{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:44:35Z","timestamp":1790387075934,"version":"4.1.0"},"reference-count":26,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3]]},"abstract":"\n OBJECTIVE<\/jats:title>\n The object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Six awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Acute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05).<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n Acute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia\u2013centric neuromodulation approach to treat medically refractory tinnitus.<\/jats:p>\n Clinical trial registration no.: NCT01988688 (clinicaltrials.gov)<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2018.10.jns181659","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T19:15:01Z","timestamp":1551208501000},"page":"705-711","source":"Crossref","is-referenced-by-count":19,"title":["Human caudate nucleus subdivisions in tinnitus modulation"],"prefix":"10.3171","volume":"132","author":[{"given":"Philip L.","family":"Perez","sequence":"first","affiliation":[{"name":"Departments of Otolaryngology\u2013Head and Neck Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurology;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Heath","sequence":"additional","affiliation":[{"name":"Surgical Services, San Francisco Veterans Affairs Medical Center; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Henderson-Sabes","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology\u2013Head and Neck Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Mizuiri","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Biomedical Imaging and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leighton B.","family":"Hinkley","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Biomedical Imaging and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikantan S.","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology\u2013Head and Neck Surgery and"},{"name":"Departments of Radiology and Biomedical Imaging and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Larson","sequence":"additional","affiliation":[{"name":"Surgical Services, San Francisco Veterans Affairs Medical Center; and"},{"name":"Neurological Surgery, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology\u2013Head and Neck Surgery and"},{"name":"Surgical Services, San Francisco Veterans Affairs Medical Center; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1002\/lary.26876","article-title":"An animal model of deep brain stimulation for treating tinnitus: a proof of concept study","volume":"128","author":"Ahsan SF","year":"2018","unstructured":"Ahsan SF, Luo H, Zhang J, Kim E, Xu Y: An animal model of deep brain stimulation for treating tinnitus: a proof of concept study. Laryngoscope 128:1213\u20131222, 20182892501310.1002\/lary.26876"},{"key":"b2","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1016\/j.neuroscience.2010.06.007","article-title":"Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC)","volume":"169","author":"Cheung SW","year":"2010","unstructured":"Cheung SW, Larson PS: Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC). Neuroscience 169:1768\u20131778, 201010.1016\/j.neuroscience.2010.06.007"},{"key":"b3","series-title":"Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1177\/0194599815591532","article-title":"Stapedectomy effects on tinnitus: relationship of change in loudness to change in severity","volume":"153","author":"Dewyer NA","year":"2015","unstructured":"Dewyer NA, Kiringoda R, Kram YA, Chang JL, Chang CY, Cheung SW: Stapedectomy effects on tinnitus: relationship of change in loudness to change in severity. Otolaryngol Head Neck Surg 153:1019\u20131023, 201510.1177\/019459981559153226115669"},{"key":"b4","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e70297","DOI":"10.1371\/journal.pone.0070297","article-title":"Epidemiology of noise-induced tinnitus and the attitudes and beliefs towards noise and hearing protection in adolescents","volume":"8","author":"Gilles A","year":"2013","unstructured":"Gilles A, Van Hal G, De Ridder D, Wouters K, Van de Heyning P: Epidemiology of noise-induced tinnitus and the attitudes and beliefs towards noise and hearing protection in adolescents. PLoS One 8:e70297, 20132389463810.1371\/journal.pone.0070297"},{"key":"b5","series-title":"J Speech Lang Hear Res","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1044\/1092-4388(2005\/084)","article-title":"General review of tinnitus: prevalence, mechanisms, effects, and management","volume":"48","author":"Henry JA","year":"2005","unstructured":"Henry JA, Dennis KC, Schechter MA: General review of tinnitus: prevalence, mechanisms, effects, and management. J Speech Lang Hear Res 48:1204\u20131235, 200510.1044\/1092-4388(2005\/084)16411806"},{"key":"b6","series-title":"Front Hum Neurosci","doi-asserted-by":"publisher","first-page":"568","DOI":"10.3389\/fnhum.2015.00568","article-title":"Increased