Volumetric Mesoscopic Electrophysiology: A New Recording Modality with a Unique Functional Profile and Wide Range of Applications

7. PROJECT SUMMARY Background. Key aspects of brain function can only be understood by recording from the entire brain in parallel, rather than parts of it in sequence. While fMRI has excellent full-brain coverage and spatial resolution, its temporal resolution is limited by the relatively slow hemodynamic response. And while electrophysiological approaches have excellent temporal resolution, they either 1) don’t cover the entire brain (microscopic electrophysiology) or 2) have limited spatial resolution (macroscopic electrophysiology). The goal of the proposed work is to develop a new recording modality for the non-human primate, called mesoscopic electrophysiology, that combines the large field of view and millimeter spatial resolution of fMRI with the millisecond spectro-temporal resolution of electrophysiology. Public/health/relevance. The non-human primate is a crucial element of a translational pipeline designed to bring novel therapeutic approaches from the bench to the bedside. The large disconnect between single-cell recordings in monkeys and EEG/MEG or fMRI recordings in humans is the weak point of this pipeline. By combining the best features of both EEG and fMRI into a single method in the non-human primate, we will be able to facilitate the comparison between findings in humans and non-human primates. In addition to being a translational Rosetta-stone, the method has immense promise for exploratory scientific discovery and to quantify and understand disease-relevant changes in the monkey brain. For example, we could show how ketamine, which is known to mimic certain aspects of psychosis, weakens communication between brain regions, and prevents the brain from settling into stable states. Methodology. Our mesoscopic electrophysiology system will consist of a chronically implanted 3-dimensional grid of 1920 intracranial electrode contacts distributed across the entire volume of one hemisphere. We aim to create two fully functional mesoscopic electrophysiology systems thus allowing us to start contributing to the scientific literature which requires concurrent findings from two animals. Innovation/Impact. If successful, the proposed work will provide a new and qualitatively distinct window into non-human primate brain function whose unique profile of strengths and weaknesses complements existing approaches in synergistic ways. Leveraging its unique functional profile that fills gaps at the intersection of existing methods, MePhys has the potential to facilitate the translation of findings across scales (micro – meso – macro); species (rodent – monkey – human); recording modalities (electrophysiology – fMRI – optical); and internal states such as learning (naïve – proficient – overtrained). Given the importance of the non-human primate model, this work will enhance our understanding of the human brain in health and disease and ultimately contribute to the NINDS’s mission of reducing the negative impact of neurological disorders and stroke.