非侵入腦刺激 (NIBS) 是一種常用的神經調節方法。 Theta-burst 刺激 (TBS) 最初是經顱磁刺激 (TMS) 的波形。之前有人提出 TBS 以更少的刺激就比傳統的 rTMS更有效;但是，TBS 作為電力波形的影響力缺乏科學證據。我們旨在研究 (1) 經顱電刺激 (tES)以不同電流大小輸入時的電流分佈和 (2) 使用 TBS 波形的 HD-tES 對健康成人運動任務期間皮層活動的影響。方法：使用商用 Soterix 醫療 HD-ExploreTM 研究 HD-tES 的聚焦空間、電場和電流分佈。此外，八名健康受試者以一周的間隔完成了 單側TBS、雙側TBS 和假設實驗，為期 10 分鐘。通過功能性近紅外光譜（NIRS）在刺激實驗前（pre）, 刺激期間（online）和刺激後 5 分鐘（post） 三個階段,記錄手指敲擊運動的血流動力學變化在前額葉皮層(PFC),感覺運動皮層（SMC）和頂葉皮層（PC）。結果：在所有條件下均觀察到磁場聚焦的情形。但是，電場分佈（V/m）隨著電流強度的增加而增加。在線 TBS 和 TBS 後的皮質活動顯著高於刺激前和假實驗條件下的皮質活動。結論：在使用TBS波形的HD-tES治療下，運動任務期間的皮質活動顯著增強。我們的實驗設計、TBS 治療和 NIRS 測量可作為未來研究和臨床應用的參考。

Non-invasive brain stimulation (NIBS) has been proposed as a promising approach for neuro-modulation to improve neuroplasticity for patients with neurological disorders. Theta-burst stimulation (TBS) was originally designed for transcranial magnetic stimulation (TMS) which has been proved be more effective but with less dose than conventional rTMS. In our research, we intended to utilize TBS for high-density transcranial electrical stimulation (HD-tES) which has not been extensively investigated. Thus, the aims of this study are first to investigate the electric current distribution during HD-TDCS with different current inputs. Furthermore, the effects of HD-tES using TBS waveform on cortical activity during motor tasks in healthy adults was studied. The commercially available Soterix medical HD-ExploreTM was used to investigate the spatial focality, electric field, and current distribution of HD-tES. In addition, eight healthy subjects completed 10-min sessions of unilateral (uni_TBS) and bilateral TBS (bi_TBS) were compared with sham control group over primary motor cortex M1 with one-week interval. The hemodynamic changes in finger-tapping exercise were recorded by functional near-infrared spectroscopy (NIRS) at bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal cortex (PC) in three phases of before intervention (pre), during intervention (online), and 5min after intervention (post). From current density simulation program, the spatial focality were observed in all conditions which the current distribution (V/m) were increased with the increase in the current intensity. The cortical activity was significantly greater at online uni_TBS and post bi_TBS than pre-treatments and those in sham condition. The cortical activity during motor task was significantly enhanced under the treatment of HD-tES using TBS waveform. Our experimental design provided a mean to observe the current distribution in HD-tES using TBS treatments to verify the safety issue. The utilization of unilateral and bilateral stimulations may provide a novel stimulation scheme for future neuromodulation for neuro-rehabilitation of stroke.

Alam, M., Truong, D. Q., Khadka, N., & Bikson, M. (2016). Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS). Phys Med Biol, 61(12), 4506-4521.
Alam, M., Truong, D. Q., Khadka, N., Bikson, M. J. P. i. M. (2016). Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS). Biology, 61(12), 4506.
Arora, Y., & Chowdhury, S. R. (2020). Cortical Excitability through Anodal Transcranial Direct Current Stimulation: a Computational Approach. Medical systems 44(2), 1-13.
Besson, P., Muthalib, M., Dray, G., Rothwell, J., & Perrey, S. (2019). Concurrent anodal transcranial direct-current stimulation and motor task to influence sensorimotor cortex activation. Brain Res, 1710, 181-187.
