Elsevier

Biological Psychiatry

Volume 45, Issue 7, 1 April 1999, Pages 817-826
Biological Psychiatry

Original Articles
Brain activation in PTSD in response to trauma-related stimuli

https://doi.org/10.1016/S0006-3223(98)00246-7Get rights and content

Abstract

Background: Repetitive recall of traumatic memories and chronic intermittent hyperarousal are characteristic of posttraumatic stress disorder (PTSD). Hyperarousal and memory dysfunction implicates “limbic” brain regions, including the amygdaloid complex, hippocampal formation, and limbic cortex, such as the orbitofrontal and anterior cingulate areas. To investigate the neurobiologic role of these brain regions in PTSD, we measured regional cerebral blood flow in PTSD with single photon emission computerized tomography (SPECT) during a symptom provocation paradigm.

Methods: Fourteen Vietnam veterans with PTSD, 11 combat control subjects, and 14 normal control subjects were studied with [99mTc]HMPAO in two sessions 48 hours apart: one session after exposure to white noise and the other following exposure to combat sounds. Skin conductance, heart rate, and subjective experience were recorded at the time of the studies.

Results: Activation for all three groups occurred in the anterior cingulate/middle prefrontal gyrus. Activation in the region of the left amygdala/nucleus accumbens was found in PTSD patients only. Deactivation was found in all three groups in the left retrosplenial region.

Conclusions: These findings implicate regions of the “limbic” brain, which may mediate the response to aversive stimuli in healthy individuals and in patients suffering from PTSD.

Introduction

Neurobiologic research in posttraumatic stress disorder (PTSD) has been focused on the aberrant regulation of the sympatoadrenal system and the hypothalamo–pituitary-adrenal (HPA) axis Kosten et al 1987, Murburg 1994, Yehuda et al 1993. While much has been learned about neuroendocrine and psychophysiologic aspects of the stress response in this condition, the neuroanatomic underpinning of PTSD symptomatology remains unknown. The characteristic symptoms of PTSD, such as intrusive memories, recurrent dreams, and “flashbacks” of the traumatic event (American Psychiatric Association 1987) suggest abnormalities in the processing of memory—memory associated with traumatic, emotional material. Thus, investigations of the neurobiology of PTSD should logically seek to understand the neuroanatomic regions involved in memory and emotional regulation, in addition to the interaction of these systems with the CNS stress response.

The so-called “limbic” regions of the brain have long been associated with both memory and emotion. A broad concept, the limbic brain generally refers to amygdala, hippocampal formation, hypothalamus, thalamus, and nearby “paralimbic” cortex, such as the anterior cingulate cortex, orbitofrontal cortex insula, and temporal poles Mesulam 1985, Nauta 1982. Given the role of aberrant, intrusive, emotional memory in PTSD symptomatology, the limbic brain defines an obvious target of investigation; however, evidence linking these structures to specific PTSD symptoms is just emerging. Recent findings of structural abnormalities in the hippocampus of PTSD patients Bremner et al 1995, Bremner et al 1997b, Gurvits et al 1996 support a strategy of investigating the functional integrity of these brain regions in PTSD.

Symptom provocation paradigms in combination with functional neuroimaging provide an important tool to visualize neuroanatomic correlates of psychiatric symptoms. Experimentally controlled exposure to trauma-related stimuli elicits exaggerated autonomic responses in PTSD Blanchard et al 1991, Pitman 1987. Similarly, by studying regional cerebral blood flow (rCBF) in PTSD patients during exposure to a trauma-specific narrative and a narrative describing neutral events, Rauch and colleagues found activation in the right amygdala, anterior cingulate cortex, and several other cortical areas (Rauch et al 1996). However, in the absence of a control group, the specificity of these findings to PTSD could not be ascertained. In a somewhat different imagery paradigm, Shin and co-workers found activation in the right amygdala of 7 PTSD patients (Shin et al 1997), but only during the mental imagery and not during the perception of combat images. As Shin and colleagues pointed out, these results are difficult to interpret. They also reported that during imagery of combat material, PTSD subjects activated the ventral anterior cingulate cortex (ACC) whereas control subjects recruited the superior ACC, relative to perception of combat material. Therefore, while preliminary findings support the involvement of limbic structures in PTSD symptom generation, questions remain about the extent, the diagnostic specificity, and the functional role of these findings.

To address some of these questions, we performed single photon emission computerized tomography (SPECT) scanning of PTSD patients and two control groups to measure regional cerebral perfusion in two settings: 1) immediately after exposure to a provocative stimulus; and 2) after a nonprovocative, control stimulus. As the provocative stimulus, we used combat sounds (e.g., helicopter sounds, small arm fire, etc.) which allowed the generation of images from the patient’s own experience. For the nonprovocative stimulus, we presented the subjects with simple, white noise. During both conditions, we also simultaneously recorded psychophysiologic responses. Given the functional role of limbic and paralimbic cortex, we tested the hypothesis that the PTSD patients would show excitation of these regions in response to traumatic stimuli.

Section snippets

Subjects

Thirty nine subjects were recruited using advertisements within the hospital, local newspapers, churches, and veterans magazines. Fourteen Vietnam veterans with posttraumatic stress disorder, 11 Vietnam veterans without PTSD (combat controls), and 14 nonveteran male control subjects participated in this study (Table 1). The diagnosis of PTSD was established according to DSM-III-R criteria using the Structured Clinical Interview for DSM-III (SCID; Spitzer and et al 1990), administered by a

Psychophysiology and subjective distress

PTSD subjects had significantly higher heart rate (repeated measure ANOVA effect of group, F [2,28] = 3.48, p < 0.05), higher skin conductance (trend level, F [2,31] = 2.95, p < 0.07), and subjective distress (F [2,28] = 2.97, p < 0.06), as compared to either control group. There was also a significant main effect of condition (combat sounds vs white noise) on skin conductance (F [1,31] = 18.8, p < 0.001) and subjective distress (F [1,31] = 36.8, p < 0.001). PTSD patients had significantly

Discussion

During exposure to traumatic stimuli, the PTSD patients demonstrated the characteristic exaggerated psychological and psychophysiologic responses, similar to those reported in the literature Pitman 1987, Pitman et al 1990. We also found that the PTSD patients increased rCBF in relevant areas of the limbic brain in the vicinity of the left amygdala/nucleus accumbens. No comparable activation was found in either control group. All three groups exhibited a response in the anterior cingulate/medial

Acknowledgements

This research was supported by Veterans Affairs Mental Health and Behavioral Sciences Research Advisory Group grant to Dr. Fig.

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