- Email: [email protected]
Tolerability of up to 4 mA tDCS using adaptive stimulation
Abstracts / Brain Stimulation 10 (2017) e21ee45
current density and Bz distributions under the same conditions. Results showed good agreement between experimental and simulated Bz and PCD distributions for both electrode configurations. These results suggest MREIT techniques would be a valuable tool in experiments designed to further understanding of TACS mechanisms, validate TDCS and TACS computational models and potentially improve TACS therapy. Abstract #37 DIFFERENTIAL COUPLING OF THE DORSOLATERAL PREFRONTAL CORTEX WITH DEFAULT NETWORK AND VISUAL CORTEX IN PATIENTS RECOVERED FROM DEPRESSION AFTER CONVULSIVE THERAPY M. Moreno-Ortega 1, a, S. Rowny 1, a, J. Prudic 1, A. Kangarlu 2, S. Lee 3, G. Patel 1, J. Grinband 1, D.C. Javitt 1. 1 Division of Experimental Therapeutics, Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, USA; 2 Department of Psychiatry, Radiology and Biomedical Engineering, Columbia University New York, NY, USA; 3 Department of Psychiatry and Biostatistics, Columbia University, New York, NY, USA
Abstract For individuals with treatment resistant depression (TRD), convulsive therapies are the present gold-standard treatments. Mechanism of action of these treatments, however, are presently unknown. The present study evaluates resting state functional connectivity (rsfcMRI) prior to and following convulsive treatment in order to both analyze brain mechanisms underlying TRD, as well as brain mechanisms associated with effective treatment response. rsfcMRI analyses focus primarily on subgenual cingulate, a region that has been associated with TRD based upon anatomical, metabolic and connectivity approaches, and interactions of subgenual cingulate with dorsolateral prefrontal cortex (DLPFC). This network has been extensively implicated in the pathophysiology of depression, but optimal approaches to manipulation remain unknown. Our rsfcMRI data from patients with TRD reveals that the left dorsolateral prefrontal cortical area, which is more anticorrelated with the subgenual cingulate in healthy subjects, is functionally connected to the visual cortex while simultaneously de-coupled from the default network after treatment. This indicates that suppression of default network activity is intimately coupled with top-down modulatory influences on sensory cortical activity. In summary, our study detected a previously unknown role for the DLPFC as an important hub in the interplay with large-scale networks. Such network dynamics between visual cortices and default network has not previously been reported as a measure of efficacy of convulsive treatments. Abstract #38 CHANGES IN HAND FUNCTION AND MOTOR CORTEX EXCITABILITY IN CHILDREN FOLLOWING TDCS AND CIMT THERAPY IN CHILDREN WITH UNILATERAL CEREBRAL PALSY WITH DIFFERENT PATTERNS OF CORTICOSPINAL ORGANIZATION Samuel Nemanich*, Bernadette Gillick. Department of Rehabilitation Medicine, Medical School, University of Minnesota. Minneapolis, MN, USA
Abstract Neuromodulatory interventions such as transcranial direct current stimulation (tDCS) have the potential to improve motor function in children with unilateral cerebral palsy (UCP). However, the neural mechanisms underlying behavioral changes following tDCS are less clear. To investigate this, we compared hand motor function and cortical excitability in children receiving active or sham tDCS paired with constraint-induced movement therapy (CIMT). In addition, we compared outcomes based upon corticospinal circuitry pattern, a potentially important predictor of response to behavioral and neuromodulatory therapies. a
The first two authors contributed equally
e31
Children with UCP were randomized to receive an intervention of tDCS (0.7 mA contralesional cathodal M1-SO montage applied for 20 min) within a 2-hour CIMT session (n ¼10) or sham tDCS and CIMT (n ¼ 10) as a control (clinicaltrials.gov NCT#02250092). Hand function (Assisting Hand Assessment-AHA) was assessed before and after the intervention. Cortical excitability assessment included resting motor threshold (RMT) and motor evoked potential (MEP). In the contralesional hemisphere of the intervention group, the MEP amplitude decreased (active ¼ 2.6±3.5%; sham ¼ -0.17±1.6%) and RMT increased (active ¼ -320±311 mV; sham ¼ 697±693mV), yet no differences were noted between children with contralateral or ipsilateral organization. Improvements in hand function were significantly greater in children with contralateral compared to those with ipsilateral organization (F(1,1) ¼ 7.79, p ¼ 0.01). No significant differences in hand function were observed between intervention and control groups (F(1,1) ¼ 1.83, p ¼ 0.20). These data suggest that corticospinal tract organization and tDCS dosing should be explored in future tDCS studies with focus on individualized treatment. Abstract #39 BEYOND HOME USE MEDICAL DEVICE: TRANSCRANIAL DIRECT CURRENT STIMULATION COMBINED WITH DIGITAL HEALTHCARE Kiwon Lee PhD*1, Seonghoon Kim PhD 2, Dohyoung Kim PhD 2, Seungwoo Lee MD 1, Jinyoung Park MD, PhD 3. 1 Ybrain Inc, Daejeon, Republic of Korea; 2 Ybrain Research Institute, Seoul, Republic of Korea; 3 Department of Psychiatry, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
