Antidepressant Effects of ECT may be related to Hippocampal Neurogenesis

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Abstracts / Brain Stimulation 8 (2015) 412e427

depression. The several treatment parameters have also varied considerably between studies and reflect the lack of consensus for optimal parameters for depression. Whilst few reports have linked patterns of rTMS response to some treatment parameters, the relationship between treatment parameters and efficacy remains to be elucidated. Furthermore, unlike several trials and meta-analyses, this analysis will exclude older depressed samples with potentially different neuropathologies that may confound findings. Methods: PubMed was used to search for peer-reviewed studies published between August 1975 and October 2014 on the efficacy of high-frequency, left prefrontal cortex rTMS treatment in mood disorder cohorts under 65 years-old. Twenty-two studies met eligibility criteria (N¼906; mean-age¼45) for random effects modelling and pooled effect sizes (ES) for improvement in depression ratings were generated. Moderator analyses were performed to identify predictors of between-study heterogeneity. Results: After controlling for significant publication bias (p<.05), active rTMS was significantly more efficacious in treating depression compared with sham rTMS (ES 0.9). There was significant heterogeneity in effect size (I2¼79%; p<.001). Intensity, frequency, total number of pulses or number of sessions did not significantly predict between-study heterogeneity (all p>.05). Conclusions: In keeping with the literature, rTMS has shown to be an overall efficacious treatment for depression in people aged under 65 years despite the large degree of heterogeneity in findings and parameters between clinical trials. It is possible that the parameters included here did not appear to influence efficacy, in part, due to the confounding effects of many other treatment parameters. Future analyses with larger samples should perform multivariate analyses with all predictors in a single model. Additionally, attempts to quantify trial quality and exclude poorer quality trials in analyses may prove insightful.

372 Prolonged continuous theta-burst stimulation is more analgesic than ‘classical’ high frequency repetitive transcranial magnetic stimulation D. Bouhassira a,b, S. Goudeau c, F. Poindessous-Jazat a, S. Baudic a, P. Clavelou c, X. Moisset a,d a Inserm U987, France b Versailles-Saint-Quentin University, France c Poitiers University, France d Clermont Ferrand University, France Introduction: The objectives of this study were (1) to evaluate the analgesic effects of neuronavigated intermettent (iTBS) and prolonged continuous (pcTBS) theta burst stimulation (TBS), comparing them with those of classical high frequency rTMS (10 Hz) over the left M1, (2) to elucidate the role of conditioned pain modulation (CPM) in the antinociceptive effect of rTMS and (3) to investigate possible correlations between analgesia and cortical excitability. Methods: Fourteen healthy volunteers participated in four experimental sessions, carried out in a random order (iTBS, pcTBS, 10 Hz rTMS or sham). Cold pain threshold, CPM and cortical excitability measurements were carried out before and after rTMS. Results: We found that 10 Hz rTMS and pcTBS were significantly superior to sham rTMS for the induction of cold analgesia. Moreover, pcTBS was significantly more effective than 10Hz rTMS (p¼0.026). Analgesia did not seem to be driven by changes in CPM or cortical excitability. Conclusion: Prolonged cTBS has considerable clinical potential, as it has a shorter treatment duration (by a factor 8) and stronger analgesic effects than the classical high frequency protocol. Studies

