Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> This paper describes a new multielectrode microprobe which utilizes integrated-circuit fabrication techniques to overcome many of the problems associated with conventional microelectrodes. The probe structure consists of an array of gold electrodes which are supported on a silicon carrier and which project beyond the carrier for a distance of about 50 ? to allow a close approach to active neurons. These electrodes are covered with a thin (0.4-?) layer of silicon dioxide which is selectively removed at the electrode tips using high-resolution photoengraving techniques to define the recording areas precisely. The processing sequence described permits any two-dimensional electrode array to be realized. Interelectrode spacings can be accurately controlled in the range from 10 to 20 ? or larger, and electrode-tip diameters can be as small as 2 ?. <s> BIB001 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> How does the brain orchestrate perceptions, thoughts and actions from the spiking activity of its neurons? Early single-neuron recording research treated spike pattern variability as noise that needed to be averaged out to reveal the brain's representation of invariant input. Another view is that variability of spikes is centrally coordinated and that this brain-generated ensemble pattern in cortical structures is itself a potential source of cognition. Large-scale recordings from neuronal ensembles now offer the opportunity to test these competing theoretical frameworks. Currently, wire and micro-machined silicon electrode arrays can record from large numbers of neurons and monitor local neural circuits at work. Achieving the full potential of massively parallel neuronal recordings, however, will require further development of the neuron-electrode interface, automated and efficient spike-sorting algorithms for effective isolation and identification of single neurons, and new mathematical insights for the analysis of network properties. <s> BIB002 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Decoding motor behavior from neuronal signals has important implications for the development of a brain–machine interface (BMI) but also provides insights into the nature of different movement representations within cortical ensembles. Motor control can be hierarchically characterized as the selection and planning of discrete movement classes and/or postures followed by the execution of continuous limb trajectories. Based on simultaneous recordings in primary motor (MI) and dorsal premotor (PMd) cortices in behaving monkeys, we demonstrate that an MI ensemble can reconstruct hand or joint trajectory more accurately than an equally sized PMd ensemble. In contrast, PMd can more precisely predict the future occurrence of one of several discrete targets to be reached. This double dissociation suggests that a general-purpose BMI could take advantage of multiple cortical areas to control a wider variety of motor actions. These results also support the hierarchical view that MI ensembles are involved in lower-level movement execution, whereas PMd populations represent the early intention to move to visually presented targets. <s> BIB003 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> The continuous monitoring of electrical brain activity with implanted electrodes is essential for understanding the neural substrates of many physiological and pathological brain functions. Although this is done in some patients before undergoing surgical treatment, such recordings are extremely difficult in experimental animals, particularly in small rodents. The wires from the implanted electrodes restrain and interfere with the natural behavior of the animals. Consequently, it has been impossible to correlate truly normal behavior with neuronal activity. In addition, it would be ideal if brain activity could be monitored while animals live in a natural and enriched environment. A neural prosthetic device is comprised of a hardware system that records neural activity from the brain and then decodes it into control signals that in turn can be used to move robotic devices or muscles. Today's neural prosthetic devices typically use tethered headstage connections that interface the brain headstage electronics to the remote spike sorting processors located at the controlled devices. In this paper we present the circuits, layouts and test data for a multi-channel wireless headstage system which includes the headstage transmitter and receiver components <s> BIB004 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Many behaviors of interest to neurophysiologists are difficult to study under laboratory conditions because such behaviors are often inhibited when an animal is restrained and socially isolated. Even under the best conditions, such behaviors may be sparse enough as to require long duration neural recordings or simultaneous recording of multiple neurons to gather a sufficient amount of data for analysis. We have developed a preparation for chronic, multi-electrode recordings in the auditory cortex of marmoset monkeys, small primates, as well as techniques for neurophysiological recordings when the animals are free-roaming while singly caged in the environment of the monkey colony. In this report, we describe our solutions to overcome the problems associated with chronic recordings in free-roaming animals, where three-dimensional movements present particular challenges. <s> BIB005 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Neural prosthetic systems have the potential to restore lost functionality to amputees or patients suffering from neurological injury or disease. Current systems have primarily been designed for immobile patients, such as tetraplegics functioning in a rather static, carefully tailored environment. However, an active patient such as amputee in a normal dynamic, everyday environment may be quite different in terms of the neural control of movement. In order to study motor control in a more unconstrained natural setting, we seek to develop an animal model of freely moving humans. Therefore, we have developed and tested HermesC-INI3, a system for recording and wirelessly transmitting neural data from electrode arrays implanted in rhesus macaques who are freely moving. This system is based on the integrated neural interface (INI3) microchip which amplifies, digitizes, and transmits neural data across a ~ 900 MHz wireless channel. The wireless transmission has a range of ~ 4 m in free space. All together this device consumes 15.8 mA and 63.2 mW. On a single 2 A-hr battery pack, this device runs contiguously for approximately six days. The smaller size and power consumption of the custom IC allows for a smaller package (51 times 38 times 38 mm3) than previous primate systems. The HