{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T17:17:47Z","timestamp":1794590267678,"version":"4.9.1"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>The habenula is a small bilateral epithalamic structure that plays a key role in the regulation of the main monoaminergic systems. It is implicated in many aspects of behavior such as reward processing, motivational behavior, behavioral adaptation, and sensory integration. A role of the habenula has been indicated in the pathophysiology of a number of neuropsychiatric disorders such as depression, addiction, obsessive-compulsive disorder, and bipolar disorder. Neuromodulation of the habenula using deep brain stimulation (DBS) as potential treatment has been proposed and a first successful case of habenula DBS was reported a decade ago. To provide an overview of the current state of habenula DBS in human subjects for the treatment of neuropsychiatric disorders we conducted a systematic review of both the published literature using PUBMED and current and past registered clinical trials using ClinicalTrials.gov as well as the International Clinical Trials Registry Platform. Using PRISMA guidelines five articles and five registered clinical trials were identified. The published articles detailed the results of habenula DBS for the treatment of schizophrenia, depression, obsessive-compulsive disorder, and bipolar disorder. Four are single case studies; one reports findings in two patients and positive clinical outcome is described in five of the six patients. Of the five registered clinical trials identified, four investigate habenula DBS for the treatment of depression and one for obsessive-compulsive disorder. One trial is listed as terminated, one is recruiting, two are not yet recruiting and the status of the fifth is unknown. The planned enrollment varies between 2 to 13 subjects and four of the five are open label trials. While the published studies suggest a potential role of habenula DBS for a number of indications, future trials and studies are necessary. The outcomes of the ongoing clinical trials will provide further valuable insights. Establishing habenula DBS, however, will depend on successful randomized clinical trials to confirm application and clinical benefit of this promising intervention.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.730931","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T07:04:00Z","timestamp":1629183840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["Deep Brain Stimulation of the Habenula: Systematic Review of the Literature and Clinical Trial Registries"],"prefix":"10.3389","volume":"12","author":[{"given":"J\u00fcrgen","family":"Germann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mameli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin J. B.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Loh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Taha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Venetucci","family":"Gouveia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Boutet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.neuron.2013.01.020","article-title":"Probing and regulating dysfunctional circuits using deep brain stimulation","volume":"77","author":"Lozano","year":"2013","journal-title":"Neuron."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1056\/NEJMra1706158","article-title":"Mapping symptoms to brain networks with the human connectome","volume":"379","author":"Fox","year":"2018","journal-title":"N Engl J Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41582-018-0128-2","article-title":"Deep brain stimulation: current challenges and future directions","volume":"15","author":"Lozano","year":"2019","journal-title":"Nat Rev Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"141","DOI":"10.31887\/DCNS.2007.9.2\/rbonelli","article-title":"Frontal-subcortical circuitry and behavior","volume":"9","author":"Bonelli","year":"2007","journal-title":"Dialogues Clin Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1002\/mds.22120","article-title":"Latest view on the mechanism of action of deep brain stimulation","volume":"23","author":"Hammond","year":"2008","journal-title":"Mov Disord."},{"key":"B6","doi-asserted-by":"publisher","first-page":"410","DOI":"10.3389\/fneur.2019.00410","article-title":"Deep brain stimulation programming for movement disorders: current concepts and evidence-Based strategies","volume":"10","author":"Koeglsperger","year":"2019","journal-title":"Front Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"E3","DOI":"10.3171\/FOC\/2008\/25\/7\/E3","article-title":"Potential surgical targets for deep brain stimulation in treatment-resistant depression","volume":"25","author":"Hauptman","year":"2008","journal-title":"Neurosurg Focus."