Functional organization of information flow in the corticospinal pathway

Abstract

Transmission of information in the corticospinal (CS) route constitutes the fundamental infrastructure for voluntary actions. The anatomy of this pathway has been studied extensively, but there is little direct evidence regarding its functional organization. Here we explored the areal specificity of CS connections by studying two related questions: the functional significance of the parallel, motor, and premotor CS pathways; and the way in which finger-related motor commands are handled by this pathway. We addressed these questions by recording from primary motor (M1) and premotor cortical sites in primates (Maccaca fascicularis) performing a motor task, while measuring the evoked intraspinal unit response to single pulse cortical stimulation. Stimulation in M1 evoked spinal neuronal responses more frequently than stimulation in premotor cortex. The number of muscles excited by M1 stimulation was higher than the number excited by premotor stimulation. Within subregions of M1 finger-related sites were sparsely connected with intermediate zone interneurons and tended to affect the ventrally located motoneurons directly. These results suggest that, despite the parallel anatomical organization, the flow of motor commands is predominantly relayed via M1 to downstream elements. The functional impact of premotor cortex is weak, possibly due to inhibitory systems that can shape the flow of information in the CS pathway. Finally, the difference in spinal processing of finger versus wrist-related motor commands points to a different motor control strategy of finger versus wrist movements.

Figure 1.

Experimental setting and recording maps. a, Monkeys sat in a primate chair and controlled an on-screen cursor by applying an isometric two-dimensional torque at the wrist. Recordings were made from the motor cortex, cervical spinal cord, and arm muscles (EMG). Cortical electrodes were used for both recording and stimulating the tissue. Stimulations (at least 200 single pulses applied at 3 Hz) were applied while monkeys performed the task. b, To quantify the spinal response to cortical stimulation, the raw spinal recordings (step 1) were processed by high-pass filtering and rectification (step 2). The SD across the sweeps was used to quantify the response. For each significantly responsive spinal site, we calculated the response width, area, peak time, and peak magnitude (step 3). c, Cortical recording maps showing the relations between the recording sites and the nearby sulci. Only arm-related sites that were identified as either M1 (squares) or PM (circles) are shown. Color coding showing the different joint movements evoked by near-threshold stimulation in each site. For monkeys A, D, and V, black dots mark CS connected sites. For monkey C, the black x's show sites where cortical stimulation was applied to measure muscle field size.

Figure 2.

Evoked spinal responses by stimulation in M1 versus PM sites. a, Examples of three spinal sites in which responses were evoked by stimulation in M1 (green traces) and/or premotor cortex (brown traces). In all three cases, the M1 and premotor sites were recorded simultaneously in parallel to the spinal recordings. In one case (right-most example), both cortical sites evoked a significant spinal response. b, M1 sites had a significantly higher tendency to evoke spinal response than PM sites (χ² test, p < 0.01). c, No significant differences were found in the dorsal-to-ventral (DV) depth of spinal sites responding to M1 and PM stimulation.

Figure 3.

Analysis of response width. a, Examples of two typical patterns of spinal responses that present short (single peaks) or long (double peaks) responses. b, Distribution of response width computed for M1 (green bars) and PM (brown bars, plotted as a mirror reflection) based on significant spinal responses obtained at all stimulation amplitudes in M1 or PM sites (n = 153). A small but significant difference was found between M1 and PM responses (t test, p < 0.05) that reflects the tendency for PM-evoked responses to be shorter than M1-evoked responses. c, Average short (black line) and long (gray line) responses defined using a 4.5 ms criterion. Stimulation artifacts were first removed, and the single responses were then normalized to emphasize the response shape. Shaded areas around each average reflect the SEM. d, the dependency of response width on stimulation amplitude computed for M1 sites (green circles) and PM (brown triangles) sites. Correlation values (ρ) and their significance level are shown as well.

Figure 4.

Responses of single spinal cells to cortical stimulation. a, Examples of single traces and PSTHs of a single spinal unit (denoted by asterisks). In the PSTH, green/red lines mark sets of bins that were significantly larger/smaller than background firing. Significant bins in this example and in the entire figure were calculated using a 2 ms time window (i.e., 10 successive bins) shifted in steps of 0.2 ms. We used the center of each significant window for indicating significant bins. Dashed blue line corresponds to the background firing rate computed during the prestimulus period (−20 to −10 ms before stimulus onset). In this case, a double-peak excitation was followed by a period of decreased firing. b, Three examples showing the different responses that were observed: excitation (top), inhibitory (middle), and excitatory-inhibitory (bottom) patterns. c, An example in which a single spinal cell was affected by stimulation in both M1 (top) and PM (bottom) sites. Note that whereas M1 only excited the cell, PM exerted both excitation and inhibition. d, Summary of the different response patterns evoked in spinal neurons by stimulation in M1 (green bars) and PM (brown bars) sites. The significance level for M1 and PM evoked responses are shown for the entire set of neurons and only the responsive cases.

Figure 5.

Site-dependency of evoked muscle field. a, The muscle field size (i.e., the number of muscles significantly recruited by cortical stimulation) was significantly larger (t test, p ≪ 0.01) for single-pulse stimulations in M1 (dark bar) than for stimulations in PM (light bar). b, The intensity dependence of the field size for M1 (circles) and PM (triangles) stimulation as a function of stimulation amplitude. Error bars are provided for each stimulation value, and asterisks denote significant differences in the mean field size between M1 and PM sites.

Figure 6.

Spinal responses evoked by stimulation in finger-related versus wrist-related cortical sites. a, b, Two examples of raw traces and quantified spinal responses (bottom plot) evoked by stimulation in cortical finger-related sites (a, orange trace) and wrist-related cortical response (b, blue trace). c, The fraction of connected CS sites obtained for M1 wrist-related (blue bar) and finger-related (orange bar) cortical sites (χ² test, p < 0.002). d, Mean recording depth (dorsal-to-ventral) of evoked spinal responses found for spinal sites responding to stimulation in finger-related (orange bar) versus wrist-related (blue bar) cortical sites.