A tale of two sites: Differential impairment of frequency and duration mismatch negativity across a primarily inpatient versus a primarily outpatient site in schizophrenia

Deficits in mismatch negativity (MMN) generation are among the best replicated neurophysiological deficits in schizophrenia, with reduced amplitude reflecting impaired information processing at the level of supratemporal auditory cortex. Differential patterns of MMN dysfunction according to deviant types have been reported across studies, with some research groups showing impairment in duration MMN but not frequency MMN, and other research groups reporting both findings. We evaluate the hypothesis that recruitment setting, reflecting current functional status, might be an important determinant of the pattern of MMN dysfunction. Here, we evaluated patterns of MMN dysfunction, along with tone matching and neuropsychological performance in subjects drawn from 1) a predominant inpatient/residential care setting (Nathan Kline Institute) and 2) a predominant outpatient setting (Columbia University). As predicted, compared to healthy controls, deficits in duration MMN were observed across sites, whereas deficits in frequency MMN/tone matching were confined to the chronic inpatient setting. Within patients, the frequency MMN deficit was highly correlated with impairments in tone matching ability across sites (r=-0.52, p<0.0001), as well as impairments in verbal learning (r=-0.54, p<0.0001). Responses to standard stimuli in the MMN paradigm were assessed using measures of alpha evoked power and inter-trial coherence (ITC). While deficits in alpha ITC were observed across sites (both p<0.05), deficits in alpha power were observed at the inpatient (p=0.001) but not outpatient (p=0.2) site. Overall, these finding indicate that impairments of frequency MMN generation and response power to standard stimuli could be particularly linked to forms of schizophrenia that are associated with poor functional outcome.