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.4103\/1673-5374.235220","article-title":"Current surgical treatments for parkinson's disease and potential therapeutic targets","volume":"13","author":"Lee","year":"2018","journal-title":"Neural Regeneration Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1017\/cjn.2016.22","article-title":"Deep brain stimulation target selection for parkinson's disease","volume":"44","author":"Honey","year":"2017","journal-title":"Can J Neurol Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"117515","DOI":"10.1016\/j.neuroimage.2020.117515","article-title":"Deep brain stimulation for psychiatric disorders: from focal brain targets to cognitive networks","volume":"225","author":"Sullivan","year":"2021","journal-title":"Neuroimage."},{"key":"B11","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1146\/annurev-neuro-061010-113638","article-title":"Deep brain stimulation for psychiatric disorders","volume":"34","author":"Holtzheimer","year":"2011","journal-title":"Annu Rev Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3171\/2019.4.JNS181761","article-title":"Current and future directions of deep brain stimulation for neurological and psychiatric disorders","volume":"131","author":"Lee","year":"2019","journal-title":"J Neurosurg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.mehy.2007.03.021","article-title":"Deep brain stimulation of the lateral habenula in treatment resistant major depression","volume":"69","author":"Sartorius","year":"2007","journal-title":"Med Hypotheses."},{"key":"B14","volume-title":"Atlas of the Human Brain","author":"Mai","year":"2015"},{"key":"B15","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.bpsc.2020.01.004","article-title":"Fully automated habenula segmentation provides robust and reliable volume estimation across large magnetic resonance imaging datasets, suggesting intriguing developmental trajectories in psychiatric disease","volume":"5","author":"Germann","year":"2020","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging."},{"key":"B16","doi-asserted-by":"publisher","first-page":"S102","DOI":"10.1016\/S1053-8119(09)70884-5","article-title":"Unbiased nonlinear average age-appropriate brain templates from birth to adulthood","volume":"47","author":"Fonov","year":"2009","journal-title":"Neuroimage."},{"key":"B17","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nrn2866","article-title":"The habenula: from stress evasion to value-based decision-making","volume":"11","author":"Hikosaka","year":"2010","journal-title":"Nat Rev Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41583-020-0292-4","article-title":"Circuits and functions of the lateral habenula in health and in disease","volume":"21","author":"Hu","year":"2020","journal-title":"Nat Rev Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.tins.2017.06.001","article-title":"The lateral habenula and adaptive behaviors","volume":"40","author":"Mizumori","year":"2017","journal-title":"Trends Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.neuroimage.2019.06.015","article-title":"Detailed mapping of human habenula resting-state functional connectivity","volume":"200","author":"Ely","year":"2019","journal-title":"Neuroimage."},{"key":"B21","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/s41597-020-00644-6","article-title":"A high-resolution in vivo magnetic resonance imaging atlas of the human hypothalamic region","volume":"7","author":"Neudorfer","year":"2020","journal-title":"Sci Data."},{"key":"B22","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.neuroimage.2016.10.034","article-title":"Resting state connectivity of the human habenula at ultra-high field","volume":"147","author":"Torrisi","year":"2017","journal-title":"Neuroimage."},{"key":"B23","doi-asserted-by":"publisher","first-page":"8909","DOI":"10.1523\/JNEUROSCI.4369-12.2013","article-title":"The synchronous activity of lateral habenular neurons is essential for regulating hippocampal theta oscillation","volume":"33","author":"Aizawa","year":"2013","journal-title":"J Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4398","DOI":"10.1038\/s41598-020-61264-z","article-title":"Altered directed functional connectivity of the right amygdala in depression: high-density eEG study","volume":"10","author":"Damborsk\u00e1","year":"2020","journal-title":"Sci Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/cne.901730107","article-title":"Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber-of-passage problem","volume":"173","author":"Herkenham","year":"1977","journal-title":"J Comp Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1111\/j.1460-9568.2012.08030.x","article-title":"Topography of descending projections from anterior insular and medial prefrontal regions to the lateral habenula