Abstract In recent years, non-invasive neuromodulation techniques have gained increasing attention not only from research communities, but also from medical and healthcare industries. As an alternative to conventional medicine, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have shown its unique advantages, such as no systemic side-effects and fast onset of efficacy. However, in spite of the advantages, these techniques have been discouraged for use at real clinical settings due to some limitations, including high cost and poor usability in comparison to conventional medicine. In order to overcome such limitations, we have developed a novel neuromodulation healthcare system consisting of two components: 1) a medical device with improved usability and reduced production cost, and 2) software-based healthcare services with enhanced patient compliance and increased quality-of-care. A multi-center, double-blind, randomized, controlled clinical trial is being conducted for the treatment of major depressive disorder at the time of abstract submission and is expected to be finished in November 2016. Abstract #40 TOLERABILITY OF UP TO 4 MA TDCS USING ADAPTIVE STIMULATION Helen Borges 1, Niranjan Khadka*1, Atta Boateng, Jr. 1, Bhaskar Paneri 1, Electra Nassis 1, Yungjae Shin 2, Hyeongseob Choi 2, Seonghoon Kim 2, Kiwon Lee 2, Marom Bikson 1. 1 Department of Biomedical Engineering, The City College of New York, CUNY, NY, USA; 2 Ybrain Inc., Seongnam-si, Republic of Korea
Abstract We develop and validate an adaptive controller to maximize tDCS intensity up to 4 mA, while regulating tolerability. The controller increases stimulation intensity incrementally up to 4 mA while querying subject discomfort. The intelligent controller can learn from historical sessions across a population and within each session in order to adjust applied current up to a tolerated level. In a single-blind design with healthy subjects, we compared: 1) sham stimulation; 2) convention fixed 2 mA; 3) adaptive stimulation up to 4 mA based only on within session history;
e32
Abstracts / Brain Stimulation 10 (2017) e21ee45
4) adaptive stimulation up to 4 mA based also on historical session data. A specially designed tablet-based stimulator regularly queried tolerability (VAS pain) and also provided a Relax and Abort button. Subjects were instructed that the Relax button should be pressed when stimulation was painful but where they could continue if provided relief, and to press Abort when they chose to stop stimulation. In the adaptive arms, current was continually adjusted based on VAS and Relax input. In all arms, stimulation was stopped when Abort was pressed or VAS exceeded a predetermined threshold. Our primary outcome was the average current delivered during a 10-minute session, with any time after an Abort press resulting in current intensity scores of 0 current, reducing the average for the session. Thus an ideal adaptive controller maximizes stimulation output while maintaining tolerability levels acceptable to individual subjects. Both adaptive controllers outperformed fixed 2 mA with use of historical data superior. Abstract #41 COMPARISON OF MATCHING PURSUIT-BASED METHODS FOR EEGBASED ALPHA SPINDLE DETECTION John LaRocco 1, 2, Piotr Franaszczuk 2, Kay Robbins 1. 1 : Department of Computer Science, University of Texas at San Antonio, San Antonio, TX, USA; 2 : Army Research Lab, Aberdeen Proving Ground, Aberdeen, MD, USA
Abstract Neurofeedback requires successful detection of non-stationary events in EEG, such as alpha spindles, which are 0.5 - 2 s bursts in the 8-12 Hz range in EEG. Alpha spindles in the parietal/occipital brain regions are correlated with fatigue, drowsiness, and reduced driving performance in experiments of prolonged driving [1]. Alpha spindles occur during periods of drowsiness and accurate detection could help prevent accidents in many industrial and military sectors. EEG-based detection methods are non-invasive and can be directly related to other brain biomarkers. We compare SDAR (Sequential Discounted AutoRegresion), a dynamic, statistically based algorithm that has successfully detected alpha spindles [2] with a new algorithm based on MP (Matching Pursuit) with Gabor atoms that we are developing. Abstract #42 DRY ELECTRODES FOR TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) Niranjan Khadka*1, Helen Borges-Delfino-De-Souza 1, Atta Boateng, Jr. 1, Bhaskar Paneri 1, Jongmin Jang 2, Byungjik Kim 2, Kiwon Lee 2, Marom Bikson 1. 1 Department of Biomedical Engineering, The City College of New York, CUNY, NY, USA; 2 Ybrain Inc., Seongnam-si, Republic of Korea
