{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:23:39Z","timestamp":1760243019995,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,5,28]],"date-time":"2015-05-28T00:00:00Z","timestamp":1432771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["103-2221-E-182-070","102-2218-E-182-003","102-2221-E-010-011-MY3","101-2622-E-010-002-CC2"],"award-info":[{"award-number":["103-2221-E-182-070","102-2218-E-182-003","102-2221-E-010-011-MY3","101-2622-E-010-002-CC2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chang Gung University and Chang Gung Memorial Hospital","award":["UERPD2D0051","CMRPD3D0221"],"award-info":[{"award-number":["UERPD2D0051","CMRPD3D0221"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design.<\/jats:p>","DOI":"10.3390\/s150612700","type":"journal-article","created":{"date-parts":[[2015,5,28]],"date-time":"2015-05-28T11:01:49Z","timestamp":1432810909000},"page":"12700-12719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9414-3798","authenticated-orcid":false,"given":"Cihun-Siyong","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Rd.,  Guishan Township, Taoyuan County 333, Taiwan"},{"name":"Portable Energy System Group, Green Technology Research Center, College of Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Rd., Guishan Township,  Taoyuan County 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Yi","family":"Lai","sequence":"additional","affiliation":[{"name":"Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University, Zhouyiqing Building, Yuquan Campus, Zhejiang University, Hangzhou 310027, China"},{"name":"School of Medicine, Chang Gung University, No. 259 Wen-Hwa 1st Rd., Guishan Township, Taoyuan County 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sy-Han","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Yang Ming University, No.155, Sec.2, Linong St., Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chun","family":"Lo","sequence":"additional","affiliation":[{"name":"Center for Optoelectronic Medicine, National Taiwan University College of Medicine,  No.1 Jen Ai Rd. Sec. 1. Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive #0412,  La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pin-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung University and Memorial Hospital at Linkou,  No.5, Fuxing St., Guishan Township, Taoyuan County 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Hsun","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung University and Memorial Hospital at Linkou,  No.5, Fuxing St., Guishan Township, Taoyuan County 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Yen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Ming-Chuan University, 5 De Ming Rd., Guishan Township, Taoyuan County 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Rd.,  Guishan Township, Taoyuan County 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Yang Ming University, No.155, Sec.2, Linong St., Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1084713813480857","article-title":"A systematic review of electric-acoustic stimulation: Device fitting ranges, outcomes, and clinical fitting practices","volume":"17","author":"Incerti","year":"2013","journal-title":"Trends Amplif."},{"key":"ref_2","unstructured":"Niparko, J.K., and Wilson, B.W. (2000). Cochlear Implants: Principles and Practices, Lippincott Williams & Wilkins."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1109\/JPROC.2008.922558","article-title":"Neural interface devices: Spinal cord stimulation technology","volume":"96","author":"North","year":"2008","journal-title":"IEEE Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jaapos.2008.08.013","article-title":"Toward an implantable functional electrical stimulation device to correct strabismus","volume":"13","author":"Velez","year":"2009","journal-title":"J. AAPOS"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s13311-014-0282-1","article-title":"Deep brain stimulation for treatment-resistant depression: Systematic review of clinical outcomes","volume":"11","author":"Morishita","year":"2014","journal-title":"Neurotherapeutics"},{"key":"ref_6","first-page":"A7015","article-title":"Deep brain stimulation for psychiatric disorders","volume":"157","author":"Overbeek","year":"2013","journal-title":"Ned. Tijdschr. Geneeskd."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1172\/JCI68341","article-title":"Deep brain stimulation (DBS) at the interface of neurology and psychiatry","volume":"123","author":"Williams","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s10548-013-0315-9","article-title":"Neuromodulation for treatment resistant depression: State of the art and recommendations for clinical and scientific conduct","volume":"27","author":"Schlaepfer","year":"2014","journal-title":"Brain Topogr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1109\/IEMBS.2006.259855","article-title":"The design and testing of an epi-retinal vision prosthesis neurostimulator capable of concurrent parallel stimulation","volume":"1","author":"Dommel","year":"2006","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ortmanns, M., Unger, N., Rocke, A., Gehrke, M., and Tietdke, H.J. (2006, January 6\u20139). A 0.1 mm\/sup 2\/, digitally programmable nerve stimulation pad cell with high-voltage capability for a retinal implant. Proceedings of the IEEE International ISSCC Conference, San Francisco, CA, USA.","DOI":"10.1109\/ISSCC.2006.1696037"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ethier, S., Sawan, M., Aboulhamid, E.M., and el-Gamal, M. (2009, January 2\u20135). A \u00b19 v fully integrated CMOS electrode driver for high-impedance microstimulation. Proceedingss of the 52nd IEEE International Midwest Symposium on Circuits and Systems, Cancun, Mexico.","DOI":"10.1109\/MWSCAS.2009.5236121"},{"key":"ref_12","unstructured":"Nadeau, P., and Sawan, M. (December, January 29). A flexible high voltage biphasic current-controlled stimulator. Proceedingss of the IEEE BIOCAS Conference, London, UK."