P 206. Monitoring short term effects of repetitive transcranial magnetic stimulation (TMS) by TMS-evoked potentials in children

Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187

(a The City College of New York, Biomedical Engineering, New York, United States, b Harvard Medical School, Boston, United States) Transcranial Electrical Stimulation (TES) encompasses all forms of non-invasive current application to the brain in regards to research and clinical applications. Approaches to TES have evolved in both terminology and dosage over the past 100 years of research. We outline the dose and historical development of TES since 1900 through modern approaches. Contemporary transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) and NeuroElectric Therapy (NET) descended from Electrosleep (ES) while others like Transcutaneous Cranial Electrical Stimulation (TCES), and Limoge, descended from Electroanesthesia (EA). Contemporary approaches such as transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS) have historical analogues. We consider the role of seminal conferences and medical device regulations in the evolution of techniques and terminology. Select commercial devices and brands are noted for context. We clarify and disambiguate TES terminology including varied conventions across countries, and non-TES techniques. Understanding the roots of contemporary TES approaches in comparable approaches spanning decades, as well as the resurgence and abandonment of past techniques, may inform ongoing TES research. doi:10.1016/j.clinph.2013.04.280

Poster Session II Novel Techniques

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treatment with low AEDs dose what can deliver patients from negative side effects. doi:10.1016/j.clinph.2013.04.281

P 205. Cortico-conus motor conduction time (CCCT)—H. Matsumoto a, R. Hanajima b, Y. Shirota b, M. Hamada b, Y. Terao b, S. Ohminami b, T. Furubayashi c, S. Nakatani-Enomoto c, Y. Ugawa c (a Japanese Red Cross Medical Center, Neurology, Tokyo, Japan, b University of Tokyo, Neurology, Tokyo, Japan, c Fukushima Medical University, Neurology, Fukushima, Japan) Objective: To measure the conduction time from the motor cortex to the conus medullaris (cortico-conus motor conduction time, CCCT) for leg muscles using magnetic stimulation. Methods: Motor evoked potentials (MEPs) were recorded from right tibialis anterior muscle in 100 healthy volunteers. To activate spinal nerves at the most proximal cauda equina level or at the conus medullaris level, magnetic stimulation was performed using a MATS coil. Transcranial magnetic stimulation of the motor cortex was also conducted to measure the cortical latency for the target muscle. To obtain the CCCT, the latency of MEPs to conus stimulation (conus latency) was subtracted from the cortical latency. Results: MATS coil stimulation evoked reproducible MEPs in all subjects, yielding CCCT data for all studied tibialis anterior muscles. Conclusions: MATS coil stimulation provides CCCT data for healthy subjects. This novel method is useful for evaluation of corticospinal tract conduction for leg muscles because no peripheral component affects the CCCT. doi:10.1016/j.clinph.2013.04.282

P 204. Additive effect of repetitive transcranial magnetic stimulation and anticonvulants—V. Kistsen a, V. Evstigneev a, B. Dubovik b (a Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus, b Belarusian State Medical University, Minsk, Belarus) Objective: The aim of our study was to reveal of rTMS and antiepileptic drugs (AEDs) interaction effects. Methods: The comparative analysis of anticonvulsive effects of rTMS combination with different AEDs (carbamazepine, valproic acid, topiramate and gabapentin) was performed. The experimental data was obtained at maximal electroshock test (MEST) on Wistar rats which took AED in minimal effective doses. RTMS with 1 Hz frequency and difference intensities was performed by circular coil (Neuro-MS, Russia) at pike concentration of AEDs time. Absence of maximal tonic hind limb extension (MTHLE) and all seizure phases durations were estimated. Results of combined therapy groups were conferred with monotherapy (AED or rTMS only) and control group (n = 10 in each group). Results: RTMS has additive effect concerning MTHLE absence when assign with carbamazepine in ED40 in 90% (p = 0.01) and topiramate in ED30 in 80% animals (p = 0.035). Tonic phase duration significant shorten practically in all rTMS + AEDs groups, particular with topiramate (p = 0.002), but had not potentiating effect with gabapentin (p = 0.12). RTMS shortened phase of clonic seizures with body turning-over reflex loss and total seizure duration for all AEDs (p < 0.05). Period after turning-over reflex recovery corrected by rTMS in carbamazepine group only (p = 0.04). Limbs “pedaling” phenomenon reduced in “rTMS + carbamazepine” (p = 0.01) and “rTMS + valproic acid” (p = 0.001) groups. Conclusions: Thereby, rTMS has an additive effect with AEDs. Magnetic stimulation causes the most important anticonvulsive effects when arrange with carbamazepine and topiramate. Results of this study can to be a reason to include low-frequency rTMS in epilepsy

P 206. Monitoring short term effects of repetitive transcranial magnetic stimulation (TMS) by TMS-evoked potentials in children—S. Bender (University of Technology, Dresden, Germany, Child and Adolescent Psychiatry, Dresden, Germany) Question: Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children. TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available. Methods: In a single-blind sham-controlled study, 25 school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition. Results: TMS-evoked N100 amplitude decr eased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation. Conclusions: The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMSevoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to

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demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition. doi:10.1016/j.clinph.2013.04.283

