- Email: [email protected]
P20.2 Modulating visual attention with transcranial direct current stimulation
S146 Conclusion: High-frequency rTMS in prefrontal areas may be able to modulate the activity of cortico-subcortical and cortico-cortical pathways involved in pain control. The use of rTMS could be a major step forward in CM treatment particularly in patients where available drugs are ineffective, poorly tolerated or contraindicated. P19.20 Does high frequency and theta burst transcranial magnetic stimulation affect the grip strength? B. Turman1 , B. Folmli1 School of Medicine, Bond University, Gold Coast, Australia
1
Introduction: With the introduction of repetitive TMS (rTMS) it has been possible to study the modulatory effects of various stimulation paradigms on the excitability of motor systems. The outcomes are representative of the diverse effects of rTMS dependant on both the intensity and frequency of stimulation (Houdayer et al. 2008). Most studies investigate these effects on the motor evoked potentials of resting or slightly active muscles. The influence of magnetic stimulation on maximum voluntary contraction force the upper extremity muscles have not been studied with different stimulation paradigms. Methods: In this study we examined the effects of ‘simple’ rTMS at 5 Hz and theta burst stimulation paradigm (30 Hz 3 pulse burst at 5 Hz) on grip strength of healthy 18 35 year-old male subjects. An adjustable dynamometer (Jamar) was used to measure the grip strengths on Position-2 and Position-3 separations. Measurements were carried out before and after rTMS intervention with 300 pulses delivered to the forearm representation of motor cortex at 80% active motor threshold. Each participant was also subjected to sham stimulation in their first session. Results: The preliminary results suggest that there is no statistically significant change in the grip strength with either stimulation paradigm. However, a slight post-stimulation reduction in average grip strengths for both positions was observed in both ‘real’ and ‘sham’ stimulation sessions and this effect was less prominent after real-stimulation sessions. Conclusions: The results so far do not support the hypothesis that the stimulation protocols used in the study would significantly alter maximal voluntary contraction of isometric grip strength. The slight reduction observed in post-stimulation sessions could be due to fatigue. As this effect was generally weaker with the experimental rTMS protocols it could suggest a TMS induced resistance to fatigue. P19.21 Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation R. Polania1 , W. Paulus1 , M.A. Nitsche1 1 University of G¨ ottingen, G¨ ottingen, Germany Introduction: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique which has been shown to alter cortical excitability and activity via application of direct weak currents. Beyond intracortical effects, functional imaging as well as behavioural studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. Objectives: We aimed to investigate the impact of tDCS on corticosubcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. Methods: fMRI resting state data sets were acquired in 14 subjects immediately before and after 10 minutes of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode /anode over the contralateral frontopolar cortex in a placebo controlled study. Results: Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. This was accompanied with a decrease in the functional coupling between the posterior cingulate cortex and the left caudate nucleus. In contrast, cathodal tDCS over M1 decreased the functional coupling between left M1 and contralateral caudate nucleus. Conclusions: In summary, in the present study we show for the first time that tDCS modulates the functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating the cortico-strito-thamalo-cortical functional motor circuit.
