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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

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., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

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., (© 2024. The Author(s).)

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.

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., (© 2023 IOP Publishing Ltd.)

Hippocampal CA1 neuronal ensembles generate sequential patterns of firing activity that contribute to episodic memory formation and spatial cognition. Here we used in vivo calcium imaging to record neural ensemble activities in mouse hippocampal CA1 and identified CA1 excitatory neuron sub-populations whose members are active across the same second-long period of time. We identified groups of hippocampal neurons sharing temporally correlated neural calcium activity during behavioral exploration and found that they also organized as clusters in anatomical space. Such clusters vary in membership and activity dynamics with respect to movement in different environments, but also appear during immobility in the dark suggesting an internal dynamic. The strong covariance between dynamics and anatomical location within the CA1 sub-region reveals a previously unrecognized form of topographic representation in hippocampus that may guide generation of hippocampal sequences across time and therefore organize the content of episodic memory., Competing Interests: All authors disclose no conflict of interests for this work., (© 2023 The Author(s).)

Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatiotemporal resolution of current methods. Since the imbalance of cortical excitation/inhibition (E:I) ratios are associated with a variety of neurological disorders, accurate monitoring of excitatory and inhibitory neurotransmitter levels is crucial for investigating the underlying neural mechanisms of these conditions. Specifically, levels of the excitatory neurotransmitter L-glutamate, and the inhibitory neurotransmitter GABA, are assumed to play critical roles in the E:I balance. Therefore, in this work, a flexible electrochemical microsensor is developed for real-time simultaneous detection of L-glutamate and GABA. The flexible polyimide substrate was used for easier handling during implantation and measurement, along with less brain damage. Further, by electrochemically depositing Pt-black nanostructures on the sensor's surface, the active surface area was enhanced for higher sensitivity. This dual neurotransmitter sensor probe was validated under various settings for its performance, including in vitro, ex vivo tests with glutamatergic neuronal cells and in vivo test with anesthetized rats. Additionally, the sensor's performance has been further investigated in terms of longevity and biocompatibility. Overall, our dual L-glutamate:GABA sensor microprobe has its unique features to enable accurate, real-time, and long-term monitoring of the E:I balance in vivo. Thus, this new tool should aid investigations of neural mechanisms of normal brain function and various neurological disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sohn, Lim, Wang, Pu, Malekzadeh-Arasteh, Shaw, Armacost, Gong, Kellis, Andersen, Liu, Heydari, Nenadic and Do.)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lim, Wang, Shaw, Gong, Armacost, Liu, Do, Heydari and Nenadic.)

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.

Electrocorticography (ECoG)-based bi-directional (BD) brain-computer interfaces (BCIs) are a forthcoming technology promising to help restore function to those with motor and sensory deficits. A major problem with this paradigm is that the cortical stimulation necessary to elicit artificial sensation creates strong electrical artifacts that can disrupt BCI operation by saturating recording amplifiers or obscuring useful neural signal. Even with state-of-the-art hardware artifact suppression methods, robust signal processing techniques are still required to suppress residual artifacts that are present at the digital back-end. Herein we demonstrate the effectiveness of a pre-whitening and null projection artifact suppression method using ECoG data recorded during a clinical neurostimulation procedure. Our method achieved a maximum artifact suppression of 21.49 dB and significantly increased the number of artifact-free frequencies in the frequency domain. This performance surpasses that of a more traditional independent component analysis methodology, while retaining a reduced complexity and increased computational efficiency.

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. Previously we developed and validated a benchtop prototype of a fully implantable BCI system for motor decoding. Here, a prototype artificial sensory stimulator was integrated into the benchtop system to develop a prototype of a fully-implantable BD-BCI. The artificial sensory stimulator incorporates an active charge balancing mechanism based on pulse-width modulation to ensure safe stimulation for chronically interfaced electrodes to prevent damage to brain tissue and electrodes. The feasibility of the BD-BCI system's active charge balancing was tested in phantom brain tissue. With the charge-balancing, the removal of the residual charges on an electrode was evident. This is a critical milestone toward fully-implantable BD-BCI systems.

