{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:56:52Z","timestamp":1790337412348,"version":"4.1.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Agonists of the \u03b3-aminobutyric acid (GABA) type A benzodiazepine (BZD) receptor exert anxiolytic effects in anxiety disorders, raising the possibility that altered GABA-ergic function may play a role in the pathophysiology of anxiety disorders, such as post-traumatic stress disorder (PTSD). However, few neuroimaging studies have assessed the function or binding potential of the central GABA<jats:sub>A<\/jats:sub> BZD receptor system in PTSD. Therefore, our aim was to compare the BZD receptor binding potential between PTSD patients and healthy controls. Twelve medication-free participants with a current diagnosis of PTSD and 15 matched healthy controls underwent positron emission tomography (PET) imaging using [<jats:sup>11<\/jats:sup>C] flumazenil. Structural magnetic resonance imaging (MRI) scans were obtained and co-registered to the PET images to permit co-location of neuroanatomical structures in the lower resolution PET image data. Compared to healthy controls, PTSD patients exhibited increased BZD binding in the caudal anterior cingulate cortex and precuneus (<jats:italic>p<\/jats:italic>\u2019s\u2009&lt;\u20090.05). Severity of PTSD symptoms positively correlated with BZD binding in the left mid- and anterior insular cortices. This study extends previous findings by suggesting that central BZD receptor system involvement in PTSD includes portions of the default mode and salience networks, along with insular regions that support interoception and autonomic arousal.<\/jats:p>","DOI":"10.1038\/s41398-018-0257-9","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T12:19:03Z","timestamp":1538655543000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Altered cerebral benzodiazepine receptor binding in post-traumatic stress disorder"],"prefix":"10.1038","volume":"8","author":[{"given":"Inbal","family":"Reuveni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison C.","family":"Nugent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Vythilingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Lerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Neumeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis S.","family":"Charney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne C.","family":"Drevets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Bonne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"257_CR1","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1176\/appi.ajp.157.7.1120","volume":"157","author":"JD Bremner","year":"2000","unstructured":"Bremner, J. D. et al. Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. Am. J. Psychiatry 157, 1120\u20131126 (2000).","journal-title":"Am. J. Psychiatry"},{"key":"257_CR2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/sj.mp.4002054","volume":"13","author":"E Geuze","year":"2008","unstructured":"Geuze, E. et al. Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder. Mol. Psychiatry 13, 74\u201383 (2008).","journal-title":"Mol. Psychiatry"},{"key":"257_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.biopsych.2004.03.010","volume":"56","author":"M Fujita","year":"2004","unstructured":"Fujita, M. et al. Central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder. Biol. Psychiatry 56, 95\u2013100 (2004).","journal-title":"Biol. Psychiatry"},{"key":"257_CR4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.biopsych.2009.03.008","volume":"66","author":"S Rossi","year":"2009","unstructured":"Rossi, S. et al. Dysfunctions of cortical excitability in drug-na\u00efve posttraumatic stress disorder patients. Biol. Psychiatry 66, 54\u201361 (2009).","journal-title":"Biol. Psychiatry"},{"key":"257_CR5","doi-asserted-by":"publisher","first-page":"893","DOI":"10.5665\/sleep.3654","volume":"37","author":"DJ Meyerhoff","year":"2014","unstructured":"Meyerhoff, D. J., Mon, A., Metzler, T. & Neylan, T. C. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep 37, 893\u2013900 (2014).","journal-title":"Sleep"},{"key":"257_CR6","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.pscychresns.2014.09.007","volume":"224","author":"L Michels","year":"2014","unstructured":"Michels, L. et al. Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: preliminary findings. Psychiatry Res. 224, 288\u2013295 (2014).","journal-title":"Psychiatry Res."},{"key":"257_CR7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/da.22155","volume":"31","author":"IM Rosso","year":"2014","unstructured":"Rosso, I. M. et al. Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy. Depress Anxiety 31, 115\u2013123 (2014).","journal-title":"Depress Anxiety"},{"key":"257_CR8","doi-asserted-by":"publisher","first-page":"3337","DOI":"10.1002\/hbm.23244","volume":"37","author":"RR Sch\u00fcr","year":"2016","unstructured":"Sch\u00fcr, R. R. et al.Brain GABA levels across psychiatric disorders: a systematic literature review and meta-analysis of (1) H-MRS studies. Hum. Brain Mapp. 37, 3337\u20133352 (2016).","journal-title":"Hum. Brain Mapp."},{"key":"257_CR9","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.neuroimage.2017.03.011","volume":"152","author":"K Dyke","year":"2017","unstructured":"Dyke, K. et al. Comparing GABA-dependent physiological measures of inhibition with proton magnetic resonance spectroscopy measurement of GABA using ultra-high-field MRI. Neuroimage 152, 360\u2013370 (2017).","journal-title":"Neuroimage"},{"key":"257_CR10","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/syn.21747","volume":"68","author":"JFM Myers","year":"2014","unstructured":"Myers, J. F. M., Evans, C. J., Kalk, N. J., Edden, R. A. E. & Lingford-Hughes, A. R. Measurement of GABA using J-difference edited 1H-MRS following modulation of synaptic GABA concentration with tiagabine. Synapse 68, 355\u2013362 (2014).","journal-title":"Synapse"},{"key":"257_CR11","doi-asserted-by":"crossref","unstructured":"First M., Spitzer R., Gibbon, M. & Williams, J.B.W. Structured Clinical Interview for DSM-IV Axis Disorders\u2014Patient Edition (SCID-I\/P Version 2.0) (New York Biometrics Res Dep New York State Psychiatr Inst., 1996)","DOI":"10.1037\/t07827-000"},{"key":"257_CR12","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/jts.2490080106","volume":"8","author":"DD Blake","year":"1995","unstructured":"Blake, D. D. et al. The development of a Clinician-Administered PTSD Scale. J. Trauma. Stress 8, 75\u201390 (1995).","journal-title":"J. Trauma. Stress"},{"key":"257_CR13","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1017\/S0033291700035558","volume":"26","author":"AJ Rush","year":"1996","unstructured":"Rush, A. J., Gullion, C. M., Basco, M. R., Jarrett, R. B. & Trivedi, M. H. The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol. Med. 26, 477\u2013486 (1996).","journal-title":"Psychol. Med."},{"key":"257_CR14","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","volume":"32","author":"M Hamilton","year":"1959","unstructured":"Hamilton, M. The assessment of anxiety states by rating. Br. J. Med. Psychol. 32, 50\u201355 (1959).","journal-title":"Br. J. Med. Psychol."},{"key":"257_CR15","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1097\/01.WCB.0000033967.83623.34","volume":"22","author":"Y Wu","year":"2002","unstructured":"Wu, Y. & Carson, R. E. Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J. Cereb. Blood Flow. Metab. 22, 1440\u20131452 (2002).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"257_CR16","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1006\/nimg.2002.1233","volume":"17","author":"P Millet","year":"2002","unstructured":"Millet, P., Graf, C., Buck, A., Walder, B. & Ib\u00e1\u00f1ez, V. Evaluation of the reference tissue models for PET and SPECT benzodiazepine binding parameters. Neuroimage 17, 928\u2013942 (2002).","journal-title":"Neuroimage"},{"key":"257_CR17","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/sj.jcbfm.9600554","volume":"28","author":"UMH Klumpers","year":"2008","unstructured":"Klumpers, U. M. H. et al. Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies. J. Cereb. Blood Flow Metab. 28, 579\u2013587 (2008).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"257_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1006\/nimg.1996.0248","volume":"5","author":"JB Poline","year":"1997","unstructured":"Poline, J. B., Worsley, K. J., Evans, A. C. & Friston, K. J. Combining spatial extent and peak intensity to test for activations in functional imaging. Neuroimage 5, 83\u201396 (1997).","journal-title":"Neuroimage"},{"key":"257_CR19","unstructured":"Talairach, J. & Tournoux, P. Co-planar Stereotaxic Atlas of the Human Brain Vol. 270, 132 (Theime, Stuttgart, Germany, 1988)."},{"key":"257_CR20","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/35094500","volume":"2","author":"DA Gusnard","year":"2001","unstructured":"Gusnard, D. A., Raichle, M. E. & Raichle, M. E. Searching for a baseline: functional imaging and the resting human brain. Nat. Rev. Neurosci. 2, 685\u2013694 (2001).","journal-title":"Nat. Rev. Neurosci."