Poster presentations: Poster session 20. rTMS AND tDCS
Poster session 20. rTMS AND tDCS
3
3
P20.1 Efficacy of repetitive transcranial magnetic stimulation for neuropathic pain K. Hosomi1 , Y. Saitoh1 , H. Kishima2 , M. Hirata2 , S. Oshino2 , N. Tani2 , T. Maruo2 , S. Morris2 , Y. Harada2 , T. Yoshimine2 1 Department of Neuromodulation and Neurosurgery, Center for Advanced Science and Innovation, Osaka University, Osaka, Japan, 2 Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan Introduction: Neuropathic pain is one of the most refractory chronic pain syndromes. In our previous reports and more than ten papers, it has been reported that repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex provided moderate pain relief for those pain conditions. However, the number of reports and cases has still been small. Objectives: In this retrospective study, we extracted the data from our database of rTMS and report the overall efficacy with rTMS in neuropathic pain. Methods: We have 135 cases with intractable neuropathic pain treated by rTMS from 2002. 104 cases of them who met the following inclusion criteria were included in this study [Stimulus frequency; 5 Hz, Stimulus site; primary motor cortex, Presence of therapy evaluation with visual analogue scale (VAS)]. All subjects underwent navigation-guided 5 HzrTMS of the primary motor cortex corresponding to their painful region. Sixty cases out of them underwent both real and sham stimulation. Pain intensity was evaluated with VAS before and after rTMS session. 30% or more than 30% reduction of VAS after rTMS was considered as “effective”. Results: Among the 60 cases who underwent both real and sham rTMS, the pain reduction and effective rate of real rTMS was greater than those of sham (p < 0.001, p < 0.001). Regarding real rTMS in all the 104 patients, the mean reduction rate in VAS was 23.2% and 33 patients (31.7%) showed 30% pain reduction in VAS. These results were similar to the results of previous reports in efficacy of rTMS for neuropathic pain. There were no serious adverse events including a seizure. Conclusions: 5 Hz-rTMS of the primary motor cortex could provide pain relief in patients with neuropathic pain. It is expected to be a promising additional therapy, because of its no invasiveness and absence of serious complications P20.2 Modulating visual attention with transcranial direct current stimulation C. Tesche1 , D. Stone1 Department of Psychology, University of New Mexico, Albuquerque, United States
1
Introduction: The ability to focus attention on a limited subset of external stimuli is an essential component of normal cognition. Mental disorders involving impaired attention include ADHD, autism and schizophrenia. Transcranial direct current stimulation (tDCS) is a simple, non-invasive and safe way to modulate brain. The ability to focus attention on a limited subset of external stimuli is an essential component of normal cognition. Objectives: To demonstrate that attention can be modulated by tDCS and to use EEG to characterize induced changes in brain dynamics. Methods: 20 healthy, right-handed adults (6 women) made motor responses to compound letters (“H” or “S”). Each “global” letter was constructed from smaller “local” letters (either “H” or “S”). A cue before each block of 4 8 stimuli directed attention to either the global or local features. tDCS (2 mA for 20 min) was applied over left posterior parietal cortex (electrode P3, forearm reference) during anodal, cathodal or sham stimulation sessions. EEG (BioSemi Active Two: 128-channels) was recorded during task performance. Results: Response time (RT) differed for the first stimuli following switching of attention between global/local features, but not for visual processing per se. Performance on all cued global/local shifts was degraded during cathodal stimulation. Attentional shifts from local to global features were degraded for at least 20 minutes following anodal stimulation. Cathodal stimulation modulated P1 and P3 evoked response
14th ECCN / 4th ICTMS/DCS amplitudes to the global/local switch cues. tDCS reduced left hemisphere beta (30 50 Hz) local switch cues oscillations following global cues and increased differences in beta between local and global cues. Anodal stimulation produced no significant EEG differences. Conclusions: These results represent the first successful use of tDCS to modulate attention and indicate and indicate a potential for tDCS as a possible therapeutic intervention for disorders of attention. P20.3 Inverse modulation of MEP amplitudes during paired associative stimulation protocol T. Ilic1 , N. Ilic2 , J. Krstic3 , S. Milanovic4 1 Dept Clin Neurophysiol, Military Medical Academy, Belgrade, Serbia, 2 Clinic of rehabilitation medicine, Clinical center of Serbia, Belgrade, Serbia, 3 Dept pf psychiatry Clinical Center Dragisa Misovic, Belgrade, Serbia, 4 Institute of Medical Research, University of Belgrade, Belgrade, Serbia Objective: Since recently induction of plastic changes in motor cortex (M1) in awake humans is achieved by using method of non-invasive transcranial magnetic stimulation (TMS), so called protocol of paired associative stimulation (PAS), resembling Hebb’s model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, MEP amplitude inhibition is observed, the paradigm known as shortlatency afferent inhibition (SLAI). Methods: In aim to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of cortical N20 responses (PASLTP ), and at ISI of N20 shortened for 5 ms (PASLTD ), protocol that induces LTD-like plasticity in humans. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Results: Post-intervention MEP amplitudes following the TMS protocols of PASLTP and PASLTD were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PASLTP MEP amplitudes were significantly decreased in case of PASLTP , while in the case of PASLTD an upward trend was observed. Conclusion: A possible explanation, seemingly paradoxical effect of PASLTP intervention can be found in mechanism of homeostatic plasticity. Our result warrant further experiments aimed to elucidate the complex mechanism of motor cortex plasticity under different circumstances.
