A functional neuroanatomy of anxiety and fear: implications for the pathophysiology and treatment of anxiety disorders.

This paper reviews the evidence that provides the basis for a functional neuroanatomy of anxiety and fear. The afferent arm of the anxiety circuit includes the exteroceptive sensory systems of the brain, which convey the sensory information contained in a fear- or anxiety-inducing stimulus to the dorsal thalamus. Visceral afferent pathways alter the function of the locus coeruleus and the amygdala. The thalamus relays sensory information to the primary sensory receptive areas of the cortex, which project to adjacent unimodal and polymodal cortical association areas. The cortical association areas send projections to the amygdala, entorhinal cortex, orbitofrontal cortex, and cingulate gyrus. A pivotal role for the amygdala in the transmission and interpretation of fear and anxiety is suggested by extensive afferents to the amygdala from thalamic and cortical exteroceptive systems, as well as by subcortical visceral afferent pathways. The neuronal interactions between the amygdala enable the individual to initiate adaptive behaviors to threat based upon the nature of the threat and prior experience. The efferent pathways involving the amygdala, locus coeruleus, hypothalamus, periaqueductal gray, and striatum mediate autonomic, neuroendocrine, and skeletal-motor responses associated with fear and anxiety. The proposed brain structures, neural mechanisms, and neural circuits related to anxiety provide a basis for increased understanding of the pathophysiology of anxiety disorders.