{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:29:42Z","timestamp":1791066582723,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The grant to Christoph Szeska is funded by the government of the state Mecklenburg-Vorpommern."},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WE 5873\/1-1"],"award-info":[{"award-number":["WE 5873\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inhibiting fear-related thoughts and defensive behaviors when they are no longer appropriate to the situation is a prerequisite for flexible and adaptive responding to changing environments. Such inhibition of defensive systems is mediated by ventromedial prefrontal cortex (vmPFC), limbic basolateral amygdala (BLA), and brain stem locus-coeruleus noradrenergic system (LC-NAs). Non-invasive, transcutaneous vagus nerve stimulation (tVNS) has shown to activate this circuit. Using a multiple-day single-cue fear conditioning and extinction paradigm, we investigated long-term effects of tVNS on inhibition of low-level amygdala modulated fear potentiated startle and cognitive risk assessments. We found that administration of tVNS during extinction training facilitated inhibition of fear potentiated startle responses and cognitive risk assessments, resulting in facilitated formation, consolidation and long-term recall of extinction memory, and prevention of the return of fear. These findings might indicate new ways to increase the efficacy of exposure-based treatments of anxiety disorders.<\/jats:p>","DOI":"10.1038\/s41598-020-58412-w","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T06:02:57Z","timestamp":1580364177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Promoting long-term inhibition of human fear responses by non-invasive transcutaneous vagus nerve stimulation during extinction training"],"prefix":"10.1038","volume":"10","author":[{"given":"Christoph","family":"Szeska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7127-6990","authenticated-orcid":false,"given":"Jan","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2299-5881","authenticated-orcid":false,"given":"Julia","family":"Wendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Weymar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfons O.","family":"Hamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"58412_CR1","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/nn.3961","volume":"18","author":"M Browning","year":"2015","unstructured":"Browning, M., Behrens, T. E., Jocham, G., O\u2019Reilly, J. X. & Bishop, S. J. Anxious individuals have difficulty learning the causal statistics of aversive environments. Nat. Neurosci. 18, 590\u2013596 (2015).","journal-title":"Nat. Neurosci."},{"key":"58412_CR2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ypmed.2014.06.010","volume":"68","author":"ME Bouton","year":"2014","unstructured":"Bouton, M. E. Why behavior change is difficult to sustain. Prev. Med. (Baltim). 68, 29\u201336 (2014).","journal-title":"Prev. Med. (Baltim)."},{"key":"58412_CR3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.neuron.2015.09.028","volume":"88","author":"JE Dunsmoor","year":"2015","unstructured":"Dunsmoor, J. E., Niv, Y., Daw, N. & Phelps, E. A. Rethinking Extinction. Neuron 88, 47\u201363 (2015).","journal-title":"Neuron"},{"key":"58412_CR4","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/j.neuron.2014.04.042","volume":"82","author":"S Duvarci","year":"2014","unstructured":"Duvarci, S. & Pare, D. Amygdala microcircuits controlling learned fear. Neuron 82, 966\u2013980 (2014).","journal-title":"Neuron"},{"key":"58412_CR5","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/nn.2499","volume":"13","author":"T Amano","year":"2010","unstructured":"Amano, T., Unal, C. T. & Par\u00e9, D. Synaptic correlates of fear extinction in the amygdala. Nat. Neurosci. 13, 489\u2013494 (2010).","journal-title":"Nat. Neurosci."