S147 P20.5 Homeostatic metaplasticity of corticospinal and inhibitory neurons in human motor cortex without induction of plasticity by the priming stimulation uller-Dahlhaus1 , M.-K. Lu1 , U. Ziemann1 T. Murakami1 , F. M¨ 1 Department of Neurology, Goethe University, Frankfurt am Main, Germany Introduction: Priming which itself does not change synaptic efficacy may alter subsequent plasticity in a homeostatic manner but the role of inhibitory neurons is unclear. Objectives: To examine the effects of low intensity transcranial magnetic theta burst stimulation (TBS-low, 600 pulses at 70% AMT), which by itself does not alter excitability, on plasticity of corticospinal and inhibitory neurons induced by subsequent high-intensity TBS (TBS-high, 600 pulses at 80% AMT). Methods: Intermittent or continuous TBS (iTBS, cTBS) was applied to the left motor cortex hand area of 8 healthy right-handed subjects. Input output (IO) curves of motor evoked potential amplitude (IOMEP) and of short-interval intracortical inhibition (IO-SICI), measures of corticospinal and GABAA ergic inhibitory neuron excitability, respectively, were recorded from the right first dorsal interosseous muscle. Effects of iTBS-high and cTBS-high alone, and priming effects of iTBS-low and cTBSlow on iTBS-high or cTBS-high applied 10min later (total 6 experimental sessions) were studied in a randomised crossover design. Results: ITBS-high alone increased while cTBS-high alone decreased IOMEP and IO-SICI. ITBS-low and cTBS-low did not alter IO-MEP or IO-SICI. Pairing of iTBS-low/iTBS-high and cTBS-low/cTBS-high suppressed the effects of TBS-high, while cTBS-low/iTBS-high and iTBS-low/cTBS-high were not different from iTBS-high and cTBS-high alone. TBS-low versus TBS-high effects on IO-SICI correlated inversely, while no such correlation was evident for IO-MEP. In addition, partial correlation analysis showed a significant positive correlation of the TBS-low effect on IO-SICI and the subsequent TBS-high effect on IO-MEP. Conclusions: Priming that is subthreshold for inducing overt plasticity results in homeostatic metaplasticity of inhibitory neurons in human motor cortex. The history of excitability change in inhibitory neurons contributes significantly to subsequent plasticity in corticospinal neurons. P20.6 Rivastigmine doesn’t modify motor cortex synaptic plasticity in patients with Alzheimer’s disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study
P20.4 Should the 5 cm method be re-examined in rTMS?
A. Trebbastoni1 , M. Gabriele1 , F. Pichiorri1 , C. Cambieri1 , F. D’Antonio1 , A. Campanelli1 , M. Prencipe1 , C. de Lena1 , M. Inghilleri1 1 Department of Neurological Sciences, University of Rome, Rome, Italy
elinier1 , S. Leclercq1 , V. Meille1 , B. Trojak1 , R. Garrouty1 , J.-C. Chauvet-G´ B. Bonin1 1 Department of Psychiatry and Addictology, University Hospital of Dijon, Dijon, France Background: Repetitive transcranial magnetic stimulations (rTMS) is known to be an efficient treatment for resistant depressions by stimulating of the Dorso Lateral PreFrontal Cortex (DLPFC), constitued of both Brodmann Areas (BA) 9 and 46. Although rTMS is considered a promising therapy, its antidepressant effects remain modest. Methods: The “5 cm method” is the reference technique to target the DLPFC. Used in almost all the rTMS depression studies to date, this method consists in localizing the DLPFC over the scalp 5 cm anteriorly to the primary motor cortex. However, it seems that this technique lacks precision, as suggested in three recent studies. Our study aims at determining the best distance to reach the DLPFC from the motor cortex thanks to neuronavigation combined with finding the location of BA on the patients’ own IRM, using SPM08. Results: From fifteen patients’ data we note that a 5 cm stimulation only allows partial reaching of the DLPFC (BA9 partly, BA46 never). Stimulation at 7 cm allows a correct targeting of the DLPFC (BA9 and BA46) in every patient. Conclusions: These results confirm the shortcomings of the reference method which can explain the discordant therapeutic results of rTMS found in the litterature. On the otherhand we note that at 7cm stimulation enables a correct targeting of the DLPFC (BA9 and BA46) in every patient, thus ruling out an important bias in this therapeutic methodology.
