Neural Circuitry Underlying the Regulation of Conditioned Fear and Its Relation to Extinction

By Mauricio R. Delgado, Katherine I. Nearing, Joseph E LeDoux, Elizabeth A. Phelps. Neuron, 2008

677 citations recorded by the source corpus.

SUMMARY Recent efforts to translate basic research to the treatment of clinical disorders have led to a growing interest in exploring mechanisms for diminishing fear. This research has emphasized two approaches: extinction of conditioned fear, examined across species; and cognitive emotion regulation, unique to humans. Here, we sought to examine the similarities and differences in the neural mechanisms underlying these two paradigms for diminishing fear. Using an emotion regulation strategy, we examine the neural mechanisms of regulating conditioned fear using fMRI and compare the resulting activation pattern with that observed during classic extinction. Our results suggest that the lateral PFC regions engaged by cognitive emotion regulation strategies may influence the amygdala, diminishing fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction. These findings further suggest that humans may have developed complex cognition that can aid in regulating emotional responses while utilizing phylogenetically shared mechanisms of extinction.

Subfields: Behavioral Neuroscience, Cognitive Neuroscience, Social Psychology

View Paper: https://www.semanticscholar.org/paper/b55ccf1dc405ac8f21926bf2014eb4719ae557d0

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Behavioral Neuroscience

In Cognitive Neuroscience

In Social Psychology

Citations in the corpus

Dealing with feeling: a meta-analysis of the effectiveness of strategies derived from the process model of emotion regulation. (2012, neutral): “…1 Negative affect S1 Cont1 23 35 0.57 0.50 Davis et al. (2009) 1 Negative affect D4 Cont1 23 35 0.05 0.55 Degen (2008) 1 Anxiety R1 D4 60 60 0.20 Delgado et al. (2008) 1 Anxiety D2 Cont4 12 0.66 Demaree, Robinson, et al. (2006) 1 Amusement S1 Cont3 20.5 20.5 0.34 1.62 0.33 Demaree, Robinson, et…”
Posttraumatic Stress Disorder (2015, background): “The hippocampus also modulates amygdala function through its role in contextual fear conditioning and consolidation of extinctionmemory.(46,50) Repeated exposure to conditioned stimuli (eg, a tone) without coupling themwith an aversive event (eg, an electrical shock) leads to a progressive decrease ”
A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry (2013, background): “, via connections with inhibitory interneurons within the amygdala) (Milad et al., 2007; Delgado et al., 2008; Linnman et al., 2011).”
Prefrontal–striatal pathway underlies cognitive regulation of craving (2010, result): “The second possibility is that the inverse relationship between dlPFC activity and craving is mediated by changes in VS activity, as predict based on prior findings of frontal–subcortical pathways mediating regulation of aversive emotion (36, 44).”
UPDATED META‐ANALYSIS OF CLASSICAL FEAR CONDITIONING IN THE ANXIETY DISORDERS (2015, background): “Furthermore, the same areas of vmPFC seem to be involved in both explicitly instructed cognitive emotion regulation of conditioned fear and classical extinction training.[51] Interestingly, one session of cognitive behavioral therapy (CBT) in patients with specific phobia already resulted in strongl”
Brain mediators of cardiovascular responses to social threat, Part I: Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity (2009, background): “Several human fear conditioning studies have found increases in the dorsal MPFC and reductions in mOFC when cues associated with shock (conditioned stimuli) are presented (Delgado et al., 2008; Phelps et al., 2004; Schiller et al., 2008).”
The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety (2011, background): “Unlike extinction, many motion regulation studies point to the ventral and dorsal lateral refrontal cortex (vlPFC and dlPFC, respectively), in addition to the entral medial prefrontal cortex, as critical for regulating amygdala ctivity [59,66,67,69,71].”
Psychobiology and molecular genetics of resilience (2009, positive): “Findings from a recent study suggest that emotion regulation — a more advanced cognitive function — of conditioned fear might act through connections with more basic mechanisms of fear extinction, which humans share with other specie”
Emotion Regulation and the Anxiety Disorders: An Integrative Review (2010, background): “Importantly, these effects are found in fear-conditioning paradigms that may provide a more ecologically valid model of anxiety disorders (Delgado et al., 2008; Phelps et al., 2004).”
Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies. (2014, methodology): “This includes paradigms such as those utilized by Delgado et al. (2008) that involve imagining a calming stimulus like the ocean during exposure to affective stimuli.”
The diagnosis of mental disorders: the problem of reification. (2010, background): “…notion that there are natural kinds, qualitatively different from each other, called panic disorder, simple phobias, social phobia, and posttraumatic stress disorder, and begin again with a cluster based on dysregulated fear circuitry (Andrews et al. 2009, Delgado et al. 2008, Rauch et al. 2006).”