Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma

Abstract

Background Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for post-traumatic stress disorder (PTSD), however understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospective study of PTSD. Methods Participants were recruited from the emergency department of a large level-I trauma center within 24 hours of trauma. PTSD symptoms were assessed at baseline, and approximately 1, 3, 6, and 12 months post-trauma. Growth curve modeling was used to estimate symptom recovery trajectories. N=31 participated in fMRI around the 1 month assessment, passively viewing fearful and neutral face stimuli. Reactivity (fearful>neutral) and habituation to fearful faces was examined. Results Amygdala reactivity, but not habituation, 5–12 weeks post-trauma was positively associated with the PTSD symptom intercept and predicted symptoms at 12 months post-trauma. Habituation in the ventral anterior cingulate cortex (vACC) was positively associated with the slope of PTSD symptoms, such that decreases in vACC activation over repeated presentations of fearful stimuli predicted increasing symptoms. Conclusions Findings point to neural signatures of risk for maintaining PTSD symptoms following trauma exposure. Specifically, chronic symptoms were predicted by amygdala hyper-reactivity and poor recovery was predicted by a failure to maintain vACC activation in response to fearful stimuli. The importance of identifying patients at risk following trauma exposure is discussed.

White matter integrity alterations in post‐traumatic stress disorder

“…In general, it is found that amygdala response is exaggerated in PTSD subjects, and is more pronounced when PTSD symptoms are more severe (Brunetti et al, ; Dickie, Brunet, Akerib, & Armony, ; Shin et al, ; Zhong et al, ). Modulation/extinction of the fear response is postulated to involve an inhibitory role of medial prefrontal structures, particularly the ACC, over the amygdala (Clausen et al, ; Shin et al, ; Stevens et al, ). In PTSD diagnosed subjects, correlational analyses from the current study identified associations between FA/RD/AD/MD values and PTSD symptoms (as measured by CAPS subscores) in WM tracts connecting the amygdala and ACC.…”

Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization

“…The mechanism of the observed plasticity presumably involves the amygdala, which is a key structure in fear learning (LeDoux, 2000; Maren & Quirk, 2004; Phelps & LeDoux, 2005) that has been implicated in anxiety disorders such as PTSD (Bryant et al, 2005; Jovanovic & Ressler, 2010; Liberzon, Taylor, Amdur, Jung, Chamberlain, Minoshima et al, 1999; Protopopescu, Pan, Tuescher, Cloitre, Goldstein, Engelien et al, 2005; Rauch, Whalen, Shin, McInerney, Macklin, Lasko et al, 2000; Stevens, Kim, Galatzer-Levy, Reddy, Ely, Nemeroff et al, 2017), and also LC noradrenaline, which is involved in odor perception, olfactory learning, and odor memory formation (Eckmeier & Shea, 2014; Linster, Nai, & Ennis, 2011; Mandairon, Peace, Karnow, Kim, Ennis, & Linster, 2008; Moreno, Bath, Kuczewski, Sacquet, Didier, & Mandairon, 2012; Sullivan, Stackenwalt, Nasr, Lemon, & Wilson, 2000; Sullivan, Zyzak, Skierkowski, & Wilson, 1992). Recent studies using auditory fear conditioning have found that the specificity of cue-evoked freezing is paralleled by the specificity of cue-evoked amygdala activity (Ghosh & Chattarji, 2015), and that the effect of fear generalization on tuning curves in the amygdala was dependent upon the neuron’s preferred stimulus, with the broadest shifts in tuning occurring when the preferred stimulus was relatively far from the CS (Resnik & Paz, 2015).…”

Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD

“…Traumatic experiences activate several brain regions that have been implicated in the pathophysiology of PTSD, including the prefrontal cortex (PFC) [33–36], amygdala [37–40], hippocampus [36, 41, 42], and the anterior cingulate [43]. White matter connections between the ventral region of the medial PFC (vmPFC) and the amygdala mediate bidirectional communication that regulates fear learning and extinction [44].…”