A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population.

BACKGROUND: In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies. METHODS: This Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally. DISCUSSION: BCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial. TRIAL REGISTRATION: The trial was registered as "BCI-FES Therapy for Stroke Rehabilitation" on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.

Electrocorticographic Encoding of Human Gait in the Leg Primary Motor Cortex.

While prior noninvasive (e.g., electroencephalographic) studies suggest that the human primary motor cortex (M1) is active during gait processes, the limitations of noninvasive recordings make it impossible to determine whether M1 is involved in high-level motor control (e.g., obstacle avoidance, walking speed), low-level motor control (e.g., coordinated muscle activation), or only nonmotor processes (e.g., integrating/relaying sensory information). This study represents the first invasive electroneurophysiological characterization of the human leg M1 during walking. Two subjects with an electrocorticographic grid over the interhemispheric M1 area were recruited. Both exhibited generalized γ-band (40-200 Hz) synchronization across M1 during treadmill walking, as well as periodic γ-band changes within each stride (across multiple walking speeds). Additionally, these changes appeared to be of motor, rather than sensory, origin. However, M1 activity during walking shared few features with M1 activity during individual leg muscle movements, and was not highly correlated with lower limb trajectories on a single channel basis. These findings suggest that M1 primarily encodes high-level gait motor control (i.e., walking duration and speed) instead of the low-level patterns of leg muscle activation or movement trajectories. Therefore, M1 likely interacts with subcortical/spinal networks, which are responsible for low-level motor control, to produce normal human walking.

Brain-controlled functional electrical stimulation therapy for gait rehabilitation after stroke: a safety study.

BACKGROUND: Many stroke survivors have significant long-term gait impairment, often involving foot drop. Current physiotherapies provide limited recovery. Orthoses substitute for ankle strength, but they provide no lasting therapeutic effect. Brain-computer interface (BCI)-controlled functional electrical stimulation (FES) is a novel rehabilitative approach that may generate permanent neurological improvements. This study explores the safety and feasibility of a foot-drop-targeted BCI-FES physiotherapy in chronic stroke survivors. METHODS: Subjects (n = 9) operated an electroencephalogram-based BCI-FES system for foot dorsiflexion in 12 one-hour sessions over four weeks. Gait speed, dorsiflexion active range of motion (AROM), six-minute walk distance (6MWD), and Fugl-Meyer leg motor (FM-LM) scores were assessed before, during, and after therapy. The primary safety outcome measure was the proportion of subjects that deteriorated in gait speed by ≥0.16 m/s at one week or four weeks post-therapy. The secondary outcome measures were the proportion of subjects that experienced a clinically relevant decrease in dorsiflexion AROM (≥2.5°), 6MWD (≥20 %), and FM-LM score (≥10 %) at either post-therapy assessment. RESULTS: No subjects (0/9) experienced a clinically significant deterioration in gait speed, dorsiflexion AROM, 6MWT distance, or FM-LM score at either post-therapy assessment. Five subjects demonstrated a detectable increase (≥0.06 m/s) in gait speed, three subjects demonstrated a detectable increase (≥2.5°) in dorsiflexion AROM, five subjects demonstrated a detectable increase (≥10 %) in 6MWD, and three subjects demonstrated a detectable increase (≥10 %) in FM-LM. Five of the six subjects that exhibited a detectable increase in either post-therapy gait speed or 6MWD also exhibited significant (p < 0.01 using a Mann-Whitney U test) increases in electroencephalogram event-related synchronization/desynchronization. Additionally, two subjects experienced a clinically important increase (≥0.16 m/s) in gait speed, and four subjects experienced a clinically important increase (≥20 %) in 6MWD. Linear mixed models of gait speed, dorsiflexion AROM, 6MWD, and FM-LM scores suggest that BCI-FES therapy is associated with an increase in lower motor performance at a statistically, yet not clinically, significant level. CONCLUSION: BCI-FES therapy is safe. If it is shown to improve post-stroke gait function in future studies, it could provide a new gait rehabilitation option for severely impaired patients. Formal clinical trials are warranted.