Chew, T., Ho, K. A., & Loo, C. K. (2015). Inter- and Intra-individual Variability in Response to Transcranial Direct Current Stimulation (tDCS) at Varying Current Intensities. Brain Stimul, 8(6), 1130-1137.
Datta, A., Zhou, X., Su, Y., Parra, L. C., & Bikson, M. J. (2013). Validation of finite element model of transcranial electrical stimulation using scalp potentials: implications for clinical dose. Neural Engineering, 10(3), 036018.
Davies, D. J., Su, Z., Clancy, M. T., Lucas, S. J., Dehghani, H., Logan, A., & Belli, A. J. (2015). Near-infrared spectroscopy in the monitoring of adult traumatic brain injury: a review. Neurotrauma, 32(13), 933-941.
Dayan, E., Censor, N., Buch, E. R., Sandrini, M., & Cohen, L. G. (2013). Noninvasive brain stimulation: from physiology to network dynamics and back. Nat. Neurosci, 16(7), 838-844.
Devor, A., Sakadžić, S., Srinivasan, V. J., Yaseen, M. A., Nizar, K., Saisan, P. A., . . . Metabolism. (2012). Frontiers in optical imaging of cerebral blood flow and metabolism. Cereb. Blood Flow Metab, 32(7), 1259-1276.
Di Lazzaro, V., Dileone, M., Pilato, F., Capone, F., Musumeci, G., Ranieri, F., . . . De Waure, C. (2011). Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation. Neurophysiology, 105(5), 2150-2156.
Di Lazzaro, V., Pilato, F., Dileone, M., Profice, P., Oliviero, A., Mazzone, P., . . . Tonali, P. J. T. J. (2008). The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. Physiology, 586(16), 3871-3879.
Flöel, A. (2014). tDCS-enhanced motor and cognitive function in neurological diseases. Neuroimage, 85 Pt 3, 934-947.
Flood, A., Waddington, G., & Cathcart, S. (2016). High-Definition Transcranial Direct Current Stimulation Enhances Conditioned Pain Modulation in Healthy Volunteers: A Randomized Trial. Pain, 17(5), 600-605.
Gratton, G. F., Monica. (2003). The event‐related optical signal (EROS) in visual cortex: replicability, consistency, localization, and resolution. Psychophysiol, 40(4), 561-571.
Huang, Y.-Z., Rothwell, J. C., Chen, R.-S., Lu, C.-S., & Chuang, W.-L. (2011). The theoretical model of theta burst form of repetitive transcranial magnetic stimulation. Clin. Neurophysiol, 122(5), 1011-1018.
Kempe, R., Huang, Y., & Parra, L. C. J. J. (2014). Simulating pad-electrodes with high-definition arrays in transcranial electric stimulation. Neural Engineering, 11(2), 026003.
Lafon, B., Rahman, A., Bikson, M., & Parra, L. C. (2017). Direct Current Stimulation Alters Neuronal Input/Output Function. Brain Stimul, 10(1), 36-45.
Leff, D. R., Orihuela-Espina, F., Elwell, C. E., Athanasiou, T., Delpy, D. T., Darzi, A. W., & Yang, G.-Z. (2011). Assessment of the cerebral cortex during motor task behaviours in adults: a systematic review of functional near infrared spectroscopy (fNIRS) studies. Neuroimage, 54(4), 2922-2936.
Li, Y.-T., Chen, S.-C., Yang, L.-Y., Hsieh, T.-H., Peng, C.-W. J. (2019). Designing and implementing a novel transcranial electrostimulation system for neuroplastic applications: A preliminary study. Rehabilitation Engineering, 27(5), 805-813.
Lin, P.-Y., Lin, S.-I., Chen, J.-J. J. (2011). Functional near infrared spectroscopy study of age-related difference in cortical activation patterns during cycling with speed feedback. Neurosystem & Rehabilitation Engineeing, 20(1), 78-84.
Lin, T.-Y., Wu, J.-S., Lin, L. L., Ho, T.-C., Lin, P.-Y., Chen, J.-J. J. (2015). Assessments of muscle oxygenation and cortical activity using functional near-infrared spectroscopy in healthy adults during hybrid activation. Neurosystem & Rehabilitation Engineeing 24(1), 1-9.
