Intraindividual neurophysiological variability in ultra-high-risk for psychosis and schizophrenia patients: single-trial analysis

BACKGROUND: Intraindividual variability in neurophysiological responses is an important factor in the study of schizophrenia. Interestingly, this variability strongly predicts individual differences in cognitive processing. Neurobiological abnormalities that present during the prodromal phase of schizophrenia are not well characterized. However, these symptoms may provide insight into the key circuits involved in the disorder. AIMS: To investigate the variability in magnetoencephalographic responses at ultrahigh risk and schizophrenia patients. METHODS: Twenty-four ultrahigh risk, 21 patients with schizophrenia and 28 healthy controls were evaluated. The intraindividual variability was estimated by calculating the s.d. of the across-trial amplitude in responses to deviant and standard stimuli. The degree of phase locking across trials was calculated by intertrial coherence. RESULTS: Greater variability in the responses to deviant and standard tones was noted in the schizophrenia and ultrahigh risk groups compared with controls. Variability in response to standard stimuli was positively correlated with the amplitude for the standard stimuli in all of the groups. Moreover, schizophrenia patients displayed lower alpha and theta intertrial coherence compared with ultrahigh risk and controls. Mismatch negativity amplitude was correlated with the alpha intertrial coherence in all groups. Taken together, the augmented variability and reduced inter-trial coherence provide empirical evidence for increased amplitude and phase inconsistencies in schizophrenia and ultrahigh risk. CONCLUSIONS: The results implicate widespread dysfunction in amplitude modulation and phase concentration in schizophrenia and ultrahigh risk, as well as evidence for early amplitude and phase disruption. These finding suggest intraindividual variability and intertrial coherence appear to be important indicators of pathophysiological processing.