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

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.

An fMRI study of anterior cingulate function in posttraumatic stress disorder.

BACKGROUND: Several recent neuroimaging studies have provided data consistent with functional abnormalities in anterior cingulate cortex in posttraumatic stress disorder (PTSD). In our study, we implemented a cognitive activation paradigm to test the functional integrity of anterior cingulate cortex in PTSD. METHODS: Eight Vietnam combat veterans with PTSD (PTSD Group) and eight Vietnam combat veterans without PTSD (non-PTSD Group) underwent functional magnetic resonance imaging (fMRI) while performing the Emotional Counting Stroop. In separate conditions, subjects counted the number of combat-related (Combat), generally negative (General Negative), and neutral (Neutral) words presented on a screen and pressed a button indicating their response. RESULTS: In the Combat versus General Negative comparison, the non-PTSD group exhibited significant fMRI blood oxygenation level-dependent signal increases in rostral anterior cingulate cortex, but the PTSD group did not. CONCLUSIONS: These findings suggest a diminished response in rostral anterior cingulate cortex in the presence of emotionally relevant stimuli in PTSD. We speculate that diminished recruitment of this region in PTSD may, in part, mediate symptoms such as distress and arousal upon exposure to reminders of trauma.

Emotion- and intrusion-based reasoning in Vietnam veterans with and without chronic posttraumatic stress disorder.

Patients suffering from anxiety disorders other than posttraumatic stress disorder (PTSD) interpret anxiety responses themselves as evidence that threat is impending: "if anxiety, then threat" (Arntz, Rauner, & van den Hout, 1995, Behaviour Research and Therapy, 33, 917-925). This "emotion-based reasoning" (ER) may render a disorder self-perpetuating. Analogous to ER, danger might also be inferred from the presence of intrusions: "intrusion-based reasoning" (IR). The aims of this study were to test whether ER and IR are involved in chronic PTSD. Vietnam combat veterans with or without PTSD or other anxiety disorders rated perceived danger of brief scenarios in which information about objective danger (danger vs safety) and response (anxiety/intrusions vs non-distressing emotion) was systematically varied. Two series were administered: ER-scenarios were non-specific for PTSD and IR-scenarios were specific for PTSD. Relative to control participants, PTSD patients engaged in both ER and IR: whereas veterans without PTSD inferred the danger of scenarios from objective stimulus information, veterans with PTSD also inferred danger from the presence of anxiety or intrusions. Further analyses showed that these effects were largely mediated by perceived uncontrollability.

Activation of anterior paralimbic structures during guilt-related script-driven imagery.

BACKGROUND: Several recent neuroimaging studies have examined the neuroanatomical correlates of normal emotional states, such as happiness, sadness, fear, anger, anxiety, and disgust; however, no previous study has examined the emotional state of guilt. METHODS: In the current study, we used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the transient emotional experience of guilt in eight healthy male participants. In the Guilt condition, participants recalled and imagined participating in a personal event involving the most guilt they had ever experienced. In the Neutral condition, participants recalled and imagined participating in an emotionally neutral personal event. RESULTS: In the Guilt versus Neutral comparison, rCBF increases occurred in anterior paralimbic regions of the brain: bilateral anterior temporal poles, anterior cingulate gyrus, and left anterior insular cortex/inferior frontal gyrus. CONCLUSIONS: These results, along with those of previous studies, are consistent with the notion that anterior paralimbic regions of the brain mediate negative emotional states in healthy individuals.

De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder.

Differential conditioning was assessed in 15 medication-free individuals meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria for chronic posttraumatic stress disorder (PTSD) and 18 trauma-exposed individuals who never developed PTSD (non-PTSD). Conditioned stimuli (CSs) were colored circles, and the unconditioned stimulus was a "highly annoying" electrical stimulus. Individuals with PTSD had higher resting heart rate (HR) and skin conductance (SC) levels and produced larger SC orienting responses. During conditioning, the PTSD group showed larger differential SC, HR, and electromyogram responses to the reinforced vs. nonreinforced stimuli (CS+ vs. CS-) compared with the non-PTSD group. Only PTSD participants continued to show differential SC responses to CS+ vs. CS- during extinction trials. Results suggest that individuals with PTSD have higher sympathetic nervous system arousal at the time of conditioning and are more conditionable than trauma-exposed individuals without PTSD.

Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study.

BACKGROUND: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli. METHODS: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD. RESULTS: The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces. CONCLUSIONS: Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the "top-down" influences of medial frontal cortex.

Neurologic soft signs in chronic posttraumatic stress disorder.

