Transcranial alternating current stimulation in the beta frequency promotes motor inhibition

Transcranial alternating current stimulation in the beta frequency promotes motor inhibition

440 Abstracts / Brain Stimulation 10 (2017) 346e540 stimulation using rTMS alone over the ipsilesional M1 in subacute stroke patients. Methods: Twen...

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440

Abstracts / Brain Stimulation 10 (2017) 346e540

stimulation using rTMS alone over the ipsilesional M1 in subacute stroke patients. Methods: Twenty-four subacute stroke patients were recruited within two weeks after their stroke onset. In the dual-mode stimulation group (DSG, 8 males and 4 females, aged 56.0±13.4 years), 10 Hz rTMS (90% of resting motor threshold, 1,000 pulses) was applied over the ipsilesional M1 for 20 minutes with the simultaneous application of cathodal tDCS (2mA) on the contralesional M1. The single stimulation group (SSG, 8 males and 4 females, aged 58.1±13.7 years) received 10 Hz rTMS without tDCS. The patients underwent a resting-state functional magnetic resonance imaging (rs-fMRI) two times; before stimulation and two months after stimulation. Motor function was assessed by using Fugl-Mayer Assessment (FMA) scale at the same time with rs-fMRI. In order to construct motor networks, twenty-four motor-related regions were extracted. To measure network balance and altered connectivity, matrix distance and graph measures were used. The repeated measures ANOVA was applied to determine whether there are any significant differences (Time or Group*Time) between both groups. Results: Degree of decrease of distance between bilateral hemispheric networks after stimulation was greater in DSG than SSG. Interhemispheric connections of contralesional M1 and interhemispheric connections between homologous regions in bilateral hemispheres were significantly increased in DSG compared to SSG. The global network efficiency was also significantly increased only in DSG. Conclusion: Dual-mode noninvasive brain stimulation is considered to promote better bilateral rebalancing and reorganization in motor network compared to single stimulation. (This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP; NRF2014R1A2A1A01005128) and the Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (NRF-2010-0018837). Keywords: Dual-mode stimulation, rTMS, tDCS, Functional motor network

[0431] SENSING ULTRASOUND DEVELOPMENT

PROMOTES

AXON

GROWTH

DURING

Keywords: ultrasound, axon growth, mechanosensing, development

[0432] THE EFFECT OF VOLUNTARY CONTRACTION ON THE DIRECTION OF THE WRIST MOVEMENT INDUCED BY FOCAL TMS ndez-Lobera*, R. Arca, J. Valls-Sole . University of Barcelona, Spain M. Ferna Introduction: Transcranial magnetic stimulation (TMS) generates motor evoked potentials (MEP) and eventually movement consequent to muscle contraction. However, during contraction, the MEP is followed by a relatively long silent period (SP). We reasoned that movements occurring during the SP must be in the opposite direction because of cessation of muscle contraction. Methods: We recorded responses to TMS in wrist extensors and flexors muscles (WE and WF) of 10 healthy volunteers. Subjects were sitting relaxed, with their right arm enclosed on a device allowing for only wrist flexion-extension movements. We applied focal TMS over the contralateral motor cortex in the spot from where the largest MEPs could be obtained simultaneously in both muscles. Five stimuli were applied at rest and when subjects were required to voluntarily activate their flexor and extensor muscles to exert 30% of maximal force towards flexion or extension. We analyzed MEP size, SP duration and the direction and amplitude of the movement generated in the wrist. Results: At rest, subjects generated tiny movements that went mostly towards flexion at latency of 60 to 100 ms, compatible with movements generated by the MEP. During contraction towards flexion, movements were also short latency flexion. However, during contraction towards extension, movements were generated towards the opposite direction (i.e., flexion) and they had a longer latency (150 to 250 ms), compatible with them being produced at the time of the SP. Discussion: WE and WF muscles differ in their behavior in response to MEP-induced movement during muscle contraction. The participation of muscle elasticity in the generation of wrist movements has to be taken into account in the interpretation of the significantly more prominent wrist flexion than extension observed in our study. Keywords: TMS, Movement, Elasticity

Z. Qiu*, L. Song, J. Wang, S. Kala, L. Sun. The Hong Kong Polytechnic University, Hong Kong During the development of the CNS, each neuron extends an axon by generating forces, and is subjected to heterogeneous mechanical environment. How the mechanical properties of developing CNS tissue influence axon growth in vivo are currently unknown, and the potential neuronal response to mechanical signals in vivo is poorly understood. To date, it is emergent to develop a mechanical based stimulation strategy for in vivo studies. Ultrasound is considered as a promising tool for brain stimulation. It is shown to be able to trigger neuron like cells to outgrowth, axon branching, and accelerate nerve regeneration. However, the detailed mechanisms are unclear. We hypotheses that neurons can sense ultrasound through piezo1 channel to promote axon growth during development. To test this hypothesis, N2A and retinal ganglion cell (RGC) which highly express Piezo1 were utilized as in vitro model. Piezo1 knockdown cells with siRNA and Piezo1 blocker GsMTx-4 pre-treated cells were severed as control to test the role of Piezo1 in sensing ultrasound. The axon lengths after 24 h, the extension velocity of axons for all the experimental groups are analyzed from live cell imaging data. Our results show that ultrasound stimulation on wild type N2A cell and primary cultured RGC can promote axon outgrowth. The axon length and the extension velocity for Piezo1 knockdown and GsMTx-4 blocked neurons is significant decreased. These results showed that ultrasound as a mechanical wave is able to stimulate neurons and modulate the axon growth through mechanosensitive ion channels. Given the ability of focused into small region in human brain non-invasively, it is capable for investigate the mechanisms of mechanical effects on neural development in vivo.

