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IS 16. Variability of the response to brain stimulation plasticity protocols: A concealed problem
e44
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
influenced the after-effects than the total number of pulses. This may be explained by the processes involved in the LTP/LTD. Voluntary contraction effects on LTP/LTD induction: Voluntary contraction abolished some phase of lasting effects transiently, but later phase effects reappear again after some lag-time. This may explain that the LTP/LTD induction has several processes, and one process may trigger the next process non-linearly to the degree of its induction. NIRS studies: The on-line changes in NIRS are not compatible with bi-directionality of QPS. This is compatible with the idea that the degree of LTP/LTD induction has no linear correlation with the amount of stimulation, whereas NIRS results have a linear relation with it. LOPA and QPS: L-dopa intake enhanced bidirectional effects of QPS even though agonist had different effects. OPS octopus:
The duration of aftereffects by QPS may
be still too short to be applied as a clinical therapeutic tool. We hypothesized that increasing the number of pulses to eight (OctoPulse Stimulation: OPS) within one burst prolongs the duration of aftereffects. In ten healthy subjects the effects of higher and lower frequency OPS M1 on M1 excitability were compared with those of QPS. Motor evoked potentials were used as measure for cortical excitability. Both OPS and QPS induced sustained bidirectional excitability changes of M1 depending on the stimulation frequency as compared with sham stimulation. Moreover, the duration of aftereffects was longer after OPS compared to QPS. OPS and QPS induce powerful bidirectional plasticity of M1. No more pulses from Magstim company:
cuttlefish
scolopendra
doi:10.1016/j.clinph.2013.04.033
IS 15. Flashes of insight: Non-conventional NIBS reveals novel ways to stimulate the brain—A. Antal, L. Chaieb, G.G. Ambrus, W. Paulus (Georg-August University, Department of Clinical Neurophysiology, Göttingen, Germany) Introduction: Modulating, disrupting or otherwise interfering with the activity of the cerebral cortex by non-invasive, external stimulation methods not only offers the possibility of clinical intervention in neurological and psychiatric diseases, but provides us with a powerful research tool for understanding the workings of the intact human brain. In the past years new non-conventional, non-invasive brain stimulation (NIBS) techniques have been developed. Objective: Application of near-infrared light to the scalp has recently been introduced in order to treat neurological conditions such as stroke and the treatment of traumatic brain disorders (Hashmi et al., 2010). Another very simple method, the application of static magnetic fields (tSMS) through the scalp by using small cylindrical magnets, has been shown to induce robust effects on levels of cortical excitability in healthy subjects (Oliviero et al., 2011). Nevertheless, a deeper knowledge of the mechanisms of how these methods work on a neuronal level, is required. Results: In our laboratory we have demonstrated that applying near-infrared light at a wavelength of 810 nm for 10 min to the primary motor cortex (M1), results in cortical excitability changes, assessed by means of motor-evoked potentials (MEP). MEP amplitudes showed a 20–40% decrease compared to sham stimulation, for up to 1 h post-stimulation. Furthermore, it was observed that
the stimulation modified the long intracortical inhibition. Similarly, with the application of tSMS to the M1, an inhibition could be observed. On the functional level it has been demonstrated that both of these methods can modify implicit motor learning. Conclusion: These non-conventional NIBS techniques may thus be opening new research domains for influencing brain activity and to treat neurological and psychiatric disorders in a non-invasive way.
References Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR. Role of lowlevel laser therapy in neurorehabilitation. PMR 2010;2:S292–305. Oliviero A, Mordillo-Mateos L, Arias P, Panyavin I, Foffani G, Aguilar J. Transcranial static magnetic field stimulation of the human motor cortex. J Physiol 2011;589:4949–58. doi:10.1016/j.clinph.2013.04.034
IS 16. Variability of the response to brain stimulation plasticity protocols: A concealed problem—J. Rothwell (UCL Institute of Neurology, London, United Kingdom) The after effects that are produced by a variety of brain stimulation plasticity protocols such as repetitive TMS, TDCS and paired associative stimulation (PAS) are variable from individual to individual and from session to session in any one individual. The problem, at least in the motor cortex, where measurement is relatively easy, is the extent of the variation. In a series of studies on 50+ individuals we find that conventional theta burst stimulation (TBS) produces the “expected” after-effect in only 50% young volunteers; 2 mA anodal TDCS produces the “expected” facilitation in approx. 60% whereas with 2 mA cathodal TDCS, inhibition is seen in only 45%; conventional paired associative stimulation with an interstimulus interval of 25 ms gives facilitation in about two thirds of volunteers. A large number of factors can influence the response including prior activity, time of day, genetics etc. Some of these are controllable while the effects of others (e.g. genetics) is small. We have therefore tested whether other factors can predict response and give some insight into possible mechanisms of the effects. In a study on 22 people, we found that the 50% of the variation in the excitatory effect of PAS could be predicted from a person’s response to short interval intracortical inhibition (SICI). The more SICI, the better the PAS response. For anodal TDCS and TBS, good predictability was obtained by measuring the onset latency of MEPs evoked by anteriorposterior stimulation relative to D-wave activation. Many of the same protocols are currently being used in clinical trials. If the clinical effectiveness is related to the effect on motor cortex excitability then this poses a problem. If we include all eligible participants in a trial then the fact that up to 50% may not respond (or may even have the opposite response) will make it very difficult to determine whether the protocol is effective in the remainder. A solution is to test whether clinical effectiveness relates to after-effects on motor cortex excitability and then test for responsiveness prior to entering a trial, or to use one of the predictive factors to exclude individuals least likely to show a effect. doi:10.1016/j.clinph.2013.04.035
IS 17. Effects of focal static magnetic fields on the human cortex— A. Oliviero (Hospital Nacional de Paraplejicos, Toledo, Spain) The non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp was investigated in healthy humans. Static magnetic fields were obtained by
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
influenced the after-effects than the total number of pulses. This may be explained by the processes involved in the LTP/LTD. Voluntary contraction effects on LTP/LTD induction: Voluntary contraction abolished some phase of lasting effects transiently, but later phase effects reappear again after some lag-time. This may explain that the LTP/LTD induction has several processes, and one process may trigger the next process non-linearly to the degree of its induction. NIRS studies: The on-line changes in NIRS are not compatible with bi-directionality of QPS. This is compatible with the idea that the degree of LTP/LTD induction has no linear correlation with the amount of stimulation, whereas NIRS results have a linear relation with it. LOPA and QPS: L-dopa intake enhanced bidirectional effects of QPS even though agonist had different effects. OPS octopus:
The duration of aftereffects by QPS may
be still too short to be applied as a clinical therapeutic tool. We hypothesized that increasing the number of pulses to eight (OctoPulse Stimulation: OPS) within one burst prolongs the duration of aftereffects. In ten healthy subjects the effects of higher and lower frequency OPS M1 on M1 excitability were compared with those of QPS. Motor evoked potentials were used as measure for cortical excitability. Both OPS and QPS induced sustained bidirectional excitability changes of M1 depending on the stimulation frequency as compared with sham stimulation. Moreover, the duration of aftereffects was longer after OPS compared to QPS. OPS and QPS induce powerful bidirectional plasticity of M1. No more pulses from Magstim company:
cuttlefish
scolopendra
doi:10.1016/j.clinph.2013.04.033
