A Role for the Human Dorsal Anterior Cingulate Cortex in Fear Expression
ABSTRACT Rodent studies implicate the prelimbic (PL) region of the medial prefrontal cortex in the expression of conditioned fear. Human studies suggest that the dorsal anterior cingulate cortex (dACC) plays a role similar to PL in mediating or modulating fear responses. This study examined the role of dACC during fear conditioning in healthy humans with magnetic resonance imaging (MRI).
Novel analyses were conducted on data from two cohorts that had previously undergone scanning to study fear extinction. Structural and functional brain data were acquired with MRI; the functional MRI (fMRI) component employed an event-related design. Skin conductance response (SCR) was the index of conditioned responses.
We found that: 1) cortical thickness within dACC is positively correlated with SCR during conditioning; 2) dACC is activated by a conditioned fear stimulus; and 3) this activation is positively correlated with differential SCR. Moreover, the dACC region implicated in this research corresponds to the target of anterior cingulotomy, an ablative surgical treatment for patients with mood and anxiety disorders.
Convergent structural, functional, and lesion findings from separate groups of subjects suggest that dACC mediates or modulates fear expression in humans. Collectively, these data implicate this territory as a potential target for future anti-anxiety therapies.
Full-textDOI: · Available from: Scott P Orr, Aug 16, 2015
[Show abstract] [Hide abstract]
- "For example, during extinction recall in the context associated with extinction learning, activity in both the vmPFC and hippocampus correlated positively with the degree of psychophysiologically expressed extinction recall, and activities in the vmPFC and hippocampus were significantly correlated with each other (Milad, Wright, et al., 2007). Milad et al. (2007) suggested that contextual information, resulting from differentiation of the conditioning and extinction contexts, was represented by such hippocampal activity. Kalisch et al. (2006) also reported correlated activation of hippocampus and vmPFC during extinction recall when the CSϩ was presented in the extinction context but not in the conditioning context. "
ABSTRACT: Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning, and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. Rapid eye movement (REM) may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction, and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep's effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).Psychological Bulletin 04/2015; 141(4). DOI:10.1037/bul0000014 · 14.39 Impact Factor
[Show abstract] [Hide abstract]
- "The current neurocircuitry model of fear extinction (Milad and Quirk 2012) implies a dual cortical control of limbic activity with opposing modulatory roles for the two subparts of the PFC: The IL inhibits amygdalar CE fear output via projections to the intercalated cells thereby mediating extinction, while the PL with its excitatory projections to the BLA is directly involved in the expression of learned fear. Although it is difficult to define homologous areas between rodents and humans, the vmPFC, including the subgenual anterior cingulate cortex and the medial orbitofrontal cortex, has been proposed as homologs to the rodent IL (Ongur and Price 2000), while numerous findings support the idea that the dorsal anterior cingulate cortex (dACC) is the human homolog of the rodent PL (Milad et al. 2007a). Although our study confirms the structural basis of vmPFC involvement in extinction learning in humans , we found no significant association between fear acquisition capacity and the thickness of the dACC or any other cortical area. "
ABSTRACT: The neural circuits underlying fear learning have been intensively investigated in pavlovian fear conditioning paradigms across species. These studies established a predominant role for the amygdala in fear acquisition, while the ventromedial prefrontal cortex (vmPFC) has been shown to be important in the extinction of conditioned fear. However, studies on morphological correlates of fear learning could not consistently confirm an association with these structures. The objective of the present study was to investigate if interindividual differences in morphology of the amygdala and the vmPFC are related to differences in fear acquisition and extinction learning in humans. We performed structural magnetic resonance imaging in 68 healthy participants who underwent a differential cued fear conditioning paradigm. Volumes of subcortical structures as well as cortical thickness were computed by the semi-automated segmentation software Freesurfer. Stronger acquisition of fear as indexed by skin conductance responses was associated with larger right amygdala volume, while the degree of extinction learning was positively correlated with cortical thickness of the right vmPFC. Both findings could be conceptually replicated in an independent sample of 53 subjects. The data complement our understanding of the role of human brain morphology in the mechanisms of the acquisition and extinction of conditioned fear.Brain Structure and Function 02/2015; DOI:10.1007/s00429-015-1013-z · 4.57 Impact Factor
[Show abstract] [Hide abstract]
- "Neuroimaging work in humans is largely consistent with these findings. During extinction learning, vmPFC activity increases (Phelps et al., 2004) and correlates with the magnitude of later extinction retention (Milad et al., 2007). The vmPFC is also active during extinction retrieval (Phelps et al., 2004; Kalisch et al., 2006) and the volume of cortical tissue in this region has been shown to be positively associated with the magnitude of extinction retrieval (Hartley et al., 2011), confirming an important role across species for this region in the successful retrieval of extinction training. "
ABSTRACT: Fear learning and regulation is as a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation), and briefly discuss other techniques (avoidance and reconsolidation) where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology.01/2015; 1:134-146. DOI:10.1016/j.ynstr.2014.11.004