},{"key":"257_CR21","doi-asserted-by":"publisher","first-page":"601","DOI":"10.2307\/1130201","volume":"58","author":"PS Goldman-Rakic","year":"1987","unstructured":"Goldman-Rakic, P. S. Development of cortical circuitry and cognitive function. Child Dev. 58, 601\u2013622 (1987).","journal-title":"Child Dev."},{"key":"257_CR22","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1093\/brain\/awl004","volume":"129","author":"AE Cavanna","year":"2006","unstructured":"Cavanna, A. E. & Trimble, M. R. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129, 564\u2013583 (2006).","journal-title":"Brain"},{"key":"257_CR23","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1523\/JNEUROSCI.4227-13.2014","volume":"34","author":"AV Utevsky","year":"2014","unstructured":"Utevsky, A. V., Smith, D. V. & Huettel, S. A. Precuneus is a functional core of the default-mode network. J. Neurosci. 34, 932\u2013940 (2014).","journal-title":"J. Neurosci."},{"key":"257_CR24","doi-asserted-by":"publisher","first-page":"20140172","DOI":"10.1098\/rstb.2014.0172","volume":"370","author":"ME Raichle","year":"2015","unstructured":"Raichle, M. E. The restless brain: how intrinsic activity organizes brain function. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370, 20140172\u201320140172 (2015).","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"257_CR25","doi-asserted-by":"publisher","first-page":"9673","DOI":"10.1073\/pnas.0504136102","volume":"102","author":"MD Fox","year":"2005","unstructured":"Fox, M. D. et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl Acad. Sci. USA 102, 9673\u20139678 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"257_CR26","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.1162\/jocn_a_00077","volume":"23","author":"AR Laird","year":"2011","unstructured":"Laird, A. R. et al. Behavioral interpretations of intrinsic connectivity networks. J. Cogn. Neurosci. 23, 4022\u20134037 (2011).","journal-title":"J. Cogn. Neurosci."},{"key":"257_CR27","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/j.neuroimage.2009.10.080","volume":"49","author":"XN Zuo","year":"2010","unstructured":"Zuo, X.-N. et al. Reliable intrinsic connectivity networks: test-retest evaluation using ICA and dual regression approach. Neuroimage 49, 2163\u20132177 (2010).","journal-title":"Neuroimage"},{"key":"257_CR28","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1002\/hbm.20737","volume":"30","author":"MP Van den Heuvel","year":"2009","unstructured":"Van den Heuvel, M. P., Mandl, R. C. W., Kahn, R. S. & Hulshoff Pol, H. E. Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain. Hum. Brain. Mapp. 30, 3127\u20133141 (2009).","journal-title":"Hum. Brain. Mapp."},{"key":"257_CR29","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.biopsych.2011.02.003","volume":"70","author":"JP Hamilton","year":"2011","unstructured":"Hamilton, J. P. et al. Default-mode and task-positive network activity in major depressive disorder: implications for adaptive and maladaptive rumination. Biol. Psychiatry 70, 327\u2013333 (2011).","journal-title":"Biol. Psychiatry"},{"key":"257_CR30","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1146\/annurev-clinpsy-032511-143049","volume":"8","author":"S Whitfield-Gabrieli","year":"2012","unstructured":"Whitfield-Gabrieli, S. & Ford, J. M. Default mode network activity and connectivity in psychopathology. Annu. Rev. Clin. Psychol. 8, 49\u201376 (2012).","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"257_CR31","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.tics.2011.12.011","volume":"16","author":"JL Price","year":"2012","unstructured":"Price, J. L. & Drevets, W. C. Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn. Sci. 16, 61\u201371 (2012).","journal-title":"Trends Cogn. Sci."},{"key":"257_CR32","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1148\/radiol.12120748","volume":"265","author":"Y Zhou","year":"2012","unstructured":"Zhou, Y. et al. Default-mode network disruption in mild traumatic brain injury. Radiology 265, 882\u2013892 (2012).","journal-title":"Radiology"},{"key":"257_CR33","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/acps.12418","volume":"132","author":"D Rabellino","year":"2015","unstructured":"Rabellino, D. et al. Intrinsic Connectivity Networks in post-traumatic stress disorder during sub- and supraliminal processing of threat-related stimuli. Acta Psychiatr. Scand. 132, 365\u2013378 (2015).","journal-title":"Acta Psychiatr. Scand."