Elevated response of human amygdala to neutral stimuli in mild post traumatic stress disorder: Neural correlates of generalized emotional response

Institute of Advanced Biomedical Technologies, University of Chieti, Chieti, Italy.
Neuroscience (Impact Factor: 3.36). 04/2010; 168(3):670-9. DOI: 10.1016/j.neuroscience.2010.04.024
Source: PubMed


Previous evidence from functional magnetic resonance imaging (fMRI) studies has shown that amygdala responses to emotionally neutral pictures are exaggerated at a group level in patients with severe post-traumatic stress disorder (PTSD) [Hendler T, Rotshtein P, Yeshurun Y, Weizmann T, Kahn I, Ben-Bashat D, Malach R, Bleich A (2003) Neuroimage 19(3):587-600]. The present fMRI study tested the hypothesis that amygdala responses are elevated not only in response to negative pictures but also to neutral pictures as a function of disease severity in patients with mild symptoms and in subjects who did not develop symptoms. To this end, fMRI scans were performed in 10 patients with mild PTSD and 10 healthy controls (both victims of a bank robbery), during the execution of a visuo-attentional task in which they were asked to observe emotionally negative or neutral pictures. Control subjects showed enhanced amygdala responses to emotionally negative stimuli compared to neutral stimuli. On the contrary, PTSD patients were characterized by high amygdala responses to both neutral and emotional pictures, with no statistically significant difference between the two classes of stimuli. In the entire group, we found correlations among the severity of the PTSD symptoms, task performance, and amygdala activation during the processing of neutral stimuli. Results of this study suggest that amygdala responses and the selectivity of the emotional response to neutral stimuli are elevated as a function of disease severity in PTSD patients with mild symptoms.

