Enhancing low-frequency oscillations using on-demand direct-current stimulation improves motor function after stroke

Abstracts / Brain Stimulation 10 (2017) 346e540

Phase two was acquiring measurements to determine image quality. Using the fBIRN phantom, we tested the presence of TMS pulse interference with EPI. We tested TMS coil off, and the following stimulation intensities: 0%, 30%, and 90%. To check for static signal dropout, the following measures were: 1) Signal to Fluctuation Noise Ratio (SFNR), 2) Temporal Fluctuation Noise Images (TFNI), 3) Signal to Noise Ratio (SNR) summary value. For possible dynamic artefacts, we selected the first volume as a benchmark for data quality assessment. We computed the percent signal change rate (SCR) of the consecutive volumes relative to the benchmark. Phase one was successfully completed. For phase two, 1) the SFNR calculations showed that the EPI data's temporal stability was not affected by the stimulation; 2) TFNI showed that the stimulation conditions with 30% and 90% intensity are very similar to that of free-stimulation condition, and 3) SNR summary value decreased with stimulation intensity increased. However, there was a static signal dropout observed due to the coil being inside the scanner. For possible dynamic artefacts, SCR values showed that although consecutive volumes showed fluctuations relative to the benchmark, these fluctuations were sufficiently small, which indicated that there were no significant dynamic artefacts produced by the stimulation. With the foundation of interleaved TMS/fMRI completed, future testing experiments will determine whether the system could be applied to human participants safely and noise-freely. Keywords: interleaved fMRI/TMS, neuroimaging, rTMS [0742] USE OF TRANSCRANIAL CHANNEL IN TDCS FOR TARGETED NEUROMODULATION - ASSESSING NEURAL POLARIZATION H. Seo*, H.-I. Kim, S.C. Jun. Gwangju Institute of Science and Technology, Republic of Korea Introduction: The transcranial channel having higher conductivity relative to the skull has been proposed in tDCS for targeted neuromodulation and improved stimulus efficacy in terms of higher intensity and focality; however, it is not clear how the transcranial channel affects neural activation in the cortex. Here, we investigated how stimulus-induced neural polarizations is maximized by the higher conductive transcranial channel through computational multi-scale modelling. Method: We constructed an anatomically realistic head model using MRI. We then positioned electrodes to form HD-tDCS montage and T-shaped transcranial channel within the skull. To access the role of transcranial channel location, two target areas were selected: the top of gyrus on the precentral gyrus (hand knob) and the sulcal wall following central sulcus. In addition, we used two established compartmental models of layer 5 and 3 pyramidal neurons and they were combined indirectly within the hand knob. Results: We found approximately 11 times higher intensity and improved focality of stimulus-induced neural polarizations at target area compared to the case without the transcranial channel. When we changed the position of the electrodes and the transcranial channel from the top of the gyrus to the sulcal wall, we observed comparable polarization patterns at each compartment, but slightly shifted to the sulcus. Discussion: The use of transcranial channel in tDCS reduced shunting currents and conveyed induced currents to the target area. Thus it has greater stimulus efficiency. However, the impact of stimulus was constrained to the gyrus and could not reach the bottom of the sulcus, even when we placed the transcranial channel and the stimulus electrodes on the sulcus. Thus, the use of transcranial channel may be promising in targeting superficial cortex and providing prolonged, stabilized and lasting effects of stimulation. Acknowledgement: This work was supported by the GIST Research Institute(GRI) in 2017. Keywords: HD-tDCS, semi-invasive brain stimulation, multi-scale modeling, pyramidal neurons [0743] REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS) SIDE EFFECT CHARACTERIZATION FOR TREATMENT RESISTANT DEPRESSION: NON-INFERIORITY RTMS TRIAL

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A. Humaira*1, J. Downar 2, D. Blumberger 2, K. Green 1, E. McLellan 1, N. Ainsworth 1, M. Danilewitz 1, C. Dobek 1, C. Pang 1, J. Brown 1. 1 University of British Columbia, Canada; 2 University of Toronto, Canada rTMS is a non-invasive neurostimulation treatment used for Treatment Resistant Depression (TRD). Conventional 10 Hz treatment (HFL) is the standard treatment, however a newer intermittent theta burst stimulation (iTBS) has shown promisse in terms of efficacy. This pilot study aims at comparing tolerability and safety profile of HFL vs. iTBS. We provide an in depth characterization of the time course of the side effect profiles of both interventions. 20 TRD patients received 20-30 treatment sessions and were randomly selected to receive either treatment course. Detailed information was obtained re hours of sleep, alcohol/substance use, and medications. Side effects and adverse events were systematically inquired about both with free recall as well as prompting questions for pain, tingling, burning, fatigue, nervousness, headache, disturbed visual perception/ sleep/ concentration, visual flash. This was completed immediately post-treatment and before the next treatment to gauge delayed phenomena. No patients dropped out of the study. Common side effects include headache(5.2%) and fatigue(0.74%) with majority reporting mild severity. Of 20 participants, 12 reported at least 1 incidence of headache, fatigue(3), or sleep issues(3). Only 2.4% of treatments required an analgesic for headache. Side effects were reported more frequently within the first 10 treatments with a steady decrease over time. Most side effects reported were self-limited and lasted < 24hrs. Both treatment conditions have similar side effect and AE reporting trajectories with HFL treatment associated with slightly higher rates of concentration, fatigue, and nervousness. No treatment-related serious AE or seizure was reported during either treatment. One patient completed suicide while going through the course of rTMS HFL tended to be associated to higher rates of concentration disturbance, fatigue and nervousness compared to iTBS. Both treatments were tolerated well and no drop-outs due to side effects occurred in either treatment modality Keywords: Treatment resistant depression, Theta Burst Stimulation, side effects [0745] ENHANCING LOW-FREQUENCY OSCILLATIONS USING ON-DEMAND DIRECT-CURRENT STIMULATION IMPROVES MOTOR FUNCTION AFTER STROKE D.S. Ramanathan*1,2, L. Guo 1, 2, T. Gulati 1, 2, S.J. Won 1, 2, G. Davidson 1,2, A. Hishinuma 1, 2, K. Ganguly 1, 2. 1 San Francisco VA Medical Center, USA; 2 University of California, San Francisco, USA Introduction: 50% of strokesurvivors continue to have chronic motor deficits when tracked up to 5 years later, with limited therapeutic options available. One novel approach for treating these patients is to design a chronic neural-interface that could deliver stimulation optimally timed to improve the neural circuits associated with skilled actions. Method: In order to develop such a neuroprosthetic device, we first conducted physiologic recordings of LFP and single-units in motor cortical regions in rodents as they performed a skilled motor task; after a stroke; and during a rehabilitation/recovery period, to identify processes most associated with motor recovery. Subsequently, we developed and tested a way to boost these recovery-related physiological processes using cranial electrical stimulation. Results: In healthy animals, we found that skilled motor actions and single-unit activity were strikingly phase-locked to low-frequency oscillations in motor cortex (< 6 Hz) ;and after stroke in these same animals phase-locking and power of these oscillations were significantly reduced. In a separate group of animals we found that motor recovery after stroke correlated strongly with restoration of these oscillatory dynamics in perilesional cortex. Finally, we found that brief DC stimulation pulses (5 seconds or less) time-locked to the reach could enhance the power of these low-frequency oscillations and significantly improved motor function (across several different experiments). Discussion: Prior attempts at delivering electrical pulses post-stroke have focused on changing excitability or enhancing cortical plasticity using longer-duration stimulation paradigms (10-20 minutes). This study, in

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Abstracts / Brain Stimulation 10 (2017) 346e540