The feasibility of a brain-computer interface functional electrical stimulation system for the restoration of overground walking after paraplegia.

BACKGROUND: Direct brain control of overground walking in those with paraplegia due to spinal cord injury (SCI) has not been achieved. Invasive brain-computer interfaces (BCIs) may provide a permanent solution to this problem by directly linking the brain to lower extremity prostheses. To justify the pursuit of such invasive systems, the feasibility of BCI controlled overground walking should first be established in a noninvasive manner. To accomplish this goal, we developed an electroencephalogram (EEG)-based BCI to control a functional electrical stimulation (FES) system for overground walking and assessed its performance in an individual with paraplegia due to SCI. METHODS: An individual with SCI (T6 AIS B) was recruited for the study and was trained to operate an EEG-based BCI system using an attempted walking/idling control strategy. He also underwent muscle reconditioning to facilitate standing and overground walking with a commercial FES system. Subsequently, the BCI and FES systems were integrated and the participant engaged in several real-time walking tests using the BCI-FES system. This was done in both a suspended, off-the-ground condition, and an overground walking condition. BCI states, gyroscope, laser distance meter, and video recording data were used to assess the BCI performance. RESULTS: During the course of 19 weeks, the participant performed 30 real-time, BCI-FES controlled overground walking tests, and demonstrated the ability to purposefully operate the BCI-FES system by following verbal cues. Based on the comparison between the ground truth and decoded BCI states, he achieved information transfer rates >3 bit/s and correlations >0.9. No adverse events directly related to the study were observed. CONCLUSION: This proof-of-concept study demonstrates for the first time that restoring brain-controlled overground walking after paraplegia due to SCI is feasible. Further studies are warranted to establish the generalizability of these results in a population of individuals with paraplegia due to SCI. If this noninvasive system is successfully tested in population studies, the pursuit of permanent, invasive BCI walking prostheses may be justified. In addition, a simplified version of the current system may be explored as a noninvasive neurorehabilitative therapy in those with incomplete motor SCI.

Extracting kinetic information from human motor cortical signals.

Brain machine interfaces (BMIs) have the potential to provide intuitive control of neuroprostheses to restore grasp to patients with paralyzed or amputated upper limbs. For these neuroprostheses to function, the ability to accurately control grasp force is critical. Grasp force can be decoded from neuronal spikes in monkeys, and hand kinematics can be decoded using electrocorticogram (ECoG) signals recorded from the surface of the human motor cortex. We hypothesized that kinetic information about grasping could also be extracted from ECoG, and sought to decode continuously-graded grasp force. In this study, we decoded isometric pinch force with high accuracy from ECoG in 10 human subjects. The predicted signals explained from 22% to 88% (60 ± 6%, mean ± SE) of the variance in the actual force generated. We also decoded muscle activity in the finger flexors, with similar accuracy to force decoding. We found that high gamma band and time domain features of the ECoG signal were most informative about kinetics, similar to our previous findings with intracortical LFPs. In addition, we found that peak cortical representations of force applied by the index and little fingers were separated by only about 4mm. Thus, ECoG can be used to decode not only kinematics, but also kinetics of movement. This is an important step toward restoring intuitively-controlled grasp to impaired patients.

A CMOS BD-BCI: Neural Recorder with Two-Step Time-Domain Quantizer and Multi-Polar Stimulator with Dual-Mode Charge Balancing.

