Timeless noncoding DNA contains cell-type preferential enhancers important for proper Drosophila circadian regulation.

To address the contribution of transcriptional regulation to clock gene expression and to behavior, we generated a series of CRISPR-mediated deletions within two regions of the circadian gene (), an intronic E-box region and an upstream E-box region that are both recognized by the key transcription factor Clock (Clk) and its heterodimeric partner Cycle. The upstream deletions but not an intronic deletion dramatically impact expression in fly heads; the biggest upstream deletion reduces peak RNA levels and RNA cycling amplitude to about 15% of normal, and there are similar effects on protein (TIM). The cycling amplitude of other clock genes is also strongly reduced, in these cases due to increases in trough levels.

Spatial patterning controls neuron numbers in the Drosophila visual system.

Neurons must be made in the correct proportions to communicate with the appropriate synaptic partners and form functional circuits. In the Drosophila visual system, multiple subtypes of distal medulla (Dm) inhibitory interneurons are made in distinct, reproducible numbers-from 5 to 800 per optic lobe. These neurons are born from a crescent-shaped neuroepithelium called the outer proliferation center (OPC), which can be subdivided into specific domains based on transcription factor and growth factor expression.

Dynamic peripheral nerve stimulation can produce cortical activation similar to punctate mechanical stimuli.

During contact, phasic and tonic responses provide feedback that is used for task performance and perceptual processes. These disparate temporal dynamics are carried in peripheral nerves, and produce overlapping signals in cortex. Using longitudinal intrafascicular electrodes inserted into the median nerve of a nonhuman primate, we delivered composite stimulation consisting of onset and release bursts to capture rapidly adapting responses and sustained stochastic stimulation to capture the ongoing response of slowly adapting receptors.

Prospective pre-operative 3-T MR neurography peripheral nerve mapping of upper extremity amputations implanted with FAST-LIFE electrode interfaces of robotic hands: technical report.

Background And Purpose: Fascicular targeting of longitudinal intrafascicular electrode (FAST-LIFE) interface enables hand dexterity with exogenous electrical microstimulation for sensory restoration, custom neural recording hardware, and deep learning-based artificial intelligence for motor intent decoding. The purpose of this technical report from a prospective pilot study was to illustrate magnetic resonance neurography (MRN) mapping of hand and nerve anatomy in amputees and incremental value of MRN over electrophysiology findings in pre-surgical planning of FAST-LIFE interface (robotic hand) patients.

Materials And Methods: After obtaining informed consent, patients with upper extremity amputations underwent pre-operative 3-T MRN, X-rays, and electrophysiology.

Artificial Intelligence Enables Real-Time and Intuitive Control of Prostheses via Nerve Interface.

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.

A portable, self-contained neuroprosthetic hand with deep learning-based finger control.

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.

Fascicle-Specific Targeting of Longitudinal Intrafascicular Electrodes for Motor and Sensory Restoration in Upper-Limb Amputees.

Multichannel longitudinal intrafascicular electrode (LIFE) interfaces provide optimized balance of invasiveness and stability for chronic sensory stimulation and motor recording/decoding of peripheral nerve signals. Using a fascicle-specific targeting (FAST)-LIFE approach, where electrodes are individually placed within discrete sensory- and motor-related fascicular subdivisions of the residual ulnar and/or median nerves in an amputated upper limb, FAST-LIFE interfacing can provide discernment of motor intent for individual digit control of a robotic hand, and restoration of touch- and movement-related sensory feedback. The authors describe their findings from clinical studies performed with 6 human amputee trials using FAST-LIFE interfacing of the residual upper limb.

Deep Learning-Based Approaches for Decoding Motor Intent From Peripheral Nerve Signals.

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.

A bioelectric neural interface towards intuitive prosthetic control for amputees.

. 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..

Human motor decoding from neural signals: a review.