P 207. Reliability of an automated protocol versus manual interpreters in analysing cortical silent period—P. Julkunen, E. Kallioniemi, L. Säisänen, M. Könönen (Kuopio University Hospital, Kuopio, Finland) Introduction: Cortical silent period (cSP) is measured after shortly interrupting active muscle contraction with transcranial magnetic stimulation (TMS) (Fuhr, 1991). The cSP is a measure of cortical inhibition and representing interneuron inhibitory effect at excited motor cortical areas. Several pathological conditions and pharmacological manipulations induce changes to cSP duration. In addition, cSP has exhibited prognostic value e.g., during stroke recovery (Curra, 2002). It has been suggested that input–output characteristics of cSP be determined for thorough assessment of inhibitory interneurons (Werhahn, 2007; Kimiskidis, 2005). These characteristics are commonly analyzed manually from measured electromyography (EMG) signal. However, to avoid inter-interpreter effects in cSP interpretation and detection, as well as to allow quick measurement in real-time, an automatic analysis routine would be preferable. Methods: We reanalyzed previously manually analyzed cSPs (Säisänen, 2008) of the right hand of 55 healthy subjects (27 male, 28 female, age range: 23–80) using a novel automatic routine. Five cSPs were induced at 120% of the resting motor threshold (rMT) focused on the left M1. Furthermore, we recruited one female (age 28) subject for whom the cSPs were induced with several stimulation intensities (SIs), and those cSPs were analyzed manually by two of the authors as well as using the automatic routine. In the automatic routine, we computed the first time-derivative of the single-trial EMG signal (smoothed), and detected longest interval with lower than 15 lV difference between consecutive samples. Results: We found that 99% of all cSPs were identified correctly by the automated routine. There was a good agreement between the cSP durations analyzed manually and automatically (ICC = 0.972, p < 0.001, Fig. 1). Based on ANOVA, the automatic and manual routine did not exhibit significant differences, while the between-subject effect was significant (p < 0.001). When studying the effects of SI and analysis type, we found SI had an effect on the cSP duration (p < 0.001), but not the analysis type (manual or automatic). Between two interpreters, the agreement in manually analyzed cSP durations was excellent (ICC = 0.990, p < 0.001, 95%CI for the difference: 12 ms), as it was between the automatic and manual analysis (mean of two interpreters) (ICC = 0.990, p < 0.001, 95%CI for the difference: 12 ms). The difference between interpreters was similar to that between manual and automated analysis (Fig. 1). Conclusions: Use of automatic cSP detection may enable new mapping modality based on cSP duration, e.g., in patients with lowered cortical excitability, the cSP having a lower threshold than motor evoked potential (Werhahn, 2007). Also, automatic analysis routine will allow for a quick assessment of input–output curve for the cSP improving its applicability.

Fig. 1. doi:10.1016/j.clinph.2013.04.284

Fig. 1. The agreement between the manually and automatically analyzed cSP durations (left). The scatter plot shows the analyzed cSPs with both techniques for 55 subjects, 5 cSP trials each. The cSP durations measured at different SIs from one subject were analyzed manually by two interpreters and automatically. Those cSPs were constructed to a threshold curve (Julkunen, 2011). The agreement between the interpreters andthe automatic routine was very similar (right). The rMT is indicated with a vertical dotted line.

P 208 A K-Rb hybrid Optically Pumped Atomic Magnetometer toward Ultra-low field Multimodal MRI Systems—T. Kobayashi, Y. Ito, M. Ohnishi, K. Mamada, T. Oida (Kyoto University, Department of Electrical Engineering, Kyoto, Japan) Introduction: To contribute for improvement of longevity and quality of human life, we have been developing optically pumped atomic magnetometers (OPAMs) to measure tiny biomagnetic fields and MRIs. In recent years, OPAMs have reached sensitivities comparable to and even surpassing those of magnetometers based on super-conducting quantum interference devices (SQUIDs) [1]. In addition, OPAMs have the intrinsic advantage of not requiring cryogenic cooling. Meanwhile, MRI is one of the most useful diagnostic imaging modalities, which enables visualization of the anatomy and function of the human. However, the conventional high magnetic field scanner has some limitations such as high cost and risk for patients with metal implants. To acquire MRIs without these limitations, ultra-low filed (ULF) MRI systems attracted attention in recent years. Objective: We have developed an OPAM using a hybrid cell of K and Rb atoms [2] toward ULF multimodal MRI systems. The objective of this study is to investigate the optimal properties of the OPAM theoretically comparing with experiment results. Materials and Methods: The sensor head of the OPAM used in this study was a cubic Pyrex glass cell, whose size was 3 x 3 x 3 cm3 and within which K and Rb atoms were enclosed with He and N2 as buffer gases at a ratio of 10 to 1 and at a total pressure of 150 kPa at room temperature. The Rb atoms were spin-polarized by a circularly-polarized pump beam and the spin polarization was transferred to the K atoms by spin exchange collisions. The spin polarization rotated around the external magnetic field orthogonal to both the pump and probe beams. Here, the plane of a linearlypolarized probe beam penetrating the group of spin-polarized atoms is rotated by Faraday effect. We applied a 100 Hz sinusoidal magnetic field of 48 pT as a test signal and examined sensitivities of the OPAM Results: We theoretically investigated the properties of the hybrid OPAM and considered the adequacy of the properties comparing with experiment results. We have found that the experimental results agree well with the theoretical values. The optimum density ratio of K and Rb atoms was expected to be 10-100 for more sensitive magnetometers. We could measure of human magnetocardiograms (MCGs) and plan to measure MR signals using the hybrid OPAM. Conclusion: We developed a K-Rb hybrid OPAM and examined its sensitivities. Results shown in this study demonstrate the feasibility