LAUSR

438 ong-standing hypotheses about schizophrenia as a “dysconnection” syndrome are consistent with the idea that mental illness arises in part from brain circuit disruptions, with impairments in cognition and behavior occurring because of a failure of coordinated action across multiple brain regions. One such theory, put forth by Andreasen and colleagues, suggested that schizophrenia involves a disruption in the integration of cortical striatal thalamic cerebellar circuits. Anatomical work in primates has shown that the thalamus is topographically organized into parallel pathways connecting specific thalamic nuclei to different regions of cortex. The medial dorsal and anterior nuclei of the thalamus project to the dorsolateral prefrontal cortex (dlPFC), whereas the lateral nuclei project more to sensorimotor regions, with similar findings in functional brain connectivity studies in humans. A large body of evidence has shown reduced connectivity from bilateral thalamic regions, medial dorsal, and anterior nuclei in particular, to the bilateral dlPFC, dorsal anterior cingulate, parts of the striatum, and bilateral cerebellum in schizophrenia. This is often coupled increased connectivity between the thalamus, lateral nuclei in particular, and motor, visual, and/or auditory sensory regions. Such altered thalamocortical connectivity has been found in individuals at both clinical and genetic high risk for schizophrenia, and even to some extent in other disorders characterized by psychosis, such as bipolar disorder. Furthermore, among individuals at clinical high risk, altered thalamic connectivity was most pronounced among those who subsequently converted to a psychosis diagnosis. These robust findings across studies are consistent with the idea that coordination among these brain regions is disrupted in individuals with schizophrenia spectrum disorders. Furthermore, the relationship of this impaired thalamic connectivity with cognitive function is consistent with the idea that thalamocortical networks are critical for organizing brain oscillations important for effective cognitive function.