The goal of this study is to estimate the thermal impact of a titanium skull unit (SU) implanted on the exterior aspect of the human skull. We envision this unit to house the front-end of a fully implantable electrocorticogram (ECoG)-based bi-directional (BD) brain-computer interface (BCI). Starting from the bio-heat transfer equation with physiologically and anatomically constrained tissue parameters, we used the finite element method (FEM) implemented in COMSOL to build a computational model of the SU's thermal impact. Based on our simulations, we predicted that the SU could consume up to 75 mW of power without raising the temperature of surrounding tissues above the safe limits (increase in temperature of 1°C). This power budget by far exceeds the power consumption of our front-end prototypes, suggesting that this design can sustain the SU's ability to record ECoG signals and deliver cortical stimulation. These predictions will be used to further refine the existing SU design and inform the design of future SU prototypes.

Objective: Electrocorticogram (ECoG)-based brain-computer interfaces (BCIs) are a promising platform for the restoration of motor and sensory functions to those with neurological deficits. Such bi-directional BCI operation necessitates simultaneous ECoG recording and stimulation, which is challenging given the presence of strong stimulation artifacts. This problem is exacerbated if the BCI's analog front-end operates in an ultra-low power regime, which is a basic requirement for fully implantable medical devices. In this study, we developed a novel method for the suppression of stimulation artifacts before they reach the analog front-end., Approach: Using elementary biophysical considerations, we devised an artifact suppression method that employs a weak auxiliary stimulation delivered between the primary stimulator and the recording grid. The exact location and amplitude of this auxiliary stimulating dipole were then found through a constrained optimization procedure. The performance of our method was tested in both simulations and phantom brain tissue experiments., Main Results: The solution found through the optimization procedure matched the optimal canceling dipole in both simulations and experiments. Artifact suppression as large as 28.7 dB and 22.9 dB were achieved in simulations and brain phantom experiments, respectively., Significance: We developed a simple constrained optimization-based method for finding the parameters of an auxiliary stimulating dipole that yields optimal artifact suppression. Our method suppresses stimulation artifacts before they reach the analog front-end and may prevent the front-end amplifiers from saturation. Additionally, it can be used along with other artifact mitigation techniques to further reduce stimulation artifacts.

This article presents an energy-efficient electrocorticography (ECoG) array architecture for fully-implantable brain machine interface systems. A novel dual-mode analog signal processing method is introduced that extracts neural features from high- γ band (80-160 Hz) at the early stages of signal acquisition. Initially, brain activity across the full-spectrum is momentarily observed to compute the feature weights in the digital back-end during full-band mode operation. Subsequently, these weights are fed back to the front-end and the system reverts to base-band mode to perform feature extraction. This approach utilizes a distinct optimized signal pathway based on power envelope extraction, resulting in 1.72× power reduction in the analog blocks and up to 50× potential power savings for digitization and processing (implemented off-chip in this article). A prototype incorporating a 32-channel ultra-low power signal acquisition front-end is fabricated in 180 nm CMOS process with 0.8 V supply. This chip consumes 1.05  μW (0.205  μW for feature extraction only) power and occupies 0.245 [Formula: see text] die area per channel. The chip measurement shows better than 76.5-dB common-mode rejection ratio (CMRR), 4.09 noise efficiency factor (NEF), and 10.04 power efficiency factor (PEF). In-vivo human tests have been carried out with electroencephalography and ECoG signals to validate the performance and dual-mode operation in comparison to commercial acquisition systems.

