Machine Learning Based Hardware Architecture for DOA Measurement From Mice EEG.

OBJECTIVE: This research aims to design a hardware optimized machine learning based Depth of Anesthesia (DOA) measurement framework for mice and its FPGA implementation. METHODS: Electroencephalography or EEG signal is acquired from 16 mice in the Neural Interface Research (NIR) Laboratory of the City University of Hong Kong. We present a logistic regression based approach with mathematically uncomplicated feature extraction techniques for efficient hardware implementation to estimate the DOA. RESULTS: With the extraction of only two features, the proposed system can classify the state of consciousness with 94% accuracy for a 1 second EEG epoch, leading to a 100% accurate channel prediction after a 7 s run-time on average. CONCLUSION: Through performance evaluation and comparative study confirmed the efficacy of the prototype. SIGNIFICANCE: DOA is the measure of consciousness to distinguish whether a patient is suitably anesthetized or not during a surgical procedure. Traditionally the DOA is estimated by checking biophysical responses of a patient during the surgery. However, the physical symptoms can be misleading for a decisive conclusion due to the patient's health condition or as a side-effect of anesthetic drugs. Recently, several neuroscientific research works are correlating the EEG signal with conscious states, which is likely to have less interference with the patient's medical condition. This research presents the first-of-its-kind hardware implemented automatic DOA computation system for mice.

ECoG Power Alterations Across Stages of Prolonged Transcorneal Electrical Stimulation in the Blind Mice.

Transcorneal electrical stimulation (TES) is a noninvasive approach for activating the retina and its downstream components through the application of electric current on the cornea. Although previous studies have demonstrated the clinical relevance of TES for modulating neurons with improvements in visual evoked potentials (VEPs) and electroretinograms (ERGs), there are still huge gaps in knowledge of its effect on the brain structures. To determine the short-term impact as well as the aftereffects of TES on neural oscillatory power in retinal degeneration mice, we performed electrocorticography (ECoG) recording in the prefrontal and primary visual cortices at different stages of prolonged TES [transient stage, following prolonged stimulation (post-stimulation stage 1) and long after the end of the retinal stimulation (post-stimulation stage 2)]) under varying stimulation current amplitudes (400 µA, 500 µA and 600 µA). The results revealed asymmetric differences between short-term and long-term pTES under different stimulation current amplitudes. Specifically, in post-stimulation stage 1 we observed significant increase in ECoG power of theta, alpha and beta oscillations respectively compared with baseline pre-stimulation results. These effects were dependent on the stimulation current amplitude and stimulation stage. Transient TES was not sufficient to cause significant changes in the ECoG power of all accessed oscillations except in medium, high and ultra-gamma oscillations which significantly decreased in 400 µA and 500 µA stimulation groups respectively compared with pre-stimulation results. Regarding long-term stimulation, the increase in ECoG power of theta, alpha and beta oscillations observed in post-stimulation stage 1 was significantly maintained in post-stimulation stage 2.Clinical Relevance- These results could be of core importance for human TES protocols suggesting that following pTES and long after the end of the stimulation, TES current amplitudes could have relatively different impacts on the power/activity of cortical oscillations. For example, by increasing the activity of oscillations that have been reported to inhibit irrelevant neural processes and enable the brain to focus on more relevant neural processes thus, inducing better coordination in the cortex.

Spontaneous Feedforward Connectivity in Electrically Stimulated Retinal Degeneration Mice.

Retinal degeneration (Rd) is a neurodegenerative disorder primarily associated with the degeneration of the retina neurons and culminates in the eventual loss of visual perception or blindness. Decrease in fronto-, parietal and occipital brain connectivity have been reported in a number of neurodegeneration diseases involving cognitive decline. However, cortical communication in the brain of retinal degeneration patients remains largely unknown and strategies to remediate observed dysfunctional brain connectivity in such instance have not be thoroughly investigated. We used rd10 mice as a model to study brain connectivity in the human retinal degeneration disease, retinitis pigmentosa. Rd10 mice with sham matched controls were electrically stimulated at varying stimulation frequencies and the consequent perturbations in feedforward brain connectivity were studied in the visual cortex and pre-frontal cortex using electrocorticography (ECoG) and normalized symbolic transfer entropy (NSTE). Contra Vcx - contra PFx feed forward connectivity significantly (p<0.05) increased in theta, alpha and beta oscillatory bands of 2 Hz and 10 Hz stimulated rd10 respectively in comparison with sham group. Also, this increase was significantly maintained even after the end of the stimulation period.

Identification of Retinal Ganglion Cells from ß-III Stained Fluorescent Microscopic Images.

