INS-fMRI reveals a mesoscale limbic organization associated with medial pulvinar in primates

The experience of emotion comprises not only the feelings (happiness, sadness), but also behavioral expression, internal awareness, and the bodys physiological response. However, it remains unclear how the brain integrates these disparate aspects of emotion. Here, to examine functional connectivity in the limbic system of macaque monkeys, we combined focal Infrared Neural Stimulation of a sensory gateway (medial pulvinar PM), with ultra-high-field 7T functional magnetic resonance imaging (INS-fMRI). We find connected sites are mesoscale (millimeter-scale) in size and arranged in patchy patterns across cingulate, insula, and amygdala. Non-overlapping connections evoked from three sequential stimulation sites in PM form clusters of multi-site integration, and appear related to known functional organization within these limbic regions. We suggest these mesoscale functional connections link the limbic axes of motor expression (cingulate), interoception (insula), and emotion-related processing (amygdala), and that, much like visual system, the limbic system is fundamentally quite orderly at mesoscale. Our results underscore the importance of millimeter-scale precision and organization in diagnosis and treatment of affective disorders.