in patients are required to confirm the potential of this new stimulation paradigm for clinical applications. 373 Cerebellar and parietal anodal transcranial direct current stimulation increases mirror drawing performance Doppelmayr M. , Pixa N. Dep. Sportscience, University Mainz, Germany Introduction: Several brain areas, including the primary motor cortex, parietal areas, basal ganglia, cerebellum and many more are involved in motor adaption. While most paradigms investigating the effects of transcranial direct current stimulation (tDCS) on motor performance focus on the stimulation of the primary motor cortex, we investigated these effects with parietal and cerebellar stimulation. Methods: 39 subjects, randomly assigned to one of three stimulation groups, had to complete a series of mirror drawing tasks. Participants (n¼39, age M¼24,44; SD¼1.62) were seated in front of a mirror and geometrical figures were presented in a way that these figures were only visible via the mirror. The task was to learn to follow the lines with a pencil, held in the right hand. Beside a pre and a posttest the participants had to perform this task for 20 minutes while stimulated. Additionally a follow up test was performed 20 minutes delayed. Stimulation was applied either at parietal or cerebellar sites or as sham stimulation. 1mA with pi-electrodes (3,14cm2) was applied for 20 minutes and multiple return sites were used. Results: Analyzing the speed of the drawing a two-way ANOVA TIME (Pre, Training, Post, Follow up) and GROUP revealed significant (p < 0,05) effects for TIME and GROUP as well as a significant interaction. Participants stimulated at cerebellar locations had the shortest and the sham stimulation group the longest drawing times with increasing group differences with TIME. Concerning drawing quality a similar result emerged indicating the best results for the cerebellar stimulation group and the worst for the sham group. Again differences increased with TIME. Discussion: Taken together the data indicate that tDCS can be effective in increasing motor adaption for small hand movements. Further research is needed to disentangle cognitive and motor aspects of these results. 374 Antidepressant Effects of ECT may be related to Hippocampal Neurogenesis Colleen Loo a,b,c, Narcis Cardoner d,e,f, Harry Hallock g, Jesus Pujol d, Christos Pantelis h,i, Dennis Velakoulis h,i, Murat Yucel j, Perminder Sachdev k,l, Oren Contreras-Rodriguez d, Mikel Urretavizcaya e,f, Jose Menchon e,f, Chao Suo g,j, Petar Djuric m, Mirjana Maletic-Savatic n, Michael Valenzuela g a University of New South Wales, Sydney, Australia b St George Hospital, Sydney, Australia c Black Dog Institute, Sydney, Australia d MRI Research Unit, Hospital del Mar, CIBERSAM G21, Barcelona e Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain f Instituto de Salud Carlos III, Centro de Investigación en Red de Salud Mental (CIBERSAM), Madrid, Spain g Regenerative Neuroscience Group, Brain and Mind Research Institute, University of Sydney, Sydney, Australia h Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, Australia i Melbourne Health, Melbourne, Australia j Monash Clinical & Imaging Neuroscience, School of Psychological Sciences, Monash University k School of Psychiatry, University of New South Wales, Sydney, Australia

Abstracts / Brain Stimulation 8 (2015) 412e427 l Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia m Stony Brook University, Stony Brook, NY n Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX

Introduction: There are reports of increases in hippocampal volume after ECT, but the relevance of this finding to antidepressant effects of ECT is uncertain. This study used a novel magnetic resonance spectroscopy (MRS) method to assess for evidence of ECT-induced neurogenesis, and examined the relationship of MRS changes to hippocampal volume change and antidepressant outcomes at the end of the ECT course. Methods: 20 depressed patients (9 female; mean age 53.9 years, range 33-79 years) treated with a course of ECT (N¼8 right unilateral, N¼12 bilateral) underwent MRS (1.28ppm signal) and structural MRI imaging prior to ECT, after 1-3 ECT, and at end of the ECT course. Mood was rated using MADRS score at the same time points. Results: ECT treatment was associated with significant improvement in mood (70% reduction in mean MADRS score, 71% response rate, 53% remission rate) and increase in hippocampal volume. Increase in the 1.28ppm MRS signal early in the ECT course was correlated with lower end-of-treatment MADRS scores (r¼-0.57, p¼0.034) and with hippocampal volume expansion (r¼0.73, p¼0.003). This increased hippocampal volume was also correlated with lower MADRS scores (r¼-0.64, p¼0.008). Conclusions: This is the first study in humans to suggest hippocampal neurogenesis may be linked to the antidepressant efficacy of ECT.

