Frontiers in neuroengineering最新文献

Microelectrode arrays (wire diameter <50 μm) were compared to traditional macroelectrodes for deep brain stimulation (DBS). Understanding the neuronal activation volume may help solve some of the mysteries associated with DBS, e.g., its mechanisms of action. We used c-fos immunohistochemistry to investigate neuronal activation in the rat hippocampus caused by multi-micro- and macroelectrode stimulation. At ± 1V stimulation at 25 Hz, microelectrodes (33 μm diameter) had a radius of activation of 100 μm, which is 50% of that seen with 150 μm diameter macroelectrode stimulation. Macroelectrodes activated about 5.8 times more neurons than a single microelectrode, but displaced ~20 times more neural tissue. The sphere of influence of stimulating electrodes can be significantly increased by reducing their impedance. By ultrasonic electroplating (sonicoplating) the microelectrodes with platinum to increase their surface area and reduce their impedance by an order of magnitude, the radius of activation increased by 50 μm and more than twice the number of neurons were activated within this increased radius compared to unplated microelectrodes. We suggest that a new approach to DBS, one that uses multiple high-surface area microelectrodes, may be more therapeutically effective due to increased neuronal activation.

Using a variety of proliferating cell types, it was shown that the surface of nanocrystalline diamond (NCD) provides a permissive substrate for cell adhesion and development without the need of complex chemical functionalization prior to cell seeding. In an extensive series of experiments we found that, unlike proliferating cells, post-mitotic primary neurons do not adhere to bare NCD surfaces when cultured in defined medium. These observations raise questions on the potential use of bare NCD as an interfacing layer for neuronal devices. Nevertheless, we also found that classical chemical functionalization methods render the "hostile" bare NCD surfaces with adhesive properties that match those of classically functionalized substrates used extensively in biomedical research and applications. Based on the results, we propose a mechanism that accounts for the conflicting results; which on one hand claim that un-functionalized NCD provides a permissive substrate for cell adhesion and growth, while other reports demonstrate the opposite.

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes.

Auditory perception and auditory imagery have been shown to activate overlapping brain regions. We hypothesized that these phenomena also share a common underlying neural representation. To assess this, we used electrocorticography intracranial recordings from epileptic patients performing an out loud or a silent reading task. In these tasks, short stories scrolled across a video screen in two conditions: subjects read the same stories both aloud (overt) and silently (covert). In a control condition the subject remained in a resting state. We first built a high gamma (70-150 Hz) neural decoding model to reconstruct spectrotemporal auditory features of self-generated overt speech. We then evaluated whether this same model could reconstruct auditory speech features in the covert speech condition. Two speech models were tested: a spectrogram and a modulation-based feature space. For the overt condition, reconstruction accuracy was evaluated as the correlation between original and predicted speech features, and was significant in each subject (p < 10(-5); paired two-sample t-test). For the covert speech condition, dynamic time warping was first used to realign the covert speech reconstruction with the corresponding original speech from the overt condition. Reconstruction accuracy was then evaluated as the correlation between original and reconstructed speech features. Covert reconstruction accuracy was compared to the accuracy obtained from reconstructions in the baseline control condition. Reconstruction accuracy for the covert condition was significantly better than for the control condition (p < 0.005; paired two-sample t-test). The superior temporal gyrus, pre- and post-central gyrus provided the highest reconstruction information. The relationship between overt and covert speech reconstruction depended on anatomy. These results provide evidence that auditory representations of covert speech can be reconstructed from models that are built from an overt speech data set, supporting a partially shared neural substrate.

Conducting polymer films offer a convenient route for the functionalization of implantable microelectrodes without compromising their performance as excellent recording units. A micron thick coating, deposited on the surface of a regular metallic electrode, can elute anti-inflammatory drugs for the treatment of glial scarring as well as growth factors for the support of surrounding neurons. Electro-activation of the polymer drives the release of the substance and should ideally provide a reliable method for controlling quantity and timing of release. Driving signals in the form of a constant potential (CP), a slow redox sweep or a fast pulse are all represented in literature. Few studies present such release in vivo from actual recording and stimulating microelectronic devices. It is essential to bridge the gap between studies based on release in vitro, and the intended application, which would mean release into living and highly delicate tissue. In the biological setting, signals are limited both by available electronics and by the biological safety. Driving signals must not be harmful to tissue and also not activate the tissue in an uncontrolled manner. This review aims at shedding more light on how to select appropriate driving parameters for the polymer electrodes for the in vivo setting. It brings together information regarding activation thresholds for neurons, as well as injury thresholds, and puts this into context with what is known about efficient driving of release from conducting polymer films.