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Available from: Claudia Catani, Apr 07, 2014
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    • "The image acquisition parameters were identical to those in our previous study (Brunetti et al., 2010). BOLD contrast functional imaging was performed with a SIEMENS MAGNETOM VISION scanner at 1.5 T by means of T2*-weighted echo planar imaging (EPI), free-induction decay (FID) sequences with the following parameters: TR 3 s, TE 60 ms, matrix size 64 × 64, FOV 256 mm, in-plane voxel size 4 mm × 4 mm, flip angle 90 • , slice thickness 4 mm and no gap. "
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    ABSTRACT: Patients with post-traumatic stress disorder (PTSD) tend to misinterpret innocuous stimuli as potential threats, possibly due to a conditioning provoked by traumatic episodes. Previous neuroimaging evidence has shown an abnormal activation of the amygdala and prefrontal cortex in PTSD patients during fear conditioning and extinction. Nevertheless, the effects of a single-type adverse stressor on that circuit remain poorly explored. We tested the hypothesis that a single-type adverse episode is able to affect the prefrontal cortex and amygdala response to conditioned stimuli. To test this hypothesis, fMRI recordings were performed in PTSD patients and trauma-exposed controls during the observation of neutral and negative paired or non-paired pictures with an adverse stimulus by means of a single association. Results showed that left amygdala activation during negative reinforced stimuli was correlated with the score of PTSD clinical scale across all subjects. Furthermore, in the traumatized non-PTSD group, the activation of the dorso-medial prefrontal cortex and bilateral amygdala was lower during the observation of the reinforced (CS(+)) vs non-reinforced pictures (CS(-)) in response to emotionally negative stimuli. This was not the case in the PTSD patients. These results suggest that in PTSD patients, a single-episode conditioning unveils the failure of an inhibitory mechanism moderating the activity of the prefrontal cortex and amygdala in response to adverse and neutral stimuli. Copyright © 2015. Published by Elsevier Inc.
    Brain research bulletin 03/2015; 114. DOI:10.1016/j.brainresbull.2015.03.001 · 2.72 Impact Factor
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    • "Like Phan et al (2006), who also did not observe an increased amygdala response to IAPS pictures in PTSD patients, we only studied males. The two studies that presented IAPS pictures and observed increased amygdala activity in PTSD patients included predominantly females (Brohawn et al. 2010; Brunetti et al. 2010). This could indicate an effect of sex on the amygdala response to (trauma-unrelated) emotional stimuli in PTSD, which has been suggested to explain the higher prevalence of PTSD in women (Hamann, 2005). "
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    ABSTRACT: Background: Post-traumatic stress disorder (PTSD) is thought to be characterized by general heightened amygdala activation. However, this hypothesis is mainly based on specific studies presenting fear or trauma-related stimuli, hence, a thorough investigation of trauma-unrelated emotional processing in PTSD is needed. Methods: In this study, 31 male medication-naive veterans with PTSD, 28 male control veterans (combat controls; CC) and 25 non-military men (healthy controls; HC) were included. Participants underwent functional MRI while trauma-unrelated neutral, negative and positive emotional pictures were presented. In addition to the group analyses, PTSD patients with and without major depressive disorder (MDD) were compared. Results: All groups showed an increased amygdala response to negative and positive contrasts, but amygdala activation did not differ between groups. However, a heightened dorsal anterior cingulate cortex (dACC) response for negative contrasts was observed in PTSD patients compared to HC. The medial superior frontal gyrus was deactivated in the negative contrast in HC, but not in veterans. PTSD+MDD patients showed decreased subgenual ACC (sgACC) activation to all pictures compared to PTSD-MDD. Conclusion: Our findings do not support the hypothesis that increased amygdala activation in PTSD generalizes to trauma-unrelated emotional processing. Instead, the increased dACC response found in PTSD patients implicates an attentional bias that extends to trauma-unrelated negative stimuli. Only HC showed decreased medial superior frontal gyrus activation. Finally, decreased sgACC activation was related to MDD status within the PTSD group.
    Psychological Medicine 07/2014; DOI:10.1017/S0033291714001706 · 5.94 Impact Factor
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    • "Patients also exhibit a stronger startle reflex response than controls during idiographic threat-related imagery, consistent with enhanced limbic (in particular, amygdalar) and paralimbic activation. Indeed, PTSD patients interpret innocuous stimuli as a potential threat (Lanius et al., 2006; Brunetti et al., 2010). An example of this is the Acoustic Startle Response (ASR), which consists of a sequence of reactions caused by muscular and neural responses to sudden and intense acoustic stimuli. "
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    ABSTRACT: High resolution thermal infrared imaging is a pioneering method giving indices of sympathetic activity via the contact-free recording of facial tissues (thermal imprints). Compared to established stress markers, the great advantage of this method is its non-invasiveness. The goal of our study was to pilot the use of thermal infrared imaging in the classical setting of human stress research. Thermal imprints were compared to established stress markers (heart rate, heart rate variability, finger temperature, alpha-amylase and cortisol) in 15 participants undergoing anticipation, stress and recovery phases of two laboratory stress tests, the Cold Pressor Test and the Trier Social Stress Test. The majority of the thermal imprints proved to be change-sensitive in both tests. While correlations between the thermal imprints and established stress markers were mostly non-significant, the thermal imprints (but not the established stress makers) did correlate with stress-induced mood changes. Multivariate pattern analysis revealed that in contrast to the established stress markers the thermal imprints could not disambiguate anticipation, stress and recovery phases of both tests. Overall, these results suggest that thermal infrared imaging is a valuable method for the estimation of sympathetic activity in the stress laboratory setting. The use of this non-invasive method may be particularly beneficial for covert recordings, in the study of special populations showing difficulties in complying with the standard instruments of data collection and in the domain of psychophysiological covariance research. Meanwhile, the established stress markers seem to be superior when it comes to the characterization of complex physiological states during the different phases of the stress cycle.
    PLoS ONE 03/2014; 9(3):e90782. DOI:10.1371/journal.pone.0090782 · 3.23 Impact Factor
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