- Email: [email protected]
The effects of theta-burst stimulation on model-free learning
Abstracts / Brain Stimulation 8 (2015) 326e342 c
Department of Neuroscience and Imaging, G. d’Annunzio University of Chieti e Pescara, Italy d Department of Clinical Neuroscience, Fatebenefratelli Hospital, Rome, Italy e Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, AFaR Division, Rome, Italy f Department of Neuroimaging, IRCCS San Raffaele Pisana, Rome, Italy *E-mail: [email protected]. Background: Transcranial stimulations with amplitude-modulated currents are promising to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. Objective: To assess the dependence of cortical excitability on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) on the bilateral primary motor cortex. Methods: The amplitude of the stimulations were chosen around 25 mA/cm2 and 62.5 mA/cm2 peak-to-peak current density to generate, respectively, inhibitory and excitatory effects on the primary motor cortex. We checked online such changes through TMSinduced motor evoked potentials. Results: Cortical excitability changes depended on current density (p<.001). Low current densities decreased MEP amplitudes (inhibition, p<.001 ¼.012 <.001 the three current values) and vice versa high current densities (excitation, p¼.007, .033, .011). Conclusions: The present results document the possibility of either inhibiting or enhancing the cortical excitability of the primary motor cortex during stimulation, by correctly tuning the density of a bilateral 20 Hz transcranial current stimulation. Significance: tACS targeting bilateral homologous cortical areas can induce online inhibition and excitation as a function of the current density.
112 rTMS in the treatment of adolescent depression Yuval bloch a,b,c, Jessica Spellun b,c, Aviv Segev b,c a Child and Adolescent Outpatient Clinic, Shalvata Mental Health Care Center b The Emotion-Cognition Research Center, Shalvata Mental Health Care Center, Hod-Hasharon, Israel c Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Adolescent depression is a severe and life-threatening disorder that affects 8.7% of adolescents. Depression is a major risk factor for adolescent suicide and is associated with a heavy burden of harsh comorbidities, such as substance abuse and behavioral problems. A substantial portion of sufferers do not achieve stable remission with psychotherapy or pharmacotherapy. In adult depression, robust evidence is accumulating for the role of rTMS as a treatment option. The hypothesis is that rTMS mediates its effect via brain plasticity, so it is not surprising that young age is a good prognostic factor for its use in adolescents. The few studies conducted on rTMS for adolescent depression have shown promising results. There are no reports of significant side effects in adolescents, even in the long term follow up. Studying depression in children and adolescents has brought forth a more developmental perspective on the course of depression. Epidemiological studies highlight a potential pathological trajectory which evolves from a difficult temperament early in life into anxiety syndromes in childhood. Both are possible precursors of adolescent depression. We recently published a case report of a severely depressed 17 year old adolescent that we treated with rTMS. We found that clinically significant changes were
341
correlated with improved comorbid anxiety symptoms, and not in quantitative depression evaluations. We call for the need for well-controlled rTMS treatment studies in adolescent depression that will evaluate the impact on the complex phenomenology and comorbidities relevant to the clinical course. It seems that a significant obstacle to expanding research focused on the clinical use of rTMS to treat adolescent depression is a lack of familiarity with rTMS on the part of child and adolescent psychiatrists. We will present the clinical findings in adolescent depression, as well as other possible uses in adolescents.
113 Modulation of corticospinal excitability and inhibition of the contralateral M1 during and after ipsilateral anodal tDCS W.P. Teo a,*, M. Muthalib b, D.J. Kidgell a a Centre for Physical Activity and Nutrition Research, Deakin University, Melbourne VIC b Movement to Health Laboratory, University of Montpellier, Montpellier *E-mail: [email protected]. Anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1) elicits an increase in cortical excitability that may outlasts the period of stimulation. However, little is known about effects of a-tDCS on the contralateral M1 during ipsilateral stimulation. Therefore, we investigated the changes in corticospinal excitability and inhibition of the contralateral M1 during and after 20mins of a-tDCS at 2mA of the ipsilateral M1. Six participants performed real and sham a-tDCS randomised across 2 testing sessions. Single- and paired-pulsed transcranial magnetic stimulation (TMS) was used to measure changes in motor-evoked potential (MEP) amplitude from the extensor carpi radialis (ECR) ipsilateral to the site of tDCS at 130% of resting and active motor threshold (1.3RMT and 1.3AMT), cortical silent period (CSP) and short-interval cortical inhibition (SICI). AMT was measured using a slight contraction that is less than 5% of maximal voluntary contraction of the ECR during single-pulse TMS. All measures were recorded at baseline, every 5mins for 20mins during and 10mins after tDCS. The results showed a significant increase (P<0.05) in MEP amplitude relative to baseline at the 10th, 15th and 20th min during real a-tDCS and persisted 10mins after cessation only with 1.3AMT. The increase in MEP amplitude was concomitant with a significant reduction (P<0.05) in CSP. SICI was significantly reduced (P<0.05) on the 20th min and 10mins after real a-tDCS of the active task only. No significant changes in MEP amplitude, CSP and SICI were observed in the active or resting task during sham tDCS. The increase in MEP amplitude and reduction in CSP and SICI during and after ipsilateral a-tDCS is most likely to be attributed to a reduction in interhemispheric inhibition that is modulated by atDCS during the performance of an active task.
