John A. Buford

Bilateral actions of the reticulospinal tract on arm and shoulder muscles in the monkey: stimulus triggered averaging

The motor output of the pontomedullary reticular formation (PMRF) was investigated to determine the reticulospinal system’s capacity for bilateral control of the upper limbs. Stimulus triggered electromyographic averages (StimulusTA) were constructed from muscles of both upper limbs while two awake monkeys (Macaca fascicularis) performed a reaching task using either arm. Extensor and flexor muscles were studied at the wrist, elbow, and shoulder; muscles acting on the scapula were also studied. Post-stimulus effects (PStEs) resulted from 435 (81%) of 535 sites tested. Of 1611 PStEs analyzed, 58% were post-stimulus suppression (PStS), and 42% were post-stimulus facilitation (PStF). Onset latency was earlier for PStF than PStS, duration was longer for PStS, and amplitude was larger for PStF. Ipsilateral and contralateral PStEs were equally prevalent; bilateral responses were typical. In the ipsilateral forelimb and shoulder, the prevalent pattern was flexor PStF and extensor PStS; the opposite pattern was prevalent contralaterally. Sites producing strong ipsilateral upper trapezius PStF were concentrated in a region caudal and ventral to abducens. The majority of muscles studied had no clear somatotopic organization. Overall, the results indicate the monkey PMRF has the capacity to support bilateral coordination of limb movements using reciprocal actions within a limb and between sides.

Bilateral Spike-Triggered Average Effects in Arm and Shoulder Muscles from the Monkey Pontomedullary Reticular Formation

Pontomedullary reticular formation (PMRF) neurons (309) were recorded simultaneously with electromyographic activity from arm and shoulder muscles in four monkeys performing arm-reaching tasks. Spike-triggered averages (SpikeTAs) were compiled for 292 neurons (3836 neuron–muscle pairs). Fourteen PMRF neurons located in a region ventral to the abducens nucleus produced 42 significant SpikeTA effects in arm and shoulder muscles. Of these 14 PMRF neurons, nine produced SpikeTA effects bilaterally. Overall, PMRF neurons facilitated ipsilateral flexors and contralateral extensors, while suppressing ipsilateral extensors and contralateral flexors. Spike- and stimulus-triggered averaging effects obtained from the same recording site were similar. These findings indicate that single PMRF neurons can directly influence movements of both upper limbs.

Movement-related and preparatory activity in the reticulospinal system of the monkey

Three monkeys (M. fascicularis) performed a center-out, two-dimensional reaching task that included an instructed delay interval based on a color-coded visuospatial cue. Neural activity in the medial pontomedullary reticular formation (mPMRF) was recorded along with hand movement. Of 176 neurons with movement-related activity, 109 (62%) had movement-related but not preparatory activity (M cells), and 67 (38%) had both movement-related and preparatory activity (MP cells). EOG analyses indicated that the preparatory activity was not consistent with control of eye movements. There were slight changes in electromyograms (EMG) late in the instructed delay period before the Go cue, but these were small compared with the movement-related EMG activity. Preparatory activity, like the EMG activity, was also confined to the end of the instructed delay period for 14 MP cells, but the remaining 53 MP cells (30%) had preparatory activity that was not reflected in the EMG. Peri-movement neural activity varied with movement direction for 70% of the cells, but this variation rarely fit circular statistics commonly used for studies of directional tuning; directional tuning was even less common in the preparatory activity. These data show that neurons in the mPMRF are strongly modulated during small reaching movements, but this modulation was rarely correlated with the trajectory of the hand. In accord with findings in the literature from other regions of the CNS, evidence of activity related to motor preparation in these cells indicates that this function is distributed in the nervous system and is not a feature limited to the cerebral cortex.

Brain–Computer Interface after Nervous System Injury

Brain–computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson’s disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders.

Reticulospinal neurons in the pontomedullary reticular formation of the monkey (Macaca fascicularis)

Recent neurophysiological studies indicate a role for reticulospinal neurons of the pontomedullary reticular formation (PMRF) in motor preparation and goal-directed reaching in the monkey. Although the macaque monkey is an important model for such investigations, little is known regarding the organization of the PMRF in the monkey. In the present study, we investigated the distribution of reticulospinal neurons in the macaque. Bilateral injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made into the cervical spinal cord. A wide band of retrogradely labeled cells was found in the gigantocellular reticular nucleus (Gi) and labeled cells continued rostrally into the caudal pontine reticular nucleus (PnC) and into the oral pontine reticular nucleus (PnO). Additional retrograde tracing studies following unilateral cervical spinal cord injections of cholera toxin subunit B revealed that there were more ipsilateral (60%) than contralateral (40%) projecting cells in Gi, while an approximately 50:50 ratio contralateral to ipsilateral split was found in PnC and more contralateral projections arose from PnO. Reticulospinal neurons in PMRF ranged widely in size from over 50 microm to under 25 microm across the major somatic axis. Labeled giant cells (soma diameters greater than 50 microm) comprised a small percentage of the neurons and were found in Gi, PnC and PnO. The present results define the origins of the reticulospinal system in the monkey and provide an important foundation for future investigations of the anatomy and physiology of this system in primates.

