INS-fMRI: a novel method for mapping mesoscale connectome networks in vivo in nonhuman primates

Mapping brain connections is paramount in neuroscience. Lacking has been a method that can systematically map mesoscale (<1mm) connections in the brain in vivo at brainwide scale. Mesoscale mapping is particularly important for NHPs in which information is represented in submillimeter clusters (e.g. cortical columns, striosomes, thalamic rods). Here, we present a method called INS-fMRI, which comprises optical stimulation of single sites in the brain using pulsed Infrared Neural Stimulation (INS), coupled with mapping of functionally connected sites in the brain using ultrahigh field fMRI. It is the only method available for mapping mesoscale connections rapidly (multiple networks mapped within single MRI sessions), systematically (allowing comparison of networks within single individuals), in vivo (no animal sacrifice needed), at whole brain scale, and without viral transfection. This method has broad applicability to a wide range of neuroscience questions. It can be used at any brain site, on different animal models, and on different MRI platforms. The ability to probe circuits repeatedly within single individuals also opens doors for studying changes in mesoscale circuits over time (e.g. for development, aging, disease studies). In addition, as this method circumvents the need for viral transfection, there is exciting potential for human clinical application.