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P168 Technical Advances in neurostimulation
Abstracts of the 13th European Congress of Clinical Neurophysiology / Clinical Neurophysiology 119 (2008), S1–S131 Method: Ten minutes, 16 channel, bipolar EEG of generalized seizure (n=13), normal eyes open (n=10) eyes close (n=10), and sleep stages 2,3,4 and Rapid eye movement sleep (REM) (n=10) were studied. Time-lagged instantaneous phases were determined using Hilbert transform across onedimensional channel data. Synchronization index (SI) was defined using Shannon entropy measures. Auto-bicoherence index (BI) was calculated using higher order spectral estimate. Results: SI of normal eyes open, eye closed and seizure EEG was 0.122±0.006, 0.164±0.034 and 0.352±0.091 respectively. SI of Stage 2,3,4 and REM sleep was 0.1143±0.009, 0.01425±0.018, 0.1562±0.014 and 0.1048±0.013 respectively. SI between the groups varied significantly (p<0.001). BI of eyes open EEG was 7.994±1.198, which was comparable with the BI of seizures EEG (12.794±11.778). BI between sleep stages did not vary significantly (p = 0.212). Seizure BI was significantly higher when compared with eyes closed BI (p=0.022) and clubbed sleep BI (p=0.003). There was no correlation between SI and BI (r=0.399, p=0.081). Conclusion: Degree of synchrony was found to be: seizure > normal eyes closed > Stage 4 > Stage 3 > eyes open > Stage 2 > REM. We found higher bicoherence in seizures and eyes open states suggesting increased quadratic phase coupling of neural networks. This was not seen in eyes closed states where phase decoupling occurs akin to what was seen in stage II/III sleep. The synchrony of neural discharge (signal morphology) and the non-Gaussian component (frequency coupling) are probably heterogeneous.
P167 Kinase pathway regulates neuro-steroids modulation of GABAA receptors in amygdala-kindling model of temporal lobe epilepsy (TLE) Arash Kia, Michael Poulter Robarts Research Institute and the Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada Hypothesis: Since phosphorylation has been implicated in regulating THDOC pharmacology, we hypothesized that perhaps kindling induces (long term) changes in the phosphorylation of GABAA receptors. Materials & methods: The experiments have been done through patch clamp recordings in coronal slices (400 µm) prepared from SD male rats (200-250 gm).GABAA synaptic responses were isolated by applying: TTX: (Na+ channel blocker), 200 nM; APV: (a selective NMDA receptor (NMDAR) antagonist), 50 µM; DNQX: (an AMPA and Kainate receptor antagonist), 20 µM. In order to enhance the phosphorylation in the receptors we applied PMA as a PKC activator, 100nM and we used FK506 as a Protein phosphatase 2B inhibitor, 100nM. To induce neuro-steroid modulation we applied THDOC (100 nM) for 10 min. Results: Through kinase activation or phosphatase inhibition, THDOC reduces the amplitude of mIPSCs, but it has no effect on THDOC induced prolongation. Total amount of inhibition (charge transfer) does not change in the cell membrane. It seems phosphorylation enhances the THDOC induced augmentation of tonic inhibition. Conclusion: These alterations in the THDOC pharmacology are nearly identical to those seen after kindling supporting our hypothesis that kindling changes the phosphorylation state of GABAA receptors.