Abstract A major contributor to the adoption of transcranial Direct Current Stimulation (tDCS) is the portability and ease-of-use. The preparation of tDCS electrodes remains the most cumbersome and prone-to-error step. Here, we validate the performance of the first “dry” electrodes for tDCS. Dry electrodes are defined as electrodes that exclude: 1) any saline or other electrolytes, that is prone to leaking; 2) an adhesive at the electrode-skin interface or 3) any electrode preparation steps. The Multilayer Hydrogel Composite (MHC) electrode design fulfill these criteria. The MHC electrode performance is verified using a skin-phantom, including measurement of current distribution characteristics at the phantom surface and inside the electrode using a novel sensor array. Experimental data were compared against the finite element method (FEM) model of MHC performance. Further validation of the MHC electrode performance was conducted in in human trial including tolerability. Under the conditions tested (2 mA and 20 minute), the MHC electrode performance was comparative with the state-of-the-art sponge electrodes (PreSaturated Snap EasyPad).
Abstract #43 TOWARDS AN IMPROVED UNDERSTANDING OF THE SENSITIVITY OF CORTICAL NEURONS TO STIMULATION Shelley Fried*1, 2, Seung Woo Lee 2. 1 Boston VA Healthcare System, Boston, MA, USA; 2 Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA
Abstract The factors influencing the sensitivity of cortical neurons to artificial stimulation are still not fully understood. While advances in computational modeling software improve the ability to estimate the fields arising from a given set of stimulating conditions, the factors governing the sensitivity of individual neurons to such fields have not been completely elucidated. Here, we used mouse brain slices to study the sensitivity of individual cortical neurons to different forms of stimulation. Small electrodes or micro-coils allowed stimulation to be confined to a narrow region within targeted cells and enabled the sensitivity of individual regions to be compared. In naïve (previously unstimulated) L5 pyramidal neurons (PNs), the proximal axon had the highest sensitivity to stimulation. Interestingly however, repetitive stimulation caused the sensitivity of the apical dendrite to increase beyond that of the axon; the number of stimuli required to induce the switch was comparable to the number delivered during common rTMS paradigms. Once the change in sensitivity occurred, it persisted for the duration of our experiments (up to ~1 hour). Consistent repetitive stimulation induced the change with fewer pulses than trains in which stimulation was intermittent. Many aspects of the response (peak firing rate, duration, etc.) were different for different types of PNs. Rotation of the micro-coil allowed the sensitivity to field orientation to be tested and revealed that fields oriented along the long axis of PNs were highly effective but those oriented orthogonally did not induce spiking, even for delivery of several thousand stimuli. Abstract #44 THE HISTORY OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) AND ETHICAL CONCERNS Pooneh Heshmati*. Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY, USA
Abstract Transcranial magnetic stimulation is a magnetic technique used to stimulate the human brain. During the procedure, a coil is placed near the head of the person receiving the treatment. The first reliable TMS was developed by Anthony Barker. Actually, the physical principles of TMS were discovered by Michael Faraday, showing that a pulse of electric current passing through a wire coil can generate a magnetic field. The study of galvanic effects in biology which is called electrophysiology has been discovered by Luigi Galvani. As the research and clinical utility of TMS raises, treatment protocols must be considered. There are different issues in terms of ethical considerations such as: Device safety, proper protocol, short and long term effects, and patient screening. Research and clinical applications of TMS must be governed by three basic ethical and legal requirements applying to all studies on human subjects, on which a full consensus has been reached: A. Informed consent. B. Risk-to-benefit ratio, the likelihood of clinical benefit should be more than the potential risks. C. Equal distribution of the burdens and benefits of research. The facts about what TMS can and cannot offer must be explicitly stated, and every effort to balance a subject’s assumptions and hopes with the unpredictable reality of science must be made. Although it is not always feasible to present effects generated in healthy subjects to the patients, the inclusion of cognitive conflict on the list of possible treatment side effects should be considered.
