Potential role of the anterior cingulate cortex in PTSD: Review and hypothesis

Hamner, Mark B.; Lorberbaum, Jeffrey P.; George, Mark S.

doi:10.1002/(sici)1520-6394(1999)9:1<1::aid-da1>3.0.co;2-4

Cited by 122 publications

(61 citation statements)

References 101 publications

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“…At the neural level, our results are consistent with findings implicating dysfunction of the ACC in the development of PTSD (Bremner et al, 2005;Hamner et al, 1999;Shin et al, 2005). Clearly, future studies are warranted to further explore possible oxytocinergic mechanisms related to SAD or PTSD.…”

Section: Discussionsupporting

confidence: 87%

Oxytocin Facilitates Pavlovian Fear Learning in Males

Eckstein

Scheele

Patin

et al. 2015

Neuropsychopharmacol

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In human evolution, social group living and Pavlovian fear conditioning have evolved as adaptive mechanisms promoting survival and reproductive success. The evolutionarily conserved hypothalamic peptide oxytocin is a key modulator of human sociality, but its effects on fear conditioning are still elusive. In the present randomized controlled study involving 97 healthy male subjects, we therefore employed functional magnetic resonance imaging and simultaneous skin conductance response (SCR) measures to characterize the modulatory influence of intranasal oxytocin (24 IU) on Pavlovian fear conditioning. We found that the peptide strengthened conditioning on both the behavioral and neural levels. Specifically, subjects exhibited faster task-related responses and enhanced SCRs to fear-associated stimuli in the late phase of conditioning, which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function. This speaks against amygdalocentric views of oxytocin having pure anxiolytic-like effects. Instead, it suggests that the peptide enables extremely rapid and flexible adaptation to fear signals in social contexts, which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma.

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Section: Discussionsupporting

confidence: 87%

Oxytocin Facilitates Pavlovian Fear Learning in Males

Eckstein

Scheele

Patin

et al. 2015

Neuropsychopharmacol

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“…Thus, another ROI and inter-regional connection were added to the model in an attempt to better approximate the neural network of fear extinction. The anterior cingulate was included in the model because of recent work suggesting that this region may play an important role in memory for footshock (Malin and McGaugh, 2006), extinction of specific phobias (Straube et al, 2006), and gating among external sensory and internally driven stimuli and limbic structures involved in emotional and behavioral responses to CSs (Hamner et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Network model of fear extinction and renewal functional pathways

2007

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The objective of this study was to examine the opposite behavior responses of conditioned fear extinction and renewal and how they are represented by network interactions between brain regions. This work is a continuation of a series of brain mapping studies of various inhibitory phenomena, including conditioned inhibition, blocking and extinction. A tone-footshock fear conditioning paradigm in rats was used, followed by extinction and testing in two different contexts. Fluorodeoxyglucose autoradiography was used to compare mean regional brain activity and interregional correlations resulting from the presentation of the extinguished tone in or out of the extinction context. A confirmatory structural equation model, constructed from a neural network proposed to underlie fear extinction, showed a reversal from negative regional interactions during extinction recall to positive interactions during fear renewal. Additionally, the magnitude of direct effects was different between groups, reflecting a change in the strength of the influences conveyed through those pathways. The results suggest that the extinguished tone encountered outside of the extinction context recruits auditory and limbic areas, which in turn influence the interactions of the infralimbic cortex with the amygdala and ventrolateral periaqueductal gray. Interestingly, the results also suggest that two independent pathways influence conditioned freezing: one from the central amygdaloid nucleus and the other from the infralimbic cortex directly to the ventrolateral periaqueductal gray. KeywordsPath analysis; Structural equation modeling; Brain mapping; Prefrontal cortex; Hippocampus; AmygdalaIn the past few years, there has been increased interest in the neural substrates of fear extinction, partly due to the relevance of fear extinction to the treatment of anxiety disorders (Craske, 1999). Brain lesion, stimulation, recording and metabolic mapping studies have addressed the question of which brain areas are important in fear extinction learning and memory in both animals and humans (Quirk et al.,

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“…Recently, significantly smaller bilateral orbital frontal and amygdala volumes, as well as a lack of the normal hemispheric asymmetry of the hippocampus-amygdala complex, were found in adult OCD (Szeszko et al 1999). Unlike adult PTSD, pediatric PTSD is associated with global adverse affects (smaller cerebral volumes and corpus callosum areas) and no anatomical changes in limbic structures (De Bellis et al 1999); however, anterior cingulate dysfunction may be associated with both adult (Bremner et al 1999;Hamner et al 1999;Shin et al 1999) and pediatric PTSD (De Bellis et al, in press). Although there are no published studies to date on the psychobiology of panic disorder in children, adult panic disorder is thought to be the result of dysfunction in the locus coeruleus-norepinephrine system (Goddard and Charney 1997).…”

Section: Discussionmentioning

confidence: 99%