of the epithalamus in the rat","volume":"35","author":"Kim","year":"2012","journal-title":"Eur J Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/cne.901870103","article-title":"Efferent connections of the habenular nuclei in the rat","volume":"187","author":"Herkenham","year":"1979","journal-title":"J Comp Neurol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"R873","DOI":"10.1016\/j.cub.2016.08.051","article-title":"The habenula","volume":"26","author":"Namboodiri","year":"2016","journal-title":"Curr Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/cne.21891","article-title":"The mesopontine rostromedial tegmental nucleus: a structure targeted by the lateral habenula that projects to the ventral tegmental area of tsai and substantia nigra compacta","volume":"513","author":"Jhou","year":"2009","journal-title":"J Comp Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.194312","article-title":"Physiological evidence for habenula as major link between forebrain and midbrain raphe","volume":"197","author":"Wang","year":"1977","journal-title":"Science."},{"key":"B31","doi-asserted-by":"publisher","first-page":"E164","DOI":"10.1073\/pnas.1119348109","article-title":"Evolutionary conservation of the habenular nuclei and their circuitry controlling the dopamine and 5-hydroxytryptophan (5-HT) systems","volume":"109","author":"Stephenson-Jones","year":"2012","journal-title":"Proc Natl Acad Sci USA."},{"key":"B32","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.bbr.2018.03.012","article-title":"Lateral habenular norepinephrine contributes to states of arousal and anxiety in male rats","volume":"347","author":"Purvis","year":"2018","journal-title":"Behav Brain Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.neubiorev.2017.02.010","article-title":"The habenula in psychiatric disorders: more than three decades of translational investigation","volume":"83","author":"Fakhoury","year":"2017","journal-title":"Neurosci Biobehav Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/jnc.14008","article-title":"The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation","volume":"142","author":"McLaughlin","year":"2017","journal-title":"J Neurochem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"112693","DOI":"10.1016\/j.bbr.2020.112693","article-title":"The increased density of the habenular neurons, high impulsivity, aggression and resistant fear memory in disc1-Q31 l genetic mouse model of depression","volume":"392","author":"Lipina","year":"2020","journal-title":"Behav Brain Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nn.2233","article-title":"Representation of negative motivational value in the primate lateral habenula","volume":"12","author":"Matsumoto","year":"2009","journal-title":"Nat Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e30697","DOI":"10.7554\/eLife.30697","article-title":"Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior","volume":"6","author":"Lecca","year":"2017","journal-title":"eLife."},{"key":"B38","doi-asserted-by":"publisher","first-page":"107752","DOI":"10.1016\/j.celrep.2020.107752","article-title":"Heterogeneous habenular neuronal ensembles during selection of defensive behaviors","volume":"31","author":"Lecca","year":"2020","journal-title":"Cell Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.neuron.2021.01.008","article-title":"Stress undermines reward-guided cognitive performance through synaptic depression in the lateral habenula","volume":"109","author":"Nuno-Perez","year":"2021","journal-title":"Neuron."},{"key":"B40","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/nm.4037","article-title":"Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice","volume":"22","author":"Lecca","year":"2016","journal-title":"Nat Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nature09742","article-title":"Synaptic potentiation onto habenula neurons in the learned helplessness model of depression","volume":"470","author":"Li","year":"2011","journal-title":"Nature."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1126\/science.1240729","article-title":"\u03b2CaMKII in lateral habenula mediates core symptoms of depression","volume":"341","author":"Li","year":"2013","journal-title":"Science."},{"key":"B43","doi-asserted-by":"publisher","first-page":"11482","DOI":"10.1523\/JNEUROSCI.2350-16.2016","article-title":"The lateral habenula circuitry: reward processing and cognitive control","volume":"36","author":"Baker","year":"2016","journal-title":"J Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.biopsych.2017.10.032","article-title":"Identification of a corticohabenular circuit regulating socially directed behavior","volume":"83","author":"Benekareddy","year":"2018","journal-title":"Biol Psychiatry."