rodents, provides proof that brief, on-demand stimulation for only a few seconds can modulate relevant motor circuits and improve motor function. This study lays the groundwork for further development of an implantable neural device that delivers brief, closed-loop bursts of electrical stimulation triggered by a combination of neural and motor activity, to motor function in an on-going and dynamic way. Keywords: stroke, physiology, oscillations, stimulation [0748] THE EFFECTS OF TSMS ON CONSCIOUS PERCEPTION OF SENSORY INPUTS FROM THE HAND A. Oliviero*1, L. Rattagan 2, M. Campolo 2, J. Casanova-Molla 2, J. Vallsejicos, Spain; 2 Hospital Clinic, Spain Sole 2. 1 Hospital Nacional de Parapl Conscious perception of sensory signals depends in part on stimulus salience, relevance and topography. Letting aside differences at skin receptor level and afferent fibres, it is the CNS that makes a contextual selection of relevant sensory inputs. Transcranial static magnetic stimulation (tSMS) over the parietal cortex increases the local oscillatory power specifically in the alpha range, without significantly affecting bottom-up thalamo-cortical inputs indexed by the early cortical component of somatosensory evoked potentials. tSMS reduced the physiological habituation to the perception of near-threshold somatosensory electrical stimuli (Carrasco-Lopez, unpublished data). We hypothesized that subjective awareness (AW) of the time at which a sensory stimulus is perceived, a cortical function, may be modified by cortical stimulation. In 8 healthy volunteers, we examined the effects of tSMS on the assessment of AW to weak electrical stimuli applied to the hand. AW was determined by using the Libet’s clock, where the subjects have to memorize the position of the clock handle at the time they received the stimulus. We also recorded the vertex-evoked potentials to the same stimuli. The assessment was done before, during and after real or sham tSMS over the parietal cortex contralateral to the hand receiving the stimuli. During the experiment, both real and sham tSMS caused a lengthening of AW to electrical stimuli (compatible with habituation or fatigue). However, during tSMS, AW was significantly shorter with real than with sham stimulation, a difference that reduced after tSMS. Our data suggest that artificially modifying parietal alpha activity by placing a powerful magnetic field over the somatosensory cortex overcomes the natural decline of conscious somatosensory perception due to habituation or fatigue in our experimental setup. Keywords: transcranial static magnetic field, parietal cortex, perception

analyzed in 36 patients in the planning system (MCP coordinates of stimulation points, closest distances to DRT border and center were recorded, cf. Figure 1). The relation of amplitude needed to reduce tremor was expressed as TiCR (tremor improvement to current ratio ¼ Ti /I [1/mA]. Results: A total of 51 out of 60 finally implanted DBS electrodes were positioned on the planned trajectory (85%) and 68 trajectories were tested in 60 electrode placements (1.13 trajectories tested per DBS). TiCR values increase significantly in proximity to the DRT (* p<0.001). Discussion: The DRT is an individually targetable fiber structure that shows tremor reducing effects when modulated with the DBS technology. Tractography techniques can be used to directly visualize the DRT and therefore optimize target definition in individual patients. Keywords: DBS, Diffusion Tensor Imaging, deterministic tracking, dentatorubro-thalamic tract

Figure 1. Ă

[0749] DIFFUSION TENSOR IMAGING TRACTOGRAPHY ASSISTED DIRECT TARGETING OF THE CEREBELLO-THALAMO-CORTICAL NETWORK FOR DEEP BRAIN STIMULATION IN TREMOR - SURGICAL STRATEGY AND INTRA-OPERATIVE EFFECTS V.A. Coenen*1,2, T. Prokop 1, 2, B. Sajonz 1, 2, N. Allert 3, B. Maedler 1, 2, C. Jenkner 1, H. Urbach 1, 2, P.C. Reinacher 1. 1 Medical Faculty Freiburg University, Germany; 2 Freibur University Medical Center, Freiburg, Germany; 3 Bonn University, Germany Introduction: Deep brain stimulation alleviates tremor of various origin. We report the intraoperative results of an uncontrolled case series of tremor patients that underwent DTI FT assisted DBS of the dentato-rubrothalamic tract (DRT) . Methods: 36 patients (64 +/- 13.6 years, 17 female) were enrolled (Essential Tremor (17), Parkinson’s tremor (8), Encephalitis disseminate (7), and myoclonic tremor in myoclonus dystonia (3)) and received 60 DBS electrodes. Preoperatively, diffusion tensor magnetic resonance imaging sequences was acquired together with high-resolution anatomical T1W and T2W sequences. The DRT was individually tracked as described before. Stereotactic surgery was performed with a Leksell G-Frame (Elekta, Sweden) with the patients awake. Electrodes were lowered into the target region via Microdrive (FHC, USA) in 2mm steps typically starting 10 mm above target. Intraoperative tremor reduction was graded on a 4 point scale (0¼no tremor reduction, 3¼full tremor control) and recorded together with the current amplitudes necessary (0.5-4 mA, 100-150Hz, 100us, Cosman LG, USA). Postoperatively, 241 stimulation points were

Figure 2. Ă

[0750] THE EFFICACY OF EEG-BIOFEEDBACK FOR ACUTE PAIN MANAGEMENT, A RANDOMIZED SHAM-CONTROLLED STUDY OF A TAILORED PROTOCOL C.V. Ide*, T. Thompson. University of Greenwich, UK Introduction: While preliminary research indicates EEG-biofeedback to be a promising treatment option for pain, previous studies are often limited by the omission of an appropriate control group. As such it is impossible to conclude whether apparent benefits are a product of genuine EEG