Multimodal Correspondence between Optogenetic fMRI, Electrophysiology, and Anatomical Maps of the Secondary Somatosensory Cortex in Nonhuman Primates

Optogenetic neuromodulation combined with functional MRI (opto-fMRI) enables noninvasive monitoring of brain-wide activity and probes causal connections. In this study, we focused on the secondary somatosensory (S2) cortex, a hub for integrating tactile and nociceptive information. By selectively stimulating excitatory neurons in the S2 cortex of monkeys using optogenetics, we observed widespread opto-fMRI activity in regions beyond the somatosensory system, as well as a strong spatial correspondence between opto-fMRI activity map and anatomical connections of the S2 cortex. Locally, optogenetically evoked fMRI BOLD signals from putative excitatory neurons exhibited standard hemodynamic response function. At low laser power, graded opto-fMRI signal changes are closely correlated with increases in local field potential (LFP) signals, but not with spiking activity. This indicates that LFP changes in excitatory neurons more accurately reflect the opto-fMRI signals than spikes. In summary, our optogenetic fMRI and anatomical findings provide causal functional and anatomical evidence supporting the role of the S2 cortex as a critical hub connecting sensory regions to higher-order cortical and subcortical regions involved in cognition and emotion. The electrophysiological basis of the opto-fMRI signals uncovered in this study offers novel insights into interpreting opto-fMRI results. Nonhuman primates are an invaluable intermediate model for translating optogenetic preclinical findings to humans.