Hare and Mitchell et al. came
close to making the discovery but were apparently hindered by their inability to interpret the signs they elicited in their patients. The experiments of Claude Bernard gave succinct accounts of the effects of damage to the cervical sympathetic nerves in animals, although there appears to be no evidence that he made similar observations in humans. Horner was the first to give a detailed, scientifically supported account and accurately interpret the signs of cervical sympathetic nerve damage in a human subject. The anatomy of the pathway is reviewed and the detailed structure of its central part updated. Evidence from computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon-emission computerized tomography (SPECT) studies have confirmed that reciprocally connected centers in the insular cortex, central nucleus of amygdala, hypothalamus, mesencephalic and pontine tegmentum, nucleus of tractus solitarius, and the ventrolateral medulla form the central pathway. The nucleus of tractus solitarius is probably the main reflex center for the sympathetic system, whereas the ventrolateral medulla serves as the pathway through which the central neurons influence the preganglionic neurons of the thoracolumbar outflow. Emotional and sensory inputs from the frontal and somatosensory cortices provide the inputs needed by the insula to drive the sympathetic nervous system to produce appropriate responses.