A Monkey Mesoscopic Electrophysiology System to Bridge the Gap Between Cells, LFP, EEG and BOLD
Presented During:
Thursday, June 27, 2024: 11:30 AM - 12:45 PM
COEX
Room:
Hall D 2
Poster No:
2385
Submission Type:
Abstract Submission
Authors:
Tobias Teichert1
Institutions:
1University of Pittsburgh, Pittsburgh, PA
First Author:
Introduction:
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).
Methods:
To address this methodological need, we developed the first electrophysiological mesoscope by distributing 992 electrode contacts across 62 multi-electrode shafts and then chronically implanting them in a regular grid that covers the entire right hemisphere of a monkey brain. Distances between electrode shafts were 5 mm in the antero-posterior dimension and 4 mm in the medio-lateral dimension. Each electrode shaft was custom designed and manufactured by hand for each grid location. The 16 electrode contacts on each shaft were distributed equidistantly across the entire length of brain penetrated by the shaft. Distance between electrode contacts on each shaft varied between 0.4 mm for the shortest shafts in orbitofrontal cortex and up to 2.7 mm for the much longer medial and posterior shafts.
Results:
Our recordings show that mesoscopic electrophysiology is feasible, safe and provides extremely rich LFP recordings over a period of months, with no noticeable degradation over time. To showcase its wide field of view as well as its excellent temporal and spatial resolution, we recorded so-called frequency-following responses (FFRs), whose neural generators are still a matter of debate. Figure 1 shows FFRs with high signal-to-noise ratio across the entire monkey hemisphere. The large field of view and the high spatial resolution allowed us to follow the propagation and functional transformation of the FFRs along the ascending auditory pathway (Fig 1B).
Next, we show that mesoscopic electrophysiology can capture brain-wide functional connectivity maps with a field of view that cannot be achieved using microscopic electrophysiology and a spectro-temporal resolution that is not possible using fMRI. Figure 2A showcases seed-based functional connectivity maps for four example regions that emerge in different frequency bands. Furthermore, mesoscopic electrophysiology is ideally suited to identify brain-wide internal states. Using spatial correlations of activity patterns recorded at different times, mesoscopic electrophysiology shows the emergence and recurrence of stable brain-wide states that last on the order of tens of seconds that are abolished by sub-anesthetic doses of ketamine, but not midazolam (Fig 2B).
Next, we show that mesoscopic electrophysiology can capture brain-wide functional connectivity maps with a field of view that cannot be achieved using microscopic electrophysiology and a spectro-temporal resolution that is not possible using fMRI. Figure 2A showcases seed-based functional connectivity maps for four example regions that emerge in different frequency bands. Furthermore, mesoscopic electrophysiology is ideally suited to identify brain-wide internal states. Using spatial correlations of activity patterns recorded at different times, mesoscopic electrophysiology shows the emergence and recurrence of stable brain-wide states that last on the order of tens of seconds that are abolished by sub-anesthetic doses of ketamine, but not midazolam (Fig 2B).
Conclusions:
Mesoscopic electrophysiology combines the strengths of the two most important neuroscientific methods: the high temporal resolution of electrophysiology with the large field of view of fMRI. Methodologically, mesoscopic electrophysiology is closely related to other electrophysiolgical approaches. Conceptually, however, it differes from each of these approaches along at least one of three dimensions: (i) Its field of view is a three-dimensional volume rather than one- or two-dimensional manifold; (ii) It spreads electrode contacts as widely as possible in order to maximise the field of view rather than spatial resolution; (iii) It prioritizes local field potentials over single-cell activity. These conceptual priorities of mesoscopic electrophysiology give rise to a functional profile of strengths and weaknesses that is unlike any other imaging method. Given this unique functional profile mesoscopic electrophysiology has the potential to facilitate the translation of findings across scales (micro – meso – macro), species (rodent – monkey – human), and recording modalities (electrophysiology – fMRI – optical).
Language:
Speech Perception
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Novel Imaging Acquisition Methods:
Imaging Methods Other 1
Keywords:
Cerebellum
Electroencephaolography (EEG)
ELECTROPHYSIOLOGY
Source Localization
Other - Brain States
1|2Indicates the priority used for review