Diminished rostral anterior cingulate activity in response to threat-related events in posttraumatic stress disorder
Introduction
Experiencing traumatic events such as war, rape, natural disasters or motor vehicle accidents, can lead to the development of posttraumatic stress disorder (PTSD). PTSD is characterized by re-experience of the traumatic event, persistent avoidance of stimuli associated with the traumatic event, and symptoms of arousal that were not present before the traumatic event (American Psychiatric Association, 1994).
Many structural and functional brain imaging studies report the abnormality of the anterior cingulate cortex (ACC), especially the rostral region (Brodmann area 24 and 32), in PTSD (Bremner et al., 2004, Liberzon and Phan, 2003, Rauch et al., 2003, Semple et al., 2000, Shin et al., 2004, Shin et al., 2005). In a structural magnetic resonance imaging (MRI) study, Rauch et al. (2003) have found reduced rostral and subcallosal ACC volumes, but not dorsal ACC volumes, in the PTSD patients. Functional imaging studies have also shown abnormalities of the rostral ACC in PTSD subjects (Bremner et al., 2004, Shin et al., 2001). In an functional MRI study by Shin et al. (2005), when passively viewing pictures of fearful faces, non-PTSD group exhibited blood oxygenation level dependent signal increases in the rostral ACC, whereas the PTSD group did not. Consistently, a prior H2O PET study by Bremner et al. (2004) have reported that PTSD patients showed a relative decrease in the anterior cingulate blood flow when performing emotional Stroop tasks compared to non-PTSD subjects.
The ACC has been known to be involved in a number of aspects of emotional and cognitive functioning (Bush et al., 2000). A number of empirical works have differentiated the dorsal subdivision (dorsal ACC) and the rostral subdivision (rostral ACC), which are involved in cognitive and emotional processing, respectively (Bush et al., 2000). This dissociation between the two subdivisions is supported by the study of Whalen et al. (1998), in which participants’ dorsal and rostral ACC were differentially activated when they were asked to perform neutral and emotional counting Stroop tasks, respectively (Whalen et al., 1998).
Evidence from clinical and psychiatric studies suggest that the ACC, especially the rostral subdivision, play an important role in the regulation of amygdala activity (Hamner et al., 1999, Pitman et al., 2001). Functional impairment of this particular brain region appears to result in the hyperactivation of the amygdala, which has been found to be one of the core neural features of PTSD.
It is also known from the psychology literature that an impaired cognitive control over threat-related information is suggested to play a key role in anxiety (Eysenck, 1997). Additionally, in response-conflict tasks, conflicting stimuli are especially disruptive when they occur infrequently and elevated ACC activations are observed in these circumstances (Carter et al., 2000, Tzelgov et al., 1992). Supporting this, in a recent functional MRI study, the rostral ACC was found to be responding to an unexpected processing conflict arising from the emotionally salient but task-irrelevant input and modulated by anxiety levels of each individual (Bishop et al., 2004). Put together, empirical data from these studies suggest that the dysfunctional rostral ACC may be the underlying neural substrate of pathological anxiety. This is interesting to note, since numerous literature points out that the abnormal rostral ACC is associated with PTSD pathology (Bremner et al., 2004, Liberzon and Phan, 2003, Rauch et al., 2003, Semple et al., 2000, Shin et al., 2004, Shin et al., 2005).
To further investigate the relationship between the rostral ACC and PTSD, it may be intriguing to directly apply the experimental paradigm used by Bishop et al. (2004) to the PTSD population. This experimental paradigm can give us new information regarding the role of rostral ACC in response to unexpected occurrences of threat-related distracter stimuli in PTSD. By applying this experimental paradigm, the results could provide more insight to the pathophysiology of PTSD by expanding the findings of previous PTSD neuroimaging studies which employed emotional Stroop task or script-driven imagery to investigate rostral ACC functioning. Currently, however, no other studies have yet attempted to use this experimental paradigm on PTSD.
In the current study, functional MR images were obtained by applying the experimental paradigm used by Bishop et al. (2004), in order to investigate the rostral ACC-amygdala response to unexpected generalized affective distracter stimuli in PTSD patients, and to compare the rostral ACC functioning between the PTSD and healthy groups. Our main hypotheses were that (1) PTSD patients would exhibit decreased a cortical activity of the ACC, especially the rostral region, compared to healthy subjects; (2) within the PTSD group, rostral ACC responses to unexpected, emotionally threatening distracter stimuli would be negatively correlated with PTSD symptom severity; and (3) cortical activity in the rostral ACC would be negatively correlated with signal changes in the amygdala. Additionally, in order to observe potential group differences in cortical activation patterns in other brain regions known to be affected by the pathophysiology of PTSD (e.g., hippocampus, thalamus), functional data were analyzed throughout the whole brain.
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Participants
Twelve survivors (seven men and five women, 33.3 ± 9.1 years, 22–50 years range) of the Taegu subway fire in February, 2003, who later developed PTSD, agreed to participate in this study. In an effort to recruit subjects who were exposed to the uniform degree of psychological trauma, we have selected survivors who had been initially trapped inside two burning compartments but successfully escaped. Those who were outside the train at the time of the event were excluded. All imaging scans were
Demographic and clinical characteristics
Demographic and clinical characteristics of twelve patients with PTSD and twelve healthy comparison subjects are described in Table 1. There were no significant differences in age, gender composition, and handedness between the two groups. All subjects had equal to or higher than high school education.
Depression and anxiety levels of the PTSD patients as assessed by the HDRS and the HARS were 6.5 ± 3.8 and 7.5 ± 3.4, respectively. The IES-R scores, which represent posttraumatic disturbance and
Discussion
PTSD patients exhibited a diminished rostral ACC activations when exposed to task-irrelevant threat-related stimuli, compared to healthy control subjects. Moreover, within the PTSD group, the rostral ACC BOLD signal activation was negatively correlated with the symptom severity of the patients. These findings are consistent, in part, with a neuroanatomical model of PTSD that postulates an impaired rostral ACC to be associated with the PTSD pathology (Hamner et al., 1999, Rauch et al., 2006).
Acknowledgements
This research was supported by Grants from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea (70%) (M103KV010022-06K2201-02210; I.K.L.), the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (A06-0434-A21018-06N1-00010 A; I.K.L.), the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2006-003-E00187; S.J.Y.), and 2006
References (33)
- et al.
Neural correlates of the classic color and emotional Stroop in women with abuse-related posttraumatic stress disorder
Biological Psychiatry
(2004) - et al.
Cognitive and emotional influences in anterior cingulate cortex
Trends in Cognitive Science
(2000) - et al.
Multisubject fMRI studies and conjunction analyses
Neuroimage
(1999) - et al.
Anatomical variability of the anterior cingulate gyrus and basic dimensions of human personality
Neuroimage
(2002) - et al.
Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research – past, present, and future
Biological Psychiatry
(2006) - et al.
An fMRI study of anterior cingulate function in posttraumatic stress disorder
Biological Psychiatry
(2001) - et al.
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain
Neuroimage
(2002) - et al.
Effects of attention and emotion on face processing in the human brain: an event-related fMRI study
Neuron
(2001) - et al.
The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division
Biological Psychiatry
(1998) Diagnostic and Statistical Manual of Mental Disorders
(1994)
Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli
Nature Neuroscience
The development of a Clinician-Administered PTSD Scale
Journal of Traumatic Stress
Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex
Proceedings in the National Academy of Sciences United States of America
The expression of the emotions in man and animals
Anxiety and cognition: a unified theory
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