Objective: State-of-the-art invasive brain-machine interfaces (BMIs) have shown significant promise, but rely on external electronics and wired connections between the brain and these external components. This configuration presents health risks and limits practical use. These limitations can be addressed by designing a fully implantable BMI similar to existing FDA-approved implantable devices. Here, a prototype BMI system whose size and power consumption are comparable to those of fully implantable medical devices was designed and implemented, and its performance was tested at the benchtop and bedside., Approach: A prototype of a fully implantable BMI system was designed and implemented as a miniaturized embedded system. This benchtop analogue was tested in its ability to acquire signals, train a decoder, perform online decoding, wirelessly control external devices, and operate independently on battery. Furthermore, performance metrics such as power consumption were benchmarked., Main Results: An analogue of a fully implantable BMI was fabricated with a miniaturized form factor. A patient undergoing epilepsy surgery evaluation with an electrocorticogram (ECoG) grid implanted over the primary motor cortex was recruited to operate the system. Seven online runs were performed with an average binary state decoding accuracy of 87.0% (lag optimized, or 85.0% at fixed latency). The system was powered by a wirelessly rechargeable battery, consumed  ∼150 mW, and operated for  >60 h on a single battery cycle., Significance: The BMI analogue achieved immediate and accurate decoding of ECoG signals underlying hand movements. A wirelessly rechargeable battery and other supporting functions allowed the system to function independently. In addition to the small footprint and acceptable power and heat dissipation, these results suggest that fully implantable BMI systems are feasible.

Background: Brain-computer interfaces (BCIs) have demonstrated the potential to provide paralyzed individuals with new means of communication, but an electroencephalography (EEG)-based endogenous BCI has never been successfully used for communication with a patient in a completely locked-in state (CLIS)., Methods: In this study, we investigated the possibility of using an EEG-based endogenous BCI paradigm for online binary communication by a patient in CLIS. A female patient in CLIS participated in this study. She had not communicated even with her family for more than one year with complete loss of motor function. Offline and online experiments were conducted to validate the feasibility of the proposed BCI system. In the offline experiment, we determined the best combination of mental tasks and the optimal classification strategy leading to the best performance. In the online experiment, we investigated whether our BCI system could be potentially used for real-time communication with the patient., Results: An online classification accuracy of 87.5% was achieved when Riemannian geometry-based classification was applied to real-time EEG data recorded while the patient was performing one of two mental-imagery tasks for 5 s., Conclusions: Our results suggest that an EEG-based endogenous BCI has the potential to be used for online communication with a patient in CLIS.

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.

Bi-directional brain-computer interfaces (BCIs) require simultaneous stimulation and recording to achieve closed-loop operation. It is therefore important that the interface be able to distinguish between neural signals of interest and stimulation artifacts. Current bi-directional BCIs address this problem by temporally multiplexing stimulation and recording. This approach, however, is suboptimal in many BCI applications. Alternative artifact mitigation methods can be devised by investigating the mechanics of artifact propagation. To characterize stimulation artifact behaviors, we collected and analyzed electrocorticography (ECoG) data from eloquent cortex mapping. Ratcheting and phase-locking of stimulation artifacts were observed, as well as dipole-like properties. Artifacts as large as ±1,100 μV appeared as far as 15-37 mm away from the stimulating channel when stimulating at 10 mA. Analysis also showed that the majority of the artifact power was concentrated at the stimulation pulse train frequency (50 Hz) and its super-harmonics (100, 150, 200 Hz). Lower frequencies (0-32 Hz) experienced minimal artifact contamination. These findings could inform the design of future bi-directional ECoG-based BCIs.

Current therapies for neurogenic bladder do not allow spinal cord injury patients to regain conscious control of urine storage or voiding. Novel neural technologies may provide means to improve or restore the connection between the brain and the bladder; however, the specific brain areas and their underlying neural activities responsible for micturition must be better understood in order to design such technologies. In this retrospective study, we analyzed electrocorticographic (ECoG) data obtained from epilepsy patients who underwent ECoG grid implantation for epilepsy surgery evaluation, in the hopes of determining specific electrophysiological activity associated with micturition. Our results indicate modulation of the delta (δ, 0.1-4 Hz) and low-gamma (\gamma, 25-50 Hz) activity in the peri-Sylvian area and the inferior temporal lobe. These findings suggest involvement of the insular cortex and the uncinate fasciculus in micturition, important structures related to sensation and decision making. To date, this is the first known study utilizing ECoG data to elucidate the electrophysiological activity of the brain associated with bladder control and sensation.