BACKGROUND: Subtle neurologic impairment has been reported in several mental disorders. The goals of the present study were to evaluate neurologic status in patients of both sexes with chronic posttraumatic stress disorder (PTSD) from different traumatic experiences. METHODS: Twenty-one adult women who were sexually abused as children (12 with PTSD, 9 without) and 38 male Vietnam War combat veterans (23 with PTSD, 15 without) underwent examination for 41 neurologic soft signs, which were scored by the examiner as well as a blind rater observing videotapes. Subject history was obtained with special attention to neurodevelopmental problems. Psychometrics included the Wender Utah Rating Scale for symptoms of childhood attention-deficit/hyperactivity disorder and the Michigan Alcoholism Screening Test. Veterans also completed the Combat Exposure Scale and subtests of the Wechsler Adult Intelligence Scale-Revised. RESULTS: Average neurologic soft sign scores (interrater reliability = 0.74) of women with PTSD owing to sexual abuse in childhood (mean [SD], 0.77 [0.32]) and veteran men (0.72 [0.20]) with combat-related PTSD were comparable and significantly (P<.001) higher than those of women sexually abused as children (0.42 [0.10]) and combat veteran men (0.43 [0.17]) without PTSD. This effect could not be explained by a history of alcoholism or head injury. Subjects with PTSD reported more neurodevelopmental problems and more childhood attention-deficit/hyperactivity disorder symptoms and had lower IQs, all of which were significantly correlated with neurologic soft signs. CONCLUSION: Neurologic compromise is evident from subject history and findings from physical examination in both women and men with chronic PTSD who had experienced different kinds of traumatic events in childhood and adulthood.

Five-year follow-up study of eye movement desensitization and reprocessing therapy for combat-related posttraumatic stress disorder.

This study reports the results of a 5-year follow-up evaluation of 13 Vietnam combat veterans with chronic posttraumatic stress disorder (PTSD) who participated in a study of eye movement desensitization and reprocessing (EMDR) therapy previously reported in this journal. Pretreatment and follow-up psychometric outcome measures were compared with those of a demographically matched control group of 14 combat veterans with chronic PTSD who did not receive EMDR. Analysis of variance showed that the modest to moderate therapeutic benefits that were manifest immediately following EMDR were lost at the 5-year follow-up evaluation, and there was an overall worsening of PTSD symptomatology over the 5-year period in both EMDR-treated and nontreated control subjects.

Neural activation during sexual and competitive arousal in healthy men.

To investigate the mediating neuroanatomy of positively valenced arousal, we used script-driven imagery in conjunction with positron emission tomography to measure relative regional cerebral blood flow (rCBF) during sexual and competitive arousal, as well as neutral comparison states. Subjects were eight healthy right-handed men. Psychophysiologic responses and subjective ratings confirmed that the desired state manipulations were achieved. Statistical parametric mapping revealed similar patterns of rCBF changes for both positively valenced arousal conditions: increases were found within anterior cingulate and anterior temporal cortex as well as the ventral globus pallidus; decreases were found within widespread heteromodal association areas. These results complement findings from studies of other normal and pathological emotional states, and provide new insights regarding the neural substrates of pleasurable arousal in healthy men.

Anger in healthy men: a PET study using script-driven imagery.

BACKGROUND: An understanding of the neurobiological basis of normal emotional processing is useful in formulating hypotheses regarding the pathophysiology of psychiatric illnesses. METHODS: This study examined the mediating functional neuroanatomy of anger in eight healthy men. Narrative scripts were developed from autobiographical information to induce anger and neutral states. The subjects imagined the content of the narrative scripts to induce anger during positron emission tomography to measure normalized regional cerebral blood flow (rCBF). Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Statistical parametric maps were constructed to reflect the Anger versus Neutral state contrast. RESULTS: Anger was associated with activation of the left orbitofrontal cortex, right anterior cingulate cortex affective division, and bilateral anterior temporal poles. CONCLUSIONS: These results suggest that the subjective experience of anger is associated with rCBF increases in anterior paralimbic regions of the brain.

Lower precombat intelligence is a risk factor for posttraumatic stress disorder.

The authors examined the relation between intelligence and posttraumatic stress disorder (PTSD) by studying the association among precombat intelligence, current intelligence, and self-reported PTSD symptoms. Military aptitude test results were obtained in 59 PTSD and 31 non-PTSD Vietnam combat veterans who had undergone a psychodiagnostic interview and current intelligence testing. People with lower precombat intelligence were more likely to develop PTSD symptoms as assessed by the Clinician-Administered PTSD Scale even after adjustment for extent of combat exposure. The association between current intelligence and PTSD was no longer significant after adjusting for precombat intelligence. These results suggest that lower pretrauma intelligence increases risk for developing PTSD symptoms, not that PTSD lowers performance on intelligence tests.

Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.

