JKPT pissn Vol. 27, No. 1, February 2015 J Kor Phys Ther 2015:27(1): eissn X Original Article

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1 pissn Vol. 27, No. 1, February eissn X Original Article Effect of Transcranial Direct Current Stimulation on Movement Variability in Repetitive - Simple Tapping Task Yong Hyun Kwon 1, Jeong Sun Cho 2 1 Department of Physical Therapy, Yeungnam University College, Daegu; 2 Science Culture Research Center, Pohang University of Science and Technology, Pohang, Korea Purpose: Accuracy and variability of movement in daily life require synchronization of muscular activities through a specific chronological order of motor performance, which is controlled by higher neural substrates and/or lower motor centers. We attempted to investigate whether transcranial direct current stimulation (tdcs) over primary sensorimotor areas (SM1) could influence movement variability in healthy subjects, using a tapping task. Methods: Twenty six right-handed healthy subjects with no neurological or psychiatric disorders participated in this study. They were randomly and equally assigned to the real tdcs group or sham control group. Direct current with intensity of 1 ma was delivered over their right SM1 for 15 minutes. For estimation of movement variability before and after tdcs, tapping task was measured, and variability was calculated as standard deviation of the inter-tap interval (SD-ITI). Results: At the baseline test, there was no significant difference in SD-ITI between the two groups. In two-way ANOVA with repeated measurement no significant differences were found in a large main effect of group and interaction effect between two main factors (i.e., group factor and time factor (pre-post test)). However, significant findings were observed in a large main effect of the pre-post test. Conclusion: Our findings showed that the anodal tdcs over SM1 for 15 minutes with intensity of 1 ma could enhance consistency of motor execution in a repetitive-simple tapping task. We suggest that tdcs has potential as an adjuvant brain facilitator for improving rhythm and consistency of movement in healthy individuals. Keywords: Transcranial direct current stimulation, Movement variability, Tapping task, Primary sensorimotor cortex 서론 율동적인움직임 (Rhythmic movement) 과움직임의타이밍 (movement timing) 은일상생활동작이나춤, 음악, 스포츠등과같은행위를하는동안쉽게관찰될수있고, 인체의움직임을실행 (execution) 하고통합 (organization) 하는근본적인요소중의하나이다. 