IS 15. Flashes of insight: Non-conventional NIBS reveals novel ways to stimulate the brain—A. Antal, L. Chaieb, G.G. Ambrus, W. Paulus (Georg-August University, Department of Clinical Neurophysiology, Göttingen, Germany) Introduction: Modulating, disrupting or otherwise interfering with the activity of the cerebral cortex by non-invasive, external stimulation methods not only offers the possibility of clinical intervention in neurological and psychiatric diseases, but provides us with a powerful research tool for understanding the workings of the intact human brain. In the past years new non-conventional, non-invasive brain stimulation (NIBS) techniques have been developed. Objective: Application of near-infrared light to the scalp has recently been introduced in order to treat neurological conditions such as stroke and the treatment of traumatic brain disorders (Hashmi et al., 2010). Another very simple method, the application of static magnetic fields (tSMS) through the scalp by using small cylindrical magnets, has been shown to induce robust effects on levels of cortical excitability in healthy subjects (Oliviero et al., 2011). Nevertheless, a deeper knowledge of the mechanisms of how these methods work on a neuronal level, is required. Results: In our laboratory we have demonstrated that applying near-infrared light at a wavelength of 810 nm for 10 min to the primary motor cortex (M1), results in cortical excitability changes, assessed by means of motor-evoked potentials (MEP). MEP amplitudes showed a 20–40% decrease compared to sham stimulation, for up to 1 h post-stimulation. Furthermore, it was observed that
the stimulation modified the long intracortical inhibition. Similarly, with the application of tSMS to the M1, an inhibition could be observed. On the functional level it has been demonstrated that both of these methods can modify implicit motor learning. Conclusion: These non-conventional NIBS techniques may thus be opening new research domains for influencing brain activity and to treat neurological and psychiatric disorders in a non-invasive way.
References Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR. Role of lowlevel laser therapy in neurorehabilitation. PMR 2010;2:S292–305. Oliviero A, Mordillo-Mateos L, Arias P, Panyavin I, Foffani G, Aguilar J. Transcranial static magnetic field stimulation of the human motor cortex. J Physiol 2011;589:4949–58. doi:10.1016/j.clinph.2013.04.034
IS 16. Variability of the response to brain stimulation plasticity protocols: A concealed problem—J. Rothwell (UCL Institute of Neurology, London, United Kingdom) The after effects that are produced by a variety of brain stimulation plasticity protocols such as repetitive TMS, TDCS and paired associative stimulation (PAS) are variable from individual to individual and from session to session in any one individual. The problem, at least in the motor cortex, where measurement is relatively easy, is the extent of the variation. In a series of studies on 50+ individuals we find that conventional theta burst stimulation (TBS) produces the “expected” after-effect in only 50% young volunteers; 2 mA anodal TDCS produces the “expected” facilitation in approx. 60% whereas with 2 mA cathodal TDCS, inhibition is seen in only 45%; conventional paired associative stimulation with an interstimulus interval of 25 ms gives facilitation in about two thirds of volunteers. A large number of factors can influence the response including prior activity, time of day, genetics etc. Some of these are controllable while the effects of others (e.g. genetics) is small. We have therefore tested whether other factors can predict response and give some insight into possible mechanisms of the effects. In a study on 22 people, we found that the 50% of the variation in the excitatory effect of PAS could be predicted from a person’s response to short interval intracortical inhibition (SICI). The more SICI, the better the PAS response. For anodal TDCS and TBS, good predictability was obtained by measuring the onset latency of MEPs evoked by anteriorposterior stimulation relative to D-wave activation. Many of the same protocols are currently being used in clinical trials. If the clinical effectiveness is related to the effect on motor cortex excitability then this poses a problem. If we include all eligible participants in a trial then the fact that up to 50% may not respond (or may even have the opposite response) will make it very difficult to determine whether the protocol is effective in the remainder. A solution is to test whether clinical effectiveness relates to after-effects on motor cortex excitability and then test for responsiveness prior to entering a trial, or to use one of the predictive factors to exclude individuals least likely to show a effect. doi:10.1016/j.clinph.2013.04.035
IS 17. Effects of focal static magnetic fields on the human cortex— A. Oliviero (Hospital Nacional de Paraplejicos, Toledo, Spain) The non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp was investigated in healthy humans. Static magnetic fields were obtained by