This work presents a bi-directional brain-computer interface (BD-BCI) including a high-dynamic-range (HDR) two-step time-domain neural acquisition (TTNA) system and a high-voltage (HV) multipolar neural stimulation system incorporating dual-mode time-based charge balancing (DTCB) technique. The proposed TTNA includes four independent recording modules that can sense microvolt neural signals while tolerating large stimulation artifacts. In addition, it exhibits an integrated input-referred noise of 2.3 µVrms from 0.1- to 250-Hz and can handle a linear input-signal swing of up to 340 mVPP. The multipolar stimulator is composed of four standalone stimulators each with a maximum current of up to 14 mA (±20-V of voltage compliance) and 8-bit resolution. An inter-channel interference cancellation circuitry is introduced to preserve the accuracy and effectiveness of the DTCB method in the multipolar-stimulation configuration. Fabricated in an HV 180-nm CMOS technology, the BD-BCI chipset undergoes extensive in-vitro and in-vivo evaluations. The recording system achieves a measured SNDR, SFDR, and CMRR of 84.8 dB, 89.6 dB, and >105 dB, respectively. The measurement results verify that the stimulation system is capable of performing high-precision charge balancing with ±2 mV and ±7.5 mV accuracy in the interpulse-bounded time-based charge balancing (TCB) and artifactless TCB modes, respectively.

Simulation-Informed Power Budget Estimate of a Fully-Implantable Brain-Computer Interface.

This study aims to estimate the maximum power consumption that guarantees a thermally safe operation for a titanium-enclosed chest wall unit (CWU) subcutaneously implanted in the pre-pectoral area. This unit is a central piece of an envisioned fully-implantable bi-directional brain-computer interface (BD-BCI). To this end, we created a thermal simulation model using the finite element method implemented in COMSOL. We also performed a sensitivity analysis to ensure that our predictions were robust against the natural variation of physiological and environmental parameters. Based on this analysis, we predict that the CWU can consume between 378 and 538 mW of power without raising the surrounding tissue's temperature above the thermal safety threshold of 2  ∘ C. This power budget should be sufficient to power all of the CWU's basic functionalities, which include training the decoder, online decoding, wireless data transmission, and cortical stimulation. This power budget assessment provides an important specification for the design of a CWU-an integral part of a fully-implantable BD-BCI system.

Complement C5a receptor 1 blockade reverses cognitive deficits following cranial radiation therapy for brain cancer.

Cranial radiation therapy (RT) for brain cancers leads to an irreversible decline in cognitive function without an available remedy. Radiation-induced cognitive deficits (RICD) are particularly a pressing problem for the survivors of pediatric and low grade glioma (LGG) patients who often live long post-RT. Radiation-induced elevated neuroinflammation and gliosis, triggered by the detrimental CNS complement cascade, lead to excessive synaptic and cognitive loss. Using intact and brain cancer-bearing mouse models, we now show that targeting anaphylatoxin complement C5a receptor (C5aR1) is neuroprotective against RICD. We used a genetic knockout, C5aR1 KO mouse, and a pharmacologic approach, employing the orally active, brain penetrant C5aR1 antagonist PMX205, to reverse RICD. Irradiated C5aR1 KO and WT mice receiving PMX205 showed significant neurocognitive improvements in object recognition memory and memory consolidation tasks. C5aR1 inhibition reduced microglial activation, astrogliosis, and synaptic loss in the irradiated brain. Importantly, C5aR1 inhibition in the syngeneic, orthotopic astrocytoma, and glioblastoma-bearing mice protected against RICD without interfering with the therapeutic efficacy of RT to reduce tumor volume in vivo . PMX205 is currently in clinical trials for amyotrophic lateral sclerosis (ALS). Thus, C5aR1 inhibition is a translationally feasible approach to address RICD, an unmet medical need.

Brain-computer interface controlled robotic gait orthosis.

