The human brain is characterized by the significant expansion of association cortex, particularly the PFC. This circuit includes the amygdala and other subcortical structures, which are necessary for identifying and coordinating behavioral and physiological responses to threats. Decades of work, both in humans and animal models, converges upon a conserved set of brain regions necessary for executing adaptive defensive responses. These behavioral and physiological changes, which are collectively referred to as defensive responses, are conserved across species, facilitating the use of translational models to characterize defensive circuitry. Disruption of specific nodes within the PFC that interface with inhibitory systems can affect the negative bias, failure to regulate autonomic arousal, and avoidance that characterize anxiety disorders.Īnxiety is a state experienced in response to threats that are either distal or uncertain, and involves changes in an individual’s subjective state, behavior and physiology that facilitate detection of a potential threat within the environment. Specialized PFC pathways to the inhibitory thalamic reticular nucleus suggest a mechanism to allow passage of relevant signals from thalamus to cortex, and in the amygdala to modulate the output to autonomic structures. Within the PFC, pathways connecting cortical regions are poised to reduce noise and enhance signals for cognitive operations that regulate anxiety processing and autonomic drive. PFC pathways that interface with distinct inhibitory systems within the cortex, the amygdala, or the thalamus can regulate responses by modulating neuronal output. The specialized primate lateral, medial, and orbital PFC sectors are connected with association and limbic cortices, the latter of which are connected with the amygdala and brainstem autonomic structures that underlie emotional and physiological arousal. This prefrontal expansion is thought to underlie primates’ increased capacity to engage high-level regulatory strategies aimed at coping with and modifying the experience of anxiety. In primates, anxiety can be regulated by the prefrontal cortex (PFC), which has expanded in evolution. While anxiety responses typically serve an adaptive purpose, when excessive, unregulated, and generalized, they can become maladaptive, leading to distress and avoidance of potentially threatening situations. Defensive and physiologic responses to threats that involve the amygdala and brainstem are conserved across species. Anxiety is experienced in response to threats that are distal or uncertain, involving changes in one’s subjective state, autonomic responses, and behavior.
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