Primary motor cortex underlies multi-joint integration for fast feedback control

Abstract

A basic difficulty for the nervous system is integrating locally ambiguous sensory information to form accurate perceptions about the outside world. This local-to-global problem is also fundamental to motor control of the arm, because complex mechanical interactions between shoulder and elbow allow a particular amount of motion at one joint to arise from an infinite combination of shoulder and elbow torques. Here we show, in humans and rhesus monkeys, that a transcortical pathway through primary motor cortex (M1) resolves this ambiguity during fast feedback control. We demonstrate that single M1 neurons of behaving monkeys can integrate shoulder and elbow motion information into motor commands that appropriately counter the underlying torque within about 50 milliseconds of a mechanical perturbation. Moreover, we reveal a causal link between M1 processing and multi-joint integration in humans by showing that shoulder muscle responses occurring ∼50 milliseconds after pure elbow displacement can be potentiated by transcranial magnetic stimulation. Taken together, our results show that transcortical processing through M1 permits feedback responses to express a level of sophistication that rivals voluntary control; this provides neurophysiological support for influential theories positing that voluntary movement is generated by the intelligent manipulation of sensory feedback.

Figure 1. Experimental methods

a, Because of the mechanical properties of the limb, an infinite combination of shoulder and elbow torques can cause the same shoulder motion. Determining which torque perturbation caused the observed shoulder motion requires integrating elbow information. b, Limb configuration before (unfilled) and after (filled) a torque perturbation was applied at either the shoulder or elbow. Opposite conditions (shoulder-extensor / elbow-flexor torque) not shown. c, Joint displacement resulting from the shoulder (red) and elbow (blue) perturbation conditions in b. The perturbations yielded similar shoulder motion but substantially different elbow motion. Solid lines represent the mean displacements and the grey lines show individual trials. d, Limb configuration before and after a multi-joint flexion or multi-joint extension torque perturbation. e, The perturbations caused substantial elbow motion but almost no shoulder motion.

Figure 2. Neurons in primary motor cortex

a, Responses of an exemplar shoulder-like neuron to either an elbow (blue) or shoulder (red) torque perturbation in Experiment 1. Data aligned on perturbation onset. Tick marks represent single action potentials and the trace depicts the average response. b, Same format as a but representing the population response across shoulder-like neurons. c and d, Same format as a and b but for Experiment 2.

Figure 3. Population analysis of neurons and muscles

a, Binned response (50–100 ms post-perturbation) across shoulder-like neurons. For Experiment 1, the red and blue bars represent responses to shoulder and elbow torque perturbations, respectively. For Experiment 2, the red and blue bars depict responses to pure elbow motion caused by a torque perturbation aligned with or opposite to the neuron’s steady-state preference, respectively. Error bars indicate SEM, the (*) indicates significant differences between conditions (paired t-test, p < 0.05) and the (†) denotes significant differences from baseline. b, Same format as a but for the population of muscles. Because of the normalization procedure, muscle baseline activity is 0 au. c, Average ROC over time for the population of neurons and muscles. Conditions are collapsed across experiments such that the vertical axis is a metric of multi-joint integration. On average, the neurons led the muscles by ~18 ms as estimated by the average temporal difference between the neural and muscle ROC curves from 50 to 100 ms post-perturbation (filled area). d, Same format as Fig. 2d but for elbow-like neurons.

Figure 4. TMS and perturbation evoked activity in human shoulder muscles

a, Response evoked in an exemplar shoulder muscle (Posterior Deltoid) when a mechanical perturbation or TMS was applied in isolation. b. Observed response (orange) and linear prediction (sum of responses in a, black) when the mechanical perturbation and TMS were applied in the same trial. c. Group muscle response (mean and STD) when TMS was paired with the perturbation normalized by the sum of their separate effects (E_norm = E_TMS,pert / (E_TMS + E_pert). Values above 1 indicate supra-linearity.