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Neurobiology of PTSD: A Review of Neuroimaging Findings
Open accessAbstract
Neuroimaging serves as an effec-tive way to investigate the neu-rocircuitry involved in the de-velopment of posttraumatic stress disorder (PTSD).1-3 A number of models describing functional neuroanatomy of PTSD symp-tom development emerged over the past decade, inspired by both basic animal re-search and an increasing number of human neuroimaging studies. These models have traditionally conceptualized PTSD as a state of heightened responsivity to threat-ening stimuli and later as a state of insuf-fi cient inhibitory control over-exaggerated threat-sensitivity. They emphasize the cen-trality of threat-related processing in the pathophysiology of PTSD and therefore
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“we have recently proposed that PTSD is associated with failure to contextualize emotional memory,30,44”
From Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder (2012) · cites this paper as [44]
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Self-citationEstrogen Levels Are Associated with Extinction Deficits in Women with Posttraumatic Stress Disorder
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“The function of two PFC subregions, the anterior cingulate cortex (ACC) and the medial PFC (mPFC), has been found to be altered in PTSD (59, 60).”
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“Cortical and subcortical findings Structural MRI and functional MRI studies in PTSD report differences in volume and activation of limbic circuitry mediating stress responding, fear memory, and emotional modulation (Garfinkel and Liberzon, 2009; Rauch et al., 2006).”
Atypical interoception as a common risk factor for psychopathology: A review
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Functional Neuroanatomy of Emotion and Its Regulation in PTSD
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“…the functional neuroanatomy of PTSD symptom development emerged over the past decade, these models mainly focus on PTSD as a state of heightened responsivity to threatening stimuli or as a state of insufficient inhibitory control overexaggerated threat-sensitivity (Garfinkel & Liberzon, 2009).”
BackgroundPretreatment biomarkers predicting PTSD psychotherapy outcomes: A systematic review
Colvonen, P. J., Glassman, L. H., Crocker, L. D., Buttner, M. M. A., Orff, H. J., Schiehser, D. M., Norman, S. B., & Afari, N. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.027 · Cited by 89
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Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction
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Self-citationConsidering PTSD from the perspective of brain processes: A psychological construction approach
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“The authors contend that existing neural accounts fail to provide a viable model that explains the emergence and maintenance of PTSD and the associated heterogeneity in the expression of this disorder (cf. Garfinkel & Liberzon, 2009).”
BackgroundResultInfluentialWhite matter integrity alterations in post‐traumatic stress disorder
O'Doherty, D. C. M., Ryder, W., Paquola, C., Tickell, A. M., Chan, C., Hermens, D. F., Bennett, M. R., & Lagopoulos, J. (2017) · Human Brain Mapping · doi:10.1002/hbm.23920 · Cited by 75
“They may also exhibit heightened responses to stimuli perceived as threatening, and subsequent inability to extinguish fear (Garfinkel and Liberzon, 2009).”
BackgroundFrontal and subcortical grey matter reductions in PTSD
O'Doherty, D. C. M., Tickell, A. M., Ryder, W., Chan, C., Hermens, D. F., Bennett, M. R., & Lagopoulos, J. (2017) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2017.05.008 · Cited by 74
“The common hyper-aroused type of PTSD is characterised by heightened responses to stimuli perceived by certain individuals as threatening, followed the inability to extinguish fear (Garfinkel and Liberzon, 2009).”
BackgroundDisner, S. G., Marquardt, C. A., Mueller, B. A., Burton, P. C., & Sponheim, S. R. (2017) · Human Brain Mapping · doi:10.1002/hbm.23886 · Cited by 70
“In addition, there are several putatively maladaptive processes involved with PTSD, including hyper-responsivity to trauma-related cues and impaired top-down regulation of emotional states, that are shown to involve regions not present in the current meta-analysis (Garfinkel & Liberzon, 2009).”
