Table of contents

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.

Objective. Brain–computer interfaces (BCI) based on event-related potentials (ERP) were proven to be a reliable synchronous communication method. For everyday life situations, however, this synchronous mode is impractical because the system will deliver a selection even if the user is not paying attention to the stimulation. So far, research into attention-aware visual ERP–BCIs (i.e., asynchronous ERP–BCIs) has led to variable success. In this study, we investigate new approaches for detection of user engagement. Approach. Classifier output and frequency-domain features of electroencephalogram signals as well as the hybridization of them were used to detect the userʼs state. We tested their capabilities for state detection in different control scenarios on offline data from 21 healthy volunteers. Main results. The hybridization of classifier output and frequency-domain features outperformed the results of the single methods, and allowed building an asynchronous P300-based BCI with an average correct state detection accuracy of more than 95%. Significance. Our results show that all introduced approaches for state detection in an asynchronous P300-based BCI can effectively avoid involuntary selections, and that the hybrid method is the most effective approach.

Objective. We developed a simulated driving environment for studying neural correlates of emergency braking in diversified driving situations. We further investigated to what extent these neural correlates can be used to detect a participantʼs braking intention prior to the behavioral response. Approach. We measured electroencephalographic (EEG) and electromyographic signals during simulated driving. Fifteen participants drove a virtual vehicle and were exposed to several kinds of traffic situations in a simulator system, while EEG signals were measured. After that, we extracted characteristic features to categorize whether the driver intended to brake or not. Main results. Our system shows excellent detection performance in a broad range of possible emergency situations. In particular, we were able to distinguish three different kinds of emergency situations (sudden stop of a preceding vehicle, sudden cutting-in of a vehicle from the side and unexpected appearance of a pedestrian) from non-emergency (soft) braking situations, as well as from situations in which no braking was required, but the sensory stimulation was similar to stimulations inducing an emergency situation (e.g., the sudden stop of a vehicle on a neighboring lane). Significance. We proposed a novel feature combination comprising movement-related potentials such as the readiness potential, event-related desynchronization features besides the event-related potentials (ERP) features used in a previous study. The performance of predicting braking intention based on our proposed feature combination was superior compared to using only ERP features. Our study suggests that emergency situations are characterized by specific neural patterns of sensory perception and processing, as well as motor preparation and execution, which can be utilized by neurotechnology based braking assistance systems.

Objective. Retinal prosthetic devices aim to restore sight in visually impaired people by means of electrical stimulation of surviving retinal ganglion cells (RGCs). This modelling study aims to demonstrate that RGC inhibition caused by high-intensity cathodic pulses greatly influences their responses to epiretinal electrical stimulation and to investigate the impact of this inhibition on spatial activation profiles as well as their implications for retinal prosthetic device design. Another aim is to take advantage of this inhibition to reduce axonal activation in the nerve fibre layer. Approach. A three-dimensional finite-element model of epiretinal electrical stimulation was utilized to obtain RGC activation and inhibition threshold profiles for a range of parameters. Main results. RGC activation and inhibition thresholds were highly dependent on cell and stimulus parameters. Activation thresholds were 1.5, 3.4 and 11.3 μA for monopolar electrodes with 5, 20 and 50 μm radii, respectively. Inhibition to activation threshold ratios were mostly within the range 2–10. Inhibition significantly altered spatial patterns of RGC activation. With concentric electrodes and appropriately high levels of stimulus amplitudes, activation of passing axons was greatly reduced. Significance. RGC inhibition significantly impacts their spatial activation profiles, and therefore it most likely influences patterns of perceived phosphenes induced by retinal prosthetic devices. Thus this inhibition should be taken into account in future studies concerning retinal prosthesis development. It might be possible to utilize this inhibitory effect to bypass activation of passing axons and selectively stimulate RGCs near their somas and dendrites to achieve more localized phosphenes.