Changes in biotic and abiotic factors can be reflected in the complex impedance spectrum of the microelectrodes chronically implanted into the neural tissue. The recording surface of the tungsten electrode in vivo undergoes abiotic changes due to recording site corrosion and insulation delamination as well as biotic changes due to tissue encapsulation as a result of the foreign body immune response. We reported earlier that large changes in electrode impedance measured at 1 kHz were correlated with poor electrode functional performance, quantified through electrophysiological recordings during the chronic lifetime of the electrode. There is a need to identity the factors that contribute to the chronic impedance variation. In this work, we use numerical simulation and regression to equivalent circuit models to evaluate both the abiotic and biotic contributions to the impedance response over chronic implant duration. COMSOL® simulation of abiotic electrode morphology changes provide a possible explanation for the decrease in the electrode impedance at long implant duration while biotic changes play an important role in the large increase in impedance observed initially.

A quarter of century ago, Farwell and Donchin (1988) described their mental prosthesis for "talking off the top of your head." This innovative communication system, later named P3-speller, has been the most investigated and tested brain-computer interface (BCI) system, to date. A main goal of the research on P3-spellers was the development of an effective assistive device for patients with severe motor diseases. Among these patients are those affected by amyotrophic lateral sclerosis (ALS). ALS patients have become a target population in P3-speller (and more generally in BCI) research. The P3-speller relies on the visual sensory modality, and it can be controlled by requiring users to actively move their eyes. Unfortunately, eye-movement control is usually not spared in the last stages of ALS, and, then, it is definitively lost in the case of complete paralysis. We reviewed the literature on ALS patients tested by means of P3-speller systems. Our aim was to investigate the evidence available to date of the P3-spellers effectiveness in ALS patients. To address this goal, a meta-analytic approach was adopted. The pooled classification accuracy performance, among retrieved studies, was about 74%. This estimation, however, was affected by significant heterogeneity and inconsistency among studies. This fact makes this percentage estimation (i.e., 74%) unreliable. Nowadays, the conclusion is that the initial hopes posed on P3-speller for ALS patients have not been met yet. In addition, no trials in which the P3-speller has been compared to current assistive technologies for communication (e.g., eye-trackers) are available. In conclusion, further studies are required to obtain a reliable index of P3-speller effectiveness in ALS. Furthermore, comparisons of P3-speller systems with the available assistive technologies are needed to assess the P3-speller usefulness with non-completely paralyzed ALS-patients.

Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive brain-machine interfaces. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We have designed a sinusoidal probe in order to reduce movement of the recording tip relative to the surrounding neural tissue. The probe was microfabricated from flexible materials and incorporated a sinusoidal shaft to minimize tethering forces and a 3D spheroid tip to anchor the recording site within the brain. Compared to standard microwire electrodes, the signal-to-noise ratio and local field potential power of sinusoidal probe recordings from rabbits was more stable across recording periods up to 678 days. Histological quantification of microglia and astrocytes showed reduced neuronal tissue damage especially for the tip region between 6 and 24 months post-implantation. We suggest that the micromotion-reducing measures incorporated into our design, at least partially, decreased the magnitude of gliosis, resulting in enhanced longevity of recording.

In recent years much effort is invested in means to control neural population responses at the whole brain level, within the context of developing advanced medical applications. The tradeoffs and constraints involved, however, remain elusive due to obvious complications entailed by studying whole brain dynamics. Here, we present effective control of response features (probability and latency) of cortical networks in vitro over many hours, and offer this approach as an experimental toy for studying controllability of neural networks in the wider context. Exercising this approach we show that enforcement of stable high activity rates by means of closed loop control may enhance alteration of underlying global input-output relations and activity dependent dispersion of neuronal pair-wise correlations across the network.