Miniussi, C., Cappa, S. F., Cohen, L. G., Floel, A., Fregni, F., Nitsche, M. A. (2008). Efficacy of repetitive transcranial magnetic stimulation/transcranial direct current stimulation in cognitive neurorehabilitation. Brain stimulation, 1(4), 326-336.
Miyai, I., Yagura, H., Hatakenaka, M., Oda, I., Konishi, I., & Kubota, K. (2003). Longitudinal optical imaging study for locomotor recovery after stroke. Stroke, 34(12), 2866-2870.
Muthalib, M., Besson, P., Rothwell, J., & Perrey, S. (2018). Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation. Neuromodulation, 21(4), 348-354.
Nikolin, S., Loo, C. K., Bai, S., Dokos, S., & Martin, D. M. (2015). Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning. Neuroimage, 117, 11-19.
Patel, R., Dawidziuk, A., Darzi, A., Singh, H., & Leff, D. (2020). Systematic review of combined functional near-infrared spectroscopy and transcranial direct-current stimulation studies. Neurophotonics, 7(2), 020901.
Ragert, P., Camus, M., Vandermeeren, Y., Dimyan, M. A., & Cohen, L. G. (2009). Modulation of effects of intermittent theta burst stimulation applied over primary motor cortex (M1) by conditioning stimulation of the opposite M1. Neurophysiology, 102(2), 766-773.
Russo, C., Souza Carneiro, M. I., Bolognini, N., & Fregni, F. (2017). Safety review of transcranial direct current stimulation in stroke. Neuromodulation: Technology at the Neural Interface, 20(3), 215-222.
Scholkmann, F., Kleiser, S., Metz, A. J., Zimmermann, R., Pavia, J. M., Wolf, U., & Wolf, M. J. N. (2014). A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology. Neuroimage, 85, 6-27.
Sharma, G., & Chowdhury, S. R. (2018). Design of NIRS probe based on computational model to find out the optimal location for non-invasive brain stimulation. Medical sytsem, M42(12), 1-15.
Suppa, A., Ortu, E., Zafar, N., Deriu, F., Paulus, W., Berardelli, A., & Rothwell, J. C. (2008). Theta burst stimulation induces after‐effects on contralateral primary motor cortex excitability in humans. Physiology, 586(18), 4489-4500.
Turski, C. A., Kessler-Jones, A., Chow, C., Hermann, B., Hsu, D., Jones, J., . . . Ikonomidou, C. (2017). Extended Multiple-Field High-Definition transcranial direct current stimulation (HD-tDCS) is well tolerated and safe in healthy adults. Restor Neurol Neurosci, 35(6), 631-642.
Villamar, M. F., Wivatvongvana, P., Patumanond, J., Bikson, M., Truong, D. Q., Datta, A., & Fregni, F. J. (2013). Focal modulation of the primary motor cortex in fibromyalgia using 4× 1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation. Pain, 14(4), 371-383.
Wiethoff, S., Hamada, M., & Rothwell, J. C. (2014). Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimul, 7(3), 468-475.
Witt, S. T., Laird, A. R., & Meyerand, M. E. J. N. (2008). Functional neuroimaging correlates of finger-tapping task variations: an ALE meta-analysis. Neuroimage, 42(1), 343-356.
Woods, A. J., Antal, A., Bikson, M., Boggio, P. S., Brunoni, A. R., Celnik, P., . . . Nitsche, M. A. (2016). A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol, 127(2), 1031-1048.
Yang, M., Yang, Z., Yuan, T., Feng, W., & Wang, P. (2019). A systemic review of functional near-infrared spectroscopy for stroke: current application and future directions. Front Neurol, 10, 58.
Yaqub, M. A., Woo, S.-W., & Hong, K.-S. (2018). Effects of HD-tDCS on Resting-State Functional Connectivity in the Prefrontal Cortex: An fNIRS Study. Complexity, 2018, 1613402.