P168 Technical Advances in neurostimulation Metin Tulgar Neurotechnology Center, Istanbul, Turkey Purpose: Neurostimulation is a process by which nerves partially loosing their function as a result of disease or travma are stimulated using electrical pulses for regeneration. Therapeutic signals used for this purpose must be consistent with the nature of human neurophysiology. Neuro-implant is a device that stimulates the nervous system under the skin after surgery, e.g. spinal cord stimulation to control chronic pain, vagus nerve stimulation for the management of epilepsy, depression and Alzheimer’s disease, phrenic nerve stimulation for diaphragm pacing in respiratory disorders, deep brain stimulation for the management of Parkinson’s disease. The existing implants generally operate utilizing either radio-frequency (RF) transmission or fully implantation techniques. In both case, some electronic compo-
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nents are implanted in the body. Totally implantable systems have also an implanted battery. To overcome the problems encountered with present implants such as component failure, limited battery life, programming difficulties and high cost, a new system, namely the Tulgar neuro-implant, that is based on trans-dermal coupling principles, has been developed and tested. Method: The Tulgar implant system mainly consists of two parts: implantable passive part and external active part. The stimulating signals produced by external stimulator are linked to active element that is placed on the skin overlying the implanted passive element, and are transmitted across the skin by inductive coupling. The implanted passive element is connected in compact to the electrode located near by target neural tissue. The main goal of the present invention is that there are neither any electronic components nor a battery in the internal part of the system, thus eliminating the risk of component failure and limitation in battery life. On the other hand, 80% reduction in size enhances the surgical procedure especially in children. Tulgar implants were tested as a spinal cord stimulator in ten sheep to evaluate the response of living tissue and technical performance of the new system after the approval by local ethics committees, Gaziantep University Faculty of Medicine and Selcuk University Experimental Medical Center. Also a pilot clinical study has recently (on May 29, 2007) been undertaken employing TULGAR TI1 Model Vagal Stimulator Implant System for the management of refractory epilepsy after the approval of Ethical Committee of the Ministry of Health of Republic of Turkey. Results: Animal tests showed that the new system could reliably be implanted in the living tissue. The patient who participated in the pilot study was a 37 year old guy complaining of refractory epilepsy with heavy seizures for 24 years, now frequency and intensity of the seizures reduced, and he is back to life. Conclusion: Tulgar implants, which are patented with full quality assurance certificates (CE, ISO 9001:2000 and EN ISO 13485:2003), appears to be competitive to the presently known neuroimplants in terms of quality, safety, reliability, reduction in size and cost.
P169 Three-dimensional probabilistic neuroanatomical correlation via the international 10–10 system oriented for brain mapping Laurent Koessler 1 , Louis Maillard 1 , Adnane Benhadid 2 , Jean-Pierre Vignal 1 , Marc Braun 2 , Hervé I. Vespignan 1 1 Neurology Department, University Hospital, Nancy, France; 2 INSERM ERI13, Nancy University, Nancy, France The advent of high resolution EEG has expanded its technical potential for human brain mapping. In the particular case of focal and superficial dysplasias, it is important to know which cerebral structure is underneath the EEG sensors. Although the knowledge of anatomical structures beneath EEG electrodes is well established for the 10-20 system, it is not clear for high number of electrodes like to the high resolution EEG. We have examined cerebral correlations using MRI via the guidance of the international 10–10 system for electrode placement. Sixty-four new EEG sensors which combined MRI markers and Ag/AgCl electrodes have been taped onto the scalp of sixteen healthy subjects. Thanks to the ALLES method, we have implemented a toolbox for the projection of the sensor positions onto the brain. We have normalized the 10–10 cortical projection points of the subjects to Talairach stereotaxic coordinates and obtained their probabilistic distributions. We have build for each EEG sensor an atlas which shows the anatomical projection in the MRI volume and onto Talairach atlas. We have obtained a mean dispersion about 4.6 mm in x, 7.1 mm in y and 7.8 mm in z. Regarding inter-subject variability, cerebral projections for 10-20 system were consistent with previous studies. For the other positions, we found that in some areas the same sensor can be projected on different anatomical structures (like T7) whereas other sensors are always projected on the same cerebral structure (like FC2). In most cases of intractable epilepsy, successful surgery entails the resection of electrophysiologically abnormal cortical tissue rather than an identifiable mass lesion. EEG electrode projection is a unique and useful pre-surgical tool in cases of focal and superficial generators because it
P167 Kinase pathway regulates neuro-steroids modulation of GABAA receptors in amygdala-kindling model of temporal lobe epilepsy (TLE) Arash Kia, Michael Poulter Robarts Research Institute and the Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada Hypothesis: Since phosphorylation has been implicated in regulating THDOC pharmacology, we hypothesized that perhaps kindling induces (long term) changes in the phosphorylation of GABAA receptors. Materials & methods: The experiments have been done through patch clamp recordings in coronal slices (400 µm) prepared from SD male rats (200-250 gm).GABAA synaptic responses were isolated by applying: TTX: (Na+ channel blocker), 200 nM; APV: (a selective NMDA receptor (NMDAR) antagonist), 50 µM; DNQX: (an AMPA and Kainate receptor antagonist), 20 µM. In order to enhance the phosphorylation in the receptors we applied PMA as a PKC activator, 100nM and we used FK506 as a Protein phosphatase 2B inhibitor, 100nM. To induce neuro-steroid modulation we applied THDOC (100 nM) for 10 min. Results: Through kinase activation or phosphatase inhibition, THDOC reduces the amplitude of mIPSCs, but it has no effect on THDOC induced prolongation. Total amount of inhibition (charge transfer) does not change in the cell membrane. It seems phosphorylation enhances the THDOC induced augmentation of tonic inhibition. Conclusion: These alterations in the THDOC pharmacology are nearly identical to those seen after kindling supporting our hypothesis that kindling changes the phosphorylation state of GABAA receptors.