},{"key":"58412_CR6","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.neuron.2009.05.026","volume":"62","author":"I Ehrlich","year":"2009","unstructured":"Ehrlich, I. et al. Amygdala Inhibitory Circuits and the Control of Fear Memory. Neuron 62, 757\u2013771 (2009).","journal-title":"Neuron"},{"key":"58412_CR7","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev.psych.121208.131631","volume":"63","author":"MR Milad","year":"2012","unstructured":"Milad, M. R. & Quirk, G. J. Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress. Annu. Rev. Psychol 63, 129\u2013151 (2012).","journal-title":"Annu. Rev. Psychol"},{"key":"58412_CR8","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41593-018-0137-x","volume":"21","author":"R Marek","year":"2018","unstructured":"Marek, R., Xu, L., Sullivan, R. K. P. & Sah, P. Excitatory connections between the prelimbic and infralimbic medial prefrontal cortex show a role for the prelimbic cortex in fear extinction. Nat. Neurosci. 21, 654\u2013658 (2018).","journal-title":"Nat. Neurosci."},{"key":"58412_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbr.2009.11.025","volume":"208","author":"D Mueller","year":"2010","unstructured":"Mueller, D. & Cahill, S. P. Noradrenergic modulation of extinction learning and exposure therapy. Behav. Brain Res. 208, 1\u201311 (2010).","journal-title":"Behav. Brain Res."},{"key":"58412_CR10","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.neuron.2004.08.042","volume":"43","author":"EA Phelps","year":"2004","unstructured":"Phelps, E. A., Delgado, M. R., Nearing, K. I. & Ledoux, J. E. Extinction Learning in Humans: Role of the Amygdala and vmPFC. Neuron 43, 897\u2013905 (2004).","journal-title":"Neuron"},{"key":"58412_CR11","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.neuron.2007.02.021","volume":"53","author":"A Burgos-Robles","year":"2007","unstructured":"Burgos-Robles, A., Vidal-Gonzalez, I., Santini, E. & Quirk, G. J. Consolidation of Fear Extinction Requires NMDA Receptor-Dependent Bursting in the Ventromedial Prefrontal Cortex. Neuron 53, 871\u2013880 (2007).","journal-title":"Neuron"},{"key":"58412_CR12","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.nlm.2005.12.008","volume":"86","author":"DJ Berlau","year":"2006","unstructured":"Berlau, D. J. & McGaugh, J. L. Enhancement of extinction memory consolidation: The role of the noradrenergic and GABAergic systems within the basolateral amygdala. Neurobiol. Learn. Mem. 86, 123\u2013132 (2006).","journal-title":"Neurobiol. Learn. Mem."},{"key":"58412_CR13","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.ijpsycho.2015.11.007","volume":"98","author":"AO Hamm","year":"2015","unstructured":"Hamm, A. O. & Flor, H. Fear learning, fear memory, and psychopathology. Int. J. Psychophysiol. 98, 497\u2013498 (2015).","journal-title":"Int. J. Psychophysiol."},{"key":"58412_CR14","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.biopsych.2006.10.011","volume":"62","author":"MR Milad","year":"2007","unstructured":"Milad, M. R. et al. Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex and Hippocampus in Concert. Biol. Psychiatry 62, 446\u2013454 (2007).","journal-title":"Biol. Psychiatry"},{"key":"58412_CR15","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1037\/0735-7044.118.1.79","volume":"118","author":"DL Hassert","year":"2004","unstructured":"Hassert, D. L., Miyashita, T. & Williams, C. L. The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala. Behav. Neurosci. 118, 79\u201388 (2004).","journal-title":"Behav. Neurosci."},{"key":"58412_CR16","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.brainres.2007.08.045","volume":"1179","author":"P Follesa","year":"2007","unstructured":"Follesa, P. et al. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res. 1179, 28\u201334 (2007).","journal-title":"Brain Res."},{"key":"58412_CR17","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.brainres.2006.08.048","volume":"1119","author":"RW Roosevelt","year":"2006","unstructured":"Roosevelt, R. W., Smith, D. C., Clough, R. W., Jensen, R. A. & Browning, R. A. Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat. Brain Res. 1119, 124\u2013132 (2006).","journal-title":"Brain Res."},{"key":"58412_CR18","first-page":"327","volume":"8","author":"DF Pe\u00f1a","year":"2014","unstructured":"Pe\u00f1a, D. F. et al. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala. Front. Behav. Neurosci. 8, 327 (2014).","journal-title":"Front. Behav. Neurosci."},{"key":"58412_CR19","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.biopsych.2012.10.021","volume":"73","author":"DF Pe\u00f1a","year":"2013","unstructured":"Pe\u00f1a, D. F., Engineer, N. D. & McIntyre, C. K. Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation. Biol. Psychiatry 73, 1071\u20131077 (2013).","journal-title":"Biol. Psychiatry"},{"key":"58412_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/4273280","volume":"2016","author":"AAC Alvarez-Dieppa","year":"2016","unstructured":"Alvarez-Dieppa, A. A. C., Griffin, K., Cavalier, S. & Mcintyre, C. K. Vagus nerve stimulation enhances extinction of conditioned fear in rats and modulates Arc protein, CaMKII, and GluN2B-containing NMDA receptors in the basolateral amygdala. Neural Plast. 2016, 1\u201319 (2016).","journal-title":"Neural Plast."},{"key":"58412_CR21","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.brs.2014.11.018","volume":"8","author":"E Frangos","year":"2015","unstructured":"Frangos, E., Ellrich, J. & Komisaruk, B. R. Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: FMRI evidence in humans. Brain Stimul. 8, 624\u2013636 (2015).","journal-title":"Brain Stimul."},{"key":"58412_CR22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/ca.1089","volume":"15","author":"ET Peuker","year":"2002","unstructured":"Peuker, E. T. & Filler, T. J. The nerve supply of the human auricle. Clin. Anat. 15, 35\u201337 (2002).","journal-title":"Clin. Anat."},{"key":"58412_CR23","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.brat.2017.07.005","volume":"97","author":"AM Burger","year":"2017","unstructured":"Burger, A. M. et al. Mixed evidence for the potential of non-invasive transcutaneous vagal nerve stimulation to improve the extinction and retention of fear. Behav. Res. Ther. 97, 64\u201374 (2017).","journal-title":"Behav. Res. Ther."},{"key":"58412_CR24","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.nlm.2016.05.007","volume":"132","author":"AM Burger","year":"2016","unstructured":"Burger, A. M. et al. The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans. Neurobiol. Learn. Mem. 132, 49\u201356 (2016).","journal-title":"Neurobiol. Learn. Mem."},{"key":"58412_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29561-w","volume":"8","author":"AM Burger","year":"2018","unstructured":"Burger, A. M. et al. Transcutaneous vagus nerve stimulation and extinction of prepared fear: A conceptual non-replication. Sci. Rep. 8, 11471 (2018).","journal-title":"Sci. Rep."},{"key":"58412_CR26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1126\/science.6681571","volume":"219","author":"TJ Carew","year":"1983","unstructured":"Carew, T. J., Hawkins, R. D. & Kandel, E. R. Differential Classical Conditioning of a Defensive Withdrawal Reflex in Aplysia californica. Science (80-.). 219, 397\u2013400 (1983).","journal-title":"Science (80-.)."},{"key":"58412_CR27","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.neubiorev.2017.02.026","volume":"77","author":"TB Lonsdorf","year":"2017","unstructured":"Lonsdorf, T. B. et al. Don\u2019t fear \u2018fear conditioning\u2019: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear. Neurosci. Biobehav. Rev. 77, 247\u2013285 (2017).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"58412_CR28","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3758\/CABN.4.3.317","volume":"4","author":"DC Knight","year":"2004","unstructured":"Knight, D. C., Smith, C. N., Cheng, D. T., Stein, E. A. & Helmstetter, F. J. Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning. Cogn. Affect. Behav. Neurosci. 