1,2 이러한율동과타이밍은연속적순서로수행되는여러동작들을성공적으로실행하기위한움직임의통합이라볼수있다. 인체의움직임에서특정동작의반복적연속과정인보행및탭핑 (tapping) 과같이동작은협응 (coordination) 능력이필요한데, 이는상위및하위신경계의상호작용이필요한리듬을일컫는다. 3-5 리듬은움직임의타이밍을요구하 Received January 13, 2015 Received February 9, 2015 Accepted February 11, 2015 Corresponding author Jeong Sun Cho cjs9691@postech.ac.kr 는대부분의일상적인활동들을위해필수적인요소이며, 반복적인리듬의속도를빠르게또는느리게하거나그속도를유지하는것이필요하다. 예를들면, 악기의연주, 춤, 박수등과같은동작들은시간적요소가필요한외적인자극과함께잘조절된협응의결과라볼수있다. 리듬과타이밍에대한움직임의특징적요소를판별하는가장효과적인도구가손가락타판과제 (finger tapping task) 이다. 6 타판과제는외부의청각적자극과함께수행될수있는데, 그첫번째단계는대상자가지속적인자극간간격 (constant inter-stimulus interval) 에의해구분되는일련의청각적자극에손가락을동기화 (synchronization) 하기위해노력하는동기화단계를거치고, 그다음으로는대상 Copylight 2015 The Korean Society of Physical Therapy This is an Open Access article distribute under the terms of the Creative Commons Attribution Non-commercial License ( creativecommons.org/license/by-nc/3.0.) which permits unrestricted non-commercial use, distribution,and reproduction in any medium, provided the original work is properly cited. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2012R1A1B ). 38

2 The Journal of Korean Physical Therapy Yong Hyun Kwon, et al. 자가청각적자극이제시되지않더라도그전에수행하여왔던속도로일관되게타판하려고노력하는지속화 (continuation) 단계로진행하게된다. 6 이러한움직임의동기화와지속화가필요한과제에서운동반응의정확성 (accuracy) 과변이성 (variability) 을측정하는것은운동과학을연구하는분야에서매우관심있는영역이다. 정확성은타판행위의결과가목표지점을얼마나정확하게수행하였는가를말하고, 변이성은타판행위의결과가얼마나일관성있게수행하였는지를의미한다. 타판과제에서정확성과변이성의측정은심인성장애또는가병 (malingering) 을판별할수있는신경심리학적평가도구로도활용되고있다. 7-9 최근생체의뇌신경세포에비침습적인방법으로 1-2 ma의미세전류를적용하여운동, 감각, 인지등의다양한뇌기능을조절할수있는기법으로경두개직류전기자극 (transcranial direct current stimulation) 이새롭게재도입되었다. 10,11 경두개직류전기자극은극성에따라서로다른효과를나타내는데, 양극에서는전극아래에있는뇌신경세포들의기능을촉진하는역할을하고음극에서는뇌세포의기능을억제하는역할을한다 이러한경두개직류전기자극의극성효과를이용하여인체의운동및감각기능을촉진하는도구로써현재까지활발한연구가진행되고있다. 경두개직류전기자극을이용한많은연구에서자극을가하는동안이나자극후일정한시간내에서다양한운동기능의촉진을제시하고있다. 현재경두개직류전기자극이운동기능의향상을입증하기위한연구에서제시한바에의하면, 자극후근력의강화, 피로에대한저항성증가, 시지각운동과제에서의협응력향상, 운동반응속도의증가를비롯하여암묵적및외현적운동학습을촉진하는것으로알려져있다 그러나인체움직임의필수적인리듬과타이밍의속성을가진운동과제를통해움직임의변이성에경두개직류전기자극이어떠한영향을미치는지에관한연구는드물다. 따라서본연구에서는경두개직류전기자극이움직임의리듬과타이밍의속성을가진반복적타판과제에서움직임의변이성에어떠한영향을미치는지를알아보고자하였다. 연구방법 1. 연구대상자본연구에참여한대상자는 Edinburg Handedness Inventory 검사에서오른손이우성으로판정된 20대성인 26명을대상으로실시하였다. 모든대상자는최근 2년동안오른쪽상지에근골력계질환을호소하지않았고신경학적질환이없는자로선정하였다. 실험에참가하기전연구의목적과방법에대해충분한설명을듣고자발적동의를한후에실험에참가하였다. 실험에참가한대상자들은무작위선정방식으로경두개직류전기자극군 (tdcs group) 과위약자극군 (sham tdcs group) 으로배정되었다. 본연구는지역의기관생명윤리심의위원회 (institutional review board) 에서사회적행동과학연구 (social behavioral research) 의승인을받은후실시되었다. 