Many people suffer from movement disability due to amputation or neurological diseases. Fortunately, with modern neurotechnology now it is possible to intercept motor control signals at various points along the neural transduction pathway and use that to drive external devices for communication or control. Here we will review the latest developments in human motor decoding.

Fascicle specific targeting for selective peripheral nerve stimulation.

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.

Deep compressive autoencoder for action potential compression in large-scale neural recording.

Objective: Understanding the coordinated activity underlying brain computations requires large-scale, simultaneous recordings from distributed neuronal structures at a cellular-level resolution. One major hurdle to design high-bandwidth, high-precision, large-scale neural interfaces lies in the formidable data streams (tens to hundreds of Gbps) that are generated by the recorder chip and need to be online transferred to a remote computer. The data rates can require hundreds to thousands of I/O pads on the recorder chip and power consumption on the order of Watts for data streaming alone.

Asymmetric Sensory-Motor Regeneration of Transected Peripheral Nerves Using Molecular Guidance Cues.

Neural interfaces are designed to decode motor intent and evoke sensory precepts in amputees. In peripheral nerves, recording movement intent is challenging because motor axons are only a small fraction compared to sensory fibers and are heterogeneously mixed particularly at proximal levels. We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve guide with sealed ends, can be modulated by luminar release of nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively.

An implantable, designed-for-human-use peripheral nerve stimulation and recording system for advanced prosthetics.

Complex suture prostheses that deliver sensory and position feedback require a more sophisticated integration with the human user. Here a micro-size active implantable system that provides many-degree-of-freedom neural feedback in both sensory stimulation and motor control is shown, as one potential human-use solution in DARPA's HAPTIX program. Various electrical and mechanical challenge and solutions in meeting both sensory /motor performance as well as ISO 14708 FDA-acceptable human use in an aspirin-size active implementation are discussed.

Chronic sensory-motor activity in behaving animals using regenerative multi-electrode interfaces.

Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control and feel of robotic prosthetic limbs. We have developed a Regenerative Multi-electrode Interface (REMI) that guides re-growing axons through an electrode array deployed in the lumen of a nerve guide. While acute studies have shown the use of the REMI in the rat sciatic nerve, the quality of chronic signal recording has not been reported.

Effects of carbon nanotube and conducting polymer coated microelectrodes on single-unit recordings in vitro.

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.

Detergent-free Decellularized Nerve Grafts for Long-gap Peripheral Nerve Reconstruction.

Background: Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks.

On the robustness of EC-PC spike detection method for online neural recording.

Background: Online spike detection is an important step to compress neural data and perform real-time neural information decoding. An unsupervised, automatic, yet robust signal processing is strongly desired, thus it can support a wide range of applications. We have developed a novel spike detection algorithm called "exponential component-polynomial component" (EC-PC) spike detection.

Botulinum toxin suppression of CNS network activity in vitro.

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).

Thiol-ene/acrylate substrates for softening intracortical electrodes.

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.

The use of a novel carbon nanotube coated microelectrode array for chronic intracortical recording and microstimulation.

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.

Normal molecular repair mechanisms in regenerative peripheral nerve interfaces allow recording of early spike activity despite immature myelination.

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.

1/f neural noise reduction and spike feature extraction using a subset of informative samples.

This article describes a study on neural noise and neural signal feature extraction, targeting real-time spike sorting with miniaturized microchip implementation. Neuronal signature, noise shaping, and adaptive bandpass filtering are reported as the techniques to enhance the signal-to-noise ratio (SNR). A subset of informative samples of the waveforms is extracted as features for classification.

Arthroscopic wafer resection for ulnar impaction syndrome: prediction of outcomes.

Twenty-six patients with mean age of 38.5 (range 18-59), from 1998 to 2005, with ulnar impaction syndrome who failed nonoperative treatments were included in our study. Patients' age, history of previous wrist fracture, presence of MRI signs and ulnar variance were recorded as variables.

Early interfaced neural activity from chronic amputated nerves.

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use.