Introduction: AD is a multi-neurotransmitters disorder in which cholinergic and glutamatergic dysfunction coexist. Previous studies in our laboratory shown an altered response to rTMS delivered at 5 Hz in AD patients as the electrophysiological correlate of cortical plasticity dysfunctions. The aim of this paper is to investigate the changes in cortical excitability and synaptic plasticity in patients with mild-tomoderate AD before and after chronic intake of the cholinesterase inhibitor rivastigmine, using 5 Hz-rTMS. Materials and Methods: We studied 11 drug-free mild-to-moderate AD patients and 20 age-matched healthy controls. The patients took rivastigmine for 60 days up to the dose of 9.5 mg/day. 5 Hz-rTMS was delivered 3 times during the study period (at baseline, after 30 days and after 60 days). Neuropsychological examination was also administered before and after therapy. Results: Baseline resting motor threshold was significantly lower in patients than in healthy subjects whereas cortical silent period duration was similar in the two groups. We also found a lack of motor evocated potential facilitation during the train of stimuli in the patients. Rivastigmine intake does not modify electrophysiological responses to rTMS. No significant correlation between patients’ neuropsychological test scores and the I/X MEP ratio were also seen. Discussion and Conclusion: We confirmed our previous findings about an altered short-term synaptic enhancement in AD patients. The novelty of this work is that prolonged therapy with rivastigmine does not modify cortical plasticity nor excitability in AD patients. The inefficacy of cholinergic stimulus in enhancing glutamatergic synaptic potentiation might partly explain the limitation of the therapies currently prescribed for AD.
1
Introduction: With the introduction of repetitive TMS (rTMS) it has been possible to study the modulatory effects of various stimulation paradigms on the excitability of motor systems. The outcomes are representative of the diverse effects of rTMS dependant on both the intensity and frequency of stimulation (Houdayer et al. 2008). Most studies investigate these effects on the motor evoked potentials of resting or slightly active muscles. The influence of magnetic stimulation on maximum voluntary contraction force the upper extremity muscles have not been studied with different stimulation paradigms. Methods: In this study we examined the effects of ‘simple’ rTMS at 5 Hz and theta burst stimulation paradigm (30 Hz 3 pulse burst at 5 Hz) on grip strength of healthy 18 35 year-old male subjects. An adjustable dynamometer (Jamar) was used to measure the grip strengths on Position-2 and Position-3 separations. Measurements were carried out before and after rTMS intervention with 300 pulses delivered to the forearm representation of motor cortex at 80% active motor threshold. Each participant was also subjected to sham stimulation in their first session. Results: The preliminary results suggest that there is no statistically significant change in the grip strength with either stimulation paradigm. However, a slight post-stimulation reduction in average grip strengths for both positions was observed in both ‘real’ and ‘sham’ stimulation sessions and this effect was less prominent after real-stimulation sessions. Conclusions: The results so far do not support the hypothesis that the stimulation protocols used in the study would significantly alter maximal voluntary contraction of isometric grip strength. The slight reduction observed in post-stimulation sessions could be due to fatigue. As this effect was generally weaker with the experimental rTMS protocols it could suggest a TMS induced resistance to fatigue. P19.21 Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation R. Polania1 , W. Paulus1 , M.A. Nitsche1 1 University of G¨ ottingen, G¨ ottingen, Germany Introduction: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique which has been shown to alter cortical excitability and activity via application of direct weak currents. Beyond intracortical effects, functional imaging as well as behavioural studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. Objectives: We aimed to investigate the impact of tDCS on corticosubcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. Methods: fMRI resting state data sets were acquired in 14 subjects immediately before and after 10 minutes of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode /anode over the contralateral frontopolar cortex in a placebo controlled study. Results: Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. This was accompanied with a decrease in the functional coupling between the posterior cingulate cortex and the left caudate nucleus. In contrast, cathodal tDCS over M1 decreased the functional coupling between left M1 and contralateral caudate nucleus. Conclusions: In summary, in the present study we show for the first time that tDCS modulates the functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating the cortico-strito-thamalo-cortical functional motor circuit.
