Anxious individuals shift emotion control from lateral frontal pole to dorsolateral prefrontal cortex

Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPI) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPI-based emotional action control fails in highly-anxious individuals. Their FPI is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPI during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPI excitability and amygdalofugal projections strength. The findings characterize circuit-level vulnerabilities in anxious individuals, showing that even mild emotional challenges can saturate FPI neural range, leading to a neural bottleneck in the control of emotional action tendencies.

Bob Bramson, Sjoerd Meijer, Annelies van Nuland, Ivan Toni, Karin Roelofs