Juan Forero

Balance-corrective responses to unexpected perturbations at the arms during treadmill walking

The arms have been shown to be involved in the regulation of balance during walking. The use of a walking aid enhances balance by increasing the base of support and reducing the load on the legs by partly transferring it to the arms. However, when actively engaged during a balance task, perturbations to the arms can destabilize balance. Previous studies have investigated postural adjustments associated with focal arm movements during standing and walking. However, balance-corrective reactions to unexpected perturbations to the arms during walking have not been well studied. In the present study, subjects walked on a treadmill while grasping a pair of handles when sudden perturbations were delivered by displacing the handles in the forward or backward direction. Instructing subjects to oppose the displacement of the handles resulted in strong responses in the arms that were accompanied by activation of muscles in the legs, comparable to those observed in other balance disturbance studies. Conversely, when subjects were instructed to allow the handles to move when displaced, no responses were observed in the arms. However, similar responses were observed in the legs whether subjects opposed the displacement of the handles or not when perturbations were applied at heel strike. The results from this study show that balance reactions can be elicited in the legs in response to perturbations applied at the arms, and that the expression of these responses is affected by the task engaged in by the arms.

Automatic postural responses following rapid displacement of a light touch contact during standing

Responses elicited by the rapid displacement of a light touch contact surface were investigated during standing with the eyes closed. During quiet standing the touch surface was moved with an imperceptible slow (0.5Hz), small (0.5cm) oscillation to entrain the participants sway. Periodically, a rapid displacement (1.25cm, 12.5cm/s peak velocity, 187.5cm/s/s peak acceleration) of the rod was applied, either forward or backward, at either the fore or aft position of the entrained sway. Each participant received 10 unexpected displacements of the same direction, with 20 participants receiving forward displacements and 6 participants receiving backward displacements. Electromyographic recordings from 4 arm and 2 ankle muscles were sampled along with center of pressure and joint kinematics. Rapid displacement of the touch surface consistently resulted in short-latency (<120ms) responses in the muscles of the arm or ankle in 21 of 26 participants. However, the first exposure to the touch displacement resulted in a distinct response in the muscles about the ankle in 13 participants, while responses in arm muscles were observed in 11 participants. Participants that responded with activation of muscles at the ankle displayed a corresponding shift in the center of pressure. Trials 2 through 10 were characterized by an absence of responses in the ankle muscles, but more consistent responses in the arm muscles. The rapid onset of ankle muscle activity following the unexpected slip of a touch surface in some instances suggests that tactile cues provide a potential sensory cue for triggering balance reactions. The importance of this sensory cue in balance control is likely dependent in part on the relevance of the tactile inputs in the context of the perceived task.

Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot

Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury.

The amplitude of interlimb cutaneous reflexes in the leg is influenced by fingertip touch and vision during treadmill locomotion

Abstract Light touch at the fingertip has been shown to influence postural control during standing and walking. Interlimb cutaneous reflexes have been proposed to provide a neural link between the upper and lower limbs to assist in interlimb coordination during activities such as walking. In this study, we tested the hypothesis that cutaneous sensory pathways linking the arm and leg will be facilitated if subjects use light touch to assist with postural control during treadmill walking. To test this, interlimb cutaneous reflexes from the median nerve, serving the skin contact region, and radial nerve, serving an irrelevant sensory territory, were tested in the legs of subjects walking on treadmill in an unstable environment. Interlimb cutaneous reflexes were tested while subjects (a) touched or (b) did not touch a stable contact with their fingertip, and while the eyes were either (c) open or (d) closed. Reflexes arising from both nerves were facilitated when vision was removed that was then ameliorated when touch was provided. These changes in reflex amplitude during the eyes closed conditions were mirrored by changes in background muscle activity. We suggest that this facilitation of interlimb reflexes from both nerves arises from a generalized increase in excitability related to the postural anxiety of walking on a treadmill with the eyes closed, which is then restored by the provision of light touch. However, the influence of touch when the eyes were open differed depending upon the nerve stimulated. Radial nerve reflexes in the legs were suppressed when touch was provided, mirroring a suppression in the background muscle activity. In contrast, median nerve reflexes in the leg were larger when touch was provided with the eyes open, despite a suppression of background muscle activity. This nerve-specific effect of touch on the amplitude of the interlimb cutaneous reflexes suggests that touch sensory information from the median nerve was facilitated when that input was functionally relevant.

The effect of light touch on the amplitude of cutaneous reflexes in the arms during treadmill walking

AbstractLight touch contact of the tip of one finger can influence the postural control of subjects standing or walking on a treadmill. It is suggested that haptic cues from the finger provide an important sensory cue for the control of posture. In the current study, we used intra-limb cutaneous reflexes in the arms to test the hypothesis that transmission in sensory pathways relevant to the light touch contact would be modulated when light touch is used to increase stability during walking in an unstable environment. Subjects walked on a treadmill and received periodic pulls to the waist. Cutaneous reflexes were evoked from stimulation of the median and radial nerves while the subjects either (a) lightly touched or (b) did not touch a stable contact with the tip of their index finger, while the eyes were either (c) open or (d) closed. The results showed that cutaneous reflexes were modulated by both touch and vision. The effect of touch depended on the nerve being stimulated. The provision of touch in the absence of vision resulted in facilitation of median nerve reflexes evoked in the posterior deltoid and the triceps brachii, but resulted in the suppression of radial nerve reflexes. The nerve-specific influence of touch observed in the responses suggests that cutaneous afferent pathways are facilitated in the presence of touch if they transport sensory information from functionally relevant sensory cues.

