Elsevier

NeuroImage

Volume 26, Issue 3, 1 July 2005, Pages 813-821
NeuroImage

Parahippocampal activation evoked by masked traumatic images in posttraumatic stress disorder: A functional MRI study

https://doi.org/10.1016/j.neuroimage.2005.02.032Get rights and content

Abstract

Posttraumatic stress disorder (PTSD) has been widely studied, but its neural mechanism is still unclear. The purpose of this study is to identify dysfunctional areas in PTSD throughout the whole brain to help to elucidate the neural mechanisms of PTSD. Sixteen patients with PTSD and sixteen healthy controls participated in this study. Traumatic images under perceptual threshold including scenes of earthquakes, traffic accidents, ambulances, emergency rooms, and crimes were presented to the participants, and brain activation was measured using functional MRI. Functional brain images of both groups were evaluated with random effect analysis for the whole brain. In the control group, activation in the ventral frontoparietal areas correlated significantly with presentation of the masked traumatic stimuli. In the PTSD group, activation was not observed in these areas, but significant activation correlated with the masked traumatic stimuli in the parahippocampal region including the left parahippocampal gyrus and tail of the left hippocampus. These results suggest that in PTSD patients activation in the ventral frontoparietal network associated with visual attention processing is attenuated, while the left hippocampal area associated with episodic and autobiographical memory is abnormally easily activated. This pattern of activation corresponds well to the clinical characteristics of PTSD, in which even slight traumatic stimuli tend to induce intrusive recollection or flashbacks, despite a general decrease in attention and ability to concentrate.

Introduction

Posttraumatic stress disorder (PTSD) is a psychiatric condition characterized by a variety of symptoms associated with memory and emotion, which arises after experiencing or witnessing traumatic life-threatening events. The symptoms of PTSD include sleep disturbance, impaired memory, depression, tendency to be easily startled, and re-experiencing, which can result in decreased social and occupational function. PTSD has attracted wide attention from a mental health care perspective for victims of disasters, accidents, terrorism, and war. However, the underlying neural mechanism of the disorder is still unclear, and investigation of the pathology of PTSD and the establishment of objective diagnostic parameters are important issues.

Previous brain volumetry studies have repeatedly shown smaller hippocampal volume in patients with PTSD (Bremner et al., 1995, Bremner et al., 1997, Gilbertson et al., 2002, Gurvits et al., 1996, Stein et al., 1997). Pitman and colleagues recently reported that PTSD patients exhibited selectively decreased anterior cingulate cortex and subcallosal cortex volumes (Rauch et al., 2003); furthermore, the presence of abnormally large cavum septum pellucidum is a familial vulnerability factor for PTSD (May et al., 2004). Concerning the relationship between hippocampal structure and function, Bremner et al. co-evaluated the structural volume of the hippocampus using MRI, and brain function using PET during hippocampal-based verbal declarative memory tasks, and observed both volume reduction and reduced function in the hippocampus in PTSD patients, compared with non-PTSD subjects (Bremner et al., 2003).

Shin et al. (2004) observed an abnormal rCBF response in the hippocampus of firefighters with PTSD during explicit recollection of nonemotional material. In the PTSD group, symptom severity was positively associated with rCBF in hippocampus and the parahippocampal gyrus. The PTSD group also had significantly smaller right (and a trend for smaller left) hippocampal volumes than the control group.

Brain functional imaging studies of symptom provocation in PTSD have been repeatedly reported, but the results are for the most part inconsistent. Bremner et al. (1999) presented images and sounds of combat scenes to 10 Vietnam combat veterans with PTSD and to 10 veterans without PTSD and performed [15O]-H2O PET measurements. Relative to controls, the PTSD group showed decreased blood flow in the medial prefrontal cortex, middle temporal gyrus, and frontal cingulate gyrus and increased blood flow in the posterior cingulate gyrus and left precentral gyrus. Shin et al. (1999) performed CO2 PET during narration of a traumatic experience with 8 females with PTSD who were victims of sexual abuse and 8 control females who had not suffered abuse. Blood flow increased in the orbitofrontal cortex and anterior temporal pole in both groups, but the increase was more marked in the PTSD group. In addition, compared with the healthy group, the PTSD group showed decreased blood flow in a wide area in the frontal, temporal, and occipital lobes. Lanius et al. (2001) performed functional MRI during narration of a traumatic experience to 9 PTSD patients and 9 non-PTSD controls. Compared with the control group, the PTSD group showed significantly decreased activity in the thalamus, anterior cingulate gyrus, and medial prefrontal cortex.

