Motor cortex is functionally organized as a set of spatially distinct representations for complex movements

Abstract

There is a long-standing debate regarding the functional organization of motor cortex. Intracortical microstimulation (ICMS) studies have provided two contrasting views depending on the duration of stimulation. In the rat, short-duration ICMS reveals two spatially distributed forelimb movement representations, the rostral forelimb area (RFA) and caudal forelimb area (CFA), eliciting identical movements. In contrast, long-duration ICMS reveals spatially distributed, complex, multijoint movement areas, with grasping found exclusively in the rostral area and reach-shaping movements of the arm located in the caudal area. To provide corroboration for which interpretation is correct, we selectively inactivated the RFA/grasp area during the performance of skilled forelimb behaviors using a reversible cortical cooling deactivation technique. A significant impairment of grasping in the single-pellet retrieval task and manipulations of pasta was observed during cooling deactivation of the RFA/grasp area, but not the CFA/arm area. Our results indicate a movement-based, rather than a muscle-based, functional organization of motor cortex, and provide evidence for a conserved homology of independent grasp and reach circuitry shared between primates and rats.

Keywords: behavior; intracortical microstimulation; rat; reversible lesion.

Figure 1.

Time course and spread of cortical cooling. a, Cortical cryoloop assembly. b, Cortical temperature time course from cooling onset recorded 1500 μm below the pial surface at varying distances from the cryoloop with a stable holding loop temperature of 4°C. The threshold deactivation isotherm of 20°C (Lomber et al., 1999), below which synaptic block occurs, is plotted as a stippled line and is achieved within 1 mm of the cryoloop configuration used in this study. A rapid onset/offset of cortical inactivation can be achieved within 120 s. c, Cortical depth temperature readings obtained from a penetration site 500 μm away from the midpoint of the cryoloop with a holding loop temperature of 4°C. Consistent temperatures were recorded across cortical laminae. d, Schematic diagrams for cryoloop implantations and the extent of cortical deactivation (loop holding temperature, 4°C) for RFA-cooled and CFA-cooled groups. Deactivation area is plotted to 1 mm away from the cryoloop using thermocline isotherm data in b. Scale bar, 10 mm.

Figure 2.

a–i, Movement patterns elicited by long-duration intracortical microstimulation. Movements were classified as either simple, when involving a single forelimb joint, or complex, when involving multiple forelimb joints. Complex movements were classified as elevations involving flexion of the elbow followed by extension of the wrist (a), advances involving forward displacement of the elbow and shoulder with wrist extension and hand opening (b), grasps involving flexion of the wrist and simultaneous digit contraction and hand closure (c), and retractions involving caudal displacement of the elbow and shoulder (d). Simple movements consisted of flexions of the digits (e) or elbow (g), extensions of the elbow (f) or wrist (i), as well as supinations of the forelimb (h).

Figure 3.

Representative forelimb movement representation topography derived in the same rat with short-duration intracortical microstimulation preceding the long-duration intracortical microstimulation. The duration of stimulation trains alters the evoked forelimb responses elicited within the RFA and CFA. Complex movements, involving coordinated activity among multiple forelimb joints, are observed under long-duration microstimulation. Nonresponsive or nonforelimb points were observed to completely surround the responsive area.

Figure 4.

Comparison of forelimb movements and representational areas (in square millimeters) evoked with SD-ICMS and LD-ICMS. Size distribution of forelimb movements elicited under SD-ICMS and LD-ICMS. Elbow flexions are the most common movement elicited under both stimulation conditions.

Figure 5.

Complex movement representation topography elicited under LD-ICMS. a, b, Cumulative distribution (a) and 95% confidence intervals (b) in 10 naive rats. Complex movements exhibit a topographical clustering across motor cortex: gasping movements are localized most anterior and are exclusive to the RFA; advances are elicited caudally from grasps; retractions are typically elicited from the posterior lateral aspect of the CFA; elevations are elicited predominantly from the posterior medial aspect of the CFA.

Figure 6.

Forelimb movement representations following skilled reach training. a, Representative forelimb movement representation topography derived in a reach-trained rat. b, Reach-trained rats did not demonstrate any specific increase in individual movement representation size relative to naive controls. c, Although forelimb representation sizes between groups were equivalent, there was a significant (p = 0.0001) increase in the proportion of forelimb movement representations that also elicited nonforelimb movements following training. d, Post hoc analyses revealed that jaw (p = 0.0022) and neck (p = 0.0001) movements overlapping within the forelimb movement representations in reach-trained rats were significantly increased. *p < 0.05.

Figure 7.

Single-pellet reaching endpoint success and attempts. Behavioral performance with repeated testing sessions under baseline, cortical cooling, and rewarm conditions. a–d, Cortical cooling was associated with significant reductions in mean (±SEM) reaching attempts and success in both RFA-cooled (a, c) and CFA-cooled (b, d) groups. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 8.

Qualitative comparison of the grasping movement subcomponent in representative rats during acute cooling of the RFA and CFA. Under baseline and rewarm conditions, rats in both groups typically clasp the food pellet securely within the hand. During cooling deactivation of the RFA, food pellets were often held between digits. A significant increase in the mean (±SEM) error score of the grasping movement was observed during cooling (baseline error scores subtracted) of the RFA compared with the CFA. *p < 0.05, ***p < 0.001.

Figure 9.

Sample reach attempt video frame stills during a successful reach in a RFA-cooled rats (left) and CFA-cooled rats (right). RFA-cooled rats did not fully clasp the food pellet within the hand without significant impairment to limb advancement and pellet retrieval. CFA-cooled rats exhibited deficits in adduction of the elbow and limb advancement without significant impairment to grasping of the pellet.

Figure 10.

Representative forelimb movement representations derived following CFA and RFA cryoloop implantation groups. Long-duration ICMS was used to confirm cortical map integrity following cryoloop implantation and behavioral testing. No differences in the size of either the RFA (p = 0.37) or CFA (p = 0.32) was observed between implanted and unimplanted groups.