Publications by authors named "Edward W Keefer"

Objective: The next generation prosthetic hand that moves and feels like a real hand requires a robust neural interconnection between the human minds and machines.

Methods: Here we present a neuroprosthetic system to demonstrate that principle by employing an artificial intelligence (AI) agent to translate the amputee's movement intent through a peripheral nerve interface. The AI agent is designed based on the recurrent neural network (RNN) and could simultaneously decode six degree-of-freedom (DOF) from multichannel nerve data in real-time.

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Deep learning-based neural decoders have emerged as the prominent approach to enable dexterous and intuitive control of neuroprosthetic hands. Yet few studies have materialized the use of deep learning in clinical settings due to its high computational requirements.Recent advancements of edge computing devices bring the potential to alleviate this problem.

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Previous literature shows that deep learning is an effective tool to decode the motor intent from neural signals obtained from different parts of the nervous system. However, deep neural networks are often computationally complex and not feasible to work in real-time. Here we investigate different approaches' advantages and disadvantages to enhance the deep learning-based motor decoding paradigm's efficiency and inform its future implementation in real-time.

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. While prosthetic hands with independently actuated digits have become commercially available, state-of-the-art human-machine interfaces (HMI) only permit control over a limited set of grasp patterns, which does not enable amputees to experience sufficient improvement in their daily activities to make an active prosthesis useful..

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Objective: Electrical stimulation is a blunt tool for evoking neural activity. Neurons are naturally activated asynchronously and non-uniformly, whereas stimulation drives simultaneous activity within a population of cells. These differences in activation pattern can result in unintended side effects, including muddled sensory percepts and undesirable muscle contractions.

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Neuronal networks cultured on microelectrode arrays (MEAs) have been utilized as biosensors that can detect all or nothing extracellular action potentials, or spikes. Coating the microelectrodes with carbon nanotubes (CNTs), either pristine or conjugated with a conductive polymer, has been previously reported to improve extracellular recordings presumably via reduction in microelectrode impedance. The goal of this work was to examine the basis of such improvement in vitro.

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The botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects of BoNT. Murine spinal cord and frontal cortex networks cultured on substrate integrated microelectrode arrays allowed monitoring of spontaneous spike and burst activity with exposure to BoNT serotype A (BoNT-A).

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Neural interfaces have traditionally been fabricated on rigid and planar substrates, including silicon and engineering thermoplastics. However, the neural tissue with which these devices interact is both 3D and highly compliant. The mechanical mismatch at the biotic-abiotic interface is expected to contribute to the tissue response that limits chronic signal recording and stimulation.

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Micro-electrode arrays (MEAs) have been used in a variety of intracortical neural prostheses. While intracortical MEAs have demonstrated their utility in neural prostheses, in many cases MEA performance declines after several months to years of in vivo implantation. The application of carbon nanotubes (CNTs) may increase the functional longevity of intracortical MEAs through enhanced biocompatibility and charge injection properties.

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Clinical use of neurally controlled prosthetics has advanced in recent years, but limitations still remain, including lacking fine motor control and sensory feedback. Indwelling multi-electrode arrays, cuff electrodes, and regenerative sieve electrodes have been reported to serve as peripheral neural interfaces, though long-term stability of the nerve-electrode interface has remained a formidable challenge. We recently developed a regenerative multi-electrode interface (REMI) that is able to record neural activity as early as seven days post-implantation.

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Implanting electrical devices in the nervous system to treat neural diseases is becoming very common. The success of these brain-machine interfaces depends on the electrodes that come into contact with the neural tissue. Here we show that conventional tungsten and stainless steel wire electrodes can be coated with carbon nanotubes using electrochemical techniques under ambient conditions.

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We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression.

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Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway.

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Carbon nanotubes (CNTs) have unique chemical and physical properties anticipated to enable broad novel biomedical applications. Yet the question concerning their biocompatibility remains controversial. We recently reported a method for rapidly preparing strong, highly electrically conducting sheets and yarns from multi-walled CNTs.

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Rett syndrome (RTT) is caused by mutations in the gene encoding methyl CpG-binding protein 2 (MeCP2). Although MeCP2 shows widespread expression in both neuronal and non-neuronal tissues, the symptoms of RTT are largely neurological. Herein, we have identified the regulatory region of the mouse Mecp2 gene that is sufficient for its restricted expression in neurons.

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Increasingly, researchers are recognizing the limitations of two-dimensional (2-D), monolayer cell culture and embracing more realistic three-dimensional (3-D) cell culture systems. Currently, 3-D culture techniques are being employed by neuroscientists to grow cells from the central nervous system. From this work, it has become clear that 3-D cell culture offers a more realistic milieu in which the functional properties of neurons can be observed and manipulated in a manner that is not possible in vivo.

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We previously demonstrated that the neural cell adhesion molecule (N-CAM) inhibited the proliferation of cultured rat hippocampal progenitor cells and increased the number of neurons generated. We demonstrate here that the continued presence of fibroblast growth factor 2 along with N-CAM or brain-derived neurotrophic factor over 12 days of culture greatly increased the number of both progenitors and neurons. These progenitor-derived neurons expressed neurotransmitters, neurotransmitter receptors, and synaptic proteins in vitro consistent with those expressed in the mature hippocampus.

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