BACKGROUND: Excessive reliance on wheelchairs in individuals with tetraplegia or paraplegia due to spinal cord injury (SCI) leads to many medical co-morbidities, such as cardiovascular disease, metabolic derangements, osteoporosis, and pressure ulcers. Treatment of these conditions contributes to the majority of SCI health care costs. Restoring able-body-like ambulation in this patient population can potentially reduce the incidence of these medical co-morbidities, in addition to increasing independence and quality of life. However, no biomedical solution exists that can reverse this loss of neurological function, and hence novel methods are needed. Brain-computer interface (BCI) controlled lower extremity prostheses may constitute one such novel approach. METHODS: One able-bodied subject and one subject with paraplegia due to SCI underwent electroencephalogram (EEG) recordings while engaged in alternating epochs of idling and walking kinesthetic motor imagery (KMI). These data were analyzed to generate an EEG prediction model for online BCI operation. A commercial robotic gait orthosis (RoGO) system (suspended over a treadmill) was interfaced with the BCI computer to allow for computerized control. The subjects were then tasked to perform five, 5-min-long online sessions where they ambulated using the BCI-RoGO system as prompted by computerized cues. The performance of this system was assessed with cross-correlation analysis, and omission and false alarm rates. RESULTS: The offline accuracy of the EEG prediction model averaged 86.30% across both subjects (chance: 50%). The cross-correlation between instructional cues and the BCI-RoGO walking epochs averaged across all subjects and all sessions was 0.812 ± 0.048 (p-value <10(-4)). Also, there were on average 0.8 false alarms per session and no omissions. CONCLUSION: These results provide preliminary evidence that restoring brain-controlled ambulation after SCI is feasible. Future work will test the function of this system in a population of subjects with SCI. If successful, this may justify the future development of BCI-controlled lower extremity prostheses for free overground walking for those with complete motor SCI. Finally, this system can also be applied to incomplete motor SCI, where it could lead to improved neurological outcomes beyond those of standard physiotherapy.

Operation of a brain-computer interface walking simulator for individuals with spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) can leave the affected individuals with paraparesis or paraplegia, thus rendering them unable to ambulate. Since there are currently no restorative treatments for this population, novel approaches such as brain-controlled prostheses have been sought. Our recent studies show that a brain-computer interface (BCI) can be used to control ambulation within a virtual reality environment (VRE), suggesting that a BCI-controlled lower extremity prosthesis for ambulation may be feasible. However, the operability of our BCI has not yet been tested in a SCI population. METHODS: Five participants with paraplegia or tetraplegia due to SCI underwent a 10-min training session in which they alternated between kinesthetic motor imagery (KMI) of idling and walking while their electroencephalogram (EEG) were recorded. Participants then performed a goal-oriented online task, where they utilized KMI to control the linear ambulation of an avatar while making 10 sequential stops at designated points within the VRE. Multiple online trials were performed in a single day, and this procedure was repeated across 5 experimental days. RESULTS: Classification accuracy of idling and walking was estimated offline and ranged from 60.5% (p = 0.0176) to 92.3% (p = 1.36×10-20) across participants and days. Offline analysis revealed that the activation of mid-frontal areas mostly in the µ and low ß bands was the most consistent feature for differentiating between idling and walking KMI. In the online task, participants achieved an average performance of 7.4±2.3 successful stops in 273±51 sec. These performances were purposeful, i.e. significantly different from the random walk Monte Carlo simulations (p<0.01), and all but one participant achieved purposeful control within the first day of the experiments. Finally, all participants were able to maintain purposeful control throughout the study, and their online performances improved over time. CONCLUSIONS: The results of this study demonstrate that SCI participants can purposefully operate a self-paced BCI walking simulator to complete a goal-oriented ambulation task. The operation of the proposed BCI system requires short training, is intuitive, and robust against participant-to-participant and day-to-day neurophysiological variations. These findings indicate that BCI-controlled lower extremity prostheses for gait rehabilitation or restoration after SCI may be feasible in the future.

Power Budget of a Skull Unit in a Fully-Implantable Brain-Computer Interface: Bio-Heat Model.

