Case study: persistent recovery of hand movement and tactile sensation in peripheral nerve injury using targeted transcutaneous spinal cord stimulation.

Peripheral nerve injury can lead to chronic pain, paralysis, and loss of sensation, severely affecting quality of life. Spinal cord stimulation has been used in the clinic to provide pain relief arising from peripheral nerve injuries, however, its ability to restore function after peripheral nerve injury have not been explored. Neuromodulation of the spinal cord through transcutaneous spinal cord stimulation (tSCS), when paired with activity-based training, has shown promising results towards restoring volitional limb control in people with spinal cord injury. We show, for the first time, the effectiveness of targeted tSCS in restoring strength (407% increase from 1.79 ± 1.24 N to up to 7.3 ± 0.93 N) and significantly increasing hand dexterity in an individual with paralysis due to a peripheral nerve injury (PNI). Furthermore, this is the first study to document a persisting 3-point improvement during clinical assessment of tactile sensation in peripheral injury after receiving 6 weeks of tSCS. Lastly, the motor and sensory gains persisted for several months after stimulation was received, suggesting tSCS may lead to long-lasting benefits, even in PNI. Non-invasive spinal cord stimulation shows tremendous promise as a safe and effective therapeutic approach with broad applications in functional recovery after debilitating injuries.

Targeted transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study.

Long-term recovery of limb function is a significant unmet need in people with paralysis. Neuromodulation of the spinal cord through epidural stimulation, when paired with intense activity-based training, has shown promising results toward restoring volitional limb control in people with spinal cord injury. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the motor and sensory rehabilitative effects of activating specific cervical spinal segments using tSCS have largely remained unexplored. We show in two individuals with motor-complete SCI that targeted stimulation of the cervical spinal cord resulted in up to a 1,136% increase in exerted force, with weekly activity-based training. Furthermore, this is the first study to document up to a 2-point improvement in clinical assessment of tactile sensation in SCI after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting that targeted tSCS may lead to persistent recovery of motor and sensory function.

Evoking highly focal percepts in the fingertips through targeted stimulation of sulcal regions of the brain for sensory restoration.

BACKGROUND: Paralysis and neuropathy, affecting millions of people worldwide, can be accompanied by significant loss of somatosensation. With tactile sensation being central to achieving dexterous movement, brain-computer interface (BCI) researchers have used intracortical and cortical surface electrical stimulation to restore somatotopically-relevant sensation to the hand. However, these approaches are restricted to stimulating the gyral areas of the brain. Since representation of distal regions of the hand extends into the sulcal regions of human primary somatosensory cortex (S1), it has been challenging to evoke sensory percepts localized to the fingertips. OBJECTIVE/HYPOTHESIS: Targeted stimulation of sulcal regions of S1, using stereoelectroencephalography (SEEG) depth electrodes, can evoke focal sensory percepts in the fingertips. METHODS: Two participants with intractable epilepsy received cortical stimulation both at the gyri via high-density electrocorticography (HD-ECoG) grids and in the sulci via SEEG depth electrode leads. We characterized the evoked sensory percepts localized to the hand. RESULTS: We show that highly focal percepts can be evoked in the fingertips of the hand through sulcal stimulation. fMRI, myelin content, and cortical thickness maps from the Human Connectome Project elucidated specific cortical areas and sub-regions within S1 that evoked these focal percepts. Within-participant comparisons showed that percepts evoked by sulcal stimulation via SEEG electrodes were significantly more focal (80% less area; p = 0.02) and localized to the fingertips more often, than by gyral stimulation via HD-ECoG electrodes. Finally, sulcal locations with consistent modulation of high-frequency neural activity during mechanical tactile stimulation of the fingertips showed the same somatotopic correspondence as cortical stimulation. CONCLUSIONS: Our findings indicate minimally invasive sulcal stimulation via SEEG electrodes could be a clinically viable approach to restoring sensation.

A Roadmap Towards Standards for Neurally Controlled End Effectors.

The control and manipulation of various types of end effectors such as powered exoskeletons, prostheses, and 'neural' cursors by brain-machine interface (BMI) systems has been the target of many research projects. A seamless "plug and play" interface between any BMI and end effector is desired, wherein similar user's intent cause similar end effectors to behave identically. This report is based on the outcomes of an IEEE Standards Association Industry Connections working group on End Effectors for Brain-Machine Interfacing that convened to identify and address gaps in the existing standards for BMI-based solutions with a focus on the end-effector component. A roadmap towards standardization of end effectors for BMI systems is discussed by identifying current device standards that are applicable for end effectors. While current standards address basic electrical and mechanical safety, and to some extent, performance requirements, several gaps exist pertaining to unified terminologies, data communication protocols, patient safety and risk mitigation.

Neural activity modulations and motor recovery following brain-exoskeleton interface mediated stroke rehabilitation.

