Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-27T08:56:27.409Z Has data issue: false hasContentIssue false
  • English
  • Français

Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder

Published online by Cambridge University Press:  13 May 2011

A. L. Gold ,
L. M. Shin ,
S. P. Orr ,
M. A. Carson ,
S. L. Rauch ,
M. L. Macklin ,
N. B. Lasko ,
L. J. Metzger ,
D. D. Dougherty  and
N. M. Alpert
...Show all authors
A. L. Gold*
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
L. M. Shin
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Department of Psychology, Tufts University, Medford, MA, USA
S. P. Orr
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Veterans Affairs Research Service, Manchester, NH, USA
M. A. Carson
Affiliation:
Department of Nursing, St. Anselm College, Manchester, NH, USA
S. L. Rauch
Affiliation:
Department of Psychiatry, McLean Hospital, Belmont, MA and Harvard Medical School, Boston MA, USA
M. L. Macklin
Affiliation:
Veterans Affairs Research Service, Manchester, NH, USA
N. B. Lasko
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Veterans Affairs Research Service, Manchester, NH, USA
L. J. Metzger
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Veterans Affairs Research Service, Manchester, NH, USA
D. D. Dougherty
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
N. M. Alpert
Affiliation:
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
A. J. Fischman
Affiliation:
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
R. K. Pitman
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
*
*Address for correspondence: A. L. Gold, M.S., Department of Psychology, Yale University, PO Box 208205, New Haven, CT 06520, USA. (Email: andrea.gold@yale.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events.

Method

Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events.

Results

Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately.