striatal functional connectivity with auditory cortex in tinnitus","volume":"9","author":"Hinkley LB","year":"2015","unstructured":"Hinkley LB, Mizuiri D, Hong O, Nagarajan SS, Cheung SW: Increased striatal functional connectivity with auditory cortex in tinnitus. Front Hum Neurosci 9:568, 20152657892410.3389\/fnhum.2015.00568"},{"key":"b7","series-title":"Tinnitus: Theory and Management","first-page":"16","article-title":"Epidemiology of tinnitus","author":"Hoffman HJ","year":"2004","unstructured":"Hoffman HJ, Reed GW: Epidemiology of tinnitus, in Snow JB (ed): Tinnitus: Theory and Management. Hamilton, ON: BC Decker, 2004, pp 16\u201341"},{"key":"b8","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e106768","DOI":"10.1371\/journal.pone.0106768","article-title":"Unravelling the intrinsic functional organization of the human striatum: a parcellation and connectivity study based on resting-state FMRI","volume":"9","author":"Jung WH","year":"2014","unstructured":"Jung WH, Jang JH, Park JW, Kim E, Goo EH, Im OS, : Unravelling the intrinsic functional organization of the human striatum: a parcellation and connectivity study based on resting-state FMRI. PLoS One 9:e106768, 20142520344110.1371\/journal.pone.0106768"},{"key":"b9","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1227\/NEU.0b013e3182320ab5","article-title":"Deep brain stimulation in area LC controllably triggers auditory phantom percepts","volume":"70","author":"Larson PS","year":"2012","unstructured":"Larson PS, Cheung SW: Deep brain stimulation in area LC controllably triggers auditory phantom percepts. Neurosurgery 70:398\u2013406, 201210.1227\/NEU.0b013e3182320ab5"},{"key":"b10","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"192","DOI":"10.3171\/2012.9.JNS12594","article-title":"A stroke of silence: tinnitus suppression following placement of a deep brain stimulation electrode with infarction in area LC","volume":"118","author":"Larson PS","year":"2013","unstructured":"Larson PS, Cheung SW: A stroke of silence: tinnitus suppression following placement of a deep brain stimulation electrode with infarction in area LC. J Neurosurg 118:192\u2013194, 201310.3171\/2012.9.JNS12594"},{"key":"b11","series-title":"Otol Neurotol","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1097\/00129492-200407000-00013","article-title":"An absence of tinnitus","volume":"25","author":"Lowry LD","year":"2004","unstructured":"Lowry LD, Eisenman LM, Saunders JC: An absence of tinnitus. Otol Neurotol 25:474\u2013478, 200410.1097\/00129492-200407000-0001315241224"},{"key":"b12","series-title":"Ear Hear","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1097\/AUD.0000000000000121","article-title":"Incidence rates of clinically significant tinnitus: 10-year trend from a cohort study in England","volume":"36","author":"Martinez C","year":"2015","unstructured":"Martinez C, Wallenhorst C, McFerran D, Hall DA: Incidence rates of clinically significant tinnitus: 10-year trend from a cohort study in England. Ear Hear 36:e69\u2013e75, 201510.1097\/AUD.000000000000012125470370"},{"key":"b13","series-title":"Ear Hear","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1097\/AUD.0b013e31822f67c0","article-title":"The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus","volume":"33","author":"Meikle MB","year":"2012","unstructured":"Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, : The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear 33:153\u2013176, 201210.1097\/AUD.0b013e31822f67c022156949"},{"key":"b14","series-title":"J Am Geriatr Soc","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine ZS","year":"2005","unstructured":"Nasreddine ZS, Phillips NA, B\u00e9dirian V, Charbonneau S, Whitehead V, Collin I, : The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695\u2013699, 200510.1111\/j.1532-5415.2005.53221.x15817019"},{"key":"b15","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"12831","DOI":"10.1523\/JNEUROSCI.3177-09.2009","article-title":"Corticostriatal interactions during learning, memory processing, and decision making","volume":"29","author":"Pennartz CM","year":"2009","unstructured":"Pennartz CM, Berke JD, Graybiel AM, Ito R, Lansink CS, van der Meer M, : Corticostriatal interactions during learning, memory processing, and decision making. J Neurosci 29:12831\u201312838, 20091982879610.1523\/JNEUROSCI.3177-09.2009"},{"key":"b16","series-title":"Otol Neurotol","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1097\/MAO.0000000000000312","article-title":"Willingness-to-accept Gamma knife radiosurgery for tinnitus among career San Francisco firefighters","volume":"35","author":"Pross SE","year":"2014","unstructured":"Pross SE, Allen CA, Hong OS, Cheung SW: Willingness-to-accept Gamma knife radiosurgery for tinnitus among career San Francisco firefighters. Otol Neurotol 35:1026\u20131032, 201410.1097\/MAO.000000000000031224662638"},{"key":"b17","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/0306-4522(83)90026-X","article-title":"Auditory