The amygdale has been attributed a key role in mood.

This evolutionarily ancient structure is responsible

for generating fight or flight responses to threats. The amygdale is heavily innervated by the prefrontal
cortex, which probably serves to modulate the fight- or flight response into a more complex emotional
behavior that defines human interactions. Along with other nearby medial temporal structures
( including the paralimbic cortex and hippocampus ), the amygdale is responsible for the perception and
regulation of emotions.

Disruption in early development within brain networks that modulate emotional behavior leads to
decreased connectivity betwwn ventral prefrontal network and limbic brain structures, especially the
amygdale. This loss of connectivity is associated with the abnormal functional responses of emotional
network to various cognitive and emotional task in imaging tudies. As well as abnormal development of
the component brain regions. Dysregulations of the limbic brain then leads ti mood instability. In the
absence of healty prefrontal striatal - pallidal - thalamic - limbicbrain network that can restore emotional
homeostasis, bipolar patiebts may develop extreme mood states and switching among mood states.
During euthymia, recovery of prefrontal function, along with compensation from other brain regions,
temporarily restores emotional homeostasis, nonetheless, the underlying functional neuroanatomic
abnormalities leave the subject at risk of disruption of dragile homeostasis under even minor stress in
the face of stably Instable prefrontal- striatal thalamic amygdale mood network.

In brief, developmental failure to establish healthy ventral prefrontal amygdale netwok may underlie
the onset of mania and , ultimately , with progressive change throughout these network over time , a
bipolar course of illness.