},{"key":"B45","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.biopsych.2016.06.003","article-title":"Translating the habenula\u2014from rodents to humans","volume":"81","author":"Boulos","year":"2017","journal-title":"Biol Psychiatry."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1111\/ejn.12353","article-title":"Functional integrity of the habenula is necessary for social play behaviour in rats","volume":"38","author":"van Kerkhof","year":"2013","journal-title":"Eur J Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e9","DOI":"10.1016\/j.biopsych.2009.08.027","article-title":"Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient","volume":"67","author":"Sartorius","year":"2010","journal-title":"Biol Psychiatry."},{"key":"B48","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.neuroimage.2017.04.070","article-title":"A probabilistic template of human mesopontine tegmental nuclei from in vivo 7 t MRI","volume":"170","author":"Bianciardi","year":"2018","journal-title":"Neuroimage."},{"key":"B49","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.neuroimage.2018.08.068","article-title":"Lead-DBS v2: towards a comprehensive pipeline for deep brain stimulation imaging","volume":"184","author":"Horn","year":"2019","journal-title":"Neuroimage."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1038\/s41467-017-01192-1","article-title":"Limiting habenular hyperactivity ameliorates maternal separation-driven depressive-like symptoms","volume":"8","author":"Tchenio","year":"2017","journal-title":"Nat Commun."},{"key":"B51","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.neuropharm.2010.06.008","article-title":"Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior","volume":"59","author":"Friedman","year":"2010","journal-title":"Neuropharmacology."},{"key":"B52","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.neuropharm.2010.10.006","article-title":"Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration","volume":"60","author":"Friedman","year":"2011","journal-title":"Neuropharmacology."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1111\/ejn.12480","article-title":"The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview","volume":"39","author":"Lecca","year":"2014","journal-title":"Eur J Neurosci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3389\/fnhum.2013.00806","article-title":"Lateral habenula deep brain stimulation for personalized treatment of drug addiction","volume":"7","author":"Yadid","year":"2013","journal-title":"Front Hum Neurosci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/schbul\/sbu165","article-title":"Dopaminergic circuitry and risk\/reward decision making: implications for schizophrenia","volume":"41","author":"Stopper","year":"2015","journal-title":"Schizophr Bull."},{"key":"B56","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1093\/schbul\/sbj083","article-title":"Schizophrenia in translation: the presence of absence: habenular regulation of dopamine neurons and the encoding of negative outcomes","volume":"32","author":"Shepard","year":"2006","journal-title":"Schizophr Bull."},{"key":"B57","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3389\/fncir.2017.00035","article-title":"Circuits regulating pleasure and happiness in bipolar disorder","volume":"11","author":"Loonen","year":"2017","journal-title":"Front Neural Circuits."},{"key":"B58","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.biopsych.2010.09.027","article-title":"Habenula volume in bipolar disorder and major depressive disorder: a high-resolution magnetic resonance imaging study","volume":"69","author":"Savitz","year":"2011","journal-title":"Biol Psychiatry."},{"key":"B59","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3389\/fpsyt.2018.00456","article-title":"Imaging habenula volume in schizophrenia and bipolar disorder","volume":"9","author":"Schafer","year":"2018","journal-title":"Front Psychiatry."},{"key":"B60","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1055\/a-0835-6447","article-title":"Consider role of glutamatergic habenula-projecting globus pallidus in OCD","volume":"52","author":"Loonen","year":"2019","journal-title":"Pharmacopsychiatry."},{"key":"B61","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41572-019-0102-3","article-title":"Obsessive-compulsive disorder","volume":"5","author":"Stein","year":"2019","journal-title":"Nat Rev Dis Primers."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1101\/2021.04.08.21255122","article-title":"Involvement of the habenula in the pathophysiology of autism spectrum disorder","author":"Germann","year":"2021","journal-title":"medRxiv."},{"key":"B63","doi-asserted-by":"publisher","first-page":"E9","DOI":"10.3171\/2020.4.FOCUS20174","article-title":"Habenula deep brain stimulation for intractable schizophrenia: a pilot study","volume":"49","author":"Wang","year":"2020","journal-title":"Neurosurg Focus."