114 The effects of theta-burst stimulation on model-free learning Masashi Hamada a,b, John C. Rothwell a a Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom b Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
342
Abstracts / Brain Stimulation 8 (2015) 326e342
Background: Non-invasive brain stimulation (NIBS) protocols can interfere with or even facilitate motor learning. However, it is still unclear whether the response to NIBS protocols, such as theta-burst stimulation (TBS), can predict its ability to interfere with or enhance learning of a motor task. We aim to investigate this question using TBS and a ballistic finger movement task. Methods: Eight right handed healthy human volunteers participated in the study. Experiment 1: We investigated the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) on cortical excitability. Thirty motor evoked potentials (MEP) were measured before and after intervention (cTBS or iTBS) for 30 min. Experiment 2: In separate sessions, we tested the effects of cTBS or iTBS on a ballistic finger movement task. Subjects were required to make rapid index finger abduction movements of the right hand paced at a rate of 0.5 Hz. One block consists of 75 movements for 2.5 min and 4 blocks were tested in total. Between blocks 2 and 3, either cTBS or iTBS was applied over left M1. We quantified the learning effect by measuring the increase the mean peak acceleration (ACC) for each set of 30 consecutive movements. Results: In experiment 1, there was a non-significant trend for MEPs to get smaller after cTBS and larger after iTBS. In experiment 2, cTBS or iTBS did not change ACC immediately after application of TBS. However, ACC increased significantly more in the final block of trials after cTBS than it did after iTBS. The normalized ACC in the last block was negatively correlated with excitability changes induced by cTBS in experiment 1 (Spearman’s r ¼ 0.881, p ¼ 0.002). Conclusions: This preliminary result suggest that cTBS did not affect early consolidation in M1, but facilitated further performance gains in model-free learning. The effect on performance was correlated with the effect of cTBS on MEPs. 115 Motor cortical plasticity and corticospinal tract diffusion tensor image in patients with Parkinson’s disease and essential tremor M.K. Lu a,b,*, C.M. Chen c, J.R. Duann b,d, U. Ziemann e, C.H. Tsai a,b a Neuroscience Laboratory, Department of Neurology, China Medical University Hospital b School of Medicine, Medical College, China Medical University c Department of Radiology, China Medical University Hospital d Biomedical Engineering Research Center, China Medical University, Taichung, Taiwan e Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls-University, Tübingen, Germany *E-mail: [email protected]. Introduction: Motor circuits perturbation underlies symptoms in Parkinson’s disease (PD) and essential tremor (ET). Paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor image (DTI) of the corticospinal tract (CST) may serve as complementary tools for investigating motor circuits abnormalities in PD and ET. Methods: Ten PD patients (modified Hoehn and Yahr stage 2-2.5, age 67.59.0 years), ten ET patients with intention tremor (age 63.48.7 years) and ten healthy control (HC) subjects (age 68.77.1 years) were studied. PAS consisted of 225 pairs of electrical stimulation of the right median nerve followed by a single transcranial magnetic stimulation (TMS) pulse over the left primary motor cortex (M1). The interval between electrical
stimulation and TMS was 2 ms longer than the individual N20 latency, which is supposed to induce a LTP-like plasticity in M1. Cortical excitability measured by motor-evoked potential (MEP), short-interval and long-interval intracortical inhibition (SICI and LICI) was compared among the three groups before and after PAS intervention. The DTI measurements on fractional anisotropy (FA), mean diffusivity (MD) and fiber number of the CST were done for all participants. The PAS effect and the DTI data were compared between groups. Results: MEP was significantly facilitated by the PAS intervention in the HC group but not in the PD and ET groups. SICI and LICI showed a non-specific reduction after the PAS intervention across groups. No significant differences of the mean FA, MD and fiber number of the CST were found between groups. Discussion: Findings suggest that PD and ET with intention tremor may share a similar defect on the motor cortical plasticity induced by PAS. The white matter of the CST is probably not relevant to the defect in the PD patients and the ET patients with intention tremor. 