},{"key":"257_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058150","volume":"8","author":"G Sartory","year":"2013","unstructured":"Sartory, G. et al. In search of the trauma memory: a meta-analysis of functional neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD). PLoS ONE 8, e58150 (2013).","journal-title":"PLoS ONE"},{"key":"257_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neulet.2013.04.032","volume":"547","author":"X Yan","year":"2013","unstructured":"Yan, X. et al. Spontaneous brain activity in combat related PTSD. Neurosci. Lett. 547, 1\u20135 (2013).","journal-title":"Neurosci. Lett."},{"key":"257_CR36","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/hbm.23051","volume":"37","author":"I Reuveni","year":"2016","unstructured":"Reuveni, I. et al. Anatomical and functional connectivity in the default mode network of post-traumatic stress disorder patients after civilian and military-related trauma. Hum. Brain. Mapp. 37, 589\u2013599 (2016).","journal-title":"Hum. Brain. Mapp."},{"key":"257_CR37","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.nicl.2017.10.032","volume":"17","author":"M Misaki","year":"2018","unstructured":"Misaki, M. et al. Connectome-wide investigation of altered resting-state functional connectivity in war veterans with and without posttraumatic stress disorder. Neuroimage Clin. 17, 285\u2013296 (2018).","journal-title":"Neuroimage Clin."},{"key":"257_CR38","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.bpsc.2016.12.006","volume":"2","author":"DR Miller","year":"2017","unstructured":"Miller, D. R. et al. Default mode network subsystems are differentially disrupted in posttraumatic stress disorder. Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 2, 363\u2013371 (2017).","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging."},{"key":"257_CR39","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1038\/nn2001","volume":"10","author":"G Northoff","year":"2007","unstructured":"Northoff, G. et al. GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI. Nat. Neurosci. 10, 1515\u20131517 (2007).","journal-title":"Nat. Neurosci."},{"key":"257_CR40","doi-asserted-by":"publisher","first-page":"8356","DOI":"10.1073\/pnas.0900728106","volume":"106","author":"SD Muthukumaraswamy","year":"2009","unstructured":"Muthukumaraswamy, S. D., Edden, R. A. E., Jones, D. K., Swettenham, J. B. & Singh, K. D. Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans. Proc. Natl Acad. Sci. USA 106, 8356\u20138361 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"257_CR41","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1038\/nn.2559","volume":"13","author":"P Sumner","year":"2010","unstructured":"Sumner, P., Edden, R. A. E., Bompas, A., Evans, C. J. & Singh, K. D. More GABA, less distraction: a neurochemical predictor of motor decision speed. Nat. Neurosci. 13, 825\u2013827 (2010).","journal-title":"Nat. Neurosci."},{"key":"257_CR42","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.neuroimage.2012.09.029","volume":"64","author":"D Kapogiannis","year":"2013","unstructured":"Kapogiannis, D., Reiter, D. A., Willette, A. A. & Mattson, M. P. Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network. Neuroimage 64, 112\u2013119 (2013).","journal-title":"Neuroimage"},{"key":"257_CR43","doi-asserted-by":"publisher","first-page":"18566","DOI":"10.1523\/JNEUROSCI.1973-13.2013","volume":"33","author":"Y Hu","year":"2013","unstructured":"Hu, Y., Chen, X., Gu, H. & Yang, Y. Resting-state glutamate and GABA concentrations predict task-induced deactivation in the default mode network. J. Neurosci. 33, 18566\u201318573 (2013).","journal-title":"J. Neurosci."},{"key":"257_CR44","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/hbm.22166","volume":"35","author":"C Wiebking","year":"2014","unstructured":"Wiebking, C. et al. External awareness and GABA-A multimodal imaging study combining fMRI and [18 F]flumazenil-PET. Hum. Brain. Mapp. 35, 173\u2013184 (2014).","journal-title":"Hum. Brain. Mapp."},{"key":"257_CR45","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1159\/000258721","volume":"17","author":"ME Bauer","year":"2010","unstructured":"Bauer, M. E., Wieck, A., Lopes, R. P., Teixeira, A. L. & Grassi-Oliveira, R. Interplay between neuroimmunoendocrine systems during post-traumatic stress disorder: a minireview. Neuroimmunomodulation 17, 192\u2013195 (2010).","journal-title":"Neuroimmunomodulation"},{"key":"257_CR46","doi-asserted-by":"publisher","first-page":"10111","DOI":"10.1523\/JNEUROSCI.1184-09.2009","volume":"29","author":"Henckens MJAG","year":"2009","unstructured":"MJAG, Henckens et al. memories: how acute stress affects memory formation in humans. J. Neurosci. 