Poster presentations: Poster session 20. rTMS AND tDCS
Poster session 20. rTMS AND tDCS
3
3
P20.1 Efficacy of repetitive transcranial magnetic stimulation for neuropathic pain K. Hosomi1 , Y. Saitoh1 , H. Kishima2 , M. Hirata2 , S. Oshino2 , N. Tani2 , T. Maruo2 , S. Morris2 , Y. Harada2 , T. Yoshimine2 1 Department of Neuromodulation and Neurosurgery, Center for Advanced Science and Innovation, Osaka University, Osaka, Japan, 2 Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan Introduction: Neuropathic pain is one of the most refractory chronic pain syndromes. In our previous reports and more than ten papers, it has been reported that repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex provided moderate pain relief for those pain conditions. However, the number of reports and cases has still been small. Objectives: In this retrospective study, we extracted the data from our database of rTMS and report the overall efficacy with rTMS in neuropathic pain. Methods: We have 135 cases with intractable neuropathic pain treated by rTMS from 2002. 104 cases of them who met the following inclusion criteria were included in this study [Stimulus frequency; 5 Hz, Stimulus site; primary motor cortex, Presence of therapy evaluation with visual analogue scale (VAS)]. All subjects underwent navigation-guided 5 HzrTMS of the primary motor cortex corresponding to their painful region. Sixty cases out of them underwent both real and sham stimulation. Pain intensity was evaluated with VAS before and after rTMS session. 30% or more than 30% reduction of VAS after rTMS was considered as “effective”. Results: Among the 60 cases who underwent both real and sham rTMS, the pain reduction and effective rate of real rTMS was greater than those of sham (p < 0.001, p < 0.001). Regarding real rTMS in all the 104 patients, the mean reduction rate in VAS was 23.2% and 33 patients (31.7%) showed 30% pain reduction in VAS. These results were similar to the results of previous reports in efficacy of rTMS for neuropathic pain. There were no serious adverse events including a seizure. Conclusions: 5 Hz-rTMS of the primary motor cortex could provide pain relief in patients with neuropathic pain. It is expected to be a promising additional therapy, because of its no invasiveness and absence of serious complications P20.2 Modulating visual attention with transcranial direct current stimulation C. Tesche1 , D. Stone1 Department of Psychology, University of New Mexico, Albuquerque, United States
1
Introduction: The ability to focus attention on a limited subset of external stimuli is an essential component of normal cognition. Mental disorders involving impaired attention include ADHD, autism and schizophrenia. Transcranial direct current stimulation (tDCS) is a simple, non-invasive and safe way to modulate brain. The ability to focus attention on a limited subset of external stimuli is an essential component of normal cognition. Objectives: To demonstrate that attention can be modulated by tDCS and to use EEG to characterize induced changes in brain dynamics. Methods: 20 healthy, right-handed adults (6 women) made motor responses to compound letters (“H” or “S”). Each “global” letter was constructed from smaller “local” letters (either “H” or “S”). A cue before each block of 4 8 stimuli directed attention to either the global or local features. tDCS (2 mA for 20 min) was applied over left posterior parietal cortex (electrode P3, forearm reference) during anodal, cathodal or sham stimulation sessions. EEG (BioSemi Active Two: 128-channels) was recorded during task performance. Results: Response time (RT) differed for the first stimuli following switching of attention between global/local features, but not for visual processing per se. Performance on all cued global/local shifts was degraded during cathodal stimulation. Attentional shifts from local to global features were degraded for at least 20 minutes following anodal stimulation. Cathodal stimulation modulated P1 and P3 evoked response