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1109\/JSSC.2011.2164667","article-title":"A neural stimulator frontend with high-voltage compliance and programmable pulse shape for epiretinal implants","volume":"47","author":"Noorsal","year":"2012","journal-title":"IEEE J. Solid State Circuits"},{"key":"ref_14","unstructured":"Ghovanloo, M. (2006, January 21\u201324). Switched-capacitor based implantable low-power wireless microstimulating systems. Proceedingss of the IEEE ISCAS Conference, Island of Kos, Greece."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jneumeth.2010.01.026","article-title":"Evaluating the impact of the deep brain stimulation induced electric field on subthalamic neurons: A computational modelling study","volume":"188","author":"Yousif","year":"2010","journal-title":"J. Neurosci. Meth."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0300-2977(00)00082-6","article-title":"Auditory nerve responses to monophasic and biphasic electric stimuli","volume":"151","author":"Miller","year":"2001","journal-title":"Hear. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1109\/TBCAS.2012.2220763","article-title":"A low-frequency versatile wireless power transfer technology for biomedical implants","volume":"7","author":"Hao","year":"2013","journal-title":"IEEE Trans. Biomed. Circuits Syst."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3109\/00207454.2013.852086","article-title":"Deep brain stimulation and ablation for obsessive compulsive disorder: Evolution of contemporary indications, targets and techniques","volume":"124","author":"Tierney","year":"2014","journal-title":"Int. J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/npp.2011.193","article-title":"Circuits, cells, and synapses: Toward a new target for deep brain stimulation in depression","volume":"37","author":"Henn","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_20","first-page":"740","article-title":"Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: A key role for the subgenual anterior cingulate and ventral striatum","volume":"47","author":"Nuttin","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_21","first-page":"105","article-title":"Deep brain stimulation for psychiatric disorders","volume":"107","author":"Kuhn","year":"2010","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1094-7159.2004.04009.x","article-title":"Evolution of brain impedance in dystonic patients treated by GPI electrical stimulation","volume":"7","author":"Hemm","year":"2004","journal-title":"Neuromodulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.brs.2013.02.001","article-title":"Long-term measurement of impedance in chronically implanted depth and subdural electrodes during responsive neurostimulation in humans","volume":"6","author":"Sillay","year":"2013","journal-title":"Brain Stimul."},{"key":"ref_24","first-page":"1237","article-title":"Constant voltage versus constant current deep brain stimulation: Is impedance fluctuation sufficient to favor constant current stimulation? [abstract]","volume":"29","author":"Waln","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s002210050304","article-title":"Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. I. Evidence from chronaxie measurements","volume":"118","author":"Nowak","year":"1998","journal-title":"Exp. Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s002210050305","article-title":"Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments","volume":"118","author":"Nowak","year":"1998","journal-title":"Exp. Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.clinph.2003.12.024","article-title":"Uncovering the mechanism(s) of action of deep brain stimulation: Activation, inhibition, or both","volume":"115","author":"McIntyre","year":"2004","journal-title":"Clin. Neurophysiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1109\/JSSC.2005.843599","article-title":"A high-voltage output driver in a 2.5-v 0.25-\u03bcm CMOS technology","volume":"40","author":"Serneels","year":"2005","journal-title":"IEEE J. Solid State Circuits"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jneumeth.2004.10.020","article-title":"Electrical stimulation of excitable tissue: Design of efficacious and safe protocols","volume":"141","author":"Merrill","year":"2005","journal-title":"J. Neurosci. Meth."},{"key":"ref_30","unstructured":"Simmons, A.D., Montgomery, E.B., and Grill, W.M. (2001, January 14\u201316). Excitation Characteristics of Paresthesias Produced by Deep Brain Stimulation. Proceedings of the IFESS Conference, Cleveland, OH, USA."},{"key":"ref_31","unstructured":"Paxinos, G., and Watson, C. (2008). The Rat Brain in Stereotaxic Coordinates: Compact, Academic Press. [6th ed.]."