BACKGROUND: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.

Emotional processing during eye movement desensitization and reprocessing therapy of Vietnam veterans with chronic posttraumatic stress disorder.

This study examined emotional processing and outcome in 17 Vietnam veterans with chronic posttraumatic stress disorder (PTSD) who underwent eye movement desensitization and reprocessing (EMDR) therapy, with and without the eye movement component, in a crossover design. Results supported the occurrence of partial emotional processing, but there were no differences in its extent in the eye-movement versus eyes-fixed conditions. Therapy produced a modest to moderate overall improvement, mostly on the impact of Event Scale. There was slightly more improvement in the eyes-fixed than eye-movement condition. There was little association between the extent of emotional processing and therapeutic outcome. In our hands, EMDR was at least as efficacious for combat-related PTSD as imaginal flooding proved to be in a previous study, and was better tolerated by subjects. However, results suggest that eye movements do not play a significant role in processing of traumatic information in EMDR and that factors other than eye movements are responsible for EMDR's therapeutic effect.

Emotional processing and outcome of imaginal flooding therapy in Vietnam veterans with chronic posttraumatic stress disorder.

This study examined emotional processing and outcome in 20 Vietnam veterans with chronic posttraumatic stress disorder (PTSD) who underwent imaginal flooding therapy. Results supported the occurrence of emotional processing, as manifest in significant activation, within-session habituation, and partial across-session habituation of physiologic and self-reported process variables. The flooding therapy produced only modest overall improvement, which was statistically significant for avoidance symptomatology measured by the impact of Events Scale (IOES) and number of intrusions per day recorded by the subject in a log. Symptomatic improvement appeared to generalize from a treated to an untreated experience. Heart rate activation during the first flooding session predicted a decrease in daily number of intrusive combat memories across the therapy. Otherwise, there was little association between extent of emotional processing and therapeutic outcome. The results provide limited support for the notion that mobilization of psychophysiologic arousal during exposure therapy predicts improvement.

Autobiographical memory disturbance in combat-related posttraumatic stress disorder.

Vietnam combat veterans with (n = 19) and without (n = 13) posttraumatic stress disorder (PTSD) participated in an autobiographical memory experiment in which they attempted to retrieve specific personal memories exemplifying traits denoted by positive (e.g. loyal) and negative (e.g. guilty) cue words. Veterans with PTSD exhibited difficulties retrieving specific autobiographical memories, especially in response to positive trait cue words. These deficits were especially pronounced in PTSD Ss who wore Vietnam War regalia (e.g. medals, fatigues) to the laboratory. Regalia-wearing PTSD Ss disproportionately retrieved memories from the Vietnam War, unlike other Ss who retrieved relatively recent memories. Wearing regalia in daily life may be emblematic of psychological fixation to a war fought more than two decades ago. Difficulties remembering one's past may underlie difficulties envisioning one's future, as reflected in the PTSD symptom of 'future foreshortening', and difficulties using memory specifically may also hamper efforts to solve personal problems.

Pre-Vietnam contents of posttraumatic stress disorder veterans' service medical and personnel records.

We reviewed the pre-Vietnam contents of the service medical and personnel records of 250 Vietnam combat veterans, in an attempt to identify factors predisposing to the development of posttraumatic stress disorder (PTSD). PTSD and non-PTSD veterans did not differ significantly on self-reported medical history items, sick call visits, or military efficiency and conduct ratings. There were trends for PTSD veterans to have lower arithmetic aptitude, more self-reported school difficulties, and (paradoxically) lower pulse rate at military induction.

Psychiatric complications during flooding therapy for posttraumatic stress disorder.

The authors use six case vignettes to illustrate underrecognized complications occurring during flooding therapy for posttraumatic stress disorder (PTSD), including exacerbation of depression, relapse of alcoholism, and precipitation of panic disorder. A common denominator to the majority of these cases appears to be the mobilization of negative posttrauma appraisal, accompanied by shame, guilt, and anger. The authors suggest that flooding may not be helpful for these negative emotions in the manner that it is for anxiety. Suggestions for preventing and treating complications of flooding therapy for PTSD include employing more cognitive forms of therapy in cases at risk; supporting abstinence from alcohol and other substances; providing adjunctive pharmacologic treatment as indicated, e.g., tricyclics for depression or panic; and providing long-term follow-up.

Prevalence of posttraumatic stress disorder in wounded Vietnam veterans.

Of 156 wounded Vietnam veterans evaluated for posttraumatic stress disorder (PTSD) by a questionnaire and a diagnostic interview in selected cases, 40% had a definite or probable lifetime diagnosis of PTSD. Of the 27 interviewed patients with lifetime PTSD, 81% currently met the PTSD criteria.