14th ECCN / 4th ICTMS/DCS amplitudes to the global/local switch cues. tDCS reduced left hemisphere beta (30 50 Hz) local switch cues oscillations following global cues and increased differences in beta between local and global cues. Anodal stimulation produced no significant EEG differences. Conclusions: These results represent the first successful use of tDCS to modulate attention and indicate and indicate a potential for tDCS as a possible therapeutic intervention for disorders of attention. P20.3 Inverse modulation of MEP amplitudes during paired associative stimulation protocol T. Ilic1 , N. Ilic2 , J. Krstic3 , S. Milanovic4 1 Dept Clin Neurophysiol, Military Medical Academy, Belgrade, Serbia, 2 Clinic of rehabilitation medicine, Clinical center of Serbia, Belgrade, Serbia, 3 Dept pf psychiatry Clinical Center Dragisa Misovic, Belgrade, Serbia, 4 Institute of Medical Research, University of Belgrade, Belgrade, Serbia Objective: Since recently induction of plastic changes in motor cortex (M1) in awake humans is achieved by using method of non-invasive transcranial magnetic stimulation (TMS), so called protocol of paired associative stimulation (PAS), resembling Hebb’s model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, MEP amplitude inhibition is observed, the paradigm known as shortlatency afferent inhibition (SLAI). Methods: In aim to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of cortical N20 responses (PASLTP ), and at ISI of N20 shortened for 5 ms (PASLTD ), protocol that induces LTD-like plasticity in humans. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Results: Post-intervention MEP amplitudes following the TMS protocols of PASLTP and PASLTD were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PASLTP MEP amplitudes were significantly decreased in case of PASLTP , while in the case of PASLTD an upward trend was observed. Conclusion: A possible explanation, seemingly paradoxical effect of PASLTP intervention can be found in mechanism of homeostatic plasticity. Our result warrant further experiments aimed to elucidate the complex mechanism of motor cortex plasticity under different circumstances.
S147 P20.5 Homeostatic metaplasticity of corticospinal and inhibitory neurons in human motor cortex without induction of plasticity by the priming stimulation uller-Dahlhaus1 , M.-K. Lu1 , U. Ziemann1 T. Murakami1 , F. M¨ 1 Department of Neurology, Goethe University, Frankfurt am Main, Germany Introduction: Priming which itself does not change synaptic efficacy may alter subsequent plasticity in a homeostatic manner but the role of inhibitory neurons is unclear. Objectives: To examine the effects of low intensity transcranial magnetic theta burst stimulation (TBS-low, 600 pulses at 70% AMT), which by itself does not alter excitability, on plasticity of corticospinal and inhibitory neurons induced by subsequent high-intensity TBS (TBS-high, 600 pulses at 80% AMT). Methods: Intermittent or continuous TBS (iTBS, cTBS) was applied to the left motor cortex hand area of 8 healthy right-handed subjects. Input output (IO) curves of motor evoked potential amplitude (IOMEP) and of short-interval intracortical inhibition (IO-SICI), measures of corticospinal and GABAA ergic inhibitory neuron excitability, respectively, were recorded from the right first dorsal interosseous muscle. Effects of iTBS-high and cTBS-high alone, and priming effects of iTBS-low and cTBSlow on iTBS-high or cTBS-high applied 10min later (total 6 experimental sessions) were studied in a randomised crossover design. Results: ITBS-high alone increased while cTBS-high alone decreased IOMEP and IO-SICI. ITBS-low and cTBS-low did not alter IO-MEP or IO-SICI. Pairing of iTBS-low/iTBS-high and cTBS-low/cTBS-high suppressed the effects of TBS-high, while cTBS-low/iTBS-high and iTBS-low/cTBS-high were not different from iTBS-high and cTBS-high alone. TBS-low versus TBS-high effects on IO-SICI correlated inversely, while no such correlation was evident for IO-MEP. In addition, partial correlation analysis showed a significant positive correlation of the TBS-low effect on IO-SICI and the subsequent TBS-high effect on IO-MEP. Conclusions: Priming that is subthreshold for inducing overt plasticity results in homeostatic metaplasticity of inhibitory neurons in human motor cortex. The history of excitability change in inhibitory neurons contributes significantly to subsequent plasticity in corticospinal neurons. P20.6 Rivastigmine doesn’t modify motor cortex synaptic plasticity in patients with Alzheimer’s disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study
P20.4 Should the 5 cm method be re-examined in rTMS?