BackgroundBrenner, L. A. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.3/lbrenner · Cited by 66
“Studies often involve diverse cohorts (eg, mild TBI, combat veterans), and employ different paradigms (symptom provocation, cognitive activation) and modalities (eg, diffusion tensor imaging [DTI], functional magnetic resonance imaging [fMRI], single photon emission computed tomography [SPECT]).(50) As such, findings…”
BackgroundInfluentialRabinak, C. A., Blanchette, A., Zabik, N. L., Peters, C., Marusak, H. A., Iadipaolo, A. S., & Elrahal, F. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05499-8 · Cited by 57
“…to insufficient top-down regulation from the mPFC/rACC, consequently leading to hyperarousal and an inability to suppress attention and responses to traumarelated stimuli (Pitman et al. 2001; Liberzon and Martis 2006; Garfinkel and Liberzon 2009; Fenster et al. 2018; Andrewes and Jenkins 2019).”
BackgroundMapping PTSD symptoms to brain networks: a machine learning study
Zandvakili, A., Barredo, J., Swearingen, H. R., Aiken, E., Berlow, Y. A., Greenberg, B. D., Carpenter, L. L., & Philip, N. S. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00879-2 · Cited by 50
Hien, D. A., López‐Castro, T., Fitzpatrick, S., Ruglass, L. M., Fertuck, E. A., & Melara, R. D. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.05.022 · Cited by 46
A critical review of negative affect and the application of CBT for PTSD
Brown, W. J., Dewey, D., Bunnell, B. E., Boyd, S. J., Wilkerson, A. K., Mitchell, M. A., & Bruce, S. E. (2018) · Trauma, Violence, & Abuse · doi:10.1177/1524838016650188 · Cited by 43
“There is a substantial body of neuroscience literature that evinces the impact of dysregulated fear circuitry within the development of PTSD (Garfinkel & Liberzon, 2009; Johnson, McGuire, Lazarus, &Palmer, 2012; VanElzakker, Dahlgren, Davis, Dubois, & Shin, 2014).”
BackgroundNeural signatures of auditory hypersensitivity following acoustic trauma
McGill, M., Hight, A. E., Watanabe, Y. L., Parthasarathy, A., Cai, D., Clayton, K. K., Hancock, K. E., Takesian, A. E., Kujawa, S. G., & Polley, D. B. (2022) · eLife · doi:10.7554/elife.80015 · Cited by 36
“…autism spectrum disorder (Klintwall et al., 2011; Robertson and Baron-Cohen, 2017), post-traumatic stress disorder (Ehlers and Clark, 2000; Garfinkel and Liberzon, 2009), fibromyalgia (Nielsen and Henriksson, 2007; Yunus, 2007), schizophrenia (González-Rodríguez et al., 2021; Luck and…”
BackgroundDisrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder
Zhang, Y., Xie, B., Chen, H., Li, M., Guo, X., & Chen, H. (2016) · Medicine · doi:10.1097/md.0000000000004083 · Cited by 41
“pathophysiological mechanism of PTSD is essential in the clinical treatment and management of this disorder.([5]) Increased efforts have been dedicated for the neuroimaging studies of PTSD; the insular cortex is suggested to be implicated in”
BackgroundNeurocognition in PTSD: Treatment Insights and Implications
Jak, A. J., Crocker, L. D., Aupperle, R. L., Clausen, A. N., & Bomyea, J. A. (2016) · Current topics in behavioral neurosciences · doi:10.1007/7854_2016_62 · Cited by 39
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“Indeed, there is evidence that traumatic exposure can alter the structure and functioning of areas of brain associated with BIS functioning, such as the hippocampus (Cherbuin et al. 2008; Garfinkel and Liberzon 2009 ).”
BackgroundPapini, S., Sullivan, G. M., Hien, D. A., Shvil, E., & Neria, Y. (2014) · Biological Psychology · doi:10.1016/j.biopsycho.2014.10.010 · Cited by 37
“…amygdala, and prefrontal cortex (Glass, Dragunow, & Faull, 1997)—brain regions with key roles in fear acquisition and extinction (Quirk & Mueller, 2008) that have exhibited structural and functional impairments in patients with PTSD (Admon, Milad, & Hendler, 2013; Garfinkel & Liberzon, 2009).”