The aim of this study is to estimate the maximum power consumption that guarantees the thermal safety of a skull unit (SU). The SU is part of a fully-implantable bi-directional brain computer-interface (BD-BCI) system that aims to restore walking and leg sensation to those with spinal cord injury (SCI). To estimate the SU power budget, we created a bio-heat model using the finite element method (FEM) implemented in COMSOL. To ensure that our predictions were robust against the natural variation of the model's parameters, we also performed a sensitivity analysis. Based on our simulations, we estimated that the SU can nominally consume up to 70 mW of power without raising the surrounding tissues' temperature above the thermal safety threshold of 1°C. When considering the natural variation of the model's parameters, we estimated that the power budget could range between 47 and 81 mW. This power budget should be sufficient to power the basic operations of the SU, including amplification, serialization and A/D conversion of the neural signals, as well as control of cortical stimulation. Determining the power budget is an important specification for the design of the SU and, in turn, the design of a fully-implantable BD-BCI system.

Suppression of cortical electrostimulation artifacts using pre-whitening and null projection.

Objective.Invasive brain-computer interfaces (BCIs) have shown promise in restoring motor function to those paralyzed by neurological injuries. These systems also have the ability to restore sensation via cortical electrostimulation. Cortical stimulation produces strong artifacts that can obscure neural signals or saturate recording amplifiers. While front-end hardware techniques can alleviate this problem, residual artifacts generally persist and must be suppressed by back-end methods.Approach.We have developed a technique based on pre-whitening and null projection (PWNP) and tested its ability to suppress stimulation artifacts in electroencephalogram (EEG), electrocorticogram (ECoG) and microelectrode array (MEA) signals from five human subjects.Main results.In EEG signals contaminated by narrow-band stimulation artifacts, the PWNP method achieved average artifact suppression between 32 and 34 dB, as measured by an increase in signal-to-interference ratio. In ECoG and MEA signals contaminated by broadband stimulation artifacts, our method suppressed artifacts by 78%-80% and 85%, respectively, as measured by a reduction in interference index. When compared to independent component analysis, which is considered the state-of-the-art technique for artifact suppression, our method achieved superior results, while being significantly easier to implement.Significance.PWNP can potentially act as an efficient method of artifact suppression to enable simultaneous stimulation and recording in bi-directional BCIs to biomimetically restore motor function.

Artifact propagation in subdural cortical electrostimulation: Characterization and modeling.

Cortical stimulation via electrocorticography (ECoG) may be an effective method for inducing artificial sensation in bi-directional brain-computer interfaces (BD-BCIs). However, strong electrical artifacts caused by electrostimulation may significantly degrade or obscure neural information. A detailed understanding of stimulation artifact propagation through relevant tissues may improve existing artifact suppression techniques or inspire the development of novel artifact mitigation strategies. Our work thus seeks to comprehensively characterize and model the propagation of artifacts in subdural ECoG stimulation. To this end, we collected and analyzed data from eloquent cortex mapping procedures of four subjects with epilepsy who were implanted with subdural ECoG electrodes. From this data, we observed that artifacts exhibited phase-locking and ratcheting characteristics in the time domain across all subjects. In the frequency domain, stimulation caused broadband power increases, as well as power bursts at the fundamental stimulation frequency and its super-harmonics. The spatial distribution of artifacts followed the potential distribution of an electric dipole with a median goodness-of-fit of R 2 = 0.80 across all subjects and stimulation channels. Artifacts as large as ±1,100 µV appeared anywhere from 4.43 to 38.34 mm from the stimulation channel. These temporal, spectral and spatial characteristics can be utilized to improve existing artifact suppression techniques, inspire new strategies for artifact mitigation, and aid in the development of novel cortical stimulation protocols. Taken together, these findings deepen our understanding of cortical electrostimulation and provide critical design specifications for future BD-BCI systems.

Benchtop and bedside validation of a low-cost programmable cortical stimulator in a testbed for bi-directional brain-computer-interface research.