P168 Technical Advances in neurostimulation Metin Tulgar Neurotechnology Center, Istanbul, Turkey Purpose: Neurostimulation is a process by which nerves partially loosing their function as a result of disease or travma are stimulated using electrical pulses for regeneration. Therapeutic signals used for this purpose must be consistent with the nature of human neurophysiology. Neuro-implant is a device that stimulates the nervous system under the skin after surgery, e.g. spinal cord stimulation to control chronic pain, vagus nerve stimulation for the management of epilepsy, depression and Alzheimer’s disease, phrenic nerve stimulation for diaphragm pacing in respiratory disorders, deep brain stimulation for the management of Parkinson’s disease. The existing implants generally operate utilizing either radio-frequency (RF) transmission or fully implantation techniques. In both case, some electronic compo-
S113
nents are implanted in the body. Totally implantable systems have also an implanted battery. To overcome the problems encountered with present implants such as component failure, limited battery life, programming difficulties and high cost, a new system, namely the Tulgar neuro-implant, that is based on trans-dermal coupling principles, has been developed and tested. Method: The Tulgar implant system mainly consists of two parts: implantable passive part and external active part. The stimulating signals produced by external stimulator are linked to active element that is placed on the skin overlying the implanted passive element, and are transmitted across the skin by inductive coupling. The implanted passive element is connected in compact to the electrode located near by target neural tissue. The main goal of the present invention is that there are neither any electronic components nor a battery in the internal part of the system, thus eliminating the risk of component failure and limitation in battery life. On the other hand, 80% reduction in size enhances the surgical procedure especially in children. Tulgar implants were tested as a spinal cord stimulator in ten sheep to evaluate the response of living tissue and technical performance of the new system after the approval by local ethics committees, Gaziantep University Faculty of Medicine and Selcuk University Experimental Medical Center. Also a pilot clinical study has recently (on May 29, 2007) been undertaken employing TULGAR TI1 Model Vagal Stimulator Implant System for the management of refractory epilepsy after the approval of Ethical Committee of the Ministry of Health of Republic of Turkey. Results: Animal tests showed that the new system could reliably be implanted in the living tissue. The patient who participated in the pilot study was a 37 year old guy complaining of refractory epilepsy with heavy seizures for 24 years, now frequency and intensity of the seizures reduced, and he is back to life. Conclusion: Tulgar implants, which are patented with full quality assurance certificates (CE, ISO 9001:2000 and EN ISO 13485:2003), appears to be competitive to the presently known neuroimplants in terms of quality, safety, reliability, reduction in size and cost.
P169 Three-dimensional probabilistic neuroanatomical correlation via the international 10–10 system oriented for brain mapping Laurent Koessler 1 , Louis Maillard 1 , Adnane Benhadid 2 , Jean-Pierre Vignal 1 , Marc Braun 2 , Hervé I. Vespignan 1 1 Neurology Department, University Hospital, Nancy, France; 2 INSERM ERI13, Nancy University, Nancy, France The advent of high resolution EEG has expanded its technical potential for human brain mapping. In the particular case of focal and superficial dysplasias, it is important to know which cerebral structure is underneath the EEG sensors. Although the knowledge of anatomical structures beneath EEG electrodes is well established for the 10-20 system, it is not clear for high number of electrodes like to the high resolution EEG. We have examined cerebral correlations using MRI via the guidance of the international 10–10 system for electrode placement. Sixty-four new EEG sensors which combined MRI markers and Ag/AgCl electrodes have been taped onto the scalp of sixteen healthy subjects. Thanks to the ALLES method, we have implemented a toolbox for the projection of the sensor positions onto the brain. We have normalized the 10–10 cortical projection points of the subjects to Talairach stereotaxic coordinates and obtained their probabilistic distributions. We have build for each EEG sensor an atlas which shows the anatomical projection in the MRI volume and onto Talairach atlas. We have obtained a mean dispersion about 4.6 mm in x, 7.1 mm in y and 7.8 mm in z. Regarding inter-subject variability, cerebral projections for 10-20 system were consistent with previous studies. For the other positions, we found that in some areas the same sensor can be projected on different anatomical structures (like T7) whereas other sensors are always projected on the same cerebral structure (like FC2). In most cases of intractable epilepsy, successful surgery entails the resection of electrophysiologically abnormal cortical tissue rather than an identifiable mass lesion. EEG electrode projection is a unique and useful pre-surgical tool in cases of focal and superficial generators because it