In vivo study of connectivity with electrical microstimulation and fMRI

Abstract

We describe a new method that combines microstimulation with fMRI for the detailed study of neural connectivity in the alive animal. We used specially constructed microelectrodes to stimulate directly a selected subcortical or cortical area while simultaneously measuring changes in brain activity, indexed by the blood oxygen level dependent (BOLD) signal. The exact location of the stimulation site was achieved by means of anatomical scans as well as by the study of the physiological properties of neurons. Imaging was carried out in a Biospec 4.7T/40 cm vertical bore scanner (Bruker, Inc), using pulse sequences described elsewhere (Logothetis et. al. Nature Neuroscience 1999). Electrical stimulation was delivered using a biphasic pulse generator attached to a constant-current stimulus isolation unit. Constant-current charge-balanced biphasic pulses (300usec, 50 to 150 uA, at 50 to 500 Hz) were delivered to the brain for 12.5 sec preceded and followed by 12.5 and 39 sec respectively. The compensation circuit, designed to minimize interference generated by the switching gradients during recording, was always active alleviating all gradient-induced currents in the range of the stimulation current. Local microstimulation of striate cortex yielded both local BOLD signals and activation of areas V2, V3, and MT. Microstimulation of dLGN resulted in the activation of striate cortex, as well as areas V2, V3, and MT. Our findings show that microstimulation combined with fMRI can be exquisitely used to find and study target areas of regions of electrophysiological interest