Michael L. Macklin

Regional Cerebral Blood Flow in the Amygdala and Medial Prefrontal Cortex During Traumatic Imagery in Male and Female Vietnam Veterans With PTSD

CONTEXT Theoretical neuroanatomic models of posttraumatic stress disorder (PTSD) and the results of previous neuroimaging studies of PTSD highlight the potential importance of the amygdala and medial prefrontal regions in this disorder. However, the functional relationship between these brain regions in PTSD has not been directly examined. OBJECTIVE To examine the relationship between the amygdala and medial prefrontal regions during symptom provocation in male combat veterans (MCVs) and female nurse veterans (FNVs) with PTSD. DESIGN Case-control study. SETTING Academic medical center. PARTICIPANTS Volunteer sample of 17 (7 men and 10 women) Vietnam veterans with PTSD (PTSD group) and 19 (9 men and 10 women) Vietnam veterans without PTSD (control group). MAIN OUTCOME MEASURES We used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the recollection of personal traumatic and neutral events. Psychophysiologic and emotional self-report data also were obtained to confirm the intended effects of script-driven imagery. RESULTS The PTSD group exhibited rCBF decreases in medial frontal gyrus in the traumatic vs neutral comparison. When this comparison was conducted separately by subgroup, MCVs and FNVs with PTSD exhibited these medial frontal gyrus decreases. Only MCVs exhibited rCBF increases in the left amygdala. However, for both subgroups with PTSD, rCBF changes in medial frontal gyrus were inversely correlated with rCBF changes in the left amygdala and the right amygdala/periamygdaloid cortex. Furthermore, in the traumatic condition, for both subgroups with PTSD, symptom severity was positively related to rCBF in the right amygdala and negatively related to rCBF in medial frontal gyrus. CONCLUSIONS These results suggest a reciprocal relationship between medial prefrontal cortex and amygdala function in PTSD and opposing associations between activity in these regions and symptom severity consistent with current functional neuroanatomic models of this disorder.

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.

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.

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.

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 EMDRs therapeutic effect.

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.

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.

Psychophysiological Responding During Script-Driven Imagery in People Reporting Abduction by Space Aliens

Is recollection of highly improbable traumatic experiences accompanied by psychophysiological responses indicative of intense emotion? To investigate this issue, we measured heart rate, skin conductance, and left lateral frontalis electro-myographic responses in individuals who reported having been abducted by space aliens. Recordings of these participants were made during script-driven imagery of their reported alien encounters and of other stressful, positive, and neutral experiences they reported. We also measured the psychophysiological responses of control participants while they heard the scripts of the abductees. We predicted that if “memories” of alien abduction function like highly stressful memories, then psycho-physiological reactivity to the abduction and stressful scripts would be greater than reactivity to the positive and neutral scripts, and this effect would be more pronounced among abductees than among control participants. Contrast analyses confirmed this prediction for all three physiological measures (ps < .05). Therefore, belief that one has been traumatized may generate emotional responses similar to those provoked by recollection of trauma (e.g., combat).

Resting Metabolic Activity in the Cingulate Cortex and Vulnerability to Posttraumatic Stress Disorder

CONTEXT Recent neuroimaging research has revealed functional abnormalities in the anterior cingulate cortex, amygdala, and hippocampus in individuals with posttraumatic stress disorder (PTSD). OBJECTIVE To determine whether resting functional abnormalities found in PTSD are acquired characteristics or familial risk factors. DESIGN Cross-sectional design including identical twins discordant for trauma exposure. SETTING Academic medical center. PARTICIPANTS Combat-exposed veterans with PTSD (n = 14) and their identical co-twins not exposed to combat (n = 14) as well as combat-exposed veterans without PTSD (n = 19) and their identical co-twins not exposed to combat (n = 19). MAIN OUTCOME MEASURES We used positron emission tomography and fluorodeoxyglucose 18 to examine resting regional cerebral metabolic rate for glucose (rCMRglu). RESULTS Veterans with PTSD and their co-twins had significantly higher resting rCMRglu in the dorsal anterior cingulate cortex/midcingulate cortex (dACC/MCC) compared with veterans without PTSD and their co-twins. Resting rCMRglu in the dACC/MCC in unexposed co-twins was positively correlated with combat exposure severity, PTSD symptom severity, and alcohol use in their exposed twins. CONCLUSIONS Enhanced resting metabolic activity in the dACC/MCC appears to represent a familial risk factor for developing PTSD after exposure to psychological trauma.

Probing reward function in post-traumatic stress disorder with beautiful facial images.

Reward dysfunction may be implicated in post-traumatic stress disorder (PTSD). This study applied a behavioral probe, known to activate brain reward regions, to subjects with PTSD. Male heterosexual Vietnam veterans with (n = 12) or without (n = 11) current PTSD were administered two tasks: (a) key pressing to change the viewing time of average or beautiful female or male facial images, and (b) rating the attractiveness of these images. There were no significant group differences in the attractiveness ratings. However, PTSD patients expended less effort to extend the viewing time of the beautiful female faces. These findings suggest a reward deficit in PTSD.