},{"key":"B64","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3389\/fpsyt.2020.00029","article-title":"Habenular stimulation for neurosurgery resistant obsessive-Compulsive disorder: a Case report","volume":"11","author":"Zhang","year":"2020","journal-title":"Front Psychiatry."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.brs.2019.05.010","article-title":"Habenula deep brain stimulation for refractory bipolar disorder","volume":"12","author":"Zhang","year":"2019","journal-title":"Brain Stimul."},{"key":"B66","doi-asserted-by":"publisher","first-page":"616501","DOI":"10.3389\/fpsyt.2020.616501","article-title":"Case report: lateral habenula deep brain stimulation for treatment-Resistant depression","volume":"11","author":"Wang","year":"2020","journal-title":"Front Psychiatry."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/nn.3779","article-title":"Reward processing by the lateral habenula in normal and depressive behaviors","volume":"17","author":"Proulx","year":"2014","journal-title":"Nat Neurosci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1136\/jnnp-2014-308883.31","article-title":"Habenula responses during appetitive and aversive conditioning in major depressive disorder","volume":"85","author":"Lawson","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B69","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1176\/appi.neuropsych.17120351","article-title":"Resting-state functional connectivity of the habenula in mood disorder patients with and without suicide-Related behaviors","volume":"31","author":"Ambrosi","year":"2019","journal-title":"J Neuropsychiatry Clin Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"636","DOI":"10.3389\/fnhum.2017.00636","article-title":"Altered volume and functional connectivity of the habenula in schizophrenia","volume":"11","author":"Zhang","year":"2017","journal-title":"Front Hum Neurosci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3109\/00207459208994773","article-title":"Pineal and habenula calcification in schizophrenia","volume":"67","author":"Sandyk","year":"1992","journal-title":"Int J Neurosci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.expneurol.2019.05.005","article-title":"Hypoactivity of the lateral habenula contributes to negative symptoms and cognitive dysfunction of schizophrenia in rats","volume":"318","author":"Li","year":"2019","journal-title":"Exp Neurol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/ijnp\/pyx088","article-title":"Mapping compulsivity in the dSM-5 obsessive compulsive and related disorders: cognitive domains, neural circuitry, and treatment","volume":"21","author":"Fineberg","year":"2018","journal-title":"Int J Neuropsychopharmacol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1192\/bjp.2021.45","article-title":"Set-shifting-related basal ganglia deformation as a novel familial marker of obsessive\u2013compulsive disorder","volume":"17","author":"Isobe","year":"2021","journal-title":"Br J Psychiatry."},{"key":"B75","doi-asserted-by":"publisher","first-page":"249","DOI":"10.31887\/DCNS.2015.17.3\/ggoodwin","article-title":"The overlap between anxiety, depression, and obsessive-compulsive disorder","volume":"17","author":"Goodwin","year":"2015","journal-title":"Dialogues Clin Neurosci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1093\/schbul\/sbq031","article-title":"Dopaminergic dysfunction in schizophrenia: salience attribution revisited","volume":"36","author":"Heinz","year":"2010","journal-title":"Schizophr Bull."},{"key":"B77","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/00004850-199311002-00011","article-title":"The serotonin hypothesis of obsessive compulsive disorder","volume":"8","author":"Barr","year":"1993","journal-title":"Int Clin Psychopharmacol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1002\/ana.25975","article-title":"Probabilistic mapping of deep brain stimulation: insights from 15 years of therapy","volume":"89","author":"Elias","year":"2020","journal-title":"Ann Neurol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/jnnp.71.2.215","article-title":"Deep brain stimulation of the subthalamic nucleus in parkinson's disease: effects of variation in stimulation parameters","volume":"71","author":"Rizzone","year":"2001","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B80","doi-asserted-by":"publisher","first-page":"S181","DOI":"10.1002\/mds.10162","article-title":"Introduction to the programming of deep brain stimulators","volume":"17","author":"Volkmann","year":"2002","journal-title":"Mov Disord."