cortical field projections to the basal ganglia of the cat","volume":"8","author":"Reale RA","year":"1983","unstructured":"Reale RA, Imig TJ: Auditory cortical field projections to the basal ganglia of the cat. Neuroscience 8:67\u201386, 198310.1016\/0306-4522(83)90026-X6835523"},{"key":"b18","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"14972","DOI":"10.1523\/JNEUROSCI.4028-10.2010","article-title":"Ringing ears: the neuroscience of tinnitus","volume":"30","author":"Roberts LE","year":"2010","unstructured":"Roberts LE, Eggermont JJ, Caspary DM, Shore SE, Melcher JR, Kaltenbach JA: Ringing ears: the neuroscience of tinnitus. J Neurosci 30:14972\u201314979, 20102106830010.1523\/JNEUROSCI.4028-10.2010"},{"key":"b19","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1523\/JNEUROSCI.05-03-00776.1985","article-title":"Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey","volume":"5","author":"Selemon LD","year":"1985","unstructured":"Selemon LD, Goldman-Rakic PS: Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neurosci 5:776\u2013794, 198510.1523\/JNEUROSCI.05-03-00776.19852983048"},{"key":"b20","series-title":"Am J Med","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.amjmed.2010.02.015","article-title":"Prevalence and characteristics of tinnitus among US adults","volume":"123","author":"Shargorodsky J","year":"2010","unstructured":"Shargorodsky J, Curhan GC, Farwell WR: Prevalence and characteristics of tinnitus among US adults. Am J Med 123:711\u2013718, 20102067072510.1016\/j.amjmed.2010.02.015"},{"key":"b21","series-title":"Physiol Rev","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1152\/physrev.00002.2002","article-title":"Plastic changes in the central auditory system after hearing loss, restoration of function, and during learning","volume":"82","author":"Syka J","year":"2002","unstructured":"Syka J: Plastic changes in the central auditory system after hearing loss, restoration of function, and during learning. Physiol Rev 82:601\u2013636, 20021208713010.1152\/physrev.00002.2002"},{"key":"b22","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1002\/lary.23242","article-title":"Audiometric asymmetry and tinnitus laterality","volume":"122","author":"Tsai BS","year":"2012","unstructured":"Tsai BS, Sweetow RW, Cheung SW: Audiometric asymmetry and tinnitus laterality. Laryngoscope 122:1148\u20131153, 20122244757710.1002\/lary.23242"},{"key":"b23","series-title":"Drug Discov Today","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/S1359-6446(05)03594-4","article-title":"Hearing loss and tinnitus: 250 million people and a US$10 billion potential market","volume":"10","author":"Vio MM","year":"2005","unstructured":"Vio MM, Holme RH: Hearing loss and tinnitus: 250 million people and a US$10 billion potential market. Drug Discov Today 10:1263\u20131265, 200510.1016\/S1359-6446(05)03594-4"},{"key":"b24","series-title":"J Pediatr","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.jpeds.2007.07.009","article-title":"MP3 players and hearing loss: adolescents\u2019 perceptions of loud music and hearing conservation","volume":"152","author":"Vogel I","year":"2008","unstructured":"Vogel I, Brug J, Hosli EJ, van der Ploeg CP, Raat H: MP3 players and hearing loss: adolescents\u2019 perceptions of loud music and hearing conservation. J Pediatr 152:400\u2013404, 20081828084910.1016\/j.jpeds.2007.07.009"},{"key":"b25","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1523\/JNEUROSCI.3711-06.2007","article-title":"The neural code of auditory phantom perception","volume":"27","author":"Weisz N","year":"2007","unstructured":"Weisz N, M\u00fcller S, Schlee W, Dohrmann K, Hartmann T, Elbert T: The neural code of auditory phantom perception. J Neurosci 27:1479\u20131484, 20071728752310.1523\/JNEUROSCI.3711-06.2007"},{"key":"b26","series-title":"J Comp Neurol","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1002\/(SICI)1096-9861(19980928)399:3<384::AID-CNE7>3.0.CO;2-X","article-title":"Corticostriatal connections of the superior temporal region in rhesus monkeys","volume":"399","author":"Yeterian EH","year":"1998","unstructured":"Yeterian EH, Pandya DN: Corticostriatal connections of the superior temporal region in rhesus monkeys. J Comp Neurol 399:384\u2013402, 199810.1002\/(SICI)1096-9861(19980928)399:3<384::AID-CNE7>3.0.CO;2-X9733085"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/132\/3\/article-p705.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/132\/3\/article-p705.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/132\/3\/article-p705.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T04:58:07Z","timestamp":1658725087000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/132\/3\/article-p705.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":26,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.3171\/2018.10.jns181659","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]}}}