cortical excitability and rsFC in responders. Furthermore, lower levels of pre-interventional rsFC might contribute to better effectiveness of iTBS. References Hamada M et al. The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 2013;23(7):1593–605. Hinder MR et al. Inter- and intra-individual variability following intermittent theta burst stimulation: implications for rehabilitation and recovery. Brain Stimul 2014;7(3):365–71.
P145. Transcranial biphasic quadro-pulse stimulation with one but not two full-sine cycles induces long-term depression-like corticomotor plasticity—N.H. Jung a, B. Gleich b, A. Kalb a, K. Limburg a, N. Gattinger b, J. Fritsch a, H.R. Siebner c, V. Mall a (a Technische Universität München, Department of Pediatrics, München, Germany, b Zentral Institut für Medizintechnik at Technische Universität München, München, Germany, c Copenhagen University Hospital Hvidovre, Danish Research Centre for Magnetic Resonance (DRCMR), Hvidovre, Denmark) Question: Neuronal plasticity in form of long-term potentiation (LTP) and long-term depression (LTD) is considered to be the neurophysiological mechanism of learning and memory. There is growing evidence that the induction of LTD-like effects plays a crucial role in mediating therapeutic effects of transcranial magnetic stimulation (TMS). We previously demonstrated that biphasic transcranial quadro-pulse stimulation (QPS) consisting of two-full sine cycles is slightly more effective than with one full-sine cycle in induction of LTP-like effects in human primary motor cortex. Here, we aimed to study the effectiveness of QPS with one and two full-sine cycles in induction of LTD-like effects of synaptic plasticity. Methods: We investigated healthy volunteers (n = 7 per protocol) with quadro-pulse stimulation consisting of one (QPS-1) and two (QPS-2) full-sine cycles (duration: 160 ls, respectively) separated by an inter-stimulus interval of 50 ms and an inter-burst interval of 200 ms with a total amount of 1440 pulses. Resting motor threshold (rMT), and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1 mV (SI1mV) were measured before (Pre) intervention, directly after (Post1), after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4). Results: We found a significant decrease of MEP amplitudes after QPS-1 but not after QPS-2 at all time points lasting for 1 h (Post 1– 4). No significant changes in rMT were observed. Conclusion: QPS with one full-sine-cycle induces LTD-like changes in human primary motor cortex at interstimulus intervals of 50 ms. Using two-full sine cycles – previously demonstrating to be more effective in induction of LTP-like plasticity at interstimulus intervals of 5 ms – did not lead to changes in corticomotor excitability. These divergence in the capability to induce corticomotor plasticity suggests different underlying neurophysiological mechanisms. The results may be of interest when applying QPS or other patterned stimulation protocols therapeutically. doi:10.1016/j.clinph.2015.04.216
P146. Comparison of alpha-entrainment with oscillatory and noisy low-voltage stimulation—A. Jooß a, L. Haberbosch a, M. Scholz b, S. Brandt a, S. Schmidt a (a Charité – Universitätsmedizin Berlin, Vision & Motor Research Group, Dept. Neurology, Berlin, Germany, b Technical University Berlin, Neural Information Processing Group, Berlin, Germany) Introduction: Non-invasive brain stimulation is an emerging field in clinical neurology. Frequency- and noise specific stimulation can induce specific oscillatory activity patterns that are associated with