Optic nerve crush in mouse model is widely used for investigating the course following retinal ganglion cell (RGCs) injury. Manual cell counting from ß-III tubulin stained microscopic images has been routinely performed to monitor RGCs after an optic nerve crush injury, but is time-consuming and prone to observer variability. This paper describes an automatic technique for RGC identification. We developed and validated (i) a sensitive cell candidate segmentation scheme and (ii) a classifier that removed false positives while retaining true positives. Two major contributions were made in cell candidate segmentation. First, a homomorphic filter was designed to adjust for the inhomogeneous illumination caused by uneven penetration of ß-III tubulin antibody. Second, the optimal segmentation parameters for cell detection are highly image-specific. To address this issue, we introduced an offline-online parameter tuning approach. Offline tuning optimized model parameters based on training images and online tuning further optimized the parameters at the testing stage without needing access to the ground truth. In the cell identification stage, 31 geometric, statistical and textural features were extracted from each segmented cell candidate, which was subsequently classified as true or false positives by support vector machine. The homomorphic filter and the online parameter tuning approach together increased cell recall by 28%. The entire pipeline attained a recall, precision and coefficient of determination (r2) of 85.3%, 97.1% and 0.994. The availability of the proposed pipeline will allow efficient, accurate and reproducible RGC quantification required for assessing the death/survival of RGCs in disease models.

Electrochemical characteristics of microelectrode designed for electrical stimulation.

BACKGROUND: Microelectrode arrays play an important role in prosthetic implants for neural signal recording or applying electrical pulses stimulation to target nerve system. Safety and long-term reliability are essential requirements for microelectrode arrays applied in electrical stimulation. In design and fabrication of the microelectrode array, soft materials are generally chosen to be the substrate for the aim of achieving better compliance with the surrounding tissue while maintaining minimal damage. By flexing of the array to the surface, the array is capable of keeping a more stable electrical contact resulting in a significantly improved signal detected. METHODS: In this study, we design and fabricate a flexible microelectrode array with gold as the electrode material and parylene-C as the substrate. The fabrication process of the array is presented. The in vitro electrochemical characteristics of the microelectrode are investigated by electrochemical impedance spectroscopy and cyclic voltammetry in a three-electrode electrochemical cell containing phosphate-buffered saline. Charge injection capacity measurements are carried out by multichannel systems and the CSC of the microarray is calculated. RESULTS: Electrochemical results showed that impedance decreased with frequency. The average impedance of the Au electrodes at 1 kHz was 36.54 ± 0.88 kΩ. The average phase angle at 1 kHz was - 73.52 ± 1.3°, and the CIC of the microelectrode was 22.3 µC/cm2. The results demonstrated that the microelectrode array performed as expected for neuronal signal recording or stimulation. CONCLUSIONS: With parylene-C as the substrate, the microarray has good flexibility. The electrochemical characteristics' results show that the array has the ability to resist any corrosion on metal-electrolyte interface and has good biocompatibility. This low-cost, flexible parylene-based, gold microelectrode array shows potential for use in implant neurological signal acquisition or neurostimulation applications.

Effect of interphase gap duration and stimulus rate on threshold of visual cortical neurons in the rat.

Stimulation threshold is a key parameter to enable an efficient design for retinal implants. Stimulation parameters such as stimulus pulse duration, pulse amplitude, pulse repetition, pulse shape and polarity have been shown to be the key factors that can influence the efficacy of retinal prosthetics. The effectiveness of these devices should best be evaluated both in the retina and in the visual cortex. Prior electrophysiological studies in the retina have shown that introducing an interphase gap make stimulation more efficient. Previous in vitro studies have also demonstrated the response properties of retinal ganglion cells are frequency dependent. However, the effect of these two stimulus parameters are not well explored at the cortical level where higher visual processing signals are processed. In this study, we examined the response properties of visual cortical neurons under stimulation of retinal ganglion cells in rat using a single-channel electrode of diameter 75 µm. We compared the response strength curves as a function of stimulus current amplitudes under different stimulus pulse duration, interphase gap and stimulus rate. Localized response to single channel epiretinal stimulation was robustly observed in V1 neurons. We found that V1 neurons were more sensitive to longer pulse and stimulus with an interphase gap, similar to previously reported results in the retina. We were also able to examine the effect of stimulus frequency on threshold in the visual cortex. Our results indicate that electrical activation of V1 neurons are more efficient at low frequency.

Information transmission in the primary visual cortex of retinal degenerated rats.

To study the information transmission in the primary visual cortex (V1) of retinal degenerated (RD) models, wild type (WT) and RD rats were used in the experiments. The neural response in V1 was recorded extracellularly while the flicker with varied intensity levels was given as the visual stimulus. The mutual information (MI) and normalized mutual information (NMI) were determined for every isolated neuron, in order to quantify the amount and efficiency of information transmission in V1 of both control and experimental groups. The results showed that, on one hand, the RD group manifested relatively decreased information transmission amount and efficiency, comparing to the control group; On the other hand, it also implied that even for the RD rat, whose early stage of visual system was impaired, the later parts of visual system, especially the primary visual cortex, were still able to capture the information on visual stimulation, thus they can be utilized for restoring the visual ability, for example, via the visual prosthesis. In addition, it certainly requires more experiments for testifying and extending those results and implications.

Unraveling the Morphological Evolution and Etching Kinetics of Porous Silicon Nanowires During Metal-Assisted Chemical Etching.

