Volumetric mesoscopic electrophysiology: a new imaging modality for the nonhuman primate

The primate brain is a densely interconnected organ whose function is best understood by recording from the entire structure in parallel, rather than parts of it in sequence. However, available methods either have limited temporal resolution (functional magnetic resonance imaging; fMRI), limited spatial resolution (macroscopic electroencephalography), or a limited field of view (microscopic electrophysiology). To address this need, we developed a volumetric, mesoscopic recording approach (MePhys) by tessellating the volume of a monkey hemisphere with 992 electrode contacts that were distributed across 62 chronically implanted multielectrode shafts. We showcase the scientific promise of MePhys by describing the functional interactions of local field potentials between the more than 300,000 simultaneously recorded pairs of electrodes. We find that a subanesthetic dose of ketamine-believed to mimic certain aspects of psychosis-can create a pronounced state of functional disconnection and prevent the formation of stable large-scale intrinsic states. We conclude that MePhys provides a new and fundamentally distinct window into brain function whose unique profile of strengths and weaknesses complements existing approaches in synergistic ways.NEW & NOTEWORTHY We created a new imaging modality for the nonhuman primate, mesoscopic electrophysiology, or MePhys by sampling local field potentials (LFPs) in a dense three-dimensional grid from across the volume of one entire hemisphere. MePhys combines the millisecond temporal resolution of electrophysiology with the large field of view and millimeter spatial resolution of functional magnetic resonance imaging (fMRI). MePhys' unique profile of strengths and limitations makes it an ideal imaging method for the nonhuman primate brain observatories of the future.