Rauch et al. (2000) performed functional MRI during presentation of masked visual stimuli to 8 Vietnam combat veterans with PTSD and 8 veterans without PTSD. As visual stimuli, frightening facial expressions masked by neutral facial expressions were presented using the following method. An image of a frightening face was presented to the subjects for too short a duration to be recognized (0.033 s), and immediately after this, an image of a neutral face was presented. Compared with the non-PTSD control group, the PTSD group showed marked activation of the amygdala while observing frightening images. Hendler et al. (2003) presented combat-related images for a very short duration (0.020–0.080 s) masked by mosaic images to 10 combat veterans with PTSD and 10 veterans without PTSD and observed significantly more marked activation of the visual cortex in the PTSD group than in the non-PTSD group.

The studies by Rauch et al. and Hendler et al. adopted a masked stimulus presentation method in which visual stimuli are presented for a very short period, such that subjects cannot recognize the image. There have been many studies on masked visual stimulation for non-PTSD subjects that have examined skin conductance responses (SCR) (Groeger, 1984), event-related potentials (Brazdil et al., 2001), and brain functional images (Sheline et al., 2001, Whalen et al., 1998). The minimum stimulus period that induces physiological responses is called the cognition threshold, and this is generally 0.030–0.050 s for visual stimulation.

Brazdil et al. (2001) reported interesting results using intracranial event-related potential measurements. They showed that the brain areas activated during masked visual stimulation are similar to those activated during recognizable visual stimulation but that the extent of the activation during masked stimulation is smaller than that during recognizable stimulation. This led to the conclusion that recognition of visual stimulation depends on an extensive neural network, including the prefrontal area and temporal neocortex activates.

The purpose of the present study is to detect dysfunctional areas common to PTSD in the whole brain at high temporal and spatial resolution and to obtain clues to elucidate the neural mechanisms of PTSD. In previous imaging studies of brain function in PTSD, narrations, photographs, or sounds of traumatic experiences have been directly presented to subjects, and brain activity during stimulation has been measured by PET or SPECT. However, in PTSD patients, one of the major symptoms is marked fear associated with traumatic experience and, therefore, explicit presentation of traumatic stimuli causes excessive distress and is difficult to perform in many subjects. The results of earlier studies have suggested functional abnormalities in the temporal area, occipital area, amygdala, cingulate gyrus, and frontal area during exposure to symptom provocation stimuli, but findings have been inconsistent among the studies.

The disagreement between the results of previous studies may be because excessively strong stimuli induced a variety of different reactions in subjects or because changes in blood flow not directly associated with PTSD symptoms were also detected due to the long scan intervals used in the PET or SPECT measurements. Only the studies by Rauch et al. (2000) and Hendler et al. (2003) avoided explicit presentation of traumatic stimuli. In these studies, masked images were presented for a very short period, which was below the cognition threshold, and measurements were performed by functional MRI with high temporal resolution. However, the regions of interest (ROI) that were examined in these studies were the amygdala and anterior cingulate gyrus or the occipital lobe, and not the whole brain. However, dysfunctions associated with PTSD are not limited to these areas, and studies that examine the whole brain are necessary.

Most previous functional imaging studies of PTSD have used only combat veterans or victims of sexual abuse as PTSD subjects. This limitation of subjects is advantageous regarding subject homogeneity. However, PTSD results from various causes, such as accidents, terrorism, and natural disasters. Hence, the investigation of functional abnormality common to PTSD arising from various causes is also important to elucidate the neural mechanism underlying PTSD.

Section snippets

Participants

Sixteen Japanese right-handed outpatients with PTSD (eight males and eight females; mean age ± standard deviation, 42.3 ± 13.6) who had visited the Kanto Medical Center NTT and the University of Tokyo Hospital participated in this study.

Diagnoses were performed according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; American Psychiatric Association) and confirmed using CAPS (Clinician-Administered PTSD Scale; National Center for Posttraumatic Stress Disorder)

Profiles of subjects

The profiles, CAPS score, DES-II score, and comorbidity of the subjects in the PTSD group are shown in Table 1. The traumatic episodes that had caused PTSD varied widely among the participants, and included major earthquakes, fires, crimes, traffic accidents, and abuse. Three participants had comorbid major depression and two had comorbid anxiety disorder. During stimulus presentation, 6 patients with PTSD and 3 controls felt that they momentarily saw human faces, but no participants developed

Discussion

During masked presentation of traumatic images, activation of the parahippocampal region including left hippocampal gyrus/tail of left hippocampus was observed in the patients with PTSD. However, activations in the bilateral inferior parietal lobules, middle frontal gyrus, and precentral gyrus, which were observed in healthy controls, were not observed in PTSD patients. Previous studies have suggested that the cooperative activation of parietal areas, including the inferior parietal lobule and

Acknowledgments

This study was financially supported by the Stress-induced Disorder Research Project, Ministry of Education, Culture, Sports, Science and Technology, Government of Japan. We express deep gratitude to the staff of Kanto Medical Center NTT, Dr. Kensaku Nomoto, Dr. Shinsuke Kondo, and Dr. Akira Iwanami of the University of Tokyo for data collection. Mark Rogers was supported by a postdoctoral fellowship from the National Health and Medical Research Council of Australia (Grant ID 237027).

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