},{"key":"B81","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1136\/jnnp-2017-317082","article-title":"Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American society for stereotactic and functional neurosurgery workshop on neuromodulation for psychiatric disorders","volume":"89","author":"Bari","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B82","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0304-3940(95)11455-6","article-title":"Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data","volume":"189","author":"Benazzouz","year":"1995","journal-title":"Neurosci Lett."},{"key":"B83","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/S0306-4522(00)00199-8","article-title":"Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat","volume":"99","author":"Benazzouz","year":"2000","journal-title":"Neuroscience."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1152\/jn.2001.85.4.1351","article-title":"High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons","volume":"85","author":"Beurrier","year":"2001","journal-title":"J Neurophysiol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/jnr.10577","article-title":"Influence of the frequency parameter on extracellular glutamate and gamma-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in rats","volume":"72","author":"Windels","year":"2003","journal-title":"J Neurosci Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1212\/WNL.59.5.706","article-title":"The impact on Parkinson's disease of electrical parameter settings in STN stimulation","volume":"59","author":"Moro","year":"2002","journal-title":"Neurology."},{"key":"B87","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1126\/science.1167093","article-title":"Optical deconstruction of parkinsonian neural circuitry","volume":"324","author":"Gradinaru","year":"2009","journal-title":"Science."},{"key":"B88","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nn.2495","article-title":"Ultrafast optogenetic control","volume":"13","author":"Gunaydin","year":"2010","journal-title":"Nat Neurosci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.1523\/JNEUROSCI.3071-19.2020","article-title":"Frequency-specific optogenetic deep brain stimulation of subthalamic nucleus improves parkinsonian motor behaviors","volume":"40","author":"Yu","year":"2020","journal-title":"J Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/nn.4559","article-title":"Cell-specific pallidal intervention induces long-lasting motor recovery in dopamine-depleted mice","volume":"20","author":"Mastro","year":"2017","journal-title":"Nat Neurosci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1126\/science.1260776","article-title":"Addiction therapy. Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology","volume":"347","author":"Creed","year":"2015","journal-title":"Science."},{"key":"B92","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/35084005","article-title":"Neurophysiological investigation of the basis of the fMRI signal","volume":"412","author":"Logothetis","year":"2001","journal-title":"Nature."},{"key":"B93","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/978-3-030-53168-3_46","article-title":"Modulation of CNS functions by deep brain stimulation: insights provided by molecular imaging","volume-title":"PET SPECT in Neurology","author":"Boutet","year":"2021"},{"key":"B94","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/B978-0-444-53497-2.00008-5","article-title":"Brain stimulation and functional imaging with fMRI and PET","volume":"116","author":"Ko","year":"2013","journal-title":"Handb Clin Neurol."},{"key":"B95","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-59745-360-8_9","article-title":"Functional imaging of deep brain stimulation: fMRI, SPECT, and PET.","volume-title":"Deep Brain Stimulation in Neurological and Psychiatric Disorders.","author":"Jech","year":"2008"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-23311-9","article-title":"Predicting optimal deep brain stimulation parameters for Parkinson's disease using functional mRI and machine learning","volume":"12","author":"Boutet","year":"2021","journal-title":"Nat Commun."},{"key":"B97","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1093\/neuros\/nyaa397","article-title":"Use of functional MRI to assess effects of deep brain stimulation frequency changes on brain activation in Parkinson disease","volume":"88","author":"DiMarzio","year":"2021","journal-title":"Neurosurgery."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.730931\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T07:04:06Z","timestamp":1629183846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.730931\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,17]]},"references-count":97,"alternative-id":["10.3389\/fpsyt.2021.730931"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.730931","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,17]]},"article-number":"730931"}}