Principles of Intrinsic Motor Cortex Connectivity in Primates

Abstract

The forelimb representation in motor cortex (M1) is an important model system in contemporary neuroscience. Efforts to understand the organization of the M1 forelimb representation in monkeys have focused on inputs and outputs. In contrast, intrinsic M1 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 M1 forelimb representation with intracortical microstimulation (ICMS) in male squirrel monkeys. Next, we determined the connectivity of individual M1 sites with ICMS 1 intrinsic signal optical imaging (ISOI). Every stimulation site activated a distinctive pattern of patches (;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 M1. 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 ICMS1ISOI and connections known from tracers. ICMS1ISOI 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 M1 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.

Cortical connections of the functional domain for climbing or running in posterior parietal cortex of galagos

“…Instead, only a few nearby sites are highly activated. Similar results were obtained when sites in M1 of macaques were stimulated (Card & Gharbawie, 2020). A reasonable interpretation of such results is that neurons that are activated at the injection site activate clusters of excitatory neurons at only a few nearby sites.…”

“…These connections indicate that a population of adjoining neurons that make up cortical modules or columns have connections within a larger functional unit, the domain (Kaas, 2012). Electrical stimulation of a site in a domain likely activates most of these adjacent neurons, as well as patches of nearby neurons (Card & Gharbawie, 2020; Stepniewska et al, 2016). The nearby projections involve the activation of both excitatory and inhibitory neurons, but a general finding is that within a sensory area of cortex, the longer axon projections more likely terminate in inhibitory neurons, and thereby contribute to the suppressive receptive field surrounds (Reed et al, 2010; Reed, Qi, & Kaas, 2011).…”

Optical imaging reveals functional domains in primate sensorimotor cortex

“…Similarly, ICMS trains in monkeys evoke specific behaviors from discrete M1 zones that could be considered functional clusters (e.g., Graziano et al, 2002 ; Stepniewska et al, 2014 ; Adelsberger et al, 2014 ). Moreover, each cluster is preferentially connected within M1 to a constellation of functionally-matching zones ( Card and Gharbawie, 2020 ). Thus, as an organizing principle in M1, functional clustering appears to be conserved across species and is readily reveled using several techniques.…”

Large-scale all-optical dissection of motor cortex connectivity reveals a segregated functional organization of mouse forelimb representations

“…4). ICMS stimulation has been recently coupled with intrinsic signal optical imaging to reconstruct activation maps related to forelimb stimulated movements in squirrel monkeys 39 . The authors demonstrated that the intrinsic motor cortex connectivity matched the forelimb somatotopic representation in the primary motor cortex 39 .…”