2. 실험절차 1) 경두개직류전기자극 (transcranial direct current stimulation, tdcs) 모든대상자는등받이가있는의자에편안하게앉아서경두개직류전기자극을받았다. 경두개직류전기자극기는미국의 IOMED사에서제작된 Phoresor II Auto (Model PM 850) 을사용하여 5 7 cm (35 cm 2 ) 크기의고무로된두개의전극에함염물 (saline) 에적셔진스폰지를사용하여 1 밀리암페어의전류가 15분동안통전되었다. 통전된총전류의양은생체조직을손상하지않는다고입증된 ma/ cm2의전류가통전되었다. 21 전극의배치는뇌파측정의 10/20 체계의국제적기준 (10/20 international electroencephalographic system) 에따라양전극 (anodal electrode) 을우측뇌반구의 C4 위에위치하였다. C4 부위는일차운동감각영역에해당하는부위로써, 손의운동기능을관할하는곳으로알려져있다. 22,23 음전극 (cathodal electrode) 는우측뇌반구의안와상영역 (supraorbital area) 에부착하였다. 모든대상자는전류가통전되는기간동안아무런불평을호소하지않고전구간을수행완료하였고, 일부대상자들은전극이배치된부위에가벼운간지러움을느꼈다. 위약자극군에서는동일한자극기를사용하여전류를통전하지않았지만, 대상자는전류가통전되는것으로인식하도록하였다. 2) 타판과제타판과제는여덟개의반응버튼을가진반응패드 (RB-830, Cedrus, USA) 와반응과제를구성하기위한자극제공프로그램 (SuperLab Pro version 4.0, Cedrus, USA) 이설치된개인용컴퓨터를사용하여통전전후의측정과제로사용되었다. 대상자는주관절이 90 가되도록높이조절이가능한탁자앞에편안한자세로앉아눈높이에있는컴퓨터모니터를응시하고, 준비 신호가모니터에표시된후, 시작 신호가제시되면대상자는왼쪽두번째손가락의중수지절관절 (metacarpophalangeal joint) 에서정해진버튼을편안한속도로일관성있게 15초동안타판하도록하였다 (Figure 1). 사전연습은 1번실시하였고, 실제측정은 2번실시하여타판간반응시간간격의표준편차 (standard deviation of inter-tap interval) 를측정하고평균값을사용하였다. 3. 통계분석대상자의일반적특성인성별에서두집단의분포비율의차이를비교하기위해카이스퀘어검정 (χ 2 test) 을사용하였고대상자의나이와경두개직류전류의자극전움직임의변이성에대한두집단비교를 39

3 Effect of tdcs in Tapping Task Table 1. Comparison of Inter-tap interval between the real tdcs group and sham tdcs group Real tdcs group Sham tdcs group Inter-tap interval Pre test 31.15± ±15.22 (ms) Post test 22.19± ±13.57 Change (pre- to post-test) 8.96± ±7.17 Statistical results Group effect F (1,24)=0.609, p= Pre-post effect F (1,24)=8.819, p= Interaction between group and pre-post effects F (1,24)=1.597, p= Figure 1. The schema of tapping task. 위해독립 t 검정을사용하였다. 움직임의변이성에대한경두개전류전기의효과입증을위해이요인반복측정분산분석 (two-way ANO- VA with repeated measurement) 을사용하였고집단간요인및훈련전후의반복요인을독립변인으로, 타판간반응시간간격의표준편차를종속변인으로설정하였다. 두집단에서타판간반응시간간격의표준편차의변화차이는독립 t 검정으로분석하였다. 모든통계처리는윈도우용 SPSS 18.0을사용하였고통계적유의수준은 α = 0.05로설정하였다. 결과참여한모든대상자는총 26명으로남자가 8명이었고, 평균나이는 ± 1.28세이었다. 경두개직류전기자극군은총 13명으로남자가 4 명이었고, 평균나이는 ± 0.76이었다. 위약자극군은총 13명으로남자가 4명이었고, 평균나이는 ± 1.66이었다. 두집단의남녀분포차이는통계적으로유의하지않았고 (p =1.000), 나이의차이도통계적으로유의하지않았다 (p = 0.456). 경두개직류전기자극군에서타판간반응시간간격의표준편차는자극전 ± 10.40에서자극후 ± 7.96으로변화하였고, 그변화량은 8.96 ± 이었다. 위약자극군에서타판간반응시간간격의표준편차는자극전 ± 에서자극후 ± 13.57으로변화하였고, 그변화량은 3.61 ± 7.17 이었다. 이요인반복측정분산분석결과, 집단간주효과검정은통계적으로유의하지않았고 (F (1,24) = 0.609, p = 0.443), 사전-사후주효과검증에서는통계적으로유의한결과를보였으며 (F (1,24) = 8.819, p = 0.007), 집단및사전-사후상호작용에서는통계적으로유의한결과를보이지않았다 (F (1,24) = 1.597, p = 0.218) (Table 1). 