Bi-directional brain-computer interfaces for the restoration of movement and sensation must simultaneously record neural signals and deliver cortical stimulation. This poses a challenge since stimulation artifacts can be orders of magnitude stronger than neural signals. In this article, we propose a novel subspace-based method for the removal of cortical electrical stimulation artifacts. We demonstrate the practical application of our approach on experimentally recorded electroencephalogram data, where artifacts were suppressed by as much as $30-40\mathrm {d}\mathrm {B}$. Our method is computationally simple, yet it achieves superior results to the state-of-the art methods.

The mechanism by which the human primary motor cortex (M1) encodes upper extremity movement kinematics is not fully understood. For example, human electrocorticogram (ECoG) signals have been shown to modulate with upper extremity movements; however, this relationship has not been explicitly characterized. To address this issue, we recorded high-density ECoG signals from patients undergoing epilepsy surgery evaluation as they performed elementary upper extremity movements while systematically varying movement speed and duration. Specifically, subjects performed intermittent pincer grasp/release, elbow flexion/extension, and shoulder flexion/extension at slow, moderate, and fast speeds. In all movements, bursts of power in the high-[Formula: see text] band (80-160 Hz) were observed in M1. In addition, the amplitude of these power bursts and the area of M1 with elevated high-[Formula: see text] activity were directly proportional to the movement speed. Likewise, the duration of elevated high-[Formula: see text] activity increased with movement duration. Based on linear regression, M1 high-[Formula: see text] power amplitude and duration covaried with movement speed and duration, respectively, with an average [Formula: see text] of [Formula: see text] and [Formula: see text]. These findings indicate that the encoding of upper extremity movement speed by M1 high-[Formula: see text] activity is primarily linear. Also, the fact that this activity remained elevated throughout a movement suggests that M1 does not merely generate transient instructions for a specific movement duration, but instead is responsible for the entirety of the movement. Finally, the spatial distribution of high-[Formula: see text] activity suggests the presence of a recruitment phenomenon in which higher speeds or increased muscle activity involve activation of larger M1 areas.

Objective: Conventional brain-computer interfaces (BCIs) are often expensive, complex to operate, and lack portability, which confines their use to laboratory settings. Portable, inexpensive BCIs can mitigate these problems, but it remains unclear whether their low-cost design compromises their performance. Therefore, we developed a portable, low-cost BCI and compared its performance to that of a conventional BCI., Methods: The BCI was assembled by integrating a custom electroencephalogram (EEG) amplifier with an open-source microcontroller and a touchscreen. The function of the amplifier was first validated against a commercial bioamplifier, followed by a head-to-head comparison between the custom BCI (using four EEG channels) and a conventional 32-channel BCI. Specifically, five able-bodied subjects were cued to alternate between hand opening/closing and remaining motionless while the BCI decoded their movement state in real time and provided visual feedback through a light emitting diode. Subjects repeated the above task for a total of 10 trials, and were unaware of which system was being used. The performance in each trial was defined as the temporal correlation between the cues and the decoded states., Results: The EEG data simultaneously acquired with the custom and commercial amplifiers were visually similar and highly correlated ( ρ = 0.79). The decoding performances of the custom and conventional BCIs averaged across trials and subjects were 0.70 ± 0.12 and 0.68 ± 0.10, respectively, and were not significantly different., Conclusion: The performance of our portable, low-cost BCI is comparable to that of the conventional BCIs., Significance: Platforms, such as the one developed here, are suitable for BCI applications outside of a laboratory.

Two brain signal acquisition (BSA) front-ends incorporating two CMOS ultralow power, low-noise amplifier arrays and serializers operating in mosfet weak inversion region are presented. To boost the amplifier's gain for a given current budget, cross-coupled-pair active load topology is used in the first stages of these two amplifiers. These two BSA front-ends are fabricated in 130 and 180 nm CMOS processes, occupying 5.45 mm 2 and 0.352 mm 2 of die areas, respectively (excluding pad rings). The CMOS 130-nm amplifier array is comprised of 64 elements, where each amplifier element consumes 0.216 μW from 0.4 V supply, has input-referred noise voltage (IRNoise) of 2.19 μV[Formula: see text] corresponding to a power efficiency factor (PEF) of 11.7, and occupies 0.044 mm 2 of die area. The CMOS 180 nm amplifier array employs 4 elements, where each element consumes 0.69 μW from 0.6 V supply with IRNoise of 2.3 μV[Formula: see text] (corresponding to a PEF of 31.3) and 0.051 mm 2 of die area. Noninvasive electroencephalographic and invasive electrocorticographic signals were recorded real time directly on able-bodied human subjects, showing feasibility of using these analog front-ends for future fully implantable BSA and brain- computer interface systems.

