Abstract
Fatal familial insomnia (FFI) is characterized by insomnia, dysautonomia, disruption of circadian rhythms, and motor dysfunction. The typical neuropathological findings in FFI are severe neuronal depletion in the mediodorsal (MD) and anteroventral nuclei of the thalamus. The interaction between the thalamus and central autonomic control mechanisms is poorly understood. The central autonomic areas include the anterior cingulate and insular cortices; amygdala, paraventricular nucleus, dorsomedial nucleus, and lateral hypothalamic area; periaqueductal gray; parabrachial nucleus; ventrolateral medulla; and nucleus of the solitary tract. Several nuclei of the thalamus have connections with areas of the central autonomic network. The paraventricular nucleus (PVT) projects to the medial prefrontal cortex, and receives multimodal visceral and somatosensory inputs. The MD nucleus is connected with several "limbic" areas involved in autonomic control. The autonomic manifestations of FFI are exaggerated sympathetic activation with preserved parasympathetic drive to the cardiovascular system. This reflects an exaggerated sympathetic drive from supramedullary structures. Bicuculline, administered into the MD, elicits an increase in arterial pressure and heart rate. The medial portion of the MD may share with the PVT a relay function for circuits controlling autonomic responses. MD involvement in FFI suggests a role of the thalamus in central autonomic and other integrative functions.