PFC-Amygdala Pathway
The PFC-amygdala pathway is a bidirectional neural circuit where the prefrontal cortex (particularly the ventromedial PFC) exerts inhibitory control over the amygdala to regulate emotional responses, fear expression, and threat detection. 1
Anatomical Organization
The prefrontal cortex and amygdala govern parasympathetic functioning by regulating the dorsal nucleus of the vagus nerve, innervating the vagus nerve itself, and ending with the sinoatrial node of the heart. 1
Under normal circumstances, environmental cues are identified by the prefrontal cortex, which inhibits sympathoexcitatory networks and maintains control over subcortical structures including the amygdala. 1
The pathway involves multiple PFC subregions with distinct roles: the ventromedial PFC (vmPFC), rostral anterior cingulate cortex, and orbitofrontal cortex all contribute to amygdala inhibition through associated inhibitory pathways. 2
Functional Mechanisms
Threat Processing and Fear Regulation
When facing threat, PFC circuits become disinhibited, which allows the emergence of fear responses mediated by the amygdala. 1
The amygdala serves as a salience detector crucial for learning new stimulus-threat contingencies and expressing cue-specific fear, while the PFC represents affect in the absence of immediate rewards and punishments. 3
The basolateral amygdala (BLA) provides excitatory input to prelimbic cortex projection cells, increasing fear signaling, while the ventral hippocampus gates this amygdala-based fear through inhibitory mechanisms. 4
Bidirectional Integration
The amygdala and PFC continuously work together during decision-making, with the amygdala computing goal value while the PFC generates and evaluates action plans. 5
The strength of amygdala-mPFC connectivity represents the capacity for efficient crosstalk between these regions, which is crucial for beneficial outcomes in emotional regulation and anxiety management. 6
In the context of OCD and related disorders, the frontolimbic circuit (which includes PFC-amygdala connections) is specifically involved in fear extinction processes. 1
Clinical Relevance
Deficient hippocampal inhibition of PFC may underlie emotional disorders, especially given reduced hippocampal volume observed in depression and PTSD. 4
The dual inhibition model posits that the rostral anterior cingulate cortex and orbitofrontal cortex must interact for adequate inhibitory control of the amygdala and emotional regulation, with dysfunction in this system contributing to PTSD pathophysiology. 2
In opioid use disorder, altered amygdala activation patterns and disrupted amygdala-orbitofrontal cortex connectivity have been demonstrated during affective processing tasks. 1