N-methyl d-aspartate receptor hypofunction reduces steady state visual evoked potentials.
Journal of neurophysiology – July 14, 2025
Source: PubMed
Summary
Coordinated brain activity, measured by steady state visual evoked potentials (SSVEP), is often disrupted in conditions like schizophrenia. One theory suggests NMDA receptor hypofunction contributes to this. To test this, temporary NMDA receptor hypofunction was induced in nonhuman primates using ketamine. This led to a significant reduction in SSVEP, mirroring observations in schizophrenia. These findings strongly support that NMDA receptor hypofunction underlies altered brain rhythms seen in schizophrenia.
Abstract
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.