29, 10111\u201310119 (2009).","journal-title":"J. Neurosci."},{"key":"257_CR47","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.pscychresns.2009.04.012","volume":"174","author":"AH Kemp","year":"2009","unstructured":"Kemp, A. H. et al. Heterogeneity of non-conscious fear perception in posttraumatic stress disorder as a function of physiological arousal: an fMRI study. Psychiatry Res. 174, 158\u2013161 (2009).","journal-title":"Psychiatry Res."},{"key":"257_CR48","doi-asserted-by":"publisher","first-page":"9429","DOI":"10.1523\/JNEUROSCI.18-22-09429.1998","volume":"18","author":"L Petit","year":"1998","unstructured":"Petit, L., Courtney, S. M., Ungerleider, L. G. & Haxby, J. V. Sustained activity in the medial wall during working memory delays. J. Neurosci. 18, 9429\u20139437 (1998).","journal-title":"J. Neurosci."},{"key":"257_CR49","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1523\/JNEUROSCI.3455-15.2016","volume":"36","author":"RJ Maddock","year":"2016","unstructured":"Maddock, R. J., Casazza, G. A., Fernandez, D. H. & Maddock, M. I. Acute modulation of cortical glutamate and GABA content by physical activity. J. Neurosci. 36, 2449\u20132457 (2016).","journal-title":"J. Neurosci."},{"key":"257_CR50","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1073\/pnas.012470999","volume":"99","author":"G Bush","year":"2002","unstructured":"Bush, G. et al. Dorsal anterior cingulate cortex: a role in reward-based decision making. Proc. Natl Acad. Sci. USA 99, 523\u2013528 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"257_CR51","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1176\/appi.ajp.2011.09121812","volume":"168","author":"LM Shin","year":"2011","unstructured":"Shin, L. M. et al. Exaggerated activation of dorsal anterior cingulate cortex during cognitive interference: a monozygotic twin study of posttraumatic stress disorder. Am. J. Psychiatry 168, 979\u2013985 (2011).","journal-title":"Am. J. Psychiatry"},{"key":"257_CR52","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.tics.2013.05.005","volume":"17","author":"R Admon","year":"2013","unstructured":"Admon, R., Milad, M. R. & Hendler, T. A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities. Trends Cogn. Sci. 17, 337\u2013347 (2013).","journal-title":"Trends Cogn. Sci."},{"key":"257_CR53","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":"257_CR54","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.nlm.2014.02.003","volume":"113","author":"E Shvil","year":"2014","unstructured":"Shvil, E. et al. Sex differences in extinction recall in posttraumatic stress disorder: a pilot fMRI study. Neurobiol. Learn. Mem. 113, 101\u2013108 (2014).","journal-title":"Neurobiol. Learn. Mem."},{"key":"257_CR55","doi-asserted-by":"publisher","first-page":"672","DOI":"10.3389\/fnhum.2013.00672","volume":"7","author":"RK Sripada","year":"2013","unstructured":"Sripada, R. K., Garfinkel, S. N. & Liberzon, I. Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction. Front. Hum. Neurosci. 7, 672 (2013).","journal-title":"Front. Hum. Neurosci."},{"key":"257_CR56","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1038\/npp.2015.257","volume":"41","author":"SJH van Rooij","year":"2016","unstructured":"van Rooij, S. J. H., Kennis, M., Vink, M. & Geuze, E. Predicting treatment outcome in PTSD: a longitudinal functional MRI study on trauma-unrelated emotional processing. Neuropsychopharmacology 41, 1156\u20131165 (2016).","journal-title":"Neuropsychopharmacology"},{"key":"257_CR57","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/da.22605","volume":"34","author":"M Kennis","year":"2017","unstructured":"Kennis, M., van Rooij, S. J. H., Reijnen, A. & Geuze, E. The predictive value of dorsal cingulate activity and fractional anisotropy on long-term PTSD symptom severity. Depress Anxiety 34, 410\u2013418 (2017).","journal-title":"Depress Anxiety"},{"key":"257_CR58","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.pharmthera.2014.12.004","volume":"149","author":"N Singewald","year":"2015","unstructured":"Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A. & Ressler, K. J. Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol. Ther. 149, 150\u2013190 (2015).","journal-title":"Pharmacol. Ther."},{"key":"257_CR59","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s11065-014-9246-9","volume":"24","author":"PG Gasquoine","year":"2014","unstructured":"Gasquoine, P. G. Contributions of the insula to cognition and emotion. Neuropsychol. Rev. 24, 77\u201387 (2014).","journal-title":"Neuropsychol. Rev."