Simultaneous monitoring of the effects of optogenetic stimulation of monkey S2 cortex using functional MRI and MRI thermometry

Combining functional magnetic resonance imaging (fMRI) with cell-type selective optogenetic stimulation offers a unique chance to dissect brain functional networks and probe causal connections. Our team employed opto-fMRI and opto-electrophysiology to map the brain circuits of the secondary somatosensory cortex (S2) in nonhuman primate brains after unilateral transfection with AAV5 and AAV9 constructs of blue light opsin ChR2 with CaMKIIa promoter, largely specific to excitatory neurons. Our results revealed that blue light stimulation of varying intensities (1, 2, 4, 8, 16, and 24 mW) in the transfected S2 hand region elicited robust local field potentials (LFPs) and spiking activity. Blue laser evoked LFP power increases peaked at 16 mW. Delivery of blue laser to transfected S2 evoked robust BOLD signal changes locally and in distant cortical and subcortical brain regions, including bilateral MCC, posterior insula, thalamus, bilateral area 3b/1, and contralateral S2 cortices. As expected, green light stimulation did not produce detectable spiking and LFP activity, but it did lead to robust BOLD signal changes in both local and distant brain regions. To monitor possible heating effects from laser stimulation, we developed an MRI method that measures temperature by computing the phase information of fMRI images. We measured small temperature increases at high laser power (e.g., 24 mW delivered through a 200 mu m diameter optical fiber) but not at low laser powers (1,2, 4, and 8 mW). The low power green light-associated BOLD signal changes require further elucidation but suggest some opto-fMRI findings should be interpreted with caution.