[0434] TRANSCRANIAL ALTERNATING CURRENT STIMULATION IN THE BETA FREQUENCY PROMOTES MOTOR INHIBITION I. Leunissen*1, J.P. Coxon 2, S.P. Swinnen 1. 1 KU Leuven, Belgium; University, Australia

2

Monash

Introduction: Excessive beta oscillations (15-30Hz), as in Parkinsons disease, are associated with slowing of movement and rigidity (Little and Brown, 2014). This has lead to the idea that beta activity might promote the inhibition of movement. Indeed, intracortical recordings have revealed increased beta oscillations in preSMA, rIFC and STN during successful stopping (Alegre, et al., 2013; Swann, et al., 2009; Wessel, et al., 2013). To investigate if beta activity in preSMA is causal to motor inhibition and not merely epiphenomenal, we used transcranial alternating current stimulation (tACS) to entrain this frequency in the brain (Helfrich, et al., 2014). Methods: Sixteen participants performed a stop-signal task, in which they responded by pressing a force sensor (Coxon, et al., 2006; Zandbelt and Vink, 2010). 20 or 70Hz stimulation was applied for 5s in 50% of the trials (DC-Stimulator Plus, NeuroConn). The target electrode was placed over preSMA (2.5cm Ø) and four return electrodes (2cm Ø) were placed at 4cm center-to-center distance from the target electrode. Results: There was no change in go response times or stop signal reaction time during 20 or 70Hz stimulation. However, on successful stop trials 20Hz stimulation resulted in a decrease in peak force (-10.15 ± 22.04%, t(15)¼-1.842, p¼0.042). Also the proportion of stop trials with perfect

Abstracts / Brain Stimulation 10 (2017) 346e540

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inhibition (i.e. a flat force trace) was increased with 3.58 ± 5.75% (t(15)¼2.489, p¼0.013). 20Hz stimulation did not affect go trial performance and 70Hz stimulation did not alter behavior. Conclusions: By using tACS to drive oscillation in the brain we show that beta oscillations are causally related to motor inhibition in a task dependent manner. Corroborating the effects of 20Hz stimulation of the motor cortex previously described (Joundi, et al., 2012; Pogosyan, et al., 2009). The effects were also frequency specific, as 70Hz stimulation of preSMA did not alter behavior. References Alegre, M., Lopez-Azcarate, J., Obeso, I., Wilkinson, L., Rodriguez-Oroz, M.C., Valencia, M., Garcia-Garcia, D., Guridi, J., Artieda, J., Jahanshahi, M., Obeso, J.A. (2013) The subthalamic nucleus is involved in successful inhibition in the stop-signal task: A local field potential study in Parkinson's disease. Experimental Neurology, 239:1-12. Coxon, J.P., Stinear, C.M., Byblow, W.D. (2006) Intracortical inhibition during volitional inhibition of prepared action. J Neurophysiol, 95:3371-83. Engel, A.K., Fries, P. (2010) Beta-band oscillations–signalling the status quo? Curr Opin Neurobiol, 20:156-65. Helfrich, R.F., Knepper, H., Nolte, G., Struber, D., Rach, S., Herrmann, C.S., Schneider, T.R., Engel, A.K. (2014) Selective modulation of interhemispheric functional connectivity by HD-tACS shapes perception. PLoS Biol,12:e1002031. Joundi, R.A., Jenkinson, N., Brittain, J.S., Aziz, T.Z., Brown, P. (2012) Driving Oscillatory Activity in the Human Cortex Enhances Motor Performance. Current Biology, 22:403-407. Little, S., Brown, P. (2014) The functional role of beta oscillations in Parkinson's disease. Parkinsonism Relat Disord, 20 Suppl 1:S44-8. Pogosyan, A., Gaynor, L.D., Eusebio, A., Brown, P. (2009) Boosting Cortical Activity at Beta-Band Frequencies Slows Movement in Humans. Current Biology, 19:1637-1641. Swann, N., Tandon, N., Canolty, R., Ellmore, T.M., McEvoy, L.K., Dreyer, S., DiSano, M., Aron, A.R. (2009) Intracranial EEG Reveals a Time- and FrequencySpecific Role for the Right Inferior Frontal Gyrus and Primary Motor Cortex in Stopping Initiated Responses. Journal of Neuroscience, 29:12675-12685. Wessel, J.R., Conner, C.R., Aron, A.R., Tandon, N. (2013) Chronometric Electrical Stimulation of Right Inferior Frontal Cortex Increases Motor Braking. Journal of Neuroscience, 33:19611-19619. Zandbelt, B.B., Vink, M. (2010) On the Role of the Striatum in Response Inhibition. Plos One, 5. Keywords: tACS, beta, response inhibition