Brain-machine interfaces (BMI) based on scalp EEG have the potential to promote cortical plasticity following stroke, which has been shown to improve motor recovery outcomes. However, the efficacy of BMI enabled robotic training for upper-limb recovery is seldom quantified using clinical, EEG-based, and kinematics-based metrics. Further, a movement related neural correlate that can predict the extent of motor recovery still remains elusive, which impedes the clinical translation of BMI-based stroke rehabilitation. To address above knowledge gaps, 10 chronic stroke individuals with stable baseline clinical scores were recruited to participate in 12 therapy sessions involving a BMI enabled powered exoskeleton for elbow training. On average, 132 ± 22 repetitions were performed per participant, per session. BMI accuracy across all sessions and subjects was 79 ± 18% with a false positives rate of 23 ± 20%. Post-training clinical assessments found that FMA for upper extremity and ARAT scores significantly improved over baseline by 3.92 ± 3.73 and 5.35 ± 4.62 points, respectively. Also, 80% participants (7 with moderate-mild impairment, 1 with severe impairment) achieved minimal clinically important difference (MCID: FMA-UE >5.2 or ARAT >5.7) during the course of the study. Kinematic measures indicate that, on average, participants' movements became faster and smoother. Moreover, modulations in movement related cortical potentials, an EEG-based neural correlate measured contralateral to the impaired arm, were significantly correlated with ARAT scores (ρ = 0.72, p < 0.05) and marginally correlated with FMA-UE (ρ = 0.63, p = 0.051). This suggests higher activation of ipsi-lesional hemisphere post-intervention or inhibition of competing contra-lesional hemisphere, which may be evidence of neuroplasticity and cortical reorganization following BMI mediated rehabilitation therapy.

Improving robotic stroke rehabilitation by incorporating neural intent detection: Preliminary results from a clinical trial.

This paper presents the preliminary findings of a multi-year clinical study evaluating the effectiveness of adding a brain-machine interface (BMI) to the MAHI-Exo II, a robotic upper limb exoskeleton, for elbow flexion/extension rehabilitation in chronic stroke survivors. The BMI was used to trigger robot motion when movement intention was detected from subjects' neural signals, thus requiring that subjects be mentally engaged during robotic therapy. The first six subjects to complete the program have shown improvements in both Fugl-Meyer Upper-Extremity scores as well as in kinematic movement quality measures that relate to movement planning, coordination, and control. These results are encouraging and suggest that increasing subject engagement during therapy through the addition of an intent-detecting BMI enhances the effectiveness of standard robotic rehabilitation.

Design and Optimization of an EEG-Based Brain Machine Interface (BMI) to an Upper-Limb Exoskeleton for Stroke Survivors.

This study demonstrates the feasibility of detecting motor intent from brain activity of chronic stroke patients using an asynchronous electroencephalography (EEG)-based brain machine interface (BMI). Intent was inferred from movement related cortical potentials (MRCPs) measured over an optimized set of EEG electrodes. Successful intent detection triggered the motion of an upper-limb exoskeleton (MAHI Exo-II), to guide movement and to encourage active user participation by providing instantaneous sensory feedback. Several BMI design features were optimized to increase system performance in the presence of single-trial variability of MRCPs in the injured brain: (1) an adaptive time window was used for extracting features during BMI calibration; (2) training data from two consecutive days were pooled for BMI calibration to increase robustness to handle the day-to-day variations typical of EEG, and (3) BMI predictions were gated by residual electromyography (EMG) activity from the impaired arm, to reduce the number of false positives. This patient-specific BMI calibration approach can accommodate a broad spectrum of stroke patients with diverse motor capabilities. Following BMI optimization on day 3, testing of the closed-loop BMI-MAHI exoskeleton, on 4th and 5th days of the study, showed consistent BMI performance with overall mean true positive rate (TPR) = 62.7 ± 21.4% on day 4 and 67.1 ± 14.6% on day 5. The overall false positive rate (FPR) across subjects was 27.74 ± 37.46% on day 4 and 27.5 ± 35.64% on day 5; however for two subjects who had residual motor function and could benefit from the EMG-gated BMI, the mean FPR was quite low (< 10%). On average, motor intent was detected -367 ± 328 ms before movement onset during closed-loop operation. These findings provide evidence that closed-loop EEG-based BMI for stroke patients can be designed and optimized to perform well across multiple days without system recalibration.

Detecting movement intent from scalp EEG in a novel upper limb robotic rehabilitation system for stroke.

Stroke can be a source of significant upper extremity dysfunction and affect the quality of life (QoL) in survivors. In this context, novel rehabilitation approaches employing robotic rehabilitation devices combined with brain-machine interfaces can greatly help in expediting functional recovery in these individuals by actively engaging the user during therapy. However, optimal training conditions and parameters for these novel therapeutic systems are still unknown. Here, we present preliminary findings demonstrating successful movement intent detection from scalp electroencephalography (EEG) during robotic rehabilitation using the MAHI Exo-II in an individual with hemiparesis following stroke. These findings have strong clinical implications for the development of closed-loop brain-machine interfaces to robotic rehabilitation systems.