Optical imaging-based methods for assessing the membrane electrophysiology of in vitro human cardiac cells allow for non-invasive temporal assessment of the effect of drugs and other stimuli. Automated methods for detecting and analyzing the depolarization events (DEs) in image-based data allow quantitative assessment of these different treatments. In this study, we use 2-photon microscopy of fluorescent voltage-sensitive dyes (VSDs) to capture the membrane voltage of actively beating human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). We built a custom and freely available Matlab software, called MaDEC, to detect, quantify, and compare DEs of hiPS-CMs treated with the β-adrenergic drugs, propranolol and isoproterenol. The efficacy of our software is quantified by comparing detection results against manual DE detection by expert analysts, and comparing DE analysis results to known drug-induced electrophysiological effects. The software accurately detected DEs with true positive rates of 98-100% and false positive rates of 1-2%, at signal-to-noise ratios (SNRs) of 5 and above. The MaDEC software was also able to distinguish control DEs from drug-treated DEs both immediately as well as 10min after drug administration., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Motor rehabilitation using brain-computer interface (BCI) systems may facilitate functional recovery in individuals after stroke or spinal cord injury. Nevertheless, these systems are typically ill-suited for widespread adoption due to their size, cost, and complexity. In this paper, a small, portable, and extremely cost-efficient (<;$200) BCI system has been developed using a custom electroencephalographic (EEG) amplifier array, and a commercial microcontroller and touchscreen. The system's performance was tested using a movement-related BCI task in 3 able-bodied subjects with minimal previous BCI experience. Specifically, subjects were instructed to alternate between relaxing and dorsiflexing their right foot, while their EEG was acquired and analyzed in real-time by the BCI system to decode their underlying movement state. The EEG signals acquired by the custom amplifier array were similar to those acquired by a commercial amplifier (maximum correlation coefficient ρ=0.85). During real-time BCI operation, the average correlation between instructional cues and decoded BCI states across all subjects (ρ=0.70) was comparable to that of full-size BCI systems. Small, portable, and inexpensive BCI systems such as the one reported here may promote a widespread adoption of BCI-based movement rehabilitation devices in stroke and spinal cord injury populations.

A fully implantable brain-computer interface (BCI) can be a practical tool to restore independence to those affected by spinal cord injury. We envision that such a BCI system will invasively acquire brain signals (e.g. electrocorticogram) and translate them into control commands for external prostheses. The feasibility of such a system was tested by implementing its benchtop analogue, centered around a commercial, ultra-low power (ULP) digital signal processor (DSP, TMS320C5517, Texas Instruments). A suite of signal processing and BCI algorithms, including (de)multiplexing, Fast Fourier Transform, power spectral density, principal component analysis, linear discriminant analysis, Bayes rule, and finite state machine was implemented and tested in the DSP. The system's signal acquisition fidelity was tested and characterized by acquiring harmonic signals from a function generator. In addition, the BCI decoding performance was tested, first with signals from a function generator, and subsequently using human electroencephalogram (EEG) during eyes opening and closing task. On average, the system spent 322 ms to process and analyze 2 s of data. Crosstalk (<;-65 dB) and harmonic distortion (~1%) were minimal. Timing jitter averaged 49 μs per 1000 ms. The online BCI decoding accuracies were 100% for both function generator and EEG data. These results show that a complex BCI algorithm can be executed on an ULP DSP without compromising performance. This suggests that the proposed hardware platform may be used as a basis for future, fully implantable BCI systems.