current density and Bz distributions under the same conditions. Results showed good agreement between experimental and simulated Bz and PCD distributions for both electrode configurations. These results suggest MREIT techniques would be a valuable tool in experiments designed to further understanding of TACS mechanisms, validate TDCS and TACS computational models and potentially improve TACS therapy. Abstract #37 DIFFERENTIAL COUPLING OF THE DORSOLATERAL PREFRONTAL CORTEX WITH DEFAULT NETWORK AND VISUAL CORTEX IN PATIENTS RECOVERED FROM DEPRESSION AFTER CONVULSIVE THERAPY M. Moreno-Ortega 1, a, S. Rowny 1, a, J. Prudic 1, A. Kangarlu 2, S. Lee 3, G. Patel 1, J. Grinband 1, D.C. Javitt 1. 1 Division of Experimental Therapeutics, Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, USA; 2 Department of Psychiatry, Radiology and Biomedical Engineering, Columbia University New York, NY, USA; 3 Department of Psychiatry and Biostatistics, Columbia University, New York, NY, USA
Abstract For individuals with treatment resistant depression (TRD), convulsive therapies are the present gold-standard treatments. Mechanism of action of these treatments, however, are presently unknown. The present study evaluates resting state functional connectivity (rsfcMRI) prior to and following convulsive treatment in order to both analyze brain mechanisms underlying TRD, as well as brain mechanisms associated with effective treatment response. rsfcMRI analyses focus primarily on subgenual cingulate, a region that has been associated with TRD based upon anatomical, metabolic and connectivity approaches, and interactions of subgenual cingulate with dorsolateral prefrontal cortex (DLPFC). This network has been extensively implicated in the pathophysiology of depression, but optimal approaches to manipulation remain unknown. Our rsfcMRI data from patients with TRD reveals that the left dorsolateral prefrontal cortical area, which is more anticorrelated with the subgenual cingulate in healthy subjects, is functionally connected to the visual cortex while simultaneously de-coupled from the default network after treatment. This indicates that suppression of default network activity is intimately coupled with top-down modulatory influences on sensory cortical activity. In summary, our study detected a previously unknown role for the DLPFC as an important hub in the interplay with large-scale networks. Such network dynamics between visual cortices and default network has not previously been reported as a measure of efficacy of convulsive treatments. Abstract #38 CHANGES IN HAND FUNCTION AND MOTOR CORTEX EXCITABILITY IN CHILDREN FOLLOWING TDCS AND CIMT THERAPY IN CHILDREN WITH UNILATERAL CEREBRAL PALSY WITH DIFFERENT PATTERNS OF CORTICOSPINAL ORGANIZATION Samuel Nemanich*, Bernadette Gillick. Department of Rehabilitation Medicine, Medical School, University of Minnesota. Minneapolis, MN, USA
Abstract Neuromodulatory interventions such as transcranial direct current stimulation (tDCS) have the potential to improve motor function in children with unilateral cerebral palsy (UCP). However, the neural mechanisms underlying behavioral changes following tDCS are less clear. To investigate this, we compared hand motor function and cortical excitability in children receiving active or sham tDCS paired with constraint-induced movement therapy (CIMT). In addition, we compared outcomes based upon corticospinal circuitry pattern, a potentially important predictor of response to behavioral and neuromodulatory therapies. a
The first two authors contributed equally
e31
Children with UCP were randomized to receive an intervention of tDCS (0.7 mA contralesional cathodal M1-SO montage applied for 20 min) within a 2-hour CIMT session (n ¼10) or sham tDCS and CIMT (n ¼ 10) as a control (clinicaltrials.gov NCT#02250092). Hand function (Assisting Hand Assessment-AHA) was assessed before and after the intervention. Cortical excitability assessment included resting motor threshold (RMT) and motor evoked potential (MEP). In the contralesional hemisphere of the intervention group, the MEP amplitude decreased (active ¼ 2.6±3.5%; sham ¼ -0.17±1.6%) and RMT increased (active ¼ -320±311 mV; sham ¼ 697±693mV), yet no differences were noted between children with contralateral or ipsilateral organization. Improvements in hand function were significantly greater in children with contralateral compared to those with ipsilateral organization (F(1,1) ¼ 7.79, p ¼ 0.01). No significant differences in hand function were observed between intervention and control groups (F(1,1) ¼ 1.83, p ¼ 0.20). These data suggest that corticospinal tract organization and tDCS dosing should be explored in future tDCS studies with focus on individualized treatment. Abstract #39 BEYOND HOME USE MEDICAL DEVICE: TRANSCRANIAL DIRECT CURRENT STIMULATION COMBINED WITH DIGITAL HEALTHCARE Kiwon Lee PhD*1, Seonghoon Kim PhD 2, Dohyoung Kim PhD 2, Seungwoo Lee MD 1, Jinyoung Park MD, PhD 3. 1 Ybrain Inc, Daejeon, Republic of Korea; 2 Ybrain Research Institute, Seoul, Republic of Korea; 3 Department of Psychiatry, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
