Abstract
Background: A subjective sense of agency over actions is thought to arise from a match between the predicted and actual sensory consequences of a movement command. A failure to appropriately generate or utilize such predictions is argued to give rise to the agency disturbances that characterize psychosis. A likely mechanism of such predictions are corollary discharge (CD) signals—“copies” of motor signals that, rather than being sent to the muscles, are sent to sensory areas. The most robust behavioral paradigms for studying CD as well as the only neurophysiological evidence for CD signals in primates have come from the oculomotor system, making it an ideal translational framework in which to investigate CD and, in turn, the mechanisms of agency disturbances in psychosis.
Methods: We conducted 2 independent studies in chronic, medicated schizophrenia patients using oculomotor paradigms that have been employed in animal studies.
Results: In both of these studies, patients with schizophrenia failed to appropriately use CD to predict gaze position following an eye movement. In the first study, patients showed evidence of failing to use CD to inform successive eye movements. In the second study, patients were impaired at using CD to inform visual perception following an eye movement, which was correlated with psychotic symptom severity.
Conclusion: Using these same paradigms, neurophysiology studies have found evidence that CD signals associated with eye movements are transmitted to visually-responsive areas in the frontal cortex via the mediodorsal thalamus. Given that the performance of schizophrenia patients in our samples looks very similar to the performance of non-human primates following mediodorsal thalamus inactivation and humans with mediodorsal thalamus lesions, the current data suggests that CD abnormalities, at least in the oculomotor system, might have their basis in abnormal functioning of this region and/or abnormal frontothalamic connectivity. Oculomotor paradigms can be used in the future to probe exactly how CD signals are disturbed (e.g., whether these signals are noisy, inaccurate, delayed, or simply not transmitted). Eye movement research has the potential to probe the precise nature of prediction impairments and to link core phenomenological experiences in schizophrenia to activity of single neurons.