- Email: [email protected]
Animal research for closed-loop stimulation setup for epilepsy treatment
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Abstracts / Brain Stimulation 8 (2015) 412e427
retinopathy this index was 86.5+ 5.5 s and 131.7+ 10.2 s respectively. In the presence of cerebellar TMS the VEP amplitude depression was less pronounced, and the restoration period of the VEP characteristics shortened to 92,1+ 7,2 s in patients with diabetic retinopathy. Discussion: Hence, gained data revealed that diabetic retinopathy development is linked to prolonged VEP latency period (P100), lowering of the N75-P100 amplitude, as well as to prolongation of the recovery period of the retina’s functional capacity in patients suffering from the second type of diabetes in the presence of photostress. Cerebellar TMS facilitates a faster recovery of the retina’s functional capacity in response to photostress in diabetic patients with retinopathy. It is supposed that antioxidative mechanisms, which are induced by cerebellar stimulation in retina, are in charge for the observed therapeutic effects. 352 Animal research for closed-loop stimulation setup for epilepsy treatment K.H. Somerlik-Fuchs a,b,c,d,*, U.G. Hofmann b,d, T. Stieglitz a,c,d, A. Schulze-Bonhage b,c,d a Laboratory for Biomedical Engineering, IMTEK, Albert-LudwigsUniversity Freiburg, Freiburg, Germany b Neurocenter, University Medical Center Freiburg, Freiburg, Germany c Bernstein Center Freiburg, Freiburg, Germany d Excellenzcluster BrainLinks-BrainTools, University Freiburg, Freiburg, Germany *E-mail: [email protected]. Introduction: The University of Freiburg BrainLinks-BrainTools Cluster of Excellence targets to develop smart devices for seizure therapy. For patients suffering from pharmacological refractory epilepsy closed-loop stimulation devices offer new treatment possibilities. Besides stimulation an important part of these devices are seizure detection or prediction algorithms. Methods: Hippocampal injection of kainic acid leads to hippocampal sclerosis and recurrent epileptic seizures resembling human temporal lobe epilepsy. After an initial status epilepticus, epileptogenesis takes place until a chronic state with spontaneous seizures occurs. Animals were video-EEG-monitored to gain a dataset from these seizures. Videos were screened manually and by using automatic detection algorithms for behavioural seizures. EEG based seizure detection and prediction algorithms were programmed in MATLAB (The MathWorks, Inc., Natick, MA, USA), applied to the data and compared to each other in respect to detection rate and online applicability. Results: 14 kainic acid injected animals are treated for evaluation. More than 400 seizures from more than 2500 h of recordings were used to evaluate seizure detection algorithms for online application. Typical features described in the literature were able to detect the seizures unfortunately with a delay of half of the seizure’s duration. This is clearly too late for our goal to abort the seizure by stimulation before secondary generalization. Seizure prediction methods were therefore adapted to the animal model. Conclusion: Different detection and prediction algorithms were evaluated using animal models of epilepsy for their performance in regard to reliability, celerity and power consumption. Detection algorithms have the problem that the signal changes at the beginning of a seizure are difficult to detect; prediction methods might therefore be more promising for an early application of the stimuli. This is a first step to evaluate closed-loop stimulation approaches and therewith the possibilities for future clinical applications.
Background: No study hitherto has examined test-retest reliability of transcranial magnetic stimulation (TMS) of lower limb muscles in people with Parkinson’s disease (PD). Objective: This study aimed to establish the test-retest reliability of TMS related measurements for tibialis anterior muscles in both healthy subjects and subjects with PD. Methods: We conducted a test-retest reliability study (1 week apart) on measures of corticomotor excitability in 5 healthy subjects (mean age 346.93 years) and 5 subjects with PD (mean age 565.15 years; mean H&Y stage 2.1 0.4) using intraclass correlation coefficients (ICC) and standard error of measurements (SEM). TMS was delivered to the cortical motor area of lower limb with a double cone coil. Motor evoked potentials (MEPs) was recorded on tibialis anterior muscle of the dominant side for healthy subjects and more affected side for subjects with PD. The TMS related measures includes resting motor threshold, slope of recruitment curve, peak MEP at plateau, cortical silent period and short interval intracortical inhibition (SICI). Results: Test-retest reliability for all TMS related measures were excellent in both healthy subjects and subjects with PD: Resting Motor Threshold (ICC¼0.978), slope of Recruitment Curve (ICC¼0.986), Peak MEP (ICC¼0.942), Cortical Silent Period (ICC¼0.98), and SICI (ICC¼0.934). The SEM was low for all measures (SEM ranged from 0.007-0.89) except for SICI (SEM¼6.31). Conclusion: This suggests that measures for corticomotor excitability using TMS are reproducible in both healthy subjects and patients with PD. 354 Repetitive magnetic stimulation induces plasticity of inhibitory postsynapses in mouse organotypic hippocampal slice cultures Maximilian Lenz a,*, Florian Müller-Dahlhaus b, Ulf Ziemann b, Thomas Deller a, Klaus Funke c, Andreas Vlachos a a Goethe-University Frankfurt, Germany b Eberhard-Karls-University Tübingen, Germany