Abstract In recent years, non-invasive neuromodulation techniques have gained increasing attention not only from research communities, but also from medical and healthcare industries. As an alternative to conventional medicine, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have shown its unique advantages, such as no systemic side-effects and fast onset of efficacy. However, in spite of the advantages, these techniques have been discouraged for use at real clinical settings due to some limitations, including high cost and poor usability in comparison to conventional medicine. In order to overcome such limitations, we have developed a novel neuromodulation healthcare system consisting of two components: 1) a medical device with improved usability and reduced production cost, and 2) software-based healthcare services with enhanced patient compliance and increased quality-of-care. A multi-center, double-blind, randomized, controlled clinical trial is being conducted for the treatment of major depressive disorder at the time of abstract submission and is expected to be finished in November 2016. Abstract #40 TOLERABILITY OF UP TO 4 MA TDCS USING ADAPTIVE STIMULATION Helen Borges 1, Niranjan Khadka*1, Atta Boateng, Jr. 1, Bhaskar Paneri 1, Electra Nassis 1, Yungjae Shin 2, Hyeongseob Choi 2, Seonghoon Kim 2, Kiwon Lee 2, Marom Bikson 1. 1 Department of Biomedical Engineering, The City College of New York, CUNY, NY, USA; 2 Ybrain Inc., Seongnam-si, Republic of Korea
Abstract We develop and validate an adaptive controller to maximize tDCS intensity up to 4 mA, while regulating tolerability. The controller increases stimulation intensity incrementally up to 4 mA while querying subject discomfort. The intelligent controller can learn from historical sessions across a population and within each session in order to adjust applied current up to a tolerated level. In a single-blind design with healthy subjects, we compared: 1) sham stimulation; 2) convention fixed 2 mA; 3) adaptive stimulation up to 4 mA based only on within session history;
e32
Abstracts / Brain Stimulation 10 (2017) e21ee45
4) adaptive stimulation up to 4 mA based also on historical session data. A specially designed tablet-based stimulator regularly queried tolerability (VAS pain) and also provided a Relax and Abort button. Subjects were instructed that the Relax button should be pressed when stimulation was painful but where they could continue if provided relief, and to press Abort when they chose to stop stimulation. In the adaptive arms, current was continually adjusted based on VAS and Relax input. In all arms, stimulation was stopped when Abort was pressed or VAS exceeded a predetermined threshold. Our primary outcome was the average current delivered during a 10-minute session, with any time after an Abort press resulting in current intensity scores of 0 current, reducing the average for the session. Thus an ideal adaptive controller maximizes stimulation output while maintaining tolerability levels acceptable to individual subjects. Both adaptive controllers outperformed fixed 2 mA with use of historical data superior. Abstract #41 COMPARISON OF MATCHING PURSUIT-BASED METHODS FOR EEGBASED ALPHA SPINDLE DETECTION John LaRocco 1, 2, Piotr Franaszczuk 2, Kay Robbins 1. 1 : Department of Computer Science, University of Texas at San Antonio, San Antonio, TX, USA; 2 : Army Research Lab, Aberdeen Proving Ground, Aberdeen, MD, USA
Abstract Neurofeedback requires successful detection of non-stationary events in EEG, such as alpha spindles, which are 0.5 - 2 s bursts in the 8-12 Hz range in EEG. Alpha spindles in the parietal/occipital brain regions are correlated with fatigue, drowsiness, and reduced driving performance in experiments of prolonged driving [1]. Alpha spindles occur during periods of drowsiness and accurate detection could help prevent accidents in many industrial and military sectors. EEG-based detection methods are non-invasive and can be directly related to other brain biomarkers. We compare SDAR (Sequential Discounted AutoRegresion), a dynamic, statistically based algorithm that has successfully detected alpha spindles [2] with a new algorithm based on MP (Matching Pursuit) with Gabor atoms that we are developing. Abstract #42 DRY ELECTRODES FOR TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) Niranjan Khadka*1, Helen Borges-Delfino-De-Souza 1, Atta Boateng, Jr. 1, Bhaskar Paneri 1, Jongmin Jang 2, Byungjik Kim 2, Kiwon Lee 2, Marom Bikson 1. 1 Department of Biomedical Engineering, The City College of New York, CUNY, NY, USA; 2 Ybrain Inc., Seongnam-si, Republic of Korea