},{"key":"257_CR60","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1002\/hbm.22113","volume":"34","author":"WK Simmons","year":"2013","unstructured":"Simmons, W. K. et al. Keeping the body in mind: insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness. Hum. Brain. Mapp. 34, 2944\u20132958 (2013).","journal-title":"Hum. Brain. Mapp."},{"key":"257_CR61","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.biopsych.2013.11.027","volume":"76","author":"JA Avery","year":"2014","unstructured":"Avery, J. A. et al. Major depressive disorder is associated with abnormal interoceptive activity and functional connectivity in the insula. Biol. Psychiatry 76, 258\u2013266 (2014).","journal-title":"Biol. Psychiatry"},{"key":"257_CR62","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1176\/appi.ajp.2015.15020162","volume":"173","author":"WK Simmons","year":"2016","unstructured":"Simmons, W. K. et al. Depression-related increases and decreases in appetite: dissociable patterns of aberrant activity in reward and interoceptive neurocircuitry. Am. J. Psychiatry 173, 418\u2013428 (2016).","journal-title":"Am. J. Psychiatry"},{"key":"257_CR63","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1523\/JNEUROSCI.5587-06.2007","volume":"27","author":"WW Seeley","year":"2007","unstructured":"Seeley, W. W. et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349\u20132356 (2007).","journal-title":"J. Neurosci."},{"key":"257_CR64","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.biopsych.2010.04.002","volume":"68","author":"LH Somerville","year":"2010","unstructured":"Somerville, L. H., Whalen, P. J. & Kelley, W. M. Human bed nucleus of the stria terminalis indexes hypervigilant threat monitoring. Biol. Psychiatry 68, 416\u2013424 (2010).","journal-title":"Biol. Psychiatry"},{"key":"257_CR65","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s00429-010-0262-0","volume":"214","author":"V Menon","year":"2010","unstructured":"Menon, V. & Uddin, L. Q. Saliency, switching, attention and control: a network model of insula function. Brain. Struct. Funct. 214, 655\u2013667 (2010).","journal-title":"Brain. Struct. Funct."},{"key":"257_CR66","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1016\/j.neubiorev.2012.06.003","volume":"36","author":"R Patel","year":"2012","unstructured":"Patel, R., Spreng, R. N., Shin, L. M. & Girard, T. A. Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neurosci. Biobehav. Rev. 36, 2130\u20132142 (2012).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"257_CR67","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1097\/PSY.0b013e318273bf33","volume":"74","author":"RK Sripada","year":"2012","unstructured":"Sripada, R. K. et al. Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks. Psychosom. Med. 74, 904\u2013911 (2012).","journal-title":"Psychosom. Med."},{"key":"257_CR68","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-017-0840-4","volume":"19","author":"TJ Akiki","year":"2017","unstructured":"Akiki, T. J., Averill, C. L. & Abdallah, C. G. A network-based neurobiological model of PTSD: evidence from structural and functional neuroimaging studies. Curr. Psychiatry Rep. 19, 81 (2017).","journal-title":"Curr. Psychiatry Rep."},{"key":"257_CR69","doi-asserted-by":"publisher","first-page":"10798","DOI":"10.1523\/JNEUROSCI.0518-14.2014","volume":"34","author":"SR Jilka","year":"2014","unstructured":"Jilka, S. R. et al. Damage to the salience network and interactions with the default mode network. J. Neurosci. 34, 10798\u201310807 (2014).","journal-title":"J. Neurosci."},{"key":"257_CR70","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jad.2015.08.043","volume":"187","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y. et al. Intranetwork and internetwork functional connectivity alterations in post-traumatic stress disorder. J. Affect Disord. 187, 114\u2013121 (2015).","journal-title":"J. Affect Disord."},{"key":"257_CR71","doi-asserted-by":"publisher","first-page":"3677","DOI":"10.1002\/hbm.22871","volume":"36","author":"X Suo","year":"2015","unstructured":"Suo, X. et al. Disrupted brain network topology in pediatric posttraumatic stress disorder: a resting-state fMRI study. Hum. Brain Mapp. 36, 3677\u20133686 (2015).","journal-title":"Hum. Brain Mapp."