Recovery of Volitional Motor Control and Overground Walking in Participants With Chronic Clinically Motor Complete Spinal Cord Injury: Restoration of Rehabilitative Function With Epidural Spinal Stimulation (RESTORES) Trial-A Preliminary Study.

Spinal cord injury (SCI) is damage to any part of the spinal cord resulting in paralysis, bowel and/or bladder incontinence, and loss of sensation and other bodily functions. Current treatments for chronic SCI are focused on managing symptoms and preventing further damage to the spinal cord with limited neuro-restorative interventions. Recent research and independent clinical trials of spinal cord stimulation (SCS) or intensive neuro-rehabilitation including neuro-robotics in participants with SCI have suggested potential malleability of the neuronal networks for neurological recovery. We hypothesize that epidural electrical stimulation (EES) delivered via SCS in conjunction with mental imagery practice and robotic neuro-rehabilitation can synergistically improve volitional motor function below the level of injury in participants with chronic clinically motor-complete SCI. In our pilot clinical RESTORES trial (RESToration Of Rehabilitative function with Epidural spinal Stimulation), we investigate the feasibility of this combined multi-modal approach in restoring volitional motor control and achieving independent overground locomotion in participants with chronic motor complete thoracic SCI. Secondary aims are to assess the safety of this combination therapy including the off-label SCS usage as well as improving functional outcome measures. To our knowledge, this is the first clinical trial that investigates the combined impact of this multi-modal EES and rehabilitation strategy in participants with chronic motor complete SCI. Two participants with chronic motor-complete thoracic SCI were recruited for this pilot trial. Both participants have successfully regained volitional motor control below their level of SCI injury and achieved independent overground walking within a month of post-operative stimulation and rehabilitation. There were no adverse events noted in our trial and there was an improvement in post-operative truncal stability score. Results from this pilot study demonstrates the feasibility of combining EES, mental imagery practice and robotic rehabilitation in improving volitional motor control below level of SCI injury and restoring independent overground walking for participants with chronic motor-complete SCI. Our team believes that this provides very exciting promise in a field currently devoid of disease-modifying therapies.

Synchronizing Motor Imagery Cue in fNIRS Brain-Computer Interface to reduce confounding effects of respiration.

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging method that measures oxygenated hemoglobin (HbO) levels in the brain to infer neural activity using near-infrared light. Measured HbO levels are directly affected by a person's respiration. Hence, respiration cycles tend to confound fNIRS readings in motor imagery-based fNIRS Brain-Computer Interfaces (BCI). To reduce this confounding effect, we propose a method of synchronizing the motor imagery cue timing with the subject's respiration cycle using a breathing sensor. We conducted an experiment to collect 160 single trials from 10 subjects performing motor imagery using an fNIRS-based BCI and the breathing sensor. We then compared the HbO levels in trials with and without respiration synchronization. The results showed that respiration synchronization yielded HbO levels that were less dispersed across trials, and a negative correlation between the dispersion index of HbO levels with MI decoding accuracies was found across the 10 subjects. This showed that synchronizing motor imagery cues to respiration can yield increased HbO level consistency leading to better MI performance. Hence, the proposed method holds promise to improve the decoding performance of fNIRS-BCI by reducing the confounding effects of respiration.

Neural correlates of learning in a linear discriminant analysis brain-computer interface paradigm.

Objective.With practice, the control of brain-computer interfaces (BCI) would improve over time; the neural correlate for such learning had not been well studied. We demonstrated here that monkeys controlling a motor BCI using a linear discriminant analysis (LDA) decoder could learn to make the firing patterns of the recorded neurons more distinct over a short period of time for different output classes to improve task performance.Approach.Using an LDA decoder, we studied two Macaque monkeys implanted with microelectrode arrays as they controlled the movement of a mobile robotic platform. The LDA decoder mapped high-dimensional neuronal firing patterns linearly onto a lower-dimensional linear discriminant (LD) space, and we studied the changes in the spatial coordinates of these neural signals in the LD space over time, and their correspondence to trial performance. Direction selectivity was quantified with permutation feature importance (FI).Main results.We observed that, within individual sessions, there was a tendency for the points in the LD space encoding different directions to diverge, leading to fewer misclassification errors, and, hence, improvement in task accuracy. Accuracy was correlated with the presence of channels with strong directional preference (i.e. high FI), as well as a varied population code (i.e. high variance in FI distribution).Significance.We emphasized the importance of studying the short-term/intra-sessional variations in neural representations during the use of BCI. Over the course of individual sessions, both monkeys could modulate their neural activities to create increasingly distinct neural representations.

