Principles of Intrinsic Motor Cortex Connectivity in Primates

The forelimb representation in motor cortex (MI) is an important model system in contemporary neuroscience. Efforts to understand the organization of the MI forelimb representation in monkeys have focused on inputs and outputs. In contrast, intrinsic MI connections remain mostly unexplored, which is surprising given that intra-areal connections universally outnumber extrinsic connections. To address this knowledge gap, we first mapped the MI forelimb representation with intracortical microstimulation (ICMS) in male squirrel monkeys. Next, we determined the connectivity of individual MI sites with ICMS + intrinsic signal optical imaging (ISOI). Every stimulation site activated a distinctive pattern of patches (similar to 0.25 to 1.0 mm radius) that we quantified in relation to the motor map. Arm sites activated patches that were mostly in arm zones. Hand sites followed the same principle, but to a lesser extent. The results collectively indicate that preferential connectivity between functionally matched patches is a prominent organizational principle in MI. Connectivity patterns for a given site were conserved across a range of current amplitudes, train durations, pulse frequencies, and microelectrode depths. In addition, we found close correspondence in somatosensory cortex between connectivity that we revealed with ICMS +ISOI and connections known from tracers. ICMS+ISOI is therefore an effective tool for mapping cortical connectivity and is particularly advantageous for sampling large numbers of sites. This feature was instrumental in revealing the spatial specificity of intrinsic MI connections, which appear to be woven into the somatotopic organization of the forelimb representation. Such a framework invokes the modular organization well-established for sensory cortical areas.