375 Accuracy of deep brain stimulation electrodes implanted by frameless system -NexframeÓ  b, M. Vaverka a, D. Krahulík a, M. Nevrlý b, P. Otruba b, J. Bardon  ovský b P. Kan a Department of Neurosurgery, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic b Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic Background: Methods for targeting the subthalamic nucleus in case of PD, ventral intermediate thalamic nucleus (ViM) in case of tremor and globus pallidus internus (GPi) in case of dystonia differ in using direct visualization of preoperative magnetic resonance scans, using intraoperative microelectrode recording or by anatomical target coordinates. A frame based stereotaxy or a frameless stereotactic system (NexFrameÓ) are used during the electrodes placement. Accurate placement of electrode is necessary for correct function of the DBS. Object: The object of study was to evaluate the placement accuracy of the DBS electrodes using the frameless navigation NexFrameÓ in our department. Methods: Coordinates of the planned target point according to anterior and posterior commissural points are found using preoperative MRI of the brain and are usually modified intraoperatively according to microrecording and clinical examination. Coordinates of the real position of the electrode are detected using the fusion of preoperative MRI with postoperative CT. To determine the placement accuracy of the electrodes, the vector error and the lateral, anteroposterior and vertical errors were calculated. Results: 50 DBS electrodes were implanted using NexFrameÓ system to 25 patients diagnosed with PD, ET or dystonia (mean age 62.1  10.1). The mean vector error was 2.43  1.32 mm, the mean lateral error was 1.08  0.08 mm, the mean anteroposterior error was 1.35  0.98 mm and the mean vertical error was

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1.20  1.18 mm. All results were compared to the results of other authors‘ studies. Conclusion: Results of our study show that using the frameless system NexFrameÓ in our department provides sufficient placement accuracy of electrodes needed for successful treatment using the DBS.

376 A novel EEG-based tool for objective assessment of pain in fibromyalgia patients under high-definition tDCS treatment Amir Geva a,b, Ziv Peremen a,c, Revital Shani-Hershkovich a, Dalia Dickman a, Michal Weiss a, Amit Reches a, Marom Bikson d,e, Felipe Fregni f,g a Eliminda Ltd, Israel b Ben Gurion University, Israel c Tel Aviv University, Israel d The City College of City University of New York, USA e Soterix Ltd, USA f Department of Physical Medicine & Rehabilitation, USA g Spaulding Rehabilitation Hospital, Harvard Medical School, USA Background: In this study we employed a novel EEG/ERP analysis tool known as Brain Network Activation (BNA) to assess the reorganization of brain dynamics following focal tDCS stimulation in fibromyalgia patients. BNA is an integral treatment progression monitoring system based on the high temporal resolution of ERPs, and by using a formal graph representation depicts the evolving network dynamics in time, location and frequency in high temporal resolution. We examined whether the BNA score, a measure reflecting the network-level synchronization, could serve as a predictor of responsiveness and the length of treatment. Methods: We conducted a single-center, open-label, phase II trial using HD-tDCS over the M1 in FM patients. All subjects completed 10 stimulation sessions in a period of two weeks, after which they completed a first response assessment. Study participants kept receiving stimulation sessions if they were deemed as non-responders (until a maximum of 26 stimulation sessions were completed). Twelve subjects participated in the study of whom 7 were responders. Response was defined as a pain intensity reduction of 50% compared to baseline as was measured by the VAS pain scale. In addition, for neurophysiological assessment, sensory-evoked potentials (SEP) were recorded as a measurement of pain-related central-sensitization. Results: A significant correlation was obtained between differential (end of treatment-minus-pre treatment) BNA scores and VAS scores (Spearman’s Rho ¼ 0.68, P<0.05). The area under the curve (AUC) demonstrated a clear separation ability between responders and non-responders (AUC¼ 0.80, specificity¼0.80, sensitivity¼0.71) based on pre-treatment BNA. Conclusion: These preliminary results may suggest that the BNA may be useful as a quantitative, sensitive tool for the assessment of network-level synchronization implicated in pain perception and can predict treatment success.

377 ABS-based brain phantom mold for validating the computational brain stimulation model Donghyeon Kim a, Jinmo Jeong b, Sohee Kim b,c, Euiheon Chung b,c, Sung Chan Jun a a School of Information and Communications, Gwangju Institute of Science and Technology, Gwangju, South Korea b Department of Medical System Engineering, Gwangju Institute of Science and Technology, Gwangju, South Korea c School of Mechatronics, Gwangju Institute of Science and Technology, Gwangju, South Korea