A motorized pellet dispenser to deliver high intensity training of the single pellet reaching and grasping task in rats

The single pellet reaching and grasping (SPG) task is widely used to study forelimb motor performance in rodents and to provide rehabilitation after neurological disorders. Nonetheless, the time necessary to train animals precludes its use in settings where high-intensity training is required. In the current study, we developed a novel high-intensity training protocol for the SPG task based on a motorized pellet dispenser and a dual-window enclosure. We tested the protocol in naive adult rats and found 1) an increase in the intensity of training without increasing the task time and without affecting the overall performance of the animals, 2) a reduction in the variability within and between experiments in comparison to manual SPG training, and 3) a reduction in the time required to conduct experiments. In summary, we developed and tested a novel protocol for SPG training that provides higher-intensity training while reducing the variability of results observed with other protocols.

Eliciting inflammation enables successful rehabilitative training in chronic spinal cord injury

Rehabilitative training is one of the most successful therapies to promote motor recovery after spinal cord injury, especially when applied early after injury. Polytrauma and management of other medical complications in the acute post-injury setting often preclude or complicate early rehabilitation. Therefore, interventions that reopen a window of opportunity for effective motor training after chronic injury would have significant therapeutic value. Here, we tested whether this could be achieved in rats with chronic (8 weeks) dorsolateral quadrant sections of the cervical spinal cord (C4) by inducing mild neuroinflammation. We found that systemic injection of a low dose of lipopolysaccharide improved the efficacy of rehabilitative training on forelimb function, as assessed using a single pellet reaching and grasping task. This enhanced recovery was found to be dependent on the training intensity, where a high-intensity paradigm induced the biggest improvements. Importantly, in contrast to training alone, the combination of systemic lipopolysaccharide and high-intensity training restored original function (reparative plasticity) rather than enhancing new motor strategies (compensatory plasticity). Accordingly, electrophysiological and tract-tracing studies demonstrated a recovery in the cortical drive to the affected forelimb muscles and a restructuration of the corticospinal innervation of the cervical spinal cord. Thus, we propose that techniques that can elicit mild neuroinflammation may be used to enhance the efficacy of rehabilitative training after chronic spinal cord injury.

A simple analogy for nervous system plasticity after injury.

When considering plasticity, the central nervous system can be viewed as a building block house. After damage, building components might be lost or loosened and may be rearranged by renovation, analogous to neuroplasticity that occurs after central nervous system injury. In both scenarios, the location and severity of damage will determine the efficacy of renovation/rehabilitation and thus the quality of the adapted structure.

Disease-modifying effects of ganglioside GM1 in Huntington's disease models

Huntingtons disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric problems. Previous studies indicated that levels of brain gangliosides are lower than normal in HD models and that administration of exogenous ganglioside GM1 corrects motor dysfunction in the YAC128 mouse model of HD. In this study, we provide evidence that intraventricular administration of GM1 has profound disease‐modifying effects across HD mouse models with different genetic background. GM1 administration results in decreased levels of mutant huntingtin, the protein that causes HD, and in a wide array of beneficial effects that include changes in levels of DARPP32, ferritin, Iba1 and GFAP, modulation of dopamine and serotonin metabolism, and restoration of normal levels of glutamate, GABA, L‐Ser and D‐Ser. Treatment with GM1 slows down neurodegeneration, white matter atrophy and body weight loss in R6/2 mice. Motor functions are significantly improved in R6/2 mice and restored to normal in Q140 mice, including gait abnormalities that are often resistant to treatments. Psychiatric‐like and cognitive dysfunctions are also ameliorated by GM1 administration in Q140 and YAC128 mice. The widespread benefits of GM1 administration, at molecular, cellular and behavioural levels, indicate that this ganglioside has strong therapeutic and disease‐modifying potential in HD.

Cortical electrical stimulation in female rats with a cervical spinal cord injury to promote axonal outgrowth

Electrical stimulation (ES) to promote corticospinal tract (CST) repair after spinal cord injury (SCI) is underinvestigated. This study is the first to detail intracortical ES of the injured CST. We hypothesize that cortical ES will promote CST collateralization and regeneration, prevent dieback, and improve recovery in an SCI rat model. The CST was transected at the the fourth cervical level in adult female Lewis rats trained in a stairwell grasping task. Animal groups included (a) ES333 (n = 14; 333 Hz, biphasic pulse for 0.2‐ms duration every 500 ms, 30 pulses per train); (b) ES20 (n = 14; 20 Hz, biphasic pulse for 0.2‐ms duration every 1 s, 60 pulses per train); (c) SCI only (n = 10); and (d) sham (n = 10). ES of the injured forelimbs motor cortex was performed for 30 min immediately prior to SCI. Comparisons between histological data were performed with a 1‐way ANOVA or Kruskal–Wallis test, and grasping scores were compared using repeated‐measures 2‐way ANOVA.