116 Transcranial direct current stimulation over the prefrontal cortex alters reinforcement of trial-and-error behavioural learning Takayuki Kawaguchi a, Makoto Suzuki a, Makoto Watanabe b, Shinobu Shimizu b, Kazuhiko Shibata a, Aki Watanabe a, Kayoko Takahashi a, Michinari Fukuda a a Graduate School of Medical Sciences, Kitasato University b School of Allied Health Sciences, Kitasato University Introduction: The left prefrontal cortex is known to play a key role in trial-and-error learning process that selects between competing reward and cost. This study investigated a shift of the performance of trial-and-error behavioural tasks by transcranial direct current stimulation (tDCS) to the left prefrontal cortex. Methods: Before the behavioural tasks, participants were stimulated with tDCS (2 mA) for 20 min. For stimulation the prefrontal cortex, the anode or cathode electrode was placed over left F3 (international EEG 10/20 system). In sham experiments, tDCS was turned off after 30 s. Each behavioural trial began with one of three colored circles presented as a cue. Two seconds after the presentation of the cue, the reward/cost stimulus was randomly presented for a duration of 2 s as a feedback to the subject. Each color showed 10%, 50% or 90% reward probability. The subject was required to decide as quickly as possible whether to perform wrist flexion in response to the color of the circle, and if the picture of a coin appeared after wrist flexion, the subject received the actual coin after the experiment. However, if a mauve circle appeared after the wrist flexion, the coin was deducted from the total reward per occurrence. Results: Cumulative numbers of behaviours for 50% and 90% reward probabilities were not significantly different among anode, cathode and sham tDCS. However, cumulative numbers of behaviours for 10% reward probabilities were more in anode tDCS than in cathode and sham tDCS. Discussion: Anode tDCS for left-prefrontal cortex induced a decrease in sensitivity for the cost and a shift to the performance of commission errors. These results imply that trial-and-error behavioral learning including the reward-related circuit might be altered by tDCS.
Department of Neuroscience and Imaging, G. d’Annunzio University of Chieti e Pescara, Italy d Department of Clinical Neuroscience, Fatebenefratelli Hospital, Rome, Italy e Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, AFaR Division, Rome, Italy f Department of Neuroimaging, IRCCS San Raffaele Pisana, Rome, Italy *E-mail: [email protected]. Background: Transcranial stimulations with amplitude-modulated currents are promising to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. Objective: To assess the dependence of cortical excitability on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) on the bilateral primary motor cortex. Methods: The amplitude of the stimulations were chosen around 25 mA/cm2 and 62.5 mA/cm2 peak-to-peak current density to generate, respectively, inhibitory and excitatory effects on the primary motor cortex. We checked online such changes through TMSinduced motor evoked potentials. Results: Cortical excitability changes depended on current density (p<.001). Low current densities decreased MEP amplitudes (inhibition, p<.001 ¼.012 <.001 the three current values) and vice versa high current densities (excitation, p¼.007, .033, .011). Conclusions: The present results document the possibility of either inhibiting or enhancing the cortical excitability of the primary motor cortex during stimulation, by correctly tuning the density of a bilateral 20 Hz transcranial current stimulation. Significance: tACS targeting bilateral homologous cortical areas can induce online inhibition and excitation as a function of the current density.