고찰본연구는타판과제를통해경두개직류전기자극이반복적이고율동적인움직임의변이성에영향을미칠수있는지를알아보고자하였다. 그결과, 위약자극군에서는타판간반응시간간격의표준편차인움직임의변이성이 3.61 ms 만큼줄었으나, 경두개직류전기자극군에서는자극전에비해자극후 8.96 ms 만큼움직임의변이성이더많이줄어든것을확인하였다. 위약자극군에서움직임의변이성이다소감소한원인은타판과제의반복으로인한습관화와학습에의한것으로생각된다. 위약자극군에서학습효과로인한변이성의감소로인해이요인반복측정분산분석에서집단간주효과검정및상호작용에서통계적유의성이나타나지않았고, 사전-사후주효과검정에서만통계적유의성을보였다. 움직임의변이성의감소는대상자가타판과제를수행할때, 일관된속도로율동적인움직임을수행했다는것을의미하며, 타판과제에관여하는근육군들의협응과근수축시너지가보다향상된결과라볼수있다. 따라서 15분간일차운동감각영역에적용된경두개직류전기자극은반복적이고율동적인움직임 (repetitive rhythmic movement) 을일관성있게수행할수있는능력을향상시켰다고볼수있다. 연속적운동과제 (sequential task) 의수행에서하부동작들의간격간변이성 (interval-to-interval variability) 은움직임의타이밍에핵심적인특성이기때문에, 인체동작의이론체계를설명하는데결정적인요소로인식되고있다. 24 또한움직임의타이밍이필요로하는과제는학습의필수적인요소이며, 동기화가필요로하는과제에서는음악전문가가비전문가에비해움직임의변이성이더낮다는것이입증되었다. 25 타판과제는상지의섬세한운동기술 (fine motor skill) 을객관적으로평가할수있으며, 움직임의장애 (movement disorder), 심인성상태 (psychogenic condition), 가병 (malingering) 등을포함한다양한신경학적질병을파악할수있는도구이다. 8,26,27 Arnold 등 26 은가병을호소하는것으로의심되는사람과치매, 뇌손상, 우울증과같은다양한신경학적질환을가진사람들에게서타판과제의변이성 40

4 The Journal of Korean Physical Therapy Yong Hyun Kwon, et al. 을비교분석한결과, 신경학적손상에도불구하고가병을가진사람에게서더많은변이성이발견되었다고보고하였다. 따라서타판과제의변이성의감소는인체움직임에서근수축활동의서니지작용과협응능력의향상으로보다섬세하고부드럽고일관된동작의수행의결과라볼수있다. 본연구에서제시한바와같이, 경두개직류전기자극에의한타판과제의변이성감소로기인하는운동기능향상의결과는운동기능의효과를입증한많은선행연구들과유사한결과를제시하고있다. 18,20,28-30 Cogiamanian 등 15 은 10분동안총 c/cm 2 의양극성경두개직류전기자극을정상인의우측뇌반구일차운동영역을자극한후, 왼쪽팔꿈치굴곡근육의최대하등척성수축에대한지구력을측정하였는데, 그결과위약자극군에비해근피로에대한저항력이강화되었다고보고하였다. 이러한결과는경두개직류전기자극이운동기능의가장근본적인요소인근수축력과지구력에직접적이고가시적효과를나타낼수있는것으로생각된다. 또한기본적인운동기능의향상을넘어시열반응과제에서운동자극에대한반응시간이단축된다거나, 시지각과제에운동수행능력의정확도가향상됨이보고되고있다. 31,32 이와같은운동기능향상에대한증거와함께, 양극성직류전기의자극이운동학습의효율성을증대시키는등운동수행에관련된다양한운동능력향상의행동학적이고정량적자료를제시하고있을뿐아니라, 이에대한신경생리학적기전을증명하는뇌지도화연구에서그효과가입증되고있다 최근경두개직류전기자극은 Nitsche와 Pauluso 10 에의해 1990년대에새롭게부각되기시작하여 1-2 ma의미세전류를생체의두피에비침습적인방법으로뇌를자극하는기법이다. 11 인체의움직임은뇌의중앙집중적제어와말초신경및근육의복합적작용으로유발되고있으며, 아직까지도움직임의양상과병리적기전을명료하게설명하기어렵다. 또한인체의움직임의능력을향상시키거나기능의손상후에회복을위한다양한노력이시도되고있다. 따라서생체에서뇌를비침습적으로안전한방법으로자극하여운동능력을조율할수있다는것은신경과학의분야에서매우흥미있는주제이다. 본연구에서는경두개직류전기자극이운동의변이성을감소하여협응력을증가시킨다는것을확인하였다. 이러한결과는뇌신경생리학적측면에서일차운동감각영역이운동의변이성에관여할수있다는것을암시하고, 운동의협응능력이필요한사람이나뇌손상으로그기능의회복이필요한환자에게안전한방법으로적용할수있을것으로생각된다. 본연구의제한점은타판과제의특이성이뇌반구편측화 (hemispheric lateralization) 에관여하고있다는사실을고려하지않고, 단지운동변이성에영향을미칠수있는지를확인하였다. 향후뇌반구편측화를고려하여경두개직류전기자극의운동변이성에관한연구가진행되어야할것으로제안한다. ACKNOWLEDGEMENTS This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2012R1A1B ). REFERENCES 1. Cousins MS, Corrow C, Finn M, et al. Temporal measures of human finger tapping: Effects of age. Pharmacol Biochem Behav. 