c Ruhr-University Bochum, Germany *E-mail: [email protected]. Repetitive transcranial magnetic stimulation (rTMS) of the human brain leads to long-lasting changes in cortical excitability. While robust experimental evidence exists that repetitive magnetic stimulation (rMS) induces structural and functional plasticity of excitatory synapses, it has remained unclear whether rMS also acts by modifying inhibitory synapses on principle neurons. Here, we used 10 Hz rMS of entorhino-hippocampal slice cultures to assess structural and functional changes of inhibitory postsynapses. Whole-cell patch-clamp recordings, immunohistochemistry and GABA-uncaging experiments disclosed that rMS induces a reduction in GABAergic synaptic strength, which is accompanied by structural reorganization of inhibitory postsynapses (at 2 - 4 hours post magnetic stimulation). These rMS-induced effects required the activation of voltage gated sodium channels (VGSC), L-type voltage gated calcium channels (L-VGCC), N-methyl-Daspartate receptors (NMDA-R) and calcineurin protein phosphatase, consistent with a Ca2+-dependent tuning of inhibitory synapses that accompanies LTP of excitatory synapses following rMS in vitro. Our study demonstrates that rMS can lead to coordinated functional and structural changes of inhibitory postsynapses, which suggests a novel mechanism through which r(T)MS can modulate excitation and inhibition (E/I)-balance in neuronal networks. (supported by Federal Ministry of Education and Research, Germany; GCBS-WP1)
353
355
Reliability of transcranial magnetic stimulation related measurements of tibialis anterior muscle in healthy subjects and subjects with Parkinson’s disease L.H. Chung , M.K. Mak * The Hong Kong Polytechnic University, Hong Kong *E-mail: [email protected].
Mapping human cortical excitability through coupling between robotized TMS and EEG Harquel Sylvain a,b, Chauvin Alan a, Beynel Lysianne a, Guyader Nathalie c, Marendaz Christian a, David Olivier d a University Grenoble Alpes, LPNC, F-38000 Grenoble, France; CNRS, LPNC, F-38000 Grenoble, France
Abstracts / Brain Stimulation 8 (2015) 412e427
retinopathy this index was 86.5+ 5.5 s and 131.7+ 10.2 s respectively. In the presence of cerebellar TMS the VEP amplitude depression was less pronounced, and the restoration period of the VEP characteristics shortened to 92,1+ 7,2 s in patients with diabetic retinopathy. Discussion: Hence, gained data revealed that diabetic retinopathy development is linked to prolonged VEP latency period (P100), lowering of the N75-P100 amplitude, as well as to prolongation of the recovery period of the retina’s functional capacity in patients suffering from the second type of diabetes in the presence of photostress. Cerebellar TMS facilitates a faster recovery of the retina’s functional capacity in response to photostress in diabetic patients with retinopathy. It is supposed that antioxidative mechanisms, which are induced by cerebellar stimulation in retina, are in charge for the observed therapeutic effects. 352 Animal research for closed-loop stimulation setup for epilepsy treatment K.H. Somerlik-Fuchs a,b,c,d,*, U.G. Hofmann b,d, T. Stieglitz a,c,d, A. Schulze-Bonhage b,c,d a Laboratory for Biomedical Engineering, IMTEK, Albert-LudwigsUniversity Freiburg, Freiburg, Germany b Neurocenter, University Medical Center Freiburg, Freiburg, Germany c Bernstein Center Freiburg, Freiburg, Germany d Excellenzcluster BrainLinks-BrainTools, University Freiburg, Freiburg, Germany *E-mail: [email protected]. Introduction: The University of Freiburg BrainLinks-BrainTools Cluster of Excellence targets to develop smart devices for seizure therapy. For patients suffering from pharmacological refractory epilepsy closed-loop stimulation devices offer new treatment possibilities. Besides stimulation an important part of these devices are seizure detection or prediction algorithms. Methods: Hippocampal injection of kainic acid leads to hippocampal sclerosis and recurrent epileptic seizures resembling human temporal lobe epilepsy. After an initial status epilepticus, epileptogenesis takes place until a chronic state with spontaneous seizures occurs. Animals were video-EEG-monitored to gain a dataset from these seizures. Videos were screened manually and by using automatic detection algorithms for behavioural seizures. EEG based seizure detection and prediction algorithms were programmed in MATLAB (The MathWorks, Inc., Natick, MA, USA), applied to the data and compared to each other in respect to detection rate and online applicability. Results: 14 kainic acid injected animals are treated for evaluation. More than 400 seizures from more than 2500 h of recordings were used to evaluate seizure detection algorithms for online application. Typical features described in the literature were able to detect the seizures unfortunately with a delay of half of the seizure’s duration. This is clearly too late for our goal to abort the seizure by stimulation before secondary generalization. Seizure prediction methods were therefore adapted to the animal model. Conclusion: Different detection and prediction algorithms were evaluated using animal models of epilepsy for their performance in regard to reliability, celerity and power consumption. Detection algorithms have the problem that the signal changes at the beginning of a seizure are difficult to detect; prediction methods might therefore be more promising for an early application of the stimuli. This is a first step to evaluate closed-loop stimulation approaches and therewith the possibilities for future clinical applications.