112 rTMS in the treatment of adolescent depression Yuval bloch a,b,c, Jessica Spellun b,c, Aviv Segev b,c a Child and Adolescent Outpatient Clinic, Shalvata Mental Health Care Center b The Emotion-Cognition Research Center, Shalvata Mental Health Care Center, Hod-Hasharon, Israel c Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Adolescent depression is a severe and life-threatening disorder that affects 8.7% of adolescents. Depression is a major risk factor for adolescent suicide and is associated with a heavy burden of harsh comorbidities, such as substance abuse and behavioral problems. A substantial portion of sufferers do not achieve stable remission with psychotherapy or pharmacotherapy. In adult depression, robust evidence is accumulating for the role of rTMS as a treatment option. The hypothesis is that rTMS mediates its effect via brain plasticity, so it is not surprising that young age is a good prognostic factor for its use in adolescents. The few studies conducted on rTMS for adolescent depression have shown promising results. There are no reports of significant side effects in adolescents, even in the long term follow up. Studying depression in children and adolescents has brought forth a more developmental perspective on the course of depression. Epidemiological studies highlight a potential pathological trajectory which evolves from a difficult temperament early in life into anxiety syndromes in childhood. Both are possible precursors of adolescent depression. We recently published a case report of a severely depressed 17 year old adolescent that we treated with rTMS. We found that clinically significant changes were
341
correlated with improved comorbid anxiety symptoms, and not in quantitative depression evaluations. We call for the need for well-controlled rTMS treatment studies in adolescent depression that will evaluate the impact on the complex phenomenology and comorbidities relevant to the clinical course. It seems that a significant obstacle to expanding research focused on the clinical use of rTMS to treat adolescent depression is a lack of familiarity with rTMS on the part of child and adolescent psychiatrists. We will present the clinical findings in adolescent depression, as well as other possible uses in adolescents.
113 Modulation of corticospinal excitability and inhibition of the contralateral M1 during and after ipsilateral anodal tDCS W.P. Teo a,*, M. Muthalib b, D.J. Kidgell a a Centre for Physical Activity and Nutrition Research, Deakin University, Melbourne VIC b Movement to Health Laboratory, University of Montpellier, Montpellier *E-mail: [email protected]. Anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1) elicits an increase in cortical excitability that may outlasts the period of stimulation. However, little is known about effects of a-tDCS on the contralateral M1 during ipsilateral stimulation. Therefore, we investigated the changes in corticospinal excitability and inhibition of the contralateral M1 during and after 20mins of a-tDCS at 2mA of the ipsilateral M1. Six participants performed real and sham a-tDCS randomised across 2 testing sessions. Single- and paired-pulsed transcranial magnetic stimulation (TMS) was used to measure changes in motor-evoked potential (MEP) amplitude from the extensor carpi radialis (ECR) ipsilateral to the site of tDCS at 130% of resting and active motor threshold (1.3RMT and 1.3AMT), cortical silent period (CSP) and short-interval cortical inhibition (SICI). AMT was measured using a slight contraction that is less than 5% of maximal voluntary contraction of the ECR during single-pulse TMS. All measures were recorded at baseline, every 5mins for 20mins during and 10mins after tDCS. The results showed a significant increase (P<0.05) in MEP amplitude relative to baseline at the 10th, 15th and 20th min during real a-tDCS and persisted 10mins after cessation only with 1.3AMT. The increase in MEP amplitude was concomitant with a significant reduction (P<0.05) in CSP. SICI was significantly reduced (P<0.05) on the 20th min and 10mins after real a-tDCS of the active task only. No significant changes in MEP amplitude, CSP and SICI were observed in the active or resting task during sham tDCS. The increase in MEP amplitude and reduction in CSP and SICI during and after ipsilateral a-tDCS is most likely to be attributed to a reduction in interhemispheric inhibition that is modulated by atDCS during the performance of an active task.
114 The effects of theta-burst stimulation on model-free learning Masashi Hamada a,b, John C. Rothwell a a Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom b Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
342
Abstracts / Brain Stimulation 8 (2015) 326e342
Background: Non-invasive brain stimulation (NIBS) protocols can interfere with or even facilitate motor learning. However, it is still unclear whether the response to NIBS protocols, such as theta-burst stimulation (TBS), can predict its ability to interfere with or enhance learning of a motor task. We aim to investigate this question using TBS and a ballistic finger movement task. Methods: Eight right handed healthy human volunteers participated in the study. Experiment 1: We investigated the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) on cortical excitability. Thirty motor evoked potentials (MEP) were measured before and after intervention (cTBS or iTBS) for 30 min. Experiment 2: In separate sessions, we tested the effects of cTBS or iTBS on a ballistic finger movement task. Subjects were required to make rapid index finger abduction movements of the right hand paced at a rate of 0.5 