Combined corticospinal and reticulospinal effects on upper limb muscles

Both the reticulospinal and corticospinal systems are known to control recruitment of upper limb muscles, yet no known studies have attempted to assess their combined effects in the same experiment in the awake, behaving primate. The purpose of this study is to present an approach for the analysis of the cooperative control from these two motor systems. Muscle responses to electrical stimulation in the reticulospinal system and corticospinal system alone or in combination were studied. The responses were categorized based on simple neural circuits that could explain the interactions of these systems. Five such circuits were identified that could explain 86% of the observed patterns of combined recruitment during stimulation. Improved understanding of the cooperation between these motor systems could provide insight for development of better rehabilitation approaches for stroke patients and others with movement disorders.

Wavelet methodology to improve single unit isolation in primary motor cortex cells.

The proper isolation of action potentials recorded extracellularly from neural tissue is an active area of research in the fields of neuroscience and biomedical signal processing. This paper presents an isolation methodology for neural recordings using the wavelet transform (WT), a statistical thresholding scheme, and the principal component analysis (PCA) algorithm. The effectiveness of five different mother wavelets was investigated: biorthogonal, Daubachies, discrete Meyer, symmetric, and Coifman; along with three different wavelet coefficient thresholding schemes: fixed form threshold, Steins unbiased estimate of risk, and minimax; and two different thresholding rules: soft and hard thresholding. The signal quality was evaluated using three different statistical measures: mean-squared error, root-mean squared, and signal to noise ratio. The clustering quality was evaluated using two different statistical measures: isolation distance, and L-ratio. This research shows that the selection of the mother wavelet has a strong influence on the clustering and isolation of single unit neural activity, with the Daubachies 4 wavelet and minimax thresholding scheme performing the best.

Intersegmental Dynamics During Gait: Implications for Control

Abstract Quantifying the active and passive forces that arise from within the body and from the physical environment during locomotion is vital for better understanding the role of the central nervous system in coordinating and regulating human locomotor action. To further explore the nature of intersegmental dynamics during human locomotion, we conducted experiments to contrast - in the same subjects - the roles of muscular, gravitational, and motion dependent torques during human walking and running. The potency of the intersegmental dynamics approach, as well as complementary synthesis and simulation approaches, for gaining insight into the control of limb motion during locomotion is illustrated by the richness of the information about the limb during the swing phase.

Measuring the motor output of the pontomedullary reticular formation in the monkey: do stimulus-triggered averaging and stimulus trains produce comparable results in the upper limbs?

The pontomedullary reticular formation (PMRF) of the monkey produces motor outputs to both upper limbs. EMG effects evoked from stimulus-triggered averaging (StimulusTA) were compared with effects from stimulus trains to determine whether both stimulation methods produced comparable results. Flexor and extensor muscles of scapulothoracic, shoulder, elbow, and wrist joints were studied bilaterally in two male M. fascicularis monkeys trained to perform a bilateral reaching task. The frequency of facilitation versus suppression responses evoked in the muscles was compared between methods. Stimulus trains were more efficient (94% of PMRF sites) in producing responses than StimulusTA (55%), and stimulus trains evoked responses from more muscles per site than from StimulusTA. Facilitation (72%) was more common from stimulus trains than StimulusTA (39%). In the overall results, a bilateral reciprocal activation pattern of ipsilateral flexor and contralateral extensor facilitation was evident for StimulusTA and stimulus trains. When the comparison was restricted to cases where both methods produced a response in a given muscle from the same site, agreement was very high, at 80%. For the remaining 20%, discrepancies were accounted for mainly by facilitation from stimulus trains when StimulusTA produced suppression, which was in agreement with the under-representation of suppression in the stimulus train data as a whole. To the extent that the stimulus train method may favor transmission through polysynaptic pathways, these results suggest that polysynaptic pathways from the PMRF more often produce facilitation in muscles that would typically demonstrate suppression with StimulusTA.

Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury

This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI). Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX). This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI). To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm (ILP). In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days) or late (42 days) after midthoracic SCI in a rodent model. Early after SCI or TX at 7 days, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between spared axonal systems and adaptive plasticity in locomotor networks and highlights a critical window for activity-based rehabilitation.