Keywords: multi-locus TMS, multi-channel transducer, multi-coil, pairedpulse TMS

[0435] MULTI-LOCUS TMS: ELECTRONIC CONTROL OF THE STIMULATION LOCATION WITH LARGE THIN OVERLAPPING COILS

[0437] EFFECT OF IPSILESIONAL ANODAL TDCS WITH CONTRALESIONAL LOWFREQUENCY RTMS FOR POST-STROKE MOTOR IMPAIRMENT

L.M. Koponen*, J.O. Nieminen, R.J. Ilmoniemi. Aalto University, Finland

Y.-H. Kim*1, E. Park 1, J.-S. Lee 2, W.-H. Chang 1, A. Lee 1. 1 Sungkyunkwan University, Republic of Korea; 2 Korea Advanced Institute of Science and Technology, Republic of Korea

Introduction: We have developed a two-channel device for multi-locus transcranial magnetic stimulation (mTMS). Our mTMS device allows continuous control of the stimulation location along a 30-mm-long line segment in the cortex without moving the transducer. Methods: Our mTMS transducer consists of a minimum-energy figure-ofeight coil and an overlapping coil with elongated shape. Power semiconductor devices are used to control the coil currents. We calibrated the stimulation intensities using our TMS-coil characteriser. Results: The electronicsetwo-coil combination allows one to control the stimulation location without moving the transducer: when the figure-ofeight coil is used alone, a target underneath its centre is stimulated; by driving a simultaneous current into the overlapping coil, the stimulation target can be shifted towards left or right. After calibration, the peak stimulation intensity varied less than 1 % between different stimulation locations. Discussion: Our mTMS device allows TMS studies in which a conditioning pulse is administered to a different location than a test pulse. This suits for, for example, studying lateral inhibition in the cortex. As the target location control is electronic, we can conduct this kind of studies in computercontrolled randomised order where neither the operator nor the subject is aware of the location of upcoming pulses.

[0436] RESTING MOTOR THRESHOLD DEPENDS ON THE DURATION OF MEMBRANE POLARISATION L.M. Koponen*1,2, T.P. Mutanen 1,2, R.J. Ilmoniemi 1,2, J.O. Nieminen 1,2. 1 Aalto University, Finland; 2 Helsinki University Hospital, Finland Introduction: Reducing the duration of a stimulation pulse increases the current required to evoke an action potential. This strengtheduration curve can be described by its rheobase and chronaxie, which describe the weakest intensity required to evoke an action potential and the minimum pulse duration with twice the rheobase intensity to evoke an action potential, respectively. The chronaxie is ln 2 times the strengtheduration curve time constant, which, in the leaky integrate-and-fire model, equals the membrane time constant. Methods: For two healthy volunteers, we measured compound muscle action potentials elicited by magnetic median nerve stimulation and motor evoked potentials elicited by transcranial magnetic stimulation. All pulses were monophasic and had equal duration for the initial positive electric field (60 ms) but the subsequent negative electric field was randomly delayed between 2.5 and 60 ms. The delay should not affect the efficacy of the pulse according to the standard leaky integrate-and-fire model. Results: We observed about 10 % lower resting motor threshold with the longest delay compared to the shortest delay (for both subjects, p < 0.0001). The relation between the delay and the reduction in the motor threshold appeared roughly exponential with a time constant of about 15 ms (95 % confidence interval, 12e18 ms). Discussion: The resting motor threshold does not depend only on the duration of the initial positive electric field but also on the time delay to the electric field in the opposite direction. This has several implications. For example, the strengtheduration curve time constant does not depend only on the membrane time constant, but also on other properties of the neurons, such as the kinetics of the voltage-sensitive sodium channels around the threshold potential. Keywords: resting motor threshold, threshold potential, magnetic nerve stimulation, transcranial magnetic stimulation

Introduction: Noninvasive brain stimulation using the repetitive transcranial magnetic stimulation (rTMS) or the transcranial direct current stimulation (tDCS) were recently adopted for modulating motor function of stroke patients. We investigated the effect of simultaneous dual-mode stimulation applying low-frequency rTMS (LF-rTMS) over the contralesional primary motor cortex (M1) and anodal tDCS over the ipsilesional M1 compared with single LF-rTMS over the contralesional M1 for motor recovery in subacute stroke patients. Methods: Twenty three subacute supratentorial stroke patients were recruited in this random-ordered, sham-controlled study. In the dual stimulation group, the 1 Hz rTMS were applied over the contralesional M1 for 20 minutes with simultaneous application of the anodal tDCS over the ipsilesional M1. The single-simulation group underwent 1 Hz rTMS over the contralesional M1 with sham tDCS over the ipsilesional M1. Ten daily sessions were conducted for two consecutive weeks. We assessed each participant’s motor function using Fugl-Meyer assessment (FMA) before intervention (Pre-stimulation; T0), after 2 weeks of intervention (Poststimulation; T1) and after 2 months of intervention (Follow-up; T2). To