Minimal handgrip force is needed for transcutaneous electrical stimulation to improve hand functions of patients with severe spinal cord injury.

Spinal cord stimulation enhanced restoration of motor function following spinal cord injury (SCI) in unblinded studies. To determine whether training combined with transcutaneous electrical spinal cord stimulation (tSCS), with or without systemic serotonergic treatment with buspirone (busp), could improve hand function in individuals with severe hand paralysis following SCI, we assessed ten subjects in a double-blind, sham-controlled, crossover study. All treatments-busp, tSCS, and the busp plus tSCS-reduced muscle tone and spasm frequency. Buspirone did not have any discernible impact on grip force or manual dexterity when administered alone or in combination with tSCS. In contrast, grip force, sinusoidal force generation and grip-release rate improved significantly after 6 weeks of tSCS in 5 out of 10 subjects who had residual grip force within the range of 0.1-1.5 N at the baseline evaluation. Improved hand function was sustained in subjects with residual grip force 2-5 months after the tSCS and buspirone treatment. We conclude that tSCS combined with training improves hand strength and manual dexterity in subjects with SCI who have residual grip strength greater than 0.1 N. Buspirone did not significantly improve the hand function nor add to the effect of stimulation.

Machine learning classifies predictive kinematic features in a mouse model of neurodegeneration.

Motor deficits are observed in Alzheimer's disease (AD) prior to the appearance of cognitive symptoms. To investigate the role of amyloid proteins in gait disturbances, we characterized locomotion in APP-overexpressing transgenic J20 mice. We used three-dimensional motion capture to characterize quadrupedal locomotion on a treadmill in J20 and wild-type mice. Sixteen J20 mice and fifteen wild-type mice were studied at two ages (4- and 13-month). A random forest (RF) classification algorithm discriminated between the genotypes within each age group using a leave-one-out cross-validation. The balanced accuracy of the RF classification was 92.3 ± 5.2% and 93.3 ± 4.5% as well as False Negative Rate (FNR) of 0.0 ± 0.0% and 0.0 ± 0.0% for the 4-month and 13-month groups, respectively. Feature ranking algorithms identified kinematic features that when considered simultaneously, achieved high genotype classification accuracy. The identified features demonstrated an age-specific kinematic profile of the impact of APP-overexpression. Trunk tilt and unstable hip movement patterns were important in classifying the 4-month J20 mice, whereas patterns of shoulder and iliac crest movement were critical for classifying 13-month J20 mice. Examining multiple kinematic features of gait simultaneously could also be developed to classify motor disorders in humans.

Reward feedback accelerates motor learning.

Recent findings have demonstrated that reward feedback alone can drive motor learning. However, it is not yet clear whether reward feedback alone can lead to learning when a perturbation is introduced abruptly, or how a reward gradient can modulate learning. In this study, we provide reward feedback that decays continuously with increasing error. We asked whether it is possible to learn an abrupt visuomotor rotation by reward alone, and if the learning process could be modulated by combining reward and sensory feedback and/or by using different reward landscapes. We designed a novel visuomotor learning protocol during which subjects experienced an abruptly introduced rotational perturbation. Subjects received either visual feedback or reward feedback, or a combination of the two. Two different reward landscapes, where the reward decayed either linearly or cubically with distance from the target, were tested. Results demonstrate that it is possible to learn from reward feedback alone and that the combination of reward and sensory feedback accelerates learning. An analysis of the underlying mechanisms reveals that although reward feedback alone does not allow for sensorimotor remapping, it can nonetheless lead to broad generalization, highlighting a dissociation between remapping and generalization. Also, the combination of reward and sensory feedback accelerates learning without compromising sensorimotor remapping. These findings suggest that the use of reward feedback is a promising approach to either supplement or substitute sensory feedback in the development of improved neurorehabilitation techniques. More generally, they point to an important role played by reward in the motor learning process.