Developmental trajectory of mismatch negativity and visual event-related potentials in healthy controls: Implications for neurodevelopmental vs. neurodegenerative models of schizophrenia.

ABSTRACT

Sensory processing deficits are core features of schizophrenia, reflected in impaired generation of event-related potential (ERP) measures such as auditory mismatch negativity (MMN) and visual P1. To understand the potential time course of development of deficits in schizophrenia, we obtained MMN to unattended duration, intensity and frequency deviants, and visual P1 to attended LSF stimuli, in 43 healthy individuals ages 6 to 25years (mean 17), and compared results to data from 30 adult schizophrenia patients (mean age 38). We analyzed "time-domain" measures of amplitude and latency, and event-related spectral perturbation (ERSP, "time-frequency") to evaluate underlying neurophysiological mechanisms. Duration and intensity MMN amplitudes increased from childhood to late adolescence, while frequency MMN reached maximum amplitude during early development. As reported previously, in ERSP analyses, MMN activity corresponded primarily to theta-band (4-7Hz) activity, while responses to standards occurred primarily in alpha (8-12Hz) across age groups. Both deviant-induced theta and standard-induced alpha activity declined significantly with age for all deviant types. Likewise, visual P1 also showed an amplitude decline over development, reflecting a reduction in both evoked power and ITC. While MMN "difference" waveform ERP data suggest failure of maturation in schizophrenia, MMN ERSP analyses instead support a neurodegenerative process, as these isolate responses to deviants and standards, showing large low-frequency evoked power for both in children. Neurodegenerative processes are also supported by large visual P1 amplitudes and large low-frequency evoked power in children, in contrast with adult schizophrenia. Sensory processing deficits in schizophrenia may be related to accelerated synaptic pruning.