Longitudinal observations using simultaneous fMRI, multiple channel electrophysiology recording, and chemical microiontophoresis in the rat brain

Background: fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. New Methods: Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months. Our artifact replacing technique is optimized for combined LFP and rsMRI data collection. Results: Intracortical implantation of a multichannel microelectrode array resulted in minimal distortion and signal loss in fMRI images inside a 9.4T MRI scanner. rsMRI-induced electrophysiology artifacts were replaced using an in-house developed algorithm. Microinjection of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) enhanced dopaminergic neuronal activity in the ventral tegmental area (VTA) and altered LFP signal and fMRI functional connectivity in the striatum. Comparisons with Existing Method(s): Nanomanufacturing advances permit the production of MRI-compatible microelectrode arrays (with 16 or more channels), extending research beyond conventional methods limited to fewer channels. Our method permits longitudinal data collection of LFP and rsMRI and our algorithm effectively detects and replaces fMRI-induced electrophysiological noise, permitting rsMRI data collection concomitant with LFP recordings. Conclusions: Our model consists of longitudinal concurrent fMRI and multichannel intracortical electrophysiological recording during microinjection of pharmacological agents to modulate neural activity in the rat brain. We used commercial micro-electrodes and recording system and can be readily generalized to other labs.