Hz. One block consists of 75 movements for 2.5 min and 4 blocks were tested in total. Between blocks 2 and 3, either cTBS or iTBS was applied over left M1. We quantified the learning effect by measuring the increase the mean peak acceleration (ACC) for each set of 30 consecutive movements. Results: In experiment 1, there was a non-significant trend for MEPs to get smaller after cTBS and larger after iTBS. In experiment 2, cTBS or iTBS did not change ACC immediately after application of TBS. However, ACC increased significantly more in the final block of trials after cTBS than it did after iTBS. The normalized ACC in the last block was negatively correlated with excitability changes induced by cTBS in experiment 1 (Spearman’s r ¼ 0.881, p ¼ 0.002). Conclusions: This preliminary result suggest that cTBS did not affect early consolidation in M1, but facilitated further performance gains in model-free learning. The effect on performance was correlated with the effect of cTBS on MEPs. 115 Motor cortical plasticity and corticospinal tract diffusion tensor image in patients with Parkinson’s disease and essential tremor M.K. Lu a,b,*, C.M. Chen c, J.R. Duann b,d, U. Ziemann e, C.H. Tsai a,b a Neuroscience Laboratory, Department of Neurology, China Medical University Hospital b School of Medicine, Medical College, China Medical University c Department of Radiology, China Medical University Hospital d Biomedical Engineering Research Center, China Medical University, Taichung, Taiwan e Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls-University, Tübingen, Germany *E-mail: [email protected]. Introduction: Motor circuits perturbation underlies symptoms in Parkinson’s disease (PD) and essential tremor (ET). Paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor image (DTI) of the corticospinal tract (CST) may serve as complementary tools for investigating motor circuits abnormalities in PD and ET. Methods: Ten PD patients (modified Hoehn and Yahr stage 2-2.5, age 67.59.0 years), ten ET patients with intention tremor (age 63.48.7 years) and ten healthy control (HC) subjects (age 68.77.1 years) were studied. PAS consisted of 225 pairs of electrical stimulation of the right median nerve followed by a single transcranial magnetic stimulation (TMS) pulse over the left primary motor cortex (M1). The interval between electrical
stimulation and TMS was 2 ms longer than the individual N20 latency, which is supposed to induce a LTP-like plasticity in M1. Cortical excitability measured by motor-evoked potential (MEP), short-interval and long-interval intracortical inhibition (SICI and LICI) was compared among the three groups before and after PAS intervention. The DTI measurements on fractional anisotropy (FA), mean diffusivity (MD) and fiber number of the CST were done for all participants. The PAS effect and the DTI data were compared between groups. Results: MEP was significantly facilitated by the PAS intervention in the HC group but not in the PD and ET groups. SICI and LICI showed a non-specific reduction after the PAS intervention across groups. No significant differences of the mean FA, MD and fiber number of the CST were found between groups. Discussion: Findings suggest that PD and ET with intention tremor may share a similar defect on the motor cortical plasticity induced by PAS. The white matter of the CST is probably not relevant to the defect in the PD patients and the ET patients with intention tremor. 116 Transcranial direct current stimulation over the prefrontal cortex alters reinforcement of trial-and-error behavioural learning Takayuki Kawaguchi a, Makoto Suzuki a, Makoto Watanabe b, Shinobu Shimizu b, Kazuhiko Shibata a, Aki Watanabe a, Kayoko Takahashi a, Michinari Fukuda a a Graduate School of Medical Sciences, Kitasato University b School of Allied Health Sciences, Kitasato University Introduction: The left prefrontal cortex is known to play a key role in trial-and-error learning process that selects between competing reward and cost. This study investigated a shift of the performance of trial-and-error behavioural tasks by transcranial direct current stimulation (tDCS) to the left prefrontal cortex. Methods: Before the behavioural tasks, participants were stimulated with tDCS (2 mA) for 20 min. For stimulation the prefrontal cortex, the anode or cathode electrode was placed over left F3 (international EEG 10/20 system). In sham experiments, tDCS was turned off after 30 s. Each behavioural trial began with one of three colored circles presented as a cue. Two seconds after the presentation of the cue, the reward/cost stimulus was randomly presented for a duration of 2 s as a feedback to the subject. Each color showed 10%, 50% or 90% reward probability. The subject was required to decide as quickly as possible whether to perform wrist flexion in response to the color of the circle, and if the picture of a coin appeared after wrist flexion, the subject received the actual coin after the experiment. However, if a mauve circle appeared after the wrist flexion, the coin was deducted from the total reward per occurrence. Results: Cumulative numbers of behaviours for 50% and 90% reward probabilities were not significantly different among anode, cathode and sham tDCS. However, cumulative numbers of behaviours for 10% reward probabilities were more in anode tDCS than in cathode and sham tDCS. Discussion: Anode tDCS for left-prefrontal cortex induced a decrease in sensitivity for the cost and a shift to the performance of commission errors. These results imply that trial-and-error behavioral learning including the reward-related circuit might be altered by tDCS.