Many potential applications of porous silicon nanowires (SiNWs) fabricated with metal-assisted chemical etching are highly dependent on the precise control of morphology for device optimization. However, the effects of key etching parameters, such as the amount of deposited metal catalyst, HF-oxidant molar ratio (χ), and solvent concentration, on the morphology and etching kinetics of the SiNWs still have not been fully explored. Here, the changes in the nanostructure and etch rate of degenerately doped p-type silicon in a HF-H2O2-H2O etching system with electrolessly deposited silver catalyst are systematically investigated. The surface morphology is found to evolve from a microporous and cratered structure to a uniform array of SiNWs at sufficiently high χ values. The etch rates at the nanostructure base and tip are correlated with the primary etching induced by Ag and the secondary etching induced by metal ions and diffused holes, respectively. The H2O concentration also affects the χ window where SiNWs form and the etch rates, mainly by modulating the reactant dilution and diffusion rate. By controlling the secondary etching and reactant diffusion via χ and H2O concentration, respectively, the fabrication of highly doped SiNWs with independent control of porosity from length is successfully demonstrated, which can be potentially utilized to improve the performance of SiNW-based devices.

Novel structure of carbon nanotube micro electrode for high-resolution stimulation of neurons.

This paper proposes a novel method to fabricate high resolution flexible electrodes. Among the steps, the carbon nanotube (CNT) electrodes synthesized facing down shows impedance improvement of about 90 times comparing with the normal facing up synthesized samples. Meanwhile, section impedance of electrodes is also defined in this paper to compare the area efficiency of impedance between electrodes with different sizes. In addition and to the best of our knowledge, high performance electrodes embedded inside parylene is reported for the first time taking into consideration the hydrophobicity change of the CNT surface.

An ERP study about the effects of different spatial frequencies and orientations on human brain activity.

Spatial, temporal frequencies as well as orientations are important visual stimulus properties, which will affect human perception. In this paper, we investigated the effects of gratings with different spatial, temporal frequencies and orientations on visual evoked potentials. Two positive components (P1 and P2) were observed after stimulation. Our results showed that the amplitude of P1 component was higher for gratings with 0.3 cycles per degree (cpd) spatial frequency compared to 0.05 and 0.1 cpd. While the amplitude differences of P2 component occurred between 0.05 and 0.1 cpd. The amplitude of both components were higher when subjects were viewing gratings at vertical orientation than horizontal orientation.

Plasticity of binocularity and visual acuity are differentially limited by nogo receptor.

The closure of developmental critical periods consolidates neural circuitry but also limits recovery from early abnormal sensory experience. Degrading vision by one eye throughout a critical period both perturbs ocular dominance (OD) in primary visual cortex and impairs visual acuity permanently. Yet understanding how binocularity and visual acuity interrelate has proven elusive. Here we demonstrate the plasticity of binocularity and acuity are separable and differentially regulated by the neuronal nogo receptor 1 (NgR1). Mice lacking NgR1 display developmental OD plasticity as adults and their visual acuity spontaneously improves after prolonged monocular deprivation. Restricting deletion of NgR1 to either cortical interneurons or a subclass of parvalbumin (PV)-positive interneurons alters intralaminar synaptic connectivity in visual cortex and prevents closure of the critical period for OD plasticity. However, loss of NgR1 in PV neurons does not rescue deficits in acuity induced by chronic visual deprivation. Thus, NgR1 functions with PV interneurons to limit plasticity of binocularity, but its expression is required more extensively within brain circuitry to limit improvement of visual acuity following chronic deprivation.

Misalignment tolerable coil structure for biomedical applications with wireless power transfer.

Coil-misalignment is one of the major hurdles for inductively coupled wireless power transfer in applications like retinal prosthesis. Weak magnetic flux linkage due to coil misalignments would significantly impair the power efficiency. A novel receiver configuration with high misalignment tolerance is presented in this paper. The proposed receiver is composed of two receiver coils placed orthogonally, so as to reduce the variation of mutual inductance between transmitting and receiving coils under misalignment conditions. Three different receiver coil structures are analyzed and compared using the same length of wire. Theoretical predictions have been confirmed with measurement results.

Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina.

Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal and S334ter line 3 (RD) rats (ages 84-782 days). We stimulated the retina in anesthetized animals and recorded evoked responses in the superior colliculus. Current pulses were delivered with a platinum-iridium (Pt-Ir) electrode of 75-µm diameter positioned on the epiretinal surface. In the same animals used for electrophysiology, SMI-32 immunolabeling of the retina enabled ganglion cell counting. An increase in threshold currents positively correlated with age of RD rats. SMI-32-labeled retinal ganglion cell density negatively correlated with age of RD rats. ANOVA shows that RD postnatal day (P)100 and P300 rats have threshold and density similar to normal rats, but RD P500 and P700 rats have threshold and density statistically different from normal rats (P < 0.05). Threshold charge densities were within the safety limits of Pt for all groups and pulse configurations, except at RD P600 and RD P700, where pulses were only safe up to 1- and 0.2-ms duration, respectively. Preservation of ganglion cells may enhance the efficiency and safety of electronic retinal implants.