<i>N</i>-Methyl <scp>d</scp>-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 <i>N</i>-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 an 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.<b>NEW & NOTEWORTHY</b> It has been hypothesized that <i>N</i>-methyl d-aspartate receptor (NMDAR) hypofunction causes symptoms of schizophrenia, including impairments in coordinated neuronal activity. Our findings support this hypothesis by showing that a drug (ketamine) that impairs NMDAR function reduces coordinated neural activity in response to flickering light, matching deficits found in schizophrenia. Developing experimental models and testing hypotheses that describe altered cortical processing is key to understanding the underlying neural deficits and developing treatments for neuropsychiatric diseases.