Introduction: Bi-directional brain-computer interfaces (BD-BCI) to restore movement and sensation must achieve concurrent operation of recording and decoding of motor commands from the brain and stimulating the brain with somatosensory feedback. Methods: A custom programmable direct cortical stimulator (DCS) capable of eliciting artificial sensorimotor response was integrated into an embedded BCI system to form a safe, independent, wireless, and battery powered testbed to explore BD-BCI concepts at a low cost. The BD-BCI stimulator output was tested in phantom brain tissue by assessing its ability to deliver electrical stimulation equivalent to an FDA-approved commercial electrical cortical stimulator. Subsequently, the stimulator was tested in an epilepsy patient with subcortical electrocorticographic (ECoG) implants covering the sensorimotor cortex to assess its ability to elicit equivalent responses as the FDA-approved counterpart. Additional safety features (impedance monitoring, artifact mitigation, and passive and active charge balancing mechanisms) were also implemeneted and tested in phantom brain tissue. Finally, concurrent operation with interleaved stimulation and BCI decoding was tested in a phantom brain as a proof-of-concept operation of BD-BCI system. Results: The benchtop prototype BD-BCI stimulator's basic output features (current amplitude, pulse frequency, pulse width, train duration) were validated by demonstrating the output-equivalency to an FDA-approved commercial cortical electrical stimulator (R 2 > 0.99). Charge-neutral stimulation was demonstrated with pulse-width modulation-based correction algorithm preventing steady state voltage deviation. Artifact mitigation achieved a 64.5% peak voltage reduction. Highly accurate impedance monitoring was achieved with R 2 > 0.99 between measured and actual impedance, which in-turn enabled accurate charge density monitoring. An online BCI decoding accuracy of 93.2% between instructional cues and decoded states was achieved while delivering interleaved stimulation. The brain stimulation mapping via ECoG grids in an epilepsy patient showed that the two stimulators elicit equivalent responses. Significance: This study demonstrates clinical validation of a fully-programmable electrical stimulator, integrated into an embedded BCI system. This low-cost BD-BCI system is safe and readily applicable as a testbed for BD-BCI research. In particular, it provides an all-inclusive hardware platform that approximates the limitations in a near-future implantable BD-BCI. This successful benchtop/human validation of the programmable electrical stimulator in a BD-BCI system is a critical milestone toward fully-implantable BD-BCI systems.

Noninvasively recorded high-gamma signals improve synchrony of force feedback in a novel neurorehabilitation brain-machine interface for brain injury.

Objective.Brain injury is the leading cause of long-term disability worldwide, often resulting in impaired hand function. Brain-machine interfaces (BMIs) offer a potential way to improve hand function. BMIs often target replacing lost function, but may also be employed in neurorehabilitation (nrBMI) by facilitating neural plasticity and functional recovery. Here, we report a novel nrBMI capable of acquiring high-γ(70-115 Hz) information through a unique post-traumatic brain injury (TBI) hemicraniectomy window model, and delivering sensory feedback that is synchronized with, and proportional to, intended grasp force.Approach. We developed the nrBMI to use electroencephalogram recorded over a hemicraniectomy (hEEG) in individuals with TBI. The nrBMI empowered users to exert continuous, proportional control of applied force, and provided continuous force feedback. We report the results of an initial testing group of three human participants with TBI, along with a control group of three skull- and motor-intact volunteers.Main results. All participants controlled the nrBMI successfully, with high initial success rates (2 of 6 participants) or performance that improved over time (4 of 6 participants). We observed high-γmodulation with force intent in hEEG but not skull-intact EEG. Most significantly, we found that high-γcontrol significantly improved the timing synchronization between neural modulation onset and nrBMI output/haptic feedback (compared to low-frequency nrBMI control).Significance. These proof-of-concept results show that high-γnrBMIs can be used by individuals with impaired ability to control force (without immediately resorting to invasive signals like electrocorticography). Of note, the nrBMI includes a parameter to change the fraction of control shared between decoded intent and volitional force, to adjust for recovery progress. The improved synchrony between neural modulations and force control for high-γsignals is potentially important for maximizing the ability of nrBMIs to induce plasticity in neural circuits. Inducing plasticity is critical to functional recovery after brain injury.

Brain-computer interface controlled functional electrical stimulation system for ankle movement.