Conclusions

Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

Keywords

Anterior cingulate cortexanxietyemotionneuroimagingpositron emission tomographypost-traumatic stress disorderscript-driven imagery
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 12 , December 2011 , pp. 2563 - 2572
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Arnsten, AFT (2009). Stress signalling pathways that impair prefrontal cortex structure and function. Nature Reviews Neuroscience 10, 410–422.Google Scholar
Arnsten, AFT, Goldman-Rakic, PS (1998). Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. Archives of General Psychiatry 55, 362–369.CrossRefGoogle ScholarPubMed
Bremner, JD, Narayan, M, Staib, LH, Southwick, SM, McGlashan, T, Charney, DS (1999 a). Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. American Journal of Psychiatry 156, 1787–1795.CrossRefGoogle ScholarPubMed
Bremner, JD, Staib, LH, Kaloupek, D, Southwick, SM, Soufer, R, Charney, DS (1999 b). Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study. Biological Psychiatry 45, 806–816.CrossRefGoogle ScholarPubMed
Bremner, JD, Vermetten, E, Vythilingam, M, Afzal, N, Schmahl, C, Elzinga, B, Charney, DS (2004). Neural correlates of the classic color and emotional Stroop in women with abuse-related posttraumatic stress disorder. Biological Psychiatry 55, 612–620.Google Scholar
Brett, M, Anton, J-L, Valabreque, R, Poline, J-B (2002). Region of interest analysis using an SPM toolbox [Abstract]. NeuroImage 16. (Available on CDROM.)Google Scholar
Britton, JC, Phan, KL, Taylor, SF, Fig, LM, Liberzon, I (2005). Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery. Biological Psychiatry 57, 832–840.CrossRefGoogle ScholarPubMed
Damasio, AR, Grabowski, TJ, Bechara, A, Damasio, H, Ponto, LLB, Parvizi, J, Hichwa, RD (2000). Subcortical and cortical brain activity during the feeling of self-generated emotions. Nature Neuroscience 3, 1049–1056.Google Scholar
Derogatis, LR (1983). SCL-90-R: Administration, Scoring, and Procedures Manual – II for the Revised Version. Clinical Psychometric Research: Townson, MD.Google Scholar
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 1476–1488.Google Scholar
First, M, Spitzer, R, Gibbon, M, Williams, J (1995). Structured Clinical Interview for DSM-IV. Biometrics Research Department, New York State Psychiatric Institute: New York.Google Scholar
Francati, V, Vermetten, E, Bremner, JD (2007). Functional neuroimaging studies in posttraumatic stress disorder: review of current methods and findings. Depression and Anxiety 24, 202–218.CrossRefGoogle ScholarPubMed
Friston, KJ, Frith, CD, Liddle, PF, Frackowiak, RS (1991). Comparing functional (PET) images: the assessment of significant change. Journal of Cerebral Blood Flow and Metabolism 11, 690–699.Google Scholar
Hou, C, Liu, J, Wang, K, Li, L, Liang, M, He, Z, Liu, Y, Zhang, Y, Li, W, Jiang, T (2007). Brain responses to symptom provocation and trauma-related short-term memory recall in coal mining accident survivors with acute severe PTSD. Brain Research 1144, 165–174.Google Scholar
Kemp, AH, Felmingham, K, Das, P, Hughes, G, Peduto, AS, Bryant, RA, Williams, LM (2007). Influence of comorbid depression on fear in posttraumatic stress disorder: an fMRI study. Psychiatry Research 155, 265–269.Google Scholar
Kim, MJ, Chey, J, Chung, A, Bae, S, Khang, H, Ham, B, Yoon, SJ, Jeong, DU, Lyoo, IK (2008). Diminished rostral anterior cingulate activity in response to threat-related events in posttraumatic stress disorder. Journal of Psychiatric Research 42, 268–277.CrossRefGoogle ScholarPubMed
Lane, RD, Reiman, EM, Ahern, GL, Schwartz, GE, Davidson, RJ (1997). Neuroanatomical correlates of happiness, sadness, and disgust. American Journal of Psychiatry 154, 926–933.Google Scholar
Lanius, RA, Frewen, PA, Girotti, M, Neufeld, RW, Stevens, TK, Densmore, M (2007). Neural correlates of trauma script-imagery in posttraumatic stress disorder with and without comorbid major depression: a functional MRI investigation. Psychiatry Research 155, 45–56.Google Scholar
Lanius, RA, Williamson, PC, Densmore, M, Boksman, K, Gupta, MA, Neufeld, RW, Gati, JS, Menon, RS (2001). Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. American Journal of Psychiatry 158, 1920–1922.CrossRefGoogle ScholarPubMed
Lanius, RA, Williamson, PC, Hopper, J, Densmore, M, Boksman, K, Gupta, MA, Neufeld, RWJ, Gati, JS, Menon, RS (2003). Recall of emotional states in posttraumatic stress disorder: an fMRI investigation. Biological Psychiatry 53, 204–210.CrossRefGoogle ScholarPubMed
Liberzon, I, Britton, JC, Phan, KL (2003). Neural correlates of traumatic recall in posttraumatic stress disorder. Stress (Amsterdam, Netherlands) 6, 151–156.Google Scholar
Liberzon, I, Martis, B (2006). Neuroimaging studies of emotional responses in PTSD. Annals of the New York Academy of Sciences 1071, 87–109.CrossRefGoogle ScholarPubMed
Liberzon, I, Sripada, CS (2008). The functional neuroanatomy of PTSD: a critical review. Progress in Brain Research 167, 151–169.Google Scholar