4, 317\u2013325 (2004).","journal-title":"Cogn. Affect. Behav. Neurosci."},{"key":"58412_CR29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1037\/h0024109","volume":"74","author":"RA Rescorla","year":"1967","unstructured":"Rescorla, R. A. Pavlovian conditioning and its proper control procedures. Psychol. Rev. 74, 71\u201380 (1967).","journal-title":"Psychol. Rev."},{"key":"58412_CR30","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/j.1469-8986.1997.tb02389.x","volume":"34","author":"C Grillon","year":"1997","unstructured":"Grillon, C. & Davis, M. Fear-potentiated startle conditioning in humans: Explicit and contextual cue conditioning following paired versus unpaired training. Psychophysiology 34, 451\u2013458 (1997).","journal-title":"Psychophysiology"},{"key":"58412_CR31","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1101\/lm.036053.114","volume":"21","author":"J Haaker","year":"2014","unstructured":"Haaker, J., Golkar, A., Hermans, D. & Lonsdorf, T. B. A review on human reinstatement studies: An overview and methodological challenges. Learning and Memory 21, 424\u2013440 (2014).","journal-title":"Learning and Memory"},{"key":"58412_CR32","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.biopsych.2005.10.006","volume":"60","author":"D Hermans","year":"2006","unstructured":"Hermans, D., Craske, M. G., Mineka, S. & Lovibond, P. F. Extinction in Human Fear Conditioning. Biol. Psychiatry 60, 361\u2013368 (2006).","journal-title":"Biol. Psychiatry"},{"key":"58412_CR33","doi-asserted-by":"crossref","unstructured":"Craske, M. G. & Mystkowski, J. L. Exposure Therapy and Extinction: Clinical Studies. in Fear and Learning: From basic processes to clinical implications (eds. Craske, M. G., Hermans, D. & Vansteenwegen, D.) 217\u2013233 (Amercian Psychological Association, 2006).","DOI":"10.1037\/11474-011"},{"key":"58412_CR34","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1001\/jamapsychiatry.2013.4186","volume":"71","author":"GS Ginsburg","year":"2014","unstructured":"Ginsburg, G. S. et al. Naturalistic follow-up of youths treated for pediatric anxiety disorders. JAMA Psychiatry 71, 310\u2013318 (2014).","journal-title":"JAMA Psychiatry"},{"key":"58412_CR35","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/sj.mp.4000812","volume":"6","author":"M Davis","year":"2001","unstructured":"Davis, M. & Whalen, P. J. The amygdala: Vigilance and emotion. Molecular Psychiatry 6, 13\u201334 (2001).","journal-title":"Molecular Psychiatry"},{"key":"58412_CR36","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1037\/0003-066X.61.8.741","volume":"61","author":"M Davis","year":"2006","unstructured":"Davis, M. Neural systems involved in fear and anxiety measured with fear-potentiated startle. Am. Psychol. 61, 741\u2013756 (2006).","journal-title":"Am. Psychol."},{"key":"58412_CR37","doi-asserted-by":"crossref","unstructured":"Hamm, A. O. Fear-Potentiated Startle. International Encyclopedia of the Social & Behavioral Sciences: Second Edition 8, (Elsevier, 2015).","DOI":"10.1016\/B978-0-08-097086-8.55023-5"},{"key":"58412_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.07.028","author":"M Kuhn","year":"2019","unstructured":"Kuhn, M. et al. The Neurofunctional Basis of Affective Startle Modulation in Humans: Evidence From Combined Facial Electromyography and Functional Magnetic Resonance Imaging. Biological Psychiatry. https:\/\/doi.org\/10.1016\/j.biopsych.2019.07.028 (2019).","journal-title":"Biological Psychiatry"},{"key":"58412_CR39","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.euroneuro.2015.03.015","volume":"25","author":"L Steenbergen","year":"2015","unstructured":"Steenbergen, L. et al. Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes. Eur. Neuropsychopharmacol. 25, 773\u2013778 (2015).","journal-title":"Eur. Neuropsychopharmacol."},{"key":"58412_CR40","doi-asserted-by":"publisher","first-page":"680","DOI":"10.3758\/s13415-018-0596-2","volume":"18","author":"R Fischer","year":"2018","unstructured":"Fischer, R., Ventura-Bort, C., Hamm, A. & Weymar, M. Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control. Cogn. Affect. Behav. Neurosci. 18, 680\u2013693 (2018).","journal-title":"Cogn. Affect. Behav. Neurosci."},{"key":"58412_CR41","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.brs.2018.09.013","volume":"12","author":"LJ Noble","year":"2019","unstructured":"Noble, L. J. et al. Vagus nerve stimulation promotes generalization of conditioned fear extinction and reduces anxiety in rats. Brain Stimul. 12, 9\u201318 (2019).","journal-title":"Brain Stimul."},{"key":"58412_CR42","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.brs.2008.02.001","volume":"1","author":"MS George","year":"2008","unstructured":"George, M. S. et al. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimul. 1, 112\u2013121 (2008).","journal-title":"Brain Stimul."},{"key":"58412_CR43","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/psyp.12553","volume":"53","author":"AO Hamm","year":"2016","unstructured":"Hamm, A. O. et al. Panic disorder with agoraphobia from a behavioral neuroscience perspective: Applying the research principles formulated by the Research Domain Criteria (RDoC) initiative. Psychophysiology 53, 312\u2013322 (2016).","journal-title":"Psychophysiology"},{"key":"58412_CR44","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.brat.2018.11.012","volume":"112","author":"C Benke","year":"2019","unstructured":"Benke, C., Krause, E., Hamm, A. O. & Pan\u00e9-Farr\u00e9, C. A. Predictors of behavioral avoidance during respiratory symptom provocation. Behav. Res. Ther. 112, 63\u201367 (2019).","journal-title":"Behav. Res. Ther."},{"key":"58412_CR45","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/nprot.2012.001","volume":"7","author":"A Schmitz","year":"2012","unstructured":"Schmitz, A. & Grillon, C. Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test). Nat. Protoc. 7, 527\u201332 (2012).","journal-title":"Nat. Protoc."},{"key":"58412_CR46","doi-asserted-by":"crossref","unstructured":"Genheimer, H., Andreatta, M., Asan, E. & Pauli, P. Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans. Sci. Rep. 7, (2017).","DOI":"10.1038\/s41598-017-18183-3"},{"key":"58412_CR47","doi-asserted-by":"crossref","unstructured":"Ventura-Bort, C. et al. Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on the P300 and Alpha-Amylase Level: A Pilot Study. Front. Hum. Neurosci. 12, (2018).","DOI":"10.3389\/fnhum.2018.00202"},{"key":"58412_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0006-8993(77)90377-8","volume":"127","author":"BE Jones","year":"1977","unstructured":"Jones, B. E., Halaris, A. E., McIlhany, M. & Moore, R. Y. Ascending projections of the locus coeruleus in the rat. I. axonal transport in central noradrenaline neurons. Brain Res. 127, 1\u201321 (1977).","journal-title":"Brain Res."},{"key":"58412_CR49","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.tins.2005.09.002","volume":"28","author":"S Bouret","year":"2005","unstructured":"Bouret, S. & Sara, S. J. Network reset: A simplified overarching theory of locus coeruleus noradrenaline function. Trends Neurosci. 28, 574\u2013582 (2005).","journal-title":"Trends Neurosci."},{"key":"58412_CR50","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/nature01138","volume":"420","author":"MRR Milad","year":"2002","unstructured":"Milad, M. R. R. & Quirk, G. J. J. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420, 70\u201374 (2002).","journal-title":"Nature"},{"key":"58412_CR51","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/da.22353","volume":"32","author":"P Duits","year":"2015","unstructured":"Duits, P. et al. Updated meta-analysis of classical fear conditioning in the anxiety disorders. Depress. Anxiety 32, 239\u2013253 (2015).","journal-title":"Depress. Anxiety"},{"key":"58412_CR52","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1016\/j.brat.2004.10.007","volume":"43","author":"S Lissek","year":"2005","unstructured":"Lissek, S. et al. Classical fear conditioning in the anxiety disorders: A meta-analysis. Behav. Res. Ther. 43, 1391\u20131424 (2005).","journal-title":"Behav. Res. Ther."},{"key":"58412_CR53","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1037\/a0016032","volume":"77","author":"RE Stewart","year":"2009","unstructured":"Stewart, R. E. & Chambless, D. L. Cognitive-Behavioral Therapy for Adult Anxiety Disorders in Clinical Practice: A Meta-Analysis of Effectiveness Studies. J. Consult. Clin. Psychol. 77, 595\u2013606 (2009).","journal-title":"J. Consult. Clin. Psychol."},{"key":"58412_CR54","unstructured":"Craske, M. G. Anxiety disorders: Psychological approaches to theory and treatment. (Westview Press, 1999)."},{"key":"58412_CR55","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nn.2271","volume":"12","author":"M Kindt","year":"2009","unstructured":"Kindt, M., Soeter, M. & Vervliet, B. Beyond extinction: erasing human fear responses and preventing the return of fear. Nat. Neurosci. 12, 256\u2013258 (2009).","journal-title":"Nat. Neurosci."},{"key":"58412_CR56","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.neubiorev.2019.09.020","volume":"107","author":"J Haaker","year":"2019","unstructured":"Haaker, J. et al. Making translation work: Harmonizing cross-species methodology in the behavioural neuroscience of Pavlovian fear conditioning. Neurosci. Biobehav. Rev. 107, 329\u2013345 (2019).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"58412_CR57","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1111\/j.1469-8986.1996.tb02366.x","volume":"33","author":"AO Hamm","year":"1996","unstructured":"Hamm, A. O. & Vaitl, D. Affective learning: Awareness and aversion. Psychophysiology 33, 698\u2013710 (1996).","journal-title":"Psychophysiology"},{"key":"58412_CR58","first-page":"1, 30","volume":"30","author":"J Globisch","year":"1993","unstructured":"Globisch, J., Hamm, A. O., Schneider, R. & Vaitl, D. A computer program for scoring reflex eyeblink and electrodermal responses written in PASCAL. Psychophysiology 30, 1, 30 (1993).","journal-title":"Psychophysiology"},{"key":"58412_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1469-8986.2005.00271.x","volume":"42","author":"TD Blumenthal","year":"2005","unstructured":"Blumenthal, T. D. et al. Committee report: Guidelines for human startle eyeblink electromyographic studies. Psychophysiology 42, 1\u201315 (2005).","journal-title":"Psychophysiology"},{"key":"58412_CR60","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/1469-8986.3710013","volume":"37","author":"E Bagiella","year":"2000","unstructured":"Bagiella, E., Sloan, R. P. & Heitjan, D. F. Mixed-effects models in psychophysiology. Psychophysiology 37, 13\u201320 (2000).","journal-title":"Psychophysiology"},{"key":"58412_CR61","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1080\/00949659308811554","volume":"48","author":"M O\u2019Connell","year":"1993","unstructured":"O\u2019Connell, M. Generalized Linear Mixed Models: A Pseudo-Likelihood Approach. J. Stat. Comput. Simul. 48, 233\u2013243 (1993).","journal-title":"J. Stat. Comput. Simul."},{"key":"58412_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpsyg.2013.00863","volume":"4","author":"D Lakens","year":"2013","unstructured":"Lakens, D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front. Psychol. 4, 1\u201312 (2013).","journal-title":"Front. Psychol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58412-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58412-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58412-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T01:25:39Z","timestamp":1670289939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58412-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,30]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["58412"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-58412-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,30]]},"assertion":[{"value":"8 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1529"}}