},{"key":"257_CR72","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1148\/radiol.15141700","volume":"276","author":"D Lei","year":"2015","unstructured":"Lei, D. et al. Disrupted functional brain connectome in patients with posttraumatic stress disorder. Radiology 276, 818\u2013827 (2015).","journal-title":"Radiology"},{"key":"257_CR73","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.neubiorev.2015.07.007","volume":"56","author":"EA Stark","year":"2015","unstructured":"Stark, E. A. et al. Post-traumatic stress influences the brain even in the absence of symptoms: a systematic, quantitative meta-analysis of neuroimaging studies. Neurosci. Biobehav. Rev. 56, 207\u2013221 (2015).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"257_CR74","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1097\/PRA.0000000000000091","volume":"21","author":"J Guina","year":"2015","unstructured":"Guina, J., Rossetter, S. R., Derhodes, B. J., Nahhas, R. W. & Welton, R. S. Benzodiazepines for PTSD: a systematic review and meta-analysis. J. Psychiatr. Pract. 21, 281\u2013303 (2015).","journal-title":"J. Psychiatr. Pract."},{"key":"257_CR75","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1056\/NEJMra1611832","volume":"376","author":"M Soyka","year":"2017","unstructured":"Soyka, M. Treatment of benzodiazepine dependence. N. Engl. J. Med. 376, 1147\u20131157 (2017).","journal-title":"N. Engl. J. Med."},{"key":"257_CR76","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/nrn1703","volume":"6","author":"D Belelli","year":"2005","unstructured":"Belelli, D. & Lambert, J. J. Neurosteroids: endogenous regulators of the GABAA receptor. Nat. Rev. Neurosci. 6, 565\u2013575 (2005).","journal-title":"Nat. Rev. Neurosci."},{"key":"257_CR77","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.biopsych.2006.03.026","volume":"60","author":"AM Rasmusson","year":"2006","unstructured":"Rasmusson, A. M. et al. Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder. Biol. Psychiatry 60, 704\u2013713 (2006).","journal-title":"Biol. Psychiatry"},{"key":"257_CR78","first-page":"73","volume":"2","author":"M Nin","year":"2011","unstructured":"Nin, M., Martinez, L. A., Pibiri, F., Nelson, M. & Pinna, G. Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression. Front. Endocrinol. (Lausanne) 2, 73 (2011).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"257_CR79","doi-asserted-by":"publisher","first-page":"5567","DOI":"10.1073\/pnas.0801853105","volume":"105","author":"F Pibiri","year":"2008","unstructured":"Pibiri, F., Nelson, M., Guidotti, A., Costa, E. & Pinna, G. Decreased corticolimbic allopregnanolone expression during social isolation enhances contextual fear: A model relevant for posttraumatic stress disorder. Proc. Natl Acad. Sci. USA 105, 5567\u20135572 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"257_CR80","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.1365-2826.2011.02234.x","volume":"24","author":"G Pinna","year":"2012","unstructured":"Pinna, G. & Rasmusson, A. M. Up-regulation of neurosteroid biosynthesis as a pharmacological strategy to improve behavioural deficits in a putative mouse model of post-traumatic stress disorder. J. Neuroendocrinol. 24, 102\u2013116 (2012).","journal-title":"J. Neuroendocrinol."},{"key":"257_CR81","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.biopsych.2012.12.008","volume":"73","author":"RK Sripada","year":"2013","unstructured":"Sripada, R. K. et al. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol. Psychiatry 73, 1045\u20131053 (2013).","journal-title":"Biol. Psychiatry"},{"key":"257_CR82","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1007\/s00213-017-4649-y","volume":"234","author":"AM Rasmusson","year":"2017","unstructured":"Rasmusson, A. M. et al. A randomized controlled trial of ganaxolone in posttraumatic stress disorder. Psychopharmacology (Berlin) 234, 2245\u20132257 (2017).","journal-title":"Psychopharmacology (Berlin)"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0257-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0257-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0257-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T11:31:10Z","timestamp":1671535870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0257-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,4]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["257"],"URL":"https:\/\/doi.org\/10.1038\/s41398-018-0257-9","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,4]]},"assertion":[{"value":"2 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"W.C.D.\u2014an employee of Janssen Research & Development, LLC of Johnson & Johnson, and holds equity in Johnson & Johnson. D.S.C.\u2014a full statement is attached to the manuscript. The remaining authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"206"}}