Review
Extending the amygdala in theories of threat processing

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Highlights

  • Central extended amygdala includes portions of the amygdala (Ce) and lateral BST.

  • Central extended amygdala regions share connectivity and gene expression patterns.

  • Animal studies show central extended amygdala to be involved in threat processing.

  • Human functional imaging studies are beginning to translate these animal findings.

  • Maladaptive central extended amygdala function may underlie stress-related psychopathology.

The central extended amygdala is an evolutionarily conserved set of interconnected brain regions that play an important role in threat processing to promote survival. Two core components of the central extended amygdala, the central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria terminalis (BST) are highly similar regions that serve complimentary roles by integrating fear- and anxiety-relevant information. Survival depends on the ability of the central extended amygdala to rapidly integrate and respond to threats that vary in their immediacy, proximity, and characteristics. Future studies will benefit from understanding alterations in central extended amygdala function in relation to stress-related psychopathology.

Section snippets

Extending the amygdala

The term amygdala refers to a group of subregions or nuclei that together comprise a core component of an emotion-related network. This anatomical concept has been of considerable value and is fundamental to theories of threat-processing and emotion dysfunction 1, 2, 3, 4, 5. In large part, based on rodent studies of threat processing, the amygdala has become a region of intense interest in psychiatric research focused on the pathogenesis of anxiety disorders and affective disorders 6, 7.

Anatomy of Ce and BST

The amygdala is not a single functional or structural unit; rather, it is composed of numerous subnuclei that have been suggested to constitute at least three different anatomical and functional networks [9] (Figure 1). The olfactory network involves the medial nucleus of the amygdala (Me) connecting with structures involved in olfaction, including olfactory predator cues [11]. The frontotemporal network involves the large basal and lateral nuclei of the amygdala with their cortical

Threat responsivity of the Ce and BST

Extensive studies examining subregions of the amygdala demonstrated involvement of different amygdala nuclei in mediating acquisition of, response to, and extinction of learned threats. In general, the basolateral amygdala (BLA) is most related to the acquisition of conditioned threat, and the medial amygdala, as a component of the medial extended amygdala, has an important role in processing threat-related odors. The central extended amygdala, including the Ce, is thought to provide an

The human central extended amygdala in fear, anxiety, and anxiety disorders

Much of the human neuroimaging work on fear, anxiety, and anxiety disorders has focused on the amygdala per se, with fewer studies attempting to parse the functions of its subnuclei. Nevertheless, a substantial number of studies have identified threat-related activation in the dorsal amygdala region that encompasses the Ce 19, 78. Recent human fMRI studies have tested BST-focused hypotheses derived from the animal literature, identifying contexts that elicit BST activation. Future studies

Concluding remarks – Opportunity and new frontier

The historical evidence, along with recent large data-based analyses at the molecular and systems levels, convincingly support the concept of the central extended amygdala. As key components of the central extended amygdala, these approaches also establish the similarity of structure and function between the Ce and BST. Based on animal and human studies, there is no question that the central extended amygdala is involved in adaptive and maladaptive threat responding. Nevertheless, much work

Acknowledgments

The authors thank P.H. Roseboom, R. Kovner, L.E. Williams, and A.J. Shackman for their insights and discussions surrounding the extended amygdala, along with the dedicated staff of the Harlow Center for Biological Psychology at the University of Wisconsin-Madison. The authors were supported by the National Institutes of Health (NIH; Intramural Research Program and extramural grants R21MH91550, R01MH81884, R01MH46729, P50MH84051, P50MH100031, R21MH092581), and the HealthEmotions Research

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