Objective: Electrocorticography (ECoG)-based brain-computer interface (BCI) is a promising platform for controlling arm prostheses. To restore functional independence, a BCI must be able to control arm prostheses along at least six degrees-of-freedoms (DOFs). Prior studies suggest that standard ECoG grids may be insufficient to decode multi-DOF arm movements. This study compared the ability of standard and high-density (HD) ECoG grids to decode the presence/absence of six elementary arm movements and the type of movement performed., Approach: Three subjects implanted with standard grids (4 mm diameter, 10 mm spacing) and three with HD grids (2 mm diameter, 4 mm spacing) had ECoG signals recorded while performing the following movements: (1) pincer grasp/release, (2) wrist flexion/extension, (3) pronation/supination, (4) elbow flexion/extension, (5) shoulder internal/external rotation, and (6) shoulder forward flexion/extension. Data from the primary motor cortex were used to train a state decoder to detect the presence/absence of movement, and a six-class decoder to distinguish between these movements., Main Results: The average performances of the state decoders trained on HD ECoG data were superior (p = 3.05 × 10(-5)) to those of their standard grid counterparts across all combinations of the μ, β, low-γ, and high-γ frequency bands. The average best decoding error for HD grids was 2.6%, compared to 8.5% of standard grids (chance 50%). The movement decoders trained on HD ECoG data were superior (p = 3.05 × 10(-5)) to those based on standard ECoG across all band combinations. The average best decoding errors of 11.9% and 33.1% were obtained for HD and standard grids, respectively (chance error 83.3%). These improvements can be attributed to higher electrode density and signal quality of HD grids., Significance: Commonly used ECoG grids are inadequate for multi-DOF BCI arm prostheses. The performance gains by HD grids may eventually lead to independence-restoring BCI arm prosthesis.

Background: Calcium imaging has become a fundamental modality for studying neuronal circuit dynamics both in vitro and in vivo. However, identifying calcium events (CEs) from spectral data remains laborious and difficult, especially since the signal-to-noise ratio (SNR) often falls below 2. Existing automated signal detection methods are generally applied at high SNRs, leaving a large need for an automated algorithm that can accurately extract CEs from fluorescence intensity data of SNR 2 and below., New Method: In this work we develop a Matched filter for Multi-unit Calcium Event (MMiCE) detection to extract CEs from fluorescence intensity traces of simulated and experimentally recorded neuronal calcium imaging data., Results: MMiCE reached perfect performance on simulated data with SNR ≥ 2 and a true positive (TP) rate of 98.27% (± 1.38% with a 95% confidence interval), and a false positive(FP) rate of 6.59% (± 2.56%) on simulated data with SNR 0.2. On real data, verified by patch-clamp recording, MMiCE performed with a TP rate of 100.00% (± 0.00) and a FP rate of 2.04% (± 4.10)., Comparison With Existing Method(s): This high level of performance exceeds existing methods at SNRs as low as 0.2, which are well below those used in previous studies (SNR ≃ 5-10)., Conclusion: Overall, the MMiCE detector performed exceptionally well on both simulated data, and experimentally recorded neuronal calcium imaging data. The MMiCE detector is accurate, reliable, well suited for wide-spread use, and freely available at sites.uci.edu/aggies or from the corresponding author., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Extracellular recordings of multi-unit neural activity have become indispensable in neuroscience research. The analysis of the recordings begins with the detection of the action potentials (APs), followed by a classification step where each AP is associated with a given neural source. A feature extraction step is required prior to classification in order to reduce the dimensionality of the data and the impact of noise, allowing source clustering algorithms to work more efficiently., New Method: In this paper, we propose a novel framework for multi-sensor AP feature extraction based on the so-called Matched Subspace Detector (MSD), which is shown to be a natural generalization of standard single-sensor algorithms., Results: Clustering using both simulated data and real AP recordings taken in the locust antennal lobe demonstrates that the proposed approach yields features that are discriminatory and lead to promising results., Comparison With Existing Method(s): Unlike existing methods, the proposed algorithm finds joint spatio-temporal feature vectors that match the dominant subspace observed in the two-dimensional data without needs for a forward propagation model and AP templates., Conclusions: The proposed MSD approach provides more discriminatory features for unsupervised AP sorting applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.