Information sparseness in cortical microelectrode channels while decoding movement direction using an artificial neural network.

Implanted microelectrode arrays can directly pick up electrode signals from the primary motor cortex (M1) during movement, and brain-machine interfaces (BMIs) can decode these signals to predict the directions of contemporaneous movements. However, it is not well known how much each individual input is responsible for the overall performance of a BMI decoder. In this paper, we seek to quantify how much each channel contributes to an artificial neural network (ANN)-based decoder, by measuring how much the removal of each individual channel degrades the accuracy of the output. If information on movement direction was equally distributed among channels, then the removal of one would have a minimal effect on decoder accuracy. On the other hand, if that information was distributed sparsely, then the removal of specific information-rich channels would significantly lower decoder accuracy. We found that for most channels, their removal did not significantly affect decoder performance. However, for a subset of channels (16 out of 61), removing them significantly reduced the decoder accuracy. This suggests that information is not uniformly distributed among the recording channels. We propose examining these channels further to optimize BMIs more effectively, as well as understand how M1 functions at the neuronal level.

Movement-specific signaling is differentially distributed across motor cortex layer 5 projection neuron classes.

Motor cortex generates descending output necessary for executing a wide range of limb movements. Although movement-related activity has been described throughout motor cortex, the spatiotemporal organization of movement-specific signaling in deep layers remains largely unknown. Here we record layer 5B population dynamics in the caudal forelimb area of motor cortex while mice perform a forelimb push/pull task and find that most neurons show movement-invariant responses, with a minority displaying movement specificity. Using cell-type-specific imaging, we identify that invariant responses dominate pyramidal tract (PT) neuron activity, with a small subpopulation representing movement type, whereas a larger proportion of intratelencephalic (IT) neurons display movement-type-specific signaling. The proportion of IT neurons decoding movement-type peaks prior to movement initiation, whereas for PT neurons, this occurs during movement execution. Our data suggest that layer 5B population dynamics largely reflect movement-invariant signaling, with information related to movement-type being routed through relatively small, distributed subpopulations of projection neurons.

Intention Estimation Based Adaptive Unscented Kalman Filter for Online Neural Decoding.

The commonly used fixed discrete Kalman filters (DKF) in neural decoders do not generalize well to the actual relationship between neuronal firing rates and movement intention. This is due to the underlying assumption that the neural activity is linearly related to the output state. They also face the issues of requiring large amount of training datasets to achieve a robust model and a degradation of decoding performance over time. In this paper, an adaptive adjustment is made to the conventional unscented Kalman filter (UKF) via intention estimation. This is done by incorporating a history of newly collected state parameters to develop a new set of model parameters. At each time point, a comparative weighted sum of old and new model parameters using matrix squared sums is used to update the neural decoding model parameters. The effectiveness of the resulting adaptive unscented Kalman filter (AUKF) is compared against the discrete Kalman filter and unscented Kalman filter-based algorithms. The results show that the proposed new algorithm provides higher decoding accuracy and stability while requiring less training data.

Decoding movement direction from cortical microelectrode recordings using an LSTM-based neural network.

Brain-machine interfaces (BMIs) allow individuals to communicate with computers using neural signals, and Kalman Filter (KF) are prevailingly used to decode movement directions from these neural signals. In this paper, we implemented a multi-layer long short-term memory (LSTM)based artificial neural network (ANN) for decoding BMI neural signals. We collected motor cortical neural signals from a nonhuman primate (NHP), implanted with microelectrode array (MEA) while performing a directional joystick task. Next, we compared the LSTM model in decoding the joystick trajectories from the neural signals against the prevailing KF model. The results showed that the LSTM model yielded significantly improved decoding accuracy measured by mean correlation coefficient (0.84, p < 10-7) than the KF model (0.72). In addition, using a principal component analysis (PCA)-based dimensionality reduction technique yielded slightly deteriorated accuracies for both the LSTM (0.80) and KF (0.70) models, but greatly reduced the computational complexity. The results showed that the LSTM decoding model holds promise to improve decoding in BMIs for paralyzed humans.