Objective. We evaluated a novel visual representation for current and near-term prosthetic vision. Augmented depth emphasizes ground obstacles and floor-wall boundaries in a depth-based visual representation. This is achieved by artificially increasing contrast between obstacles and the ground surface via a novel ground plane extraction algorithm specifically designed to preserve low-contrast ground-surface boundaries. Approach. The effectiveness of augmented depth was examined in human mobility trials compared against standard intensity-based (Intensity), depth-based (Depth) and random (Random) visual representations. Eight participants with normal vision used simulated prosthetic vision with 20 phosphenes and eight perceivable brightness levels to traverse a course with randomly placed small and low-contrast obstacles on the ground. Main results. The number of collisions was significantly reduced using augmented depth, compared with intensity, depth and random representations (48%, 44% and 72% less collisions, respectively). Significance. These results indicate that augmented depth may enable safe mobility in the presence of low-contrast obstacles with current and near-term implants. This is the first demonstration that an augmentation of the scene ensuring key objects are visible may provide better outcomes for prosthetic vision.

Objectives. The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Approaches. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. Main results. The pyramidal and extrapyramidal pathways possessed CVs of 3–11 and 16–80 m s⁻¹, respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. Significance. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

Objective. Lack of efficient calibration and task guidance in motor imagery (MI) based brain-computer interface (BCI) would result in the failure of communication or control, especially in patients, such as a stroke with motor impairment and intact sensation, locked-in state amyotrophic lateral sclerosis, in which the sources of data for calibration may worsen the subsequent decoding. In addition, enhancing the proprioceptive experience in MI might improve the BCI performance. Approach. In this work, we propose a new calibrating and task guidance methodology to further improve the MI BCI, exploiting the afferent nerve system through tendon vibration stimulation to induce a sensation with kinesthesia illusion. A total of 30 subjects' experiments were carried out, and randomly divided into a control group (control-group) and calibration and task guidance group (CTG-group). Main results. Online experiments have shown that MI could be decoded by classifier calibrated solely using sensation data, with 8 of the 15 subjects in the CTG-Group above 80%, 3 above 95% and all above 65%. Offline chronological cross-validation analysis shows that it has reached a comparable performance with the traditional calibration method ($F(1,14)=0.14,P=0.7176$). In addition, the discrimination accuracy of MI in the CTG-Group is significantly 12.17% higher on average than that in the control-group (unpaired-T test, P = 0.0086), and illusory sensation indicates no significant difference (unpaired-T test, p = 0.3412). The finding of the existed similarity of the discriminative brain patterns and grand averaged ERD/ERS between imagined movement (actively induced) and illusory movement (passively evoked) also validates the proposed calibration and task guidance framework. Significance. The cognitive complexity of the illusory sensation task is much lower and more objective than that of MI. In addition, subjects' kinesthetic experience mentally simulated during the MI task might be enhanced by accessing sensory experiences from the illusory stimulation. This sensory stimulation aided BCI design could help make MI BCI more applicable.

Objective. Epiretinal prostheses seek to effectively stimulate the retina by positioning electrode arrays close to its surface so current pulses generate narrow retinal electric fields. Our objective was to evaluate the use of the electrical impedance of insulated platinum electrodes as a measure of the proximity of insulated platinum electrodes to the inner surface of the retina. Approach. We examined the impedance of platinum disk electrodes, 0.25 mm in diameter, insulated with two widths (0.8 and 1.6 mm outer diameter) of transparent fluoropolymer in a rabbit retinal eyecup preparation. Optical coherence tomography measured the electrode's proximity to the retinal surface which was correlated with changes in the voltage waveform at the electrode. Electrode impedance changes during retinal deformation were also studied. Main results. When the 1.6 mm diameter insulated electrodes advanced towards the retinal surface from 1000 μm, their voltage step at current pulse onset increased, reflecting an access resistance increase of 3880 ± 630 Ω, with the 50% midpoint averaging 30 μm, while thin 0.8 mm insulated electrode advancement showed an access resistance increase 50% midpoint averaging 16 μm. Using impedance spectroscopy, electrode–retina proximity differences were seen in the 1.6 mm insulated electrode impedance modulus between 1 and 100 kHz and the waveform phase angle at 0.3–10 kHz, while thin 0.8 mm insulated electrode advancement produced smaller impedance modulus changes with retinal proximity between 3 and 100 kHz. These impedance changes with retinal proximity may reflect different sized zones of eye wall being coupled in series with the insulated platinum electrode. Significance. The proximity of stimulus electrodes to neural tissue in fluid-filled spaces can be estimated from access resistance changes in the stimulus pulse waveform. Because many prosthetic devices allow back telemetry communication of the stimulus electrode waveform, it is possible these series resistance increases observed with retinal proximity could be used as a metric of stimulus electrode placement.

Objective. The aim of this research is to explore the coupling patterns of brain dynamics during an auditory oddball task in schizophrenia (SCH). Approach. Event-related electroencephalographic (ERP) activity was recorded from 20 SCH patients and 20 healthy controls. The coupling changes between auditory response and pre-stimulus baseline were calculated in conventional EEG frequency bands (theta, alpha, beta-1, beta-2 and gamma), using three coupling measures: coherence, phase-locking value and Euclidean distance. Main results. Our results showed a statistically significant increase from baseline to response in theta coupling and a statistically significant decrease in beta-2 coupling in controls. No statistically significant changes were observed in SCH patients. Significance. Our findings support the aberrant salience hypothesis, since SCH patients failed to change their coupling dynamics between stimulus response and baseline when performing an auditory cognitive task. This result may reflect an impaired communication among neural areas, which may be related to abnormal cognitive functions.

Objective. The dorsal root ganglion is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity. Approach. Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-wall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as a result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB. Main results. Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced. Significance. This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities.

Objective. For intracortical brain–machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials ('spikes') requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials. Approach. We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of Gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position. Main results. We found the highest performance for thresholding when placing a threshold between −3 and −4.5 × V_rms. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data were thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded. Significance. For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated.

Objective. No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. Approach. We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. Main results. We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was $\sim 290$μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON–OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. Significance. We provide strong support for the feasibility of an epiretinal neurotransmitter-based retinal prosthesis. Our findings suggest that chemical stimulation of RGCs is a viable alternative to electrical stimulation and could offer distinct advantages such as the selective stimulation of RGC somata.

Objective. In a previous study we demonstrated continuous translation, orientation and one-dimensional grasping control of a prosthetic limb (seven degrees of freedom) by a human subject with tetraplegia using a brain−machine interface (BMI). The current study, in the same subject, immediately followed the previous work and expanded the scope of the control signal by also extracting hand-shape commands from the two 96-channel intracortical electrode arrays implanted in the subject's left motor cortex. Approach. Four new control signals, dictating prosthetic hand shape, replaced the one-dimensional grasping in the previous study, allowing the subject to control the prosthetic limb with ten degrees of freedom (three-dimensional (3D) translation, 3D orientation, four-dimensional hand shaping) simultaneously. Main results. Robust neural tuning to hand shaping was found, leading to ten-dimensional (10D) performance well above chance levels in all tests. Neural unit preferred directions were broadly distributed through the 10D space, with the majority of units significantly tuned to all ten dimensions, instead of being restricted to isolated domains (e.g. translation, orientation or hand shape). The addition of hand shaping emphasized object-interaction behavior. A fundamental component of BMIs is the calibration used to associate neural activity to intended movement. We found that the presence of an object during calibration enhanced successful shaping of the prosthetic hand as it closed around the object during grasping. Significance. Our results show that individual motor cortical neurons encode many parameters of movement, that object interaction is an important factor when extracting these signals, and that high-dimensional operation of prosthetic devices can be achieved with simple decoding algorithms. ClinicalTrials.gov Identifier: NCT01364480.