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1166\/jnsne.2012.1025","article-title":"A low-cost multi-electrode array system for the simultaneous acquisition of electrophysiological signal and cellular morphology","volume":"1","author":"Chang","year":"2012","journal-title":"J. Neurosci. Neuroeng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.3390\/s100504238","article-title":"Development of a three dimensional neural sensing device by a stacking method","volume":"10","author":"Chang","year":"2010","journal-title":"Sensors"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jneumeth.2009.05.010","article-title":"Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain","volume":"182","author":"Chen","year":"2009","journal-title":"J. Neurosci. Meth."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.clinph.2005.10.007","article-title":"Sources and effects of electrode impedance during deep brain stimulation","volume":"117","author":"Butson","year":"2006","journal-title":"Clin. Neurophysiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10470-008-9153-1","article-title":"Wireless monitoring of electrode-tissues interfaces for long term characterization","volume":"55","author":"Sawan","year":"2008","journal-title":"Analog Integr. Circuits Signal Process."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e58665","DOI":"10.1371\/journal.pone.0058665","article-title":"Management of deep brain stimulator battery failure: Battery estimators, charge density, and importance of clinical symptoms","volume":"8","author":"Fakhar","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1097\/NRL.0b013e3181492c48","article-title":"Deep brain stimslation","volume":"13","author":"Kern","year":"2007","journal-title":"Neurologist"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.seizure.2011.03.001","article-title":"Chronic deep brain stimulation in mesial temporal lobe epilepsy","volume":"20","author":"Boex","year":"2011","journal-title":"Seizure"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1152\/jn.00420.2012","article-title":"Deep brain stimulation entrains local neuronal firing in human globus pallidus internus","volume":"109","author":"Cleary","year":"2013","journal-title":"J. Neurophysiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1016\/j.clinph.2007.05.061","article-title":"Differences among implanted pulse generator waveforms cause variations in the neural response to deep brain stimulation","volume":"118","author":"Butson","year":"2007","journal-title":"Clin. Neurophysiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fnhum.2012.00155","article-title":"High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson\u2019s disease","volume":"6","author":"Whitmer","year":"2012","journal-title":"Front. Hum. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev.bioeng.10.061807.160518","article-title":"Neural Stimulation and Recording Electrodes","volume":"10","author":"Cogan","year":"2008","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"015007","DOI":"10.1088\/1748-6041\/5\/1\/015007","article-title":"In vitro comparison of sputtered iridium oxide and platinum-coated neural implantable microelectrode arrays","volume":"5","author":"Negi","year":"2010","journal-title":"Biomed. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1109\/10.335862","article-title":"A three-dimensional microelectrode array for chronic neural recording","volume":"41","author":"Hoogerwerf","year":"1994","journal-title":"IEEE Trans. Bio-Med. Eng."},{"key":"ref_46","unstructured":"Irazoqui-Pastor, P., Mody, I., and Judy, J.W. (2003, January 20\u201322). In-vivo EEG recording using a wireless implantable neural transceiver. Proceedings of the IEEE EMBS Conference, Capri Island, Italy."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1109\/JSSC.2005.858479","article-title":"A three-dimensional neural recording microsystem with implantable data compression circuitry","volume":"40","author":"Olsson","year":"2005","journal-title":"IEEE J. Solid-State Circuits"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1109\/JSSC.2006.886567","article-title":"A low-power integrated circuit for a wireless 100-electrode neural recording system","volume":"42","author":"Harrison","year":"2007","journal-title":"IEEE J. Solid State Circuits"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10470-008-9233-2","article-title":"An implanted system for multi-site nerve cuff-based ENG recording using velocity selectivity","volume":"58","author":"Clarke","year":"2009","journal-title":"Analog Integr. Circuits Signal Process."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1136\/jnnp-2013-306066","article-title":"Temporal macrodynamics and microdynamics of the postoperative impedance at the tissue-electrode interface in deep brain stimulation patients","volume":"85","author":"Lungu","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"036001","DOI":"10.1088\/1741-2560\/9\/3\/036001","article-title":"Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording","volume":"9","author":"Lai","year":"2012","journal-title":"J. Neural Eng."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.brs.2013.11.001","article-title":"FMRI of deep brain stimulation at the rat ventral posteromedial thalamus","volume":"7","author":"Shih","year":"2014","journal-title":"Brain Stimul."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/15\/6\/12700\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:06Z","timestamp":1760215626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/15\/6\/12700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,28]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["s150612700"],"URL":"https:\/\/doi.org\/10.3390\/s150612700","relation":{},"ISSN":["1424-8220"],"issn-type":[{"type":"electronic","value":"1424-8220"}],"subject":[],"published":{"date-parts":[[2015,5,28]]}}}