Lindauer, RJ, Booij, J, Habraken, JB, Uylings, HB, Olff, M, Carlier, IV, den Heeten, GJ, van Eck-Smit, BL, Gersons, BP (2004). Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder. Biological Psychiatry 56, 853–861.CrossRefGoogle ScholarPubMed
McTeague, LM, Lang, PJ, Laplante, MC, Cuthbert, BN, Shumen, JR, Bradley, MM (2010). Aversive imagery in posttraumatic stress disorder: trauma recurrence, comorbidity, and physiological reactivity. Biological Psychiatry 67, 346–356.Google Scholar
Milad, MR, Pitman, RK, Ellis, CB, Gold, AL, Shin, LM, Lasko, NB, Zeidan, MA, Handwerger, K, Orr, SP, Rauch, SL (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological Psychiatry 66, 1075–1082.Google Scholar
Orr, SP, Lasko, NB, Metzger, LJ, Berry, NJ, Ahern, CE, Pitman, RK (1998). Psychophysiologic assessment of women with posttraumatic stress disorder resulting from childhood sexual abuse. Journal of Consulting and Clinical Psychology 66, 906–913.Google Scholar
Phan, KL, Britton, JC, Taylor, SF, Fig, LM, Liberzon, I (2006). Corticolimbic blood flow during nontraumatic emotional processing in posttraumatic stress disorder. Archives of General Psychiatry 63, 184–192.CrossRefGoogle ScholarPubMed
Phan, KL, Wager, T, Taylor, SF, Liberzon, I (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16, 331–348.CrossRefGoogle ScholarPubMed
Pitman, RK, Gilbertson, MW, Gurvits, TV, May, FS, Lasko, NB, Metzger, LJ, Shenton, ME, Yehuda, R, Orr, SP; Harvard/VA PTSD Twin Study Investigators (2006). Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure. Annals of the New York Academy of Sciences 1071, 242–254.CrossRefGoogle Scholar
Pitman, RK, Orr, SP, Forgue, DF, Altman, B, de Jong, JB, Herz, LR (1990). Psychophysiologic responses to combat imagery of Vietnam veterans with posttraumatic stress disorder versus other anxiety disorders. Journal of Abnormal Psychology 99, 49–54.CrossRefGoogle ScholarPubMed
Pitman, RK, Orr, SP, Forgue, DF, de Jong, JB, Claiborn, JM (1987). Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Archives of General Psychiatry 44, 970–975.Google Scholar
Radley, JJ, Sisti, HM, Hao, J, Rocher, AB, McCall, T, Hof, PR, McEwen, BS, Morrison, JH (2004). Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125, 1–6.Google Scholar
Rauch, SL, Shin, LM, Phelps, EA (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research – past, present, and future. Biological Psychiatry 60, 376–382.CrossRefGoogle ScholarPubMed
Rauch, SL, van der Kolk, BA, Fisler, RE, Alpert, NM, Orr, SP, Savage, CR, Fischman, AJ, Jenike, MA, Pitman, RK (1996). A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Archives of General Psychiatry 53, 380–387.CrossRefGoogle ScholarPubMed
Rauch, SL, Whalen, PJ, Shin, LM, McInerney, SC, Macklin, ML, Lasko, NB, Orr, SP, Pitman, RK (2000). Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biological Psychiatry 47, 769–776.CrossRefGoogle ScholarPubMed
Reiman, EM, Lane, RD, Ahern, GL, Schwartz, GE, Davidson, RJ, Friston, KJ, Yun, LS, Chen, K (1997). Neuroanatomical correlates of externally and internally generated human emotion. American Journal of Psychiatry 154, 918–925.Google Scholar
Shin, LM, Liberzon, I (2010). The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35, 169–191.Google Scholar
Shin, LM, McNally, RJ, Kosslyn, SM, Thompson, WL, Rauch, SL, Alpert, NM, Metzger, LJ, Lasko, NB, Orr, SP, Pitman, RK (1999). Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. American Journal of Psychiatry 156, 575–584.Google Scholar
Shin, LM, Orr, SP, Carson, MA, Rauch, SL, Macklin, ML, Lasko, NB, Peters, PM, Metzger, LJ, Dougherty, DD, Cannistraro, PA, Alpert, NM, Fischman, AJ, Pitman, RK (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Archives of General Psychiatry 61, 168–176.Google Scholar
Shin, LM, Rauch, SL, Pitman, RK (2006). Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Annals of the New York Academy of Sciences 1071, 67–79.CrossRefGoogle ScholarPubMed
Shin, LM, Whalen, PJ, Pitman, RK, Bush, G, Macklin, ML, Lasko, NB, Orr, SP, McInerney, SC, Rauch, SL (2001). An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biological Psychiatry 50, 932–942.CrossRefGoogle ScholarPubMed
Shin, LM, Wright, CI, Cannistraro, PA, Wedig, MM, McMullin, K, Martis, B, Macklin, ML, Lasko, NB, Cavanagh, SR, Krangel, TS, Orr, SP, Pitman, RK, Whalen, PJ, Rauch, SL (2005). A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry 62, 273–281.CrossRefGoogle ScholarPubMed
Weathers, FW, Keane, TM, Davidson, JR (2001). Clinician-administered PTSD scale: a review of the first ten years of research. Depression and Anxiety 13, 132–156.CrossRefGoogle Scholar
Williams, LM, Kemp, AH, Felmingham, K, Barton, M, Olivieri, G, Peduto, A, Gordon, E, Bryant, RA (2006). Trauma modulates amygdala and medial prefrontal responses to consciously attended fear. NeuroImage 29, 347–357.CrossRefGoogle ScholarPubMed
Yang, P, Wu, MT, Hsu, CC, Ker, JH (2004). Evidence of early neurobiological alternations in adolescents with posttraumatic stress disorder: a functional MRI study. Neuroscience Letters 370, 13–18.Google Scholar