1998;59(2): Iannarilli F, Vannozzi G, Iosa M, et al. Effects of task complexity on rhythmic reproduction performance in adults. Hum Mov Sci. 2013;32 (1): Chen Y, Ding M, Kelso JA. Origins of timing errors in human sensorimotor coordination. J Mot Behav. 2001;33(1): Hausdorff JM, Yogev G, Springer S, et al. Walking is more like catching than tapping: Gait in the elderly as a complex cognitive task. Exp Brain Res. 2005;164(4): Ijspeert AJ. Central pattern generators for locomotion control in animals and robots: A review. Neural Netw. 2008;21(4): Claassen DO, Jones CR, Yu M, et al. Deciphering the impact of cerebellar and basal ganglia dysfunction in accuracy and variability of motor timing. Neuropsychologia. 2013;51(2): Demakis GJ. Serial malingering on verbal and nonverbal fluency and memory measures: An analog investigation. Arch Clin Neuropsychol. 1999;14(4): Kalogjera-Sackellares D, Sackellares JC. Intellectual and neuropsychological features of patients with psychogenic pseudoseizures. Psychiatry Res. 1999;86(1): Matheson LN, Bohr PC, Hart DL. Use of maximum voluntary effort grip strength testing to identify symptom magnification syndrome in persons with low back pain. J Back Musculoskelet Rehabil. 1998;10(3): Nitsche MA, Paulus W. Transcranial direct current stimulation--update Restor Neurol Neurosci. 2011;29(6): Priori A, Berardelli A, Rona S, et al. Polarization of the human motor cortex through the scalp. Neuroreport. 1998;9(10): Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist. 2011;17(1): Rushworth MF, Johansen-Berg H, Gobel SM, et al. The left parietal and premotor cortices: Motor attention and selection. Neuroimage. 2003;20 (Suppl 1):S Krause V, Weber J, Pollok B. The posterior parietal cortex (ppc) mediates anticipatory motor control. Brain Stimul Cogiamanian F, Marceglia S, Ardolino G, et al. Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas. Eur J Neurosci. 2007;26(1): Hunter T, Sacco P, Nitsche MA, et al. Modulation of internal model formation during force field-induced motor learning by anodal transcranial direct current stimulation of primary motor cortex. J Physiol. 2009; 587(Pt 12): Furubayashi T, Terao Y, Arai N, et al. Short and long duration transcra- 41

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