Background: No study hitherto has examined test-retest reliability of transcranial magnetic stimulation (TMS) of lower limb muscles in people with Parkinson’s disease (PD). Objective: This study aimed to establish the test-retest reliability of TMS related measurements for tibialis anterior muscles in both healthy subjects and subjects with PD. Methods: We conducted a test-retest reliability study (1 week apart) on measures of corticomotor excitability in 5 healthy subjects (mean age 346.93 years) and 5 subjects with PD (mean age 565.15 years; mean H&Y stage 2.1 0.4) using intraclass correlation coefficients (ICC) and standard error of measurements (SEM). TMS was delivered to the cortical motor area of lower limb with a double cone coil. Motor evoked potentials (MEPs) was recorded on tibialis anterior muscle of the dominant side for healthy subjects and more affected side for subjects with PD. The TMS related measures includes resting motor threshold, slope of recruitment curve, peak MEP at plateau, cortical silent period and short interval intracortical inhibition (SICI). Results: Test-retest reliability for all TMS related measures were excellent in both healthy subjects and subjects with PD: Resting Motor Threshold (ICC¼0.978), slope of Recruitment Curve (ICC¼0.986), Peak MEP (ICC¼0.942), Cortical Silent Period (ICC¼0.98), and SICI (ICC¼0.934). The SEM was low for all measures (SEM ranged from 0.007-0.89) except for SICI (SEM¼6.31). Conclusion: This suggests that measures for corticomotor excitability using TMS are reproducible in both healthy subjects and patients with PD. 354 Repetitive magnetic stimulation induces plasticity of inhibitory postsynapses in mouse organotypic hippocampal slice cultures Maximilian Lenz a,*, Florian Müller-Dahlhaus b, Ulf Ziemann b, Thomas Deller a, Klaus Funke c, Andreas Vlachos a a Goethe-University Frankfurt, Germany b Eberhard-Karls-University Tübingen, Germany c Ruhr-University Bochum, Germany *E-mail: [email protected]. Repetitive transcranial magnetic stimulation (rTMS) of the human brain leads to long-lasting changes in cortical excitability. While robust experimental evidence exists that repetitive magnetic stimulation (rMS) induces structural and functional plasticity of excitatory synapses, it has remained unclear whether rMS also acts by modifying inhibitory synapses on principle neurons. Here, we used 10 Hz rMS of entorhino-hippocampal slice cultures to assess structural and functional changes of inhibitory postsynapses. Whole-cell patch-clamp recordings, immunohistochemistry and GABA-uncaging experiments disclosed that rMS induces a reduction in GABAergic synaptic strength, which is accompanied by structural reorganization of inhibitory postsynapses (at 2 - 4 hours post magnetic stimulation). These rMS-induced effects required the activation of voltage gated sodium channels (VGSC), L-type voltage gated calcium channels (L-VGCC), N-methyl-Daspartate receptors (NMDA-R) and calcineurin protein phosphatase, consistent with a Ca2+-dependent tuning of inhibitory synapses that accompanies LTP of excitatory synapses following rMS in vitro. Our study demonstrates that rMS can lead to coordinated functional and structural changes of inhibitory postsynapses, which suggests a novel mechanism through which r(T)MS can modulate excitation and inhibition (E/I)-balance in neuronal networks. (supported by Federal Ministry of Education and Research, Germany; GCBS-WP1)
353
355
Reliability of transcranial magnetic stimulation related measurements of tibialis anterior muscle in healthy subjects and subjects with Parkinson’s disease L.H. Chung , M.K. Mak * The Hong Kong Polytechnic University, Hong Kong *E-mail: [email protected].
Mapping human cortical excitability through coupling between robotized TMS and EEG Harquel Sylvain a,b, Chauvin Alan a, Beynel Lysianne a, Guyader Nathalie c, Marendaz Christian a, David Olivier d a University Grenoble Alpes, LPNC, F-38000 Grenoble, France; CNRS, LPNC, F-38000 Grenoble, France