BACKGROUND: Many neurological conditions, such as stroke, spinal cord injury, and traumatic brain injury, can cause chronic gait function impairment due to foot-drop. Current physiotherapy techniques provide only a limited degree of motor function recovery in these individuals, and therefore novel therapies are needed. Brain-computer interface (BCI) is a relatively novel technology with a potential to restore, substitute, or augment lost motor behaviors in patients with neurological injuries. Here, we describe the first successful integration of a noninvasive electroencephalogram (EEG)-based BCI with a noninvasive functional electrical stimulation (FES) system that enables the direct brain control of foot dorsiflexion in able-bodied individuals. METHODS: A noninvasive EEG-based BCI system was integrated with a noninvasive FES system for foot dorsiflexion. Subjects underwent computer-cued epochs of repetitive foot dorsiflexion and idling while their EEG signals were recorded and stored for offline analysis. The analysis generated a prediction model that allowed EEG data to be analyzed and classified in real time during online BCI operation. The real-time online performance of the integrated BCI-FES system was tested in a group of five able-bodied subjects who used repetitive foot dorsiflexion to elicit BCI-FES mediated dorsiflexion of the contralateral foot. RESULTS: Five able-bodied subjects performed 10 alternations of idling and repetitive foot dorsifiexion to trigger BCI-FES mediated dorsifiexion of the contralateral foot. The epochs of BCI-FES mediated foot dorsifiexion were highly correlated with the epochs of voluntary foot dorsifiexion (correlation coefficient ranged between 0.59 and 0.77) with latencies ranging from 1.4 sec to 3.1 sec. In addition, all subjects achieved a 100% BCI-FES response (no omissions), and one subject had a single false alarm. CONCLUSIONS: This study suggests that the integration of a noninvasive BCI with a lower-extremity FES system is feasible. With additional modifications, the proposed BCI-FES system may offer a novel and effective therapy in the neuro-rehabilitation of individuals with lower extremity paralysis due to neurological injuries.

A Fully-Integrated 1µW/Channel Dual-Mode Neural Data Acquisition System for Implantable Brain-Machine Interfaces.

This paper presents an ultra-low power mixed-signal neural data acquisition (MSN-DAQ) system that enables a novel low-power hybrid-domain neural decoding architecture for implantable brain-machine interfaces with high channel count. Implemented in 180nm CMOS technology, the 32-channel custom chip operates at 1V supply voltage and achieves excellent performance including 1.07µW/channel, 2.37/5.62 NEF/PEF and 88dB common-mode rejection ratio (CMRR) with significant back-end power-saving advantage compared to prior works. The fabricated prototype was further evaluated with in vivo human tests at bedside, and its performance closely follows that of a commercial recording system.

Electromyogram (EMG) Removal by Adding Sources of EMG (ERASE)-A Novel ICA-Based Algorithm for Removing Myoelectric Artifacts From EEG.

Electroencephalographic (EEG) recordings are often contaminated by electromyographic (EMG) artifacts, especially when recording during movement. Existing methods to remove EMG artifacts include independent component analysis (ICA), and other high-order statistical methods. However, these methods can not effectively remove most of EMG artifacts. Here, we proposed a modified ICA model for EMG artifacts removal in the EEG, which is called EMG Removal by Adding Sources of EMG (ERASE). In this new approach, additional channels of real EMG from neck and head muscles (reference artifacts) were added as inputs to ICA in order to "force" the most power from EMG artifacts into a few independent components (ICs). The ICs containing EMG artifacts (the "artifact ICs") were identified and rejected using an automated procedure. ERASE was validated first using both simulated and experimentally-recorded EEG and EMG. Simulation results showed ERASE removed EMG artifacts from EEG significantly more effectively than conventional ICA. Also, it had a low false positive rate and high sensitivity. Subsequently, EEG was collected from 8 healthy participants while they moved their hands to test the realistic efficacy of this approach. Results showed that ERASE successfully removed EMG artifacts (on average, about 75% of EMG artifacts were removed when using real EMGs as reference artifacts) while preserving the expected EEG features related to movement. We also tested the ERASE procedure using simulated EMGs as reference artifacts (about 63% of EMG artifacts removed). Compared to conventional ICA, ERASE removed on average 26% more EMG artifacts from EEG. These findings suggest that ERASE can achieve significant separation of EEG signal and EMG artifacts without a loss of the underlying EEG features. These results indicate that using additional real or simulated EMG sources can increase the effectiveness of ICA in removing EMG artifacts from EEG. Combined with automated artifact IC rejection, ERASE also minimizes potential user bias. Future work will focus on improving ERASE so that it can also be used in real-time applications.

