Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: An fMRI study

Bryant, Richard A.; Kemp, Andrew H.; Felmingham, Kim L.; Liddell, Belinda J.; Olivieri, Gloria; Peduto, Anthony; Gordon, Evian; Williams, Leanne M.

doi:10.1002/hbm.20415

Cited by 219 publications

(188 citation statements)

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“…The increased regional activity and reduced functional connectivity in frontolimbic and striatal regions occurred in areas known to be important for emotion processing (22). Atypical function in these areas has been implicated in previous studies of patients with chronic stress- related disorders (5,6,8,12,23) and was related to the reported level of emotional distress in our sample. Thus, the present investigation expands understanding of stress-related changes of brain function in humans in two important ways.…”

Section: Discussionmentioning

confidence: 54%

“…Human studies (4)(5)(6)(7)(8)(9)(10)(11)(12) have focused primarily on patients who already have an established psychiatric disorder, such as ASD and PTSD. Despite some inconsistencies (6,7,(9)(10)(11), findings from clinical studies also implicate limbic, paralimbic, striatal, and prefrontal structures in the pathophysiology of stress-related psychiatric disorders. However, because the majority of these studies were performed with victims of trauma that took place years or even decades earlier, it is not clear whether this represents a slowly evolving pattern of brain alteration or one that emerges shortly after traumatic experiences.…”

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confidence: 99%

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High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China

Lui¹,

Huang

Chen³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

130

114

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Besides the enormous medical and economic consequences, national disasters, such as the Wenchuan 8.0 earthquake, also pose a risk to the mental health of survivors. In this context, a better understanding is needed of how functional brain systems adapt to severe emotional stress. Previous animal studies have demonstrated the importance of limbic, paralimbic, striatal, and prefrontal structures in stress and fear responses. Human studies, which have focused primarily on patients with clinically established posttraumatic stress disorders, have reported abnormalities in similar brain structures. At present, little is known about potential alterations of brain function in trauma survivors shortly after traumatic events. Here, we show alteration of brain function in a cohort of healthy survivors within 25 days after the Wenchuan earthquake by a recently discovered method known as ''restingstate'' functional MRI. The current investigation demonstrates that regional activity in frontolimbic and striatal areas increased significantly and connectivity among limbic and striatal networks was attenuated in our participants who had recently experienced severe emotional trauma. Trauma victims also had a reduced temporal synchronization within the ''default mode'' of restingstate brain function, which has been characterized in humans and other species. Taken together, our findings provide evidence that significant alterations in brain function, similar in many ways to those observed in posttraumatic stress disorders, can be seen shortly after major traumatic experiences, highlighting the need for early evaluation and intervention for trauma survivors.neuroimaging ͉ stress ͉ anxiety ͉ depression ͉ posttraumatic stress disorder I n the afternoon on May 12, 2008, the epicenter of a devastating earthquake occurred in Wenchuan, in the Sichuan Province of China. It measured 8.0 on the Richter scale. The most severely affected geographical regions were Yingxiu, Wenchuan, Dujiangyan, and Shifang, where 45 million people were directly affected. Among them, 69,146 people were confirmed dead, 374,131 were seriously injured, and 17,516 are missing. A significant proportion of the survivors (Ϸ20%) (1) are likely to develop stress-related disorders, such as acute stress disorder (ASD) and posttraumatic stress disorder (PTSD). Given the serious and persistent impact of these highly prevalent psychiatric disorders, it is vital to develop a better understanding of the alterations of cerebral function evident in the early stages of adaptation to trauma. Such knowledge may lead to a better understanding of posttraumatic responses and the development of more effective early interventions.Studies of animal models of acute and chronic stress have provided evidence of physiological and morphological changes in several brain regions, including the amygdala, hippocampus, and prefrontal cortex (2, 3). Human studies (4-12) have focused primarily on patients who already have an established psychiatric disorder, such as ASD and PTSD. Despite some inconsis...

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 99%

High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China

Lui¹,

Huang

Chen³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

130

114

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“…In addition, OT administration increased resting-state functional connectivity between the amygdala and vmPFC in healthy males (Sripada et al, 2013) and in males with GSAD, normalizing the diminished functional connectivity observed under placebo in GSAD patients (Dodhia et al, 2014). Notably, higher amygdala reactivity in PTSD patients before treatment predicted worse treatment outcome, possibly due to (more) impaired extinction learning and fear regulation (Bryant et al, 2008b). Additionally, vmPFC-amygdala connectivity is important in fear extinction learning (Milad et al, 2007), assumed to be the underlying mechanism of exposure therapy in PTSD (Rothbaum and Davis, 2003).…”

Section: Introductionmentioning

confidence: 89%

Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

Koch

Zuiden

Nawijn

et al. 2016

Neuropsychopharmacol

125

106

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The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n = 37, 21 males) and without PTSD (n = 40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

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“…The fact that emotional faces were presented for only 33 ms (i.e., without the subject's conscious awareness of their display) may have minimized the role of the mPFC, justifying the absence of results regarding these high-order areas (Williams et al, 2006). However, another work that used masked faces in a shorter period of time (16.7 ms) found not only amygdala activation in response to fearful faces but also activation of the mPFC (Bryant et al, 2008). Armony, Corbo, Clement, and Brunet (2005) examined the amygdala response to the visualization of happy and fearful facial expressions.…”

Section: Processing Of Nontrauma-related Stimulimentioning

confidence: 99%

The neurobiology of posttraumatic stress disorder: Dysfunction in the prefrontal-amygdala circuit?

Lobo¹,

Oliveira²,

David³

et al. 2011

Psychology & Neuroscience

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Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop following exposure to a traumatic event, including terrifying or life-threatening situations such as sexual assault or natural disasters. The disorder is characterized by a reaction of intense fear, helplessness, or horror when the individual experiences, testifies about, or is faced with one or more events that involve death, severe wounds, or a threat to one's own or another's physical integrity. One of the most important symptoms of PTSD is the revival of the traumatic event, which has been interpreted as an inability to downregulate negative emotions. Neuroimaging studies that probed the ability to regulate emotions in healthy volunteers have found a pattern characterized by activation of the prefrontal cortex associated with a reduction in amygdala activity. This suggests an inhibitory prefrontal cortexamygdala circuit that underlies emotional regulation. The hypothesis that increased amygdala activation associated with PTSD results from dysfunction in the inhibitory mechanism exerted by the prefrontal cortex has been the topic of debate. The present review investigates the validity of dysfunction in the prefrontal-amygdala pathway in PTSD. The studies provide evidence that the amygdala and prefrontal cortex exhibit distinct activation patterns in PTSD, thus supporting the model of a dysfunctional circuit. Inconsistencies in the literature may be attributable to distinct PTSD subgroups, different experimental approaches, different contrasts employed in neuroimaging studies, and small sample sizes.

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Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: An fMRI study

Cited by 219 publications

References 47 publications

High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China

High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China

Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

The neurobiology of posttraumatic stress disorder: Dysfunction in the prefrontal-amygdala circuit?

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