N-methyl d-aspartate receptor hypofunction reduces steady state visual evoked potentials.

The dynamic coordination of neural activity across populations of neurons is impaired in neuropsychiatric disorders. Here, we focused on the large-scale rhythmic responses induced by flickering light. These so-called steady-state visual evoked potentials (SSVEPs) are reduced in people with schizophrenia (Sz). A large body of work has identified hypofunction of the N-methyl d-aspartate receptor (NMDAR) as a potential contributor to the symptoms of Sz. Here, we tested the hypothesis that NMDAR hypofunction can account for a reduced ability to generate the coordinated activity reflected in SSVEPs. We recorded SSVEPs using multielectrode arrays permanently implanted in the primary visual cortex of nonhuman primates. In separate sessions, animals were injected with saline (control) or a subanesthetic dose of ketamine (an NMDAR antagonist) to induce a NMDAR hypofunction state. SSVEPs generated during NMDAR hypofunction were substantially reduced and, consistent with findings in Sz, this reduction was found across a range of frequencies from 5 to 40 Hz. These findings provide novel insight into the role of NMDAR hypofunction in the generation of altered coordinated activity and provide experimental support for the hypothesis that NMDAR hypofunction underlies some of the symptoms of schizophrenia.