Feasibility of Wearable Sensing for In-Home Finger Rehabilitation Early After Stroke.

Wearable grip sensing shows potential for hand rehabilitation, but few studies have studied feasibility early after stroke. Here, we studied a wearable grip sensor integrated with a musical computer game (MusicGlove). Among the stroke patients admitted to a hospital without limiting complications, 13% had adequate hand function for system use. Eleven subjects used MusicGlove at home over three weeks with a goal of nine hours of use. On average they achieved 4.1 ± 3.2 (SD) hours of use and completed 8627 ± 7500 grips, an amount comparable to users in the chronic phase of stroke measured in a previous study. The rank-order usage data were well fit by distributions that arise in machine failure theory. Users operated the game at high success levels, achieving note-hitting success >75% for 84% of the 1061 songs played. They changed game parameters infrequently (31% of songs), but in a way that logically modulated challenge, consistent with the Challenge Point Hypothesis from motor learning. Thus, a therapy based on wearable grip sensing was feasible for home rehabilitation, but only for a fraction of subacute stroke subjects. Subjects made usage decisions consistent with theoretical models of machine failure and motor learning.

Refinement of High-Gamma EEG Features From TBI Patients With Hemicraniectomy Using an ICA Informed by Simulated Myoelectric Artifacts.

Recent studies have shown the ability to record high-γ signals (80-160 Hz) in electroencephalogram (EEG) from traumatic brain injury (TBI) patients who have had hemicraniectomies. However, extraction of the movement-related high-γ remains challenging due to a confounding bandwidth overlap with surface electromyogram (EMG) artifacts related to facial and head movements. In our previous work, we described an augmented independent component analysis (ICA) approach for removal of EMG artifacts from EEG, and referred to as EMG Reduction by Adding Sources of EMG (ERASE). Here, we tested this algorithm on EEG recorded from six TBI patients with hemicraniectomies while they performed a thumb flexion task. ERASE removed a mean of 52 ± 12% (mean ± S.E.M) (maximum 73%) of EMG artifacts. In contrast, conventional ICA removed a mean of 27 ± 19% (mean ± S.E.M) of EMG artifacts from EEG. In particular, high-γ synchronization was significantly improved in the contralateral hand motor cortex area within the hemicraniectomy site after ERASE was applied. A more sophisticated measure of high-γ complexity is the fractal dimension (FD). Here, we computed the FD of EEG high-γ on each channel. Relative FD of high-γ was defined as that the FD in move state was subtracted by FD in idle state. We found relative FD of high-γ over hemicraniectomy after applying ERASE were strongly correlated to the amplitude of finger flexion force. Results showed that significant correlation coefficients across the electrodes related to thumb flexion averaged ~0.76, while the coefficients across the homologous electrodes in non-hemicraniectomy areas were nearly 0. After conventional ICA, a correlation between relative FD of high-γ and force remained high in both hemicraniectomy areas (up to 0.86) and non-hemicraniectomy areas (up to 0.81). Across all subjects, an average of 83% of electrodes significantly correlated with force was located in the hemicraniectomy areas after applying ERASE. After conventional ICA, only 19% of electrodes with significant correlations were located in the hemicraniectomy. These results indicated that the new approach isolated electrophysiological features during finger motor activation while selectively removing confounding EMG artifacts. This approach removed EMG artifacts that can contaminate high-gamma activity recorded over the hemicraniectomy.