Brain recordings in large animal models and humans typically rely on a tethered connection, which has restricted the spectrum of accessible experimental and clinical applications. To overcome this limitation, we have engineered a compact, lightweight, high data rate wireless neurosensor capable of recording the full spectrum of electrophysiological signals from the cortex of mobile subjects. The wireless communication system exploits a spatially distributed network of synchronized receivers that is scalable to hundreds of channels and vast environments. To demonstrate the versatility of our wireless neurosensor, we monitored cortical neuron populations in freely behaving nonhuman primates during natural locomotion and sleep-wake transitions in ecologically equivalent settings. The interface is electrically safe and compatible with the majority of existing neural probes, which may support previously inaccessible experimental and clinical research.

Teneurin C-terminal associated peptide (TCAP) is an ancient paracrine signalling agent that evolved via lateral gene transfer from prokaryotes into an early metazoan ancestor. Although it bears structural similarity to corticotrophin-releasing hormone (CRH), it inhibits the in vivo actions of CRH. The TCAPs are highly expressed in neurones, where they induce rapid cytoskeletal rearrangement and are neuroprotective. Because these processes are highly energy-dependent, this suggests that TCAP has the potential to regulate glucose uptake because glucose is the primary energy substrate in brain, and neurones require a steady supply to meet the high metabolic demands of neuronal communication. Therefore, the objective of the present study was to assess the effect of TCAP-mediated glucose uptake in the brain and in neuronal cell models. TCAP-mediated F-deoxyglucose (FDG) uptake into brain tissue was assessed in male wild-type Wistar rats by functional positron emission tomography. TCAP-1 increased FDG uptake by over 40% into cortical regions of the brain, demonstrating that TCAP-1 can significantly enhance glucose supply. Importantly, a single nanomolar injection of TCAP-1 increased brain glucose after 3 days and decreased blood glucose after 1 week. This is corroborated by a decreased serum concentration of insulin and an increased serum concentration of glucagon. In immortalised hypothalamic neurones, TCAP-1 increased ATP production and enhanced glucose uptake by increasing glucose transporter recruitment to the plasma membrane likely via AKT and mitogen-activated protein kinase/ERK phosphorylation events. Taken together, these data demonstrate that TCAP-1 increases glucose metabolism in neurones, and may represent a peptide signalling agent that regulated glucose uptake before insulin and related peptides.

We have designed, fabricated, and characterized a microminiaturized "neuroport" for brain implantable neuroprosthesis applications, using an analog CMOS integrated circuit and a silicon based microelectrode array. An ultra-low power, low-noise CMOS preamplifier array with integral multiplexing was designed to accommodate stringent thermal and electrophysiological requirements for implantation in the brain, and a hybrid integration approach was developed to fabricate a functional microminiaturized neuroprobe device. Measurements showed that our fully scalable 16-channel CMOS amplifier chip had an average gain of 44 dB, bandwidth from 10 Hz to 7.3 kHz, and an equivalent input noise of approximately 9 microVrms with an average power consumption per preamplifier of 52 microW, which is consistent with simulation results. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, showing oscillatory behavior with an amplitude about 0.5 mV and a period ranging 80-120 ms. The results suggest that the hybrid integrated neuroport can form a prime platform for the development of a next level microminiaturized neural interface to the brain in a single implantable unit.

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature’s amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic “brain-interfaces” within the body, a point of special emphasis of this paper.

We have built a wireless implantable microelectronic device for transmitting cortical signals transcutaneously. The device is aimed at interfacing a microelectrode array cortical to an external computer for neural control applications. Our implantable microsystem enables presently 16-channel broadband neural recording in a non-human primate brain by converting these signals to a digital stream of infrared light pulses for transmission through the skin. The implantable unit employs a flexible polymer substrate onto which we have integrated ultra-low power amplification with analog multiplexing, an analog-to-digital converter, a low power digital controller chip, and infrared telemetry. The scalable 16-channel microsystem can employ any of several modalities of power supply, including via radio frequency by induction, or infrared light via a photovoltaic converter. As of today, the implant has been tested as a sub-chronic unit in non-human primates (~ 1 month), yielding robust spike and broadband neural data on all available channels.

An ultralow power analog CMOS chip and a silicon based microelectrode array have been fully integrated to a microminiaturized "neuroport" for brain implantable neuroengineering applications. The CMOS integrated circuit (IC) includes preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional, encapsulated microminiaturized neuroprobe device. Our neuroport has been evaluated using various methods, including pseudospike detection and local excitation measurement, and showed suitable characteristics for recording neural activities. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, suggesting that the new neuroport can form a prime platform for the development of a microminiaturized neural interface to the brain in a single implantable unit. An alternative power delivery scheme using photovoltaic power converter, and an encapsulation strategy for chronic implantation are also discussed.

A prototype cortical neural interface microsystem has been developed for brain implantable neuroengineering applications, featuring hybrid RF (radio-frequency) inductive and IR (infrared) optical telemetries. The system is aimed at neural recording from primates by converting cortical signals to a digital stream of IR light pulses, while acquiring clock signal and electrical power through RF induction. The implantable unit employs a flexible LCP (liquid crystal polymer) substrate for integration of analog, digital, and optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. An ultra-low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the immediate cortical neuroprobe device. A 16-channel version of the probe has been tested in various in-vivo animal experiments, including measurements of neural activity in somatosensory cortex of a rat.

Recent advances in functional electrical stimulation (FES) show significant promise for restoring voluntary movement in patients with paralysis or other severe motor impairments. Current approaches for implantable FES systems involve multisite stimulation, posing research issues related to their physical size, power and signal delivery, surgical and safety challenges. To explore a different means for delivering the stimulus to a distant muscle nerve site, we have elicited in vitro FES response using a high efficiency microcrystal photovoltaic device as a neurostimulator, integrated with a biocompatible glass optical fiber which forms a lossless, interference-free lightwave conduit for signal and energy transport. As a proof of concept demonstration, a sciatic nerve of a frog is stimulated by the microcrystal device connected to a multimode optical fiber (core diameter of 62.5 microm), which converts optical activation pulses ( approximately 100 micros) from an infrared semiconductor laser source (at 852 nm wavelength) into an FES signal.