BackgroundUntangling PTSD and TBI: Challenges and Strategies in Clinical Care and Research
Hendrickson, R. C., Schindler, A. G., & Pagulayan, K. F. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0908-5 · Cited by 39
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Interoception in Fear Learning and Posttraumatic Stress Disorder
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Melara, R. D., Ruglass, L. M., Fertuck, E. A., & Hien, D. A. (2018) · Biological Psychology · doi:10.1016/j.biopsycho.2018.01.017 · Cited by 33
Baclofen Add-on to Citalopram in Treatment of Posttraumatic Stress Disorder
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Psychopharmacological treatment for military posttraumatic stress disorder: An integrative review
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“Evers (2007), Antai-Otong (2007), Garfinkel and Liberzon (2009), Mirkes (2010), and Robinson and Shergill (2011) examined the differences between people who experienced similar traumatic events and found that individuals who are vulnerable to PTSD have structural abnormalities of the brain,…”
BackgroundBarredo, J., Aiken, E., Wout‐Frank, M. V. ‘., Greenberg, B. D., Carpenter, L. L., & Philip, N. S. (2018) · Brain Connectivity · doi:10.1089/brain.2018.0634 · Cited by 23
“While these models account for the threat sensitivity and intrusions characteristic of PTSD, they offer an incomplete explanation for the full range of clinical symptoms [e.g., dissociation and avoidance (Garfinkel and Liberzon, 2009)].”
Pharmacological Prevention of Combat-Related PTSD: A Literature Review
Searcy, C. P., Bobadilla, L., Gordon, W. A., Jacques, S., & Elliott, L. (2012) · Military Medicine · doi:10.7205/milmed-d-11-00390 · Cited by 23
Electrophysiological responses to threat in youth with and without Posttraumatic Stress Disorder
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Clausen, A. N., Thelen, J., Francisco, A. J., Bruce, J. M., Martin, L. E., McDowd, J. M., & Aupperle, R. L. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00062 · Cited by 21
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There Is More Than One Kind of Extinction Learning
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Traumatic stress: established knowledge, current debates and new horizons
Eagle, G. T., & Kaminer, D. (2014) · South African Journal of Psychology · doi:10.1177/0081246314547124 · Cited by 23
Tackling hyperarousal: an integrative multimodal approach
Krupnik, V. (2021) · Cognitive Neuropsychiatry · doi:10.1080/13546805.2021.1907177 · Cited by 14
“In studies of the neurobiology of PTSD, physiological hyper-reactivity to trauma-related cues has consistently been demonstrated in PTSD patients and correlated with hyperactivation of the amygdala and hypoactivation of the prefrontal cortex (Garfinkel & Liberzon, 2009; Weston, 2014).”
BackgroundFacco, E., Mendozzi, L., Bona, A., Motta, A., Garegnani, M., Costantini, I., Dipasquale, O., Cecconi, P., Menotti, R., Coscioli, E., et al. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.109274 · Cited by 16
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Bomyea, J. A., Simmons, A. N., Shenton, M. E., Coleman, M. J., Sylvain Bouix, A., Yogesh Rathi, A., Pasternak, O., Coimbra, R. S. M., Shutter, L., George, M. S., et al. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.11.012 · Cited by 13
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Clausen, A. N., Billinger, S. A., Sisante, J.-F. V., Suzuki, H., & Aupperle, R. L. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.02151 · Cited by 12
Violence Exposure Is Associated With Atypical Appraisal of Threat Among Women: An EEG Study
Perizzolo, V. C., Moser, D. A., Vital, M., Serpa, S. R., Todorov, A. T., & Schechter, D. S. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.576852 · Cited by 12
“Inferences, such as threat evaluation, could be positively and/or negatively affected by one’s own history of stressful interpersonal experiences and adverse life events, such as childhood maltreatment (Gibb et al., 2009; Nazarov et al., 2014; Neukel et al., 2019).”