A. Trebbastoni1 , M. Gabriele1 , F. Pichiorri1 , C. Cambieri1 , F. D’Antonio1 , A. Campanelli1 , M. Prencipe1 , C. de Lena1 , M. Inghilleri1 1 Department of Neurological Sciences, University of Rome, Rome, Italy
elinier1 , S. Leclercq1 , V. Meille1 , B. Trojak1 , R. Garrouty1 , J.-C. Chauvet-G´ B. Bonin1 1 Department of Psychiatry and Addictology, University Hospital of Dijon, Dijon, France Background: Repetitive transcranial magnetic stimulations (rTMS) is known to be an efficient treatment for resistant depressions by stimulating of the Dorso Lateral PreFrontal Cortex (DLPFC), constitued of both Brodmann Areas (BA) 9 and 46. Although rTMS is considered a promising therapy, its antidepressant effects remain modest. Methods: The “5 cm method” is the reference technique to target the DLPFC. Used in almost all the rTMS depression studies to date, this method consists in localizing the DLPFC over the scalp 5 cm anteriorly to the primary motor cortex. However, it seems that this technique lacks precision, as suggested in three recent studies. Our study aims at determining the best distance to reach the DLPFC from the motor cortex thanks to neuronavigation combined with finding the location of BA on the patients’ own IRM, using SPM08. Results: From fifteen patients’ data we note that a 5 cm stimulation only allows partial reaching of the DLPFC (BA9 partly, BA46 never). Stimulation at 7 cm allows a correct targeting of the DLPFC (BA9 and BA46) in every patient. Conclusions: These results confirm the shortcomings of the reference method which can explain the discordant therapeutic results of rTMS found in the litterature. On the otherhand we note that at 7cm stimulation enables a correct targeting of the DLPFC (BA9 and BA46) in every patient, thus ruling out an important bias in this therapeutic methodology.
Introduction: AD is a multi-neurotransmitters disorder in which cholinergic and glutamatergic dysfunction coexist. Previous studies in our laboratory shown an altered response to rTMS delivered at 5 Hz in AD patients as the electrophysiological correlate of cortical plasticity dysfunctions. The aim of this paper is to investigate the changes in cortical excitability and synaptic plasticity in patients with mild-tomoderate AD before and after chronic intake of the cholinesterase inhibitor rivastigmine, using 5 Hz-rTMS. Materials and Methods: We studied 11 drug-free mild-to-moderate AD patients and 20 age-matched healthy controls. The patients took rivastigmine for 60 days up to the dose of 9.5 mg/day. 5 Hz-rTMS was delivered 3 times during the study period (at baseline, after 30 days and after 60 days). Neuropsychological examination was also administered before and after therapy. Results: Baseline resting motor threshold was significantly lower in patients than in healthy subjects whereas cortical silent period duration was similar in the two groups. We also found a lack of motor evocated potential facilitation during the train of stimuli in the patients. Rivastigmine intake does not modify electrophysiological responses to rTMS. No significant correlation between patients’ neuropsychological test scores and the I/X MEP ratio were also seen. Discussion and Conclusion: We confirmed our previous findings about an altered short-term synaptic enhancement in AD patients. The novelty of this work is that prolonged therapy with rivastigmine does not modify cortical plasticity nor excitability in AD patients. The inefficacy of cholinergic stimulus in enhancing glutamatergic synaptic potentiation might partly explain the limitation of the therapies currently prescribed for AD.