Both Corticospinal and Reticulospinal Tracts Control Force of Contraction.

The control of contraction strength is a key part of movement control. In primates, both corticospinal and reticulospinal cells provide input to motoneurons. Corticospinal discharge is known to correlate with force, but there are no previous reports of how reticular formation (RF) activity modulates with different contractions. Here we trained two female macaque monkeys (body weight, 5.9-6.9 kg) to pull a handle that could be loaded with 0.5-6 kg weights and recorded from identified pyramidal tract neurons (PTNs) in primary motor cortex and RF cells during task performance. Population-averaged firing rate increased monotonically with higher force for the RF, but showed a complex profile with little net modulation for PTNs. This reflected a more heterogeneous profile of rate modulation across the PTN population, leading to cancellation in the average. Linear discriminant analysis classified the force based on the time course of rate modulation equally well for PTNs and RF cells. Peak firing rate had significant linear correlation with force for 43 of 92 PTNs (46.7%) and 21 of 46 RF cells (43.5%). For almost all RF cells (20 of 21), the correlation coefficient was positive; similar numbers of PTNs (22 vs 21) had positive versus negative coefficients. Considering the timing of force representation, similar fractions (PTNs: 61.2%; RF cells: 55.5%) commenced coding before the onset of muscle activity. We conclude that both corticospinal and reticulospinal tracts contribute to the control of contraction force; the reticulospinal tract seems to specify an overall signal simply related to force, whereas corticospinal cell activity would be better suited for fine-scale adjustments.SIGNIFICANCE STATEMENT For the first time, we compare the coding of force for corticospinal and reticular formation cells in awake behaving monkeys, over a wide range of contraction strengths likely to come close to maximum voluntary contraction. Both cortical and brainstem systems coded similarly well for force, but whereas reticular formation cells carried a simple uniform signal, corticospinal neurons were more heterogeneous. This may reflect a role in the gross specification of a coordinated movement, versus more fine-grained adjustments around individual joints.

Cortical, Corticospinal, and Reticulospinal Contributions to Strength Training.

Following a program of resistance training, there are neural and muscular contributions to the gain in strength. Here, we measured changes in important central motor pathways during strength training in 2 female macaque monkeys. Animals were trained to pull a handle with one arm; weights could be added to increase load. On each day, motor-evoked potentials in upper limb muscles were first measured after stimulation of the primary motor cortex (M1), corticospinal tract (CST), and reticulospinal tract (RST). Monkeys then completed 50 trials with weights progressively increased over 8-9 weeks (final weight ∼6 kg, close to the animal's body weight). Muscle responses to M1 and RST stimulation increased during strength training; there were no increases in CST responses. Changes persisted during a 2 week washout period without weights. After a further 3 months of strength training, an experiment under anesthesia mapped potential responses to CST and RST stimulation in the cervical enlargement of the spinal cord. We distinguished the early axonal volley and later spinal synaptic field potentials, and used the slope of the relationship between these at different stimulus intensities as a measure of spinal input-output gain. Spinal gain was increased on the trained compared with the untrained side of the cord within the intermediate zone and motor nuclei for RST, but not CST, stimulation. We conclude that neural adaptations to strength training involve adaptations in the RST, as well as intracortical circuits within M1. By contrast, there appears to be little contribution from the CST.SIGNIFICANCE STATEMENT We provide the first report of a strength training intervention in nonhuman primates. Our results indicate that strength training is associated with neural adaptations in intracortical and reticulospinal circuits, whereas corticospinal and motoneuronal adaptations are not dominant factors.

Multimodal stimuli modulate rapid visual responses during reaching.

The reticulospinal tract plays an important role in primate upper limb function, but methods for assessing its activity are limited. One promising approach is to measure rapid visual responses (RVRs) in arm muscle activity during a visually cued reaching task; these may arise from a tecto-reticulospinal pathway. We investigated whether changes in reticulospinal excitability can be assessed noninvasively using RVRs, by pairing the visual stimuli of the reaching task with electrical stimulation of the median nerve, galvanic vestibular stimulation, or loud sounds, all of which are known to activate the reticular formation. Surface electromyogram (EMG) recordings were made from the right deltoid of healthy human subjects as they performed fast reaching movements toward visual targets. Stimuli were delivered up to 200 ms before target appearance, and RVR was quantified as the EMG amplitude in a window 75-125 ms after visual target onset. Median nerve, vestibular, and auditory stimuli all consistently facilitated the RVRs, as well as reducing the latency of responses. We propose that this facilitation reflects modulation of tecto-reticulospinal excitability, which is consistent with the idea that the amplitude of RVRs can be used to assess changes in brain stem excitability noninvasively in humans.NEW & NOTEWORTHY Short-latency responses in arm muscles evoked during a visually driven reaching task have previously been proposed to be tecto-reticulospinal in origin. We demonstrate that these responses can be facilitated by pairing the appearance of a visual target with stimuli that activate the reticular formation: median nerve, vestibular, and auditory stimuli. We propose that this reflects noninvasive measurement and modulation of reticulospinal excitability.

Automated FES for Upper Limb Rehabilitation Following Stroke and Spinal Cord Injury.

Neurorehabilitation aims to induce beneficial neural plasticity in order to restore function following injury to the nervous system. There is an increasing evidence that appropriately timed functional electrical stimulation (FES) can promote associative plasticity, but the dosage is critical for lasting functional benefits. Here, we present a novel approach to closed-loop control of muscle stimulation for the rehabilitation of reach-to-grasp movements following stroke and spinal cord injury (SCI). We developed a simple, low-cost device to deliver assistive stimulation contingent on users' self-initiated movements. The device allows repeated practice with minimal input by a therapist, and is potentially suitable for home use. Pilot data demonstrate usability by people with upper limb weakness following SCI and stroke, and participant feedback was positive. Moreover, repeated training with the device over 1-2 weeks led to functional benefits on a general object manipulation assessment. Thus, automated FES delivered by this novel device may provide a promising and readily translatable therapy for upper limb rehabilitation for people with stroke and SCI.