Cortico-cerebellar coordination facilitates neuroprosthetic control.

Temporally coordinated neural activity is central to nervous system function and purposeful behavior. Still, there is a paucity of evidence demonstrating how this coordinated activity within cortical and subcortical regions governs behavior. We investigated this between the primary motor (M1) and contralateral cerebellar cortex as rats learned a neuroprosthetic/brain-machine interface (BMI) task. In neuroprosthetic task, actuator movements are causally linked to M1 "direct" neurons that drive the decoder for successful task execution. However, it is unknown how task-related M1 activity interacts with the cerebellum. We observed a notable 3 to 6 hertz coherence that emerged between these regions' local field potentials (LFPs) with learning that also modulated task-related spiking. We identified robust task-related indirect modulation in the cerebellum, which developed a preferential relationship with M1 task-related activity. Inhibiting cerebellar cortical and deep nuclei activity through optogenetics led to performance impairments in M1-driven neuroprosthetic control. Together, these results demonstrate that cerebellar influence is necessary for M1-driven neuroprosthetic control.

Disturbed laterality of non-rapid eye movement sleep oscillations in post-stroke human sleep: a pilot study.

Sleep is known to promote recovery post-stroke. However, there is a paucity of data profiling sleep oscillations in the post-stroke human brain. Recent rodent work showed that resurgence of physiologic spindles coupled to sleep slow oscillations (SOs) and concomitant decrease in pathological delta (δ) waves is associated with sustained motor performance gains during stroke recovery. The goal of this study was to evaluate bilaterality of non-rapid eye movement (NREM) sleep-oscillations (namely SOs, δ-waves, spindles, and their nesting) in post-stroke patients vs. healthy control subjects. We analyzed NREM-marked electroencephalography (EEG) data in hospitalized stroke-patients (n = 5) and healthy subjects (n = 3). We used a laterality index to evaluate symmetry of NREM oscillations across hemispheres. We found that stroke subjects had pronounced asymmetry in the oscillations, with a predominance of SOs, δ-waves, spindles, and nested spindles in affected hemisphere, when compared to the healthy subjects. Recent preclinical work classified SO-nested spindles as restorative post-stroke and δ-wave-nested spindles as pathological. We found that the ratio of SO-nested spindles laterality index to δ-wave-nested spindles laterality index was lower in stroke subjects. Using linear mixed models (which included random effects of concurrent pharmacologic drugs), we found large and medium effect size for δ-wave nested spindle and SO-nested spindle, respectively. Our results in this pilot study indicate that considering laterality index of NREM oscillations might be a useful metric for assessing recovery post-stroke and that factoring in pharmacologic drugs may be important when targeting sleep modulation for neurorehabilitation post-stroke.

Disturbed laterality of non-rapid eye movement sleep oscillations in post-stroke human sleep: a pilot study.

Sleep is known to promote recovery post-stroke. However, there is a paucity of data profiling sleep oscillations post-stroke in the human brain. Recent rodent work showed that resurgence of physiologic spindles coupled to sleep slow oscillations(SOs) and concomitant decrease in pathological delta(δ) waves is associated with sustained motor performance gains during stroke recovery. The goal of this study was to evaluate bilaterality of non-rapid eye movement (NREM) sleep-oscillations (namely SOs, δ-waves, spindles and their nesting) in post-stroke patients versus healthy control subjects. We analyzed NREM-marked electroencephalography (EEG) data in hospitalized stroke-patients (n=5) and healthy subjects (n=3) from an open-sourced dataset. We used a laterality index to evaluate symmetry of NREM oscillations across hemispheres. We found that stroke subjects had pronounced asymmetry in the oscillations, with a predominance of SOs, δ-waves, spindles and nested spindles in one hemisphere, when compared to the healthy subjects. Recent preclinical work classified SO-nested spindles as restorative post-stroke and δ-wave-nested spindles as pathological. We found that the ratio of SO-nested spindles laterality index to δ-wave-nested spindles laterality index was lower in stroke subjects. Using linear mixed models (which included random effects of concurrent pharmacologic drugs), we found large and medium effect size for δ-wave nested spindle and SO-nested spindle, respectively. Our results indicate considering laterality index of NREM oscillations might be a useful metric for assessing recovery post-stroke and that factoring in pharmacologic drugs may be important when targeting sleep modulation for neurorehabilitation post-stroke.

A new approach of inducing proprioceptive illusion by transcutaneous electrical stimulation.

BACKGROUND: Neurotraumas or neurodegenerative diseases often result in proprioceptive deficits, which makes it challenging for the nervous system to adapt to the compromised sensorimotor conditions. Also, in human machine interactions, such as prosthesis control and teleoperation, proprioceptive mismatch limits accuracy and intuitiveness of controlling active joints in robotic agents. To address these proprioceptive deficits, several invasive and non-invasive approaches like vibration, electrical nerve stimulation, and skin stretch have been introduced. However, proprioceptive modulation is still challenging as the current solutions have limitations in terms of effectiveness, usability, and consistency. In this paper, we propose a new way of modulating proprioception using transcutaneous electrical stimulation. We hypothesized that transcutaneous electrical stimulation on elbow flexor muscles will induce illusion of elbow joint extension. METHOD: Eight healthy human subjects participated in the study to test the hypothesis. Transcutaneous electrodes were placed on different locations targeting elbow flexor muscles on human subjects and experiments were conducted to identify the best locations for electrode placement, and best electrical stimulation parameters, to maximize induced proprioceptive effect. Arm matching experiments and Pinocchio illusion test were performed for quantitative and qualitative analysis of the observed effects. One-way repeated ANOVA test was performed on the data collected in arm matching experiment for statistical analysis. RESULTS: We identified the best location for transcutaneous electrodes to induce the proprioceptive illusion, as one electrode on the muscle belly of biceps brachii short head and the other on the distal myotendinous junction of brachioradialis. The results for arm-matching and Pinocchio illusion tests showed that transcutaneous electrical stimulation using identified electrode location and electrical stimulation parameters evoked the illusion of elbow joint extension for all eight subjects, which supports our hypothesis. On average, subjects reported 6.81° angular illusion of elbow joint extension in arm-matching tests and nose elongated to 1.78 × height in Pinocchio illusion test. CONCLUSIONS: Transcutaneous electrical stimulation, applied between the the synergistic elbow flexor muscles, consistently modulated elbow joint proprioception with the illusion of elbow joint extension, which has immense potential to be translated into various real-world applications, including neuroprosthesis, rehabilitation, teleoperation, mixed reality, and etc.