BackgroundKnight, L. K., Naaz, F., Stoica, T., & Depue, B. E. (2017) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2017.07.003 · Cited by 12
López‐Castro, T., Martin, L., Nickley, S., Saraiya, T. C., & Melara, R. D. (2021) · Clinical EEG and Neuroscience · doi:10.1177/15500594211046703 · Cited by 10
“Deficits in inhibitory control in PTSD have been traced in part to dysfunction in the prefrontal cortex (PFC).(9) Yet little is known about the prefrontal processes linking cognitive deficits to PTSD symptomatology.”
Affect and neural activity in women with PTSD during a task of emotional interference
Brown, W. J., Wojtalik, J. A., Dewey, D., Bruce, S. E., Yang, Z., & Sheline, Y. I. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.05.065 · Cited by 9
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“Supporting this model, researchers have observed PTSD-related abnormalities in fronto-limbic regions (Garfinkel & Liberzon, 2009; Hayes et al., 2012; Patel et al., 2012; Rauch et al., 1998) and reduced volumes in the left amygdala, anterior cingulate cortex, and ventral medial prefrontal cortex…”
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Regional Gray Matter Volume Related to High Occupational Stress in Firefighters
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Cannabis for posttraumatic stress disorder
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PTSD and other operational stress injuries among police officers
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Post-traumatic stress and decision-making: research prospects in the paradigm of neuroeconomics
Bogolyubova, O., & Шестакова, А. Н. (2015) · Experimental Psychology (Russia) · doi:10.17759/exppsy.2015080206 · Cited by 5
Brain Structural Abnormalities in Posttraumatic Stress Disorder and Relations with Sleeping Problems
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Self-citationNeuroanatomical Correlates of PTSD: Risk, Resiliency, and Sequelae
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Neurobiology of Posttraumatic Stress Disorder
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Traumatic Stress and Pediatric Pain: Towards a Neurobiological Stress-Health Perspective
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TOLERANCE OF UNCERTAINTY AND EXECUTIVE DYSFUNCTION IN PEOPLE WITH PSYCHOLOGICAL TRAUMA
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“Thus, it can be stated that persons with a history of psychological trauma have manifestations of executive dysfunctions [1, 3, 4, 7, 19, 24, 27].”
BackgroundGrey Matter Changes in the Brain Following Stress and Trauma
Bennett, M. R., & Lagopoulos, J. (2018) · Springer eBooks · doi:10.1007/978-3-319-91116-8_1 · Cited by 2
Pupillary Response to Affective Voices: Physiological Responsivity and Posttraumatic Stress Disorder
Rubin, M., & Telch, M. J. (2020) · Journal of Traumatic Stress · doi:10.1002/jts.22574 · Cited by 3
Neuroanatomical Correlates of PTSD: Risk, Resiliency, and Sequelae
Clausen, A. N., & Aupperle, R. L. (2016) · Springer eBooks · doi:10.1007/978-3-319-08359-9_22 · Cited by 2
Dunn, N., Esplin, J. A., & Fitzgerald, M. (2022) · Journal of American College Health · doi:10.1080/07448481.2022.2066956 · Cited by 1
“These same brain regions are impacted by both childhood maltreatment 57 and PTSD; 8 likewise, yoga promotes regulation of the autonomic nervous system which is often a problem among adults who were maltreated in childhood.”