Abstract A major contributor to the adoption of transcranial Direct Current Stimulation (tDCS) is the portability and ease-of-use. The preparation of tDCS electrodes remains the most cumbersome and prone-to-error step. Here, we validate the performance of the first “dry” electrodes for tDCS. Dry electrodes are defined as electrodes that exclude: 1) any saline or other electrolytes, that is prone to leaking; 2) an adhesive at the electrode-skin interface or 3) any electrode preparation steps. The Multilayer Hydrogel Composite (MHC) electrode design fulfill these criteria. The MHC electrode performance is verified using a skin-phantom, including measurement of current distribution characteristics at the phantom surface and inside the electrode using a novel sensor array. Experimental data were compared against the finite element method (FEM) model of MHC performance. Further validation of the MHC electrode performance was conducted in in human trial including tolerability. Under the conditions tested (2 mA and 20 minute), the MHC electrode performance was comparative with the state-of-the-art sponge electrodes (PreSaturated Snap EasyPad).
Abstract #43 TOWARDS AN IMPROVED UNDERSTANDING OF THE SENSITIVITY OF CORTICAL NEURONS TO STIMULATION Shelley Fried*1, 2, Seung Woo Lee 2. 1 Boston VA Healthcare System, Boston, MA, USA; 2 Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA
Abstract The factors influencing the sensitivity of cortical neurons to artificial stimulation are still not fully understood. While advances in computational modeling software improve the ability to estimate the fields arising from a given set of stimulating conditions, the factors governing the sensitivity of individual neurons to such fields have not been completely elucidated. Here, we used mouse brain slices to study the sensitivity of individual cortical neurons to different forms of stimulation. Small electrodes or micro-coils allowed stimulation to be confined to a narrow region within targeted cells and enabled the sensitivity of individual regions to be compared. In naïve (previously unstimulated) L5 pyramidal neurons (PNs), the proximal axon had the highest sensitivity to stimulation. Interestingly however, repetitive stimulation caused the sensitivity of the apical dendrite to increase beyond that of the axon; the number of stimuli required to induce the switch was comparable to the number delivered during common rTMS paradigms. Once the change in sensitivity occurred, it persisted for the duration of our experiments (up to ~1 hour). Consistent repetitive stimulation induced the change with fewer pulses than trains in which stimulation was intermittent. Many aspects of the response (peak firing rate, duration, etc.) were different for different types of PNs. Rotation of the micro-coil allowed the sensitivity to field orientation to be tested and revealed that fields oriented along the long axis of PNs were highly effective but those oriented orthogonally did not induce spiking, even for delivery of several thousand stimuli. Abstract #44 THE HISTORY OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) AND ETHICAL CONCERNS Pooneh Heshmati*. Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY, USA
Abstract Transcranial magnetic stimulation is a magnetic technique used to stimulate the human brain. During the procedure, a coil is placed near the head of the person receiving the treatment. The first reliable TMS was developed by Anthony Barker. Actually, the physical principles of TMS were discovered by Michael Faraday, showing that a pulse of electric current passing through a wire coil can generate a magnetic field. The study of galvanic effects in biology which is called electrophysiology has been discovered by Luigi Galvani. As the research and clinical utility of TMS raises, treatment protocols must be considered. There are different issues in terms of ethical considerations such as: Device safety, proper protocol, short and long term effects, and patient screening. Research and clinical applications of TMS must be governed by three basic ethical and legal requirements applying to all studies on human subjects, on which a full consensus has been reached: A. Informed consent. B. Risk-to-benefit ratio, the likelihood of clinical benefit should be more than the potential risks. C. Equal distribution of the burdens and benefits of research. The facts about what TMS can and cannot offer must be explicitly stated, and every effort to balance a subject’s assumptions and hopes with the unpredictable reality of science must be made. Although it is not always feasible to present effects generated in healthy subjects to the patients, the inclusion of cognitive conflict on the list of possible treatment side effects should be considered.