Objective. The human auditory system acquires environmental information under sound stimuli faster than visual or touch systems, which in turn, allows for faster human responses to such stimuli. It also complements senses such as sight, where direct line-of-view is necessary to identify objects, in the environment recognition process. This work focuses on implementing human reaction to sound stimuli and environment recognition on assistive robotic devices, such as robotic wheelchairs or robotized cars. These vehicles need environment information to ensure safe navigation. Approach. In the field of environment recognition, range sensors (such as LiDAR and ultrasonic systems) and artificial vision devices are widely used; however, these sensors depend on environment constraints (such as lighting variability or color of objects), and sound can provide important information for the characterization of an environment. In this work, we propose a sound-based approach to enhance the environment recognition process, mainly for cases that compromise human integrity, according to the International Classification of Functioning (ICF). Our proposal is based on a neural network implementation that is able to classify up to 15 different environments, each selected according to the ICF considerations on environment factors in the community-based physical activities of people with disabilities. Main results. The accuracy rates in environment classification ranges from 84% to 93%. This classification is later used to constrain assistive vehicle navigation in order to protect the user during daily activities. This work also includes real-time outdoor experimentation (performed on an assistive vehicle) by seven volunteers with different disabilities (but without cognitive impairment and experienced in the use of wheelchairs), statistical validation, comparison with previously published work, and a discussion section where the pros and cons of our system are evaluated. Significance. The proposed sound-based system is very efficient at providing general descriptions of the environment. Such descriptions are focused on vulnerable situations described by the ICF. The volunteers answered a questionnaire regarding the importance of constraining the vehicle velocities in risky environments, showing that all the volunteers felt comfortable with the system and its performance.

Objective. The P300 speller is a brain–computer interface (BCI) that can possibly restore communication abilities to individuals with severe neuromuscular disabilities, such as amyotrophic lateral sclerosis (ALS), by exploiting elicited brain signals in electroencephalography (EEG) data. However, accurate spelling with BCIs is slow due to the need to average data over multiple trials to increase the signal-to-noise ratio (SNR) of the elicited brain signals. Probabilistic approaches to dynamically control data collection have shown improved performance in non-disabled populations; however, validation of these approaches in a target BCI user population has not occurred. Approach. We have developed a data-driven algorithm for the P300 speller based on Bayesian inference that improves spelling time by adaptively selecting the number of trials based on the acute SNR of a user's EEG data. We further enhanced the algorithm by incorporating information about the user's language. In this current study, we test and validate the algorithms online in a target BCI user population, by comparing the performance of the dynamic stopping (DS) (or early stopping) algorithms against the current state-of-the-art method, static data collection, where the amount of data collected is fixed prior to online operation. Main results. Results from online testing of the DS algorithms in participants with ALS demonstrate a significant increase in communication rate as measured in bits/min (100–300%), and theoretical bit rate (100–550%), while maintaining selection accuracy. Participants also overwhelmingly preferred the DS algorithms. Significance. We have developed a viable BCI algorithm that has been tested in a target BCI population which has the potential for translation to improve BCI speller performance towards more practical use for communication.

Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)–carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1–1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT–CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT–CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT–CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

Objective. Brain–computer interfaces (BCIs) are being developed to assist paralyzed people and amputees by translating neural activity into movements of a computer cursor or prosthetic limb. Here we introduce a novel BCI task paradigm, intended to help accelerate improvements to BCI systems. Through this task, we can push the performance limits of BCI systems, we can quantify more accurately how well a BCI system captures the user's intent, and we can increase the richness of the BCI movement repertoire. Approach. We have implemented an instructed path task, wherein the user must drive a cursor along a visible path. The instructed path task provides a versatile framework to increase the difficulty of the task and thereby push the limits of performance. Relative to traditional point-to-point tasks, the instructed path task allows more thorough analysis of decoding performance and greater richness of movement kinematics. Main results. We demonstrate that monkeys are able to perform the instructed path task in a closed-loop BCI setting. We further investigate how the performance under BCI control compares to native arm control, whether users can decrease their movement variability in the face of a more demanding task, and how the kinematic richness is enhanced in this task. Significance. The use of the instructed path task has the potential to accelerate the development of BCI systems and their clinical translation.