BackgroundShahkaram, H., Bakhtiari, M., Ganjali, A., & Kianimoghadam, A. S. (2025) · Journal of Education and Health Promotion · doi:10.4103/jehp.jehp_1014_24 · Cited by 1
Gillavry, D. W. M., & Ullrich, D. C. (2020) · Military Psychology · doi:10.1080/08995605.2020.1730111 · Cited by 1
Porter, K. E., Cochran, H. M., Richards, S. K. H., & Sexton, M. B. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800951-2.00046-7 · Cited by 2
Stocco, A., Smith, B. M., PeConga, E. K., & Zoellner, L. A. (2021) · doi:10.31234/osf.io/rwz6u · Cited by 1
Garfinkel, S. N., & Critchley, H. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-397025-1.00121-4
Self-citationNicotine and Posttraumatic Stress Disorder
Acheson, D. T., & Glenn, D. E. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802574-1.00016-8
Brown, W. J. (2015) · IRL - University of Missouri, St. Louis (University of Missouri–St. Louis)
Neurobiology and Neuroimaging of PTSD
Milad, M. R., & Moore, K. N. (2018) · Oxford University Press eBooks · doi:10.1093/med/9780190457136.003.0015 · Cited by 1
Complex Assessment of Combat Neurotrauma
Bowen, M., & Chang, A. (2018) · Journal of Neurology and Neurological Disorders · doi:10.15744/2454-4981.4.107
“Aupperle and colleagues (2012) summarized investigations regarding executive function and PTSD, and identified subtle impairments in response inhibition and attention regulation among those with PTSD [37].”
BackgroundResultInfluentialThe impact of posttraumatic stress disorder on executive functioning
Kock, D., & Johannes, C. (2019)
A mixed-methods analysis of Iraqi refugees with potential trauma histories
Ibrahim, A. Y., & Herbert, J. D. (2013) · doi:10.17918/etd-4472
Transcranial Doppler (TCD): Role for Patients After Concussion
Razumovsky, A. Y. (2021) · Springer eBooks · doi:10.1007/978-3-030-81419-9_71
Ehrenreich, H., Krampe, H., & Sirén, A. (2020) · Wiley eBooks · doi:10.1002/9781119159322.ch24
Incorporating a neuropsychological perspective into practice: A practical guide
Fairfax, H. (2017) · Counselling Psychology Review · doi:10.53841/bpscpr.2017.32.4.29
A Comprehensive study on the application of deep brain stimulation in PTSD
Zhang, J. (2023) · Theoretical and Natural Science · doi:10.54254/2753-8818/22/20230987
PTSD and Violence: Understanding the Connection and Implications for Treatment
Robinson, L. K. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.1007488
James, L. M., Engdahl, B. E., Leuthold, A. C., & Georgopoulos, A. P. (2025) · Journal of Neurophysiology · doi:10.1152/jn.00560.2025
Feingold, D., Quiquempoix, M., Remadi, M., Sipahimalani, G., Lahutte, B., Léger, D., Gomez-Mérino, D., Chennaoui, M., & Saguin, E. (2026) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.70038
Trauma-related nightmares: A Comprehensive and Integrative review
Feingold, D., Roseau, J.-B., Verdonk, C., Richards, A. L., Chennaoui, M., Saguin, E., & Léger, D. (2026) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2026.102259 · Cited by 1
Lipschutz, R. S., Dahlgren, K., Santos, J., Chambers, K., McAfee, E., Abrams, C., Merrill, N. A., Brennan, P. A., Rilling, J. K., Michopoulos, V., et al. (2026) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2026.04.009
Metadata
- Authors
- Garfinkel, S. N., & Liberzon, I.
- Affiliations
- University of Michigan (US)
- Houston Methodist (US)
- Venue
- Psychiatric Annals
- Publisher
- SLACK, Inc.
- Published
- 2009-06
- Volume
- 39
- Issue
- 6
- Pages
- 370-381
- ISSN
- 0048-5713 (ISSN-L)
- 1938-2456
- OpenAlex
- W2100532508
- Cited by
- 102
- References
- 79
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 12 · 2020: 10 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 5 · 2013: 4 · 2012: 8
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychiatric Annals (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- post-traumatic stress disorder, neurobiology of PTSD, neuroimaging findings, threat processing, threat sensitivity, inhibitory control, functional neuroanatomy, PTSD pathophysiology
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