Objective. In this study we present the development and testing in a rat model of the self-opening neural interface (SELINE), a novel flexible peripheral neural interface. Approach. This polyimide-based electrode has a three-dimensional structure that provides an anchorage system to the nerve and confers stability after implant. This geometry has been achieved by means of the plastic deformation of polyimide. Mechanical and electrochemical characterizations have been performed to prove the integrity of the electrode with very good results. Functionality of SELINEs for fascicular stimulation has been tested during in vivo acute experiments in the rat. Chronic implants were made to test the biocompatibility of the device. Main results. Results showed that SELINEs significantly improve mechanical anchorage to the nerve. Stimulation stability is considerably enhanced compared to common planar transversal electrodes and stimulation selectivity is increased for some motor fascicles. Chronic experimental results showed that SELINEs neither produce changes in the fascicular organization of sciatic nerves nor signs of nerve degeneration. Significance. The presented three-dimensional electrode provides an effective anchorage system to the nervous tissue that can improve the stability of the implant for acute and chronic studies.

Objective. Neural interface technologies could provide controlling connections between the nervous system and external technologies, such as limb prosthetics. The recording of efferent, motor potentials is a critical requirement for a peripheral neural interface, as these signals represent the user-generated neural output intended to drive external devices. Our objective was to evaluate structural and functional neural regeneration through a microchannel neural interface and to characterize potentials recorded from electrodes placed within the microchannels in awake and behaving animals. Approach. Female rats were implanted with muscle EMG electrodes and, following unilateral sciatic nerve transection, the cut nerve was repaired either across a microchannel neural interface or with end-to-end surgical repair. During a 13 week recovery period, direct muscle responses to nerve stimulation proximal to the transection were monitored weekly. In two rats repaired with the neural interface, four wire electrodes were embedded in the microchannels and recordings were obtained within microchannels during proximal stimulation experiments and treadmill locomotion. Main results. In these proof-of-principle experiments, we found that axons from cut nerves were capable of functional reinnervation of distal muscle targets, whether regenerating through a microchannel device or after direct end-to-end repair. Discrete stimulation-evoked and volitional potentials were recorded within interface microchannels in a small group of awake and behaving animals and their firing patterns correlated directly with intramuscular recordings during locomotion. Of 38 potentials extracted, 19 were identified as motor axons reinnervating tibialis anterior or soleus muscles using spike triggered averaging. Significance. These results are evidence for motor axon regeneration through microchannels and are the first report of in vivo recordings from regenerated motor axons within microchannels in a small group of awake and behaving animals. These unique findings provide preliminary evidence that efferent, volitional motor potentials can be recorded from the microchannel-based peripheral neural interface; a critical requirement for any neural interface intended to facilitate direct neural control of external technologies.

Objective. Recently, significant advances have been made in the early diagnosis of Alzheimer's disease (AD) from electroencephalography (EEG). However, choosing suitable measures is a challenging task. Among other measures, frequency relative power (RP) and loss of complexity have been used with promising results. In the present study we investigate the early diagnosis of AD using synchrony measures and frequency RP on EEG signals, examining the changes found in different frequency ranges. Approach. We first explore the use of a single feature for computing the classification rate (CR), looking for the best frequency range. Then, we present a multiple feature classification system that outperforms all previous results using a feature selection strategy. These two approaches are tested in two different databases, one containing mild cognitive impairment (MCI) and healthy subjects (patients age: 71.9 ± 10.2, healthy subjects age: 71.7 ± 8.3), and the other containing Mild AD and healthy subjects (patients age: 77.6 ± 10.0; healthy subjects age: 69.4 ± 11.5). Main results. Using a single feature to compute CRs we achieve a performance of 78.33% for the MCI data set and of 97.56% for Mild AD. Results are clearly improved using the multiple feature classification, where a CR of 95% is found for the MCI data set using 11 features, and 100% for the Mild AD data set using four features. Significance. The new features selection method described in this work may be a reliable tool that could help to design a realistic system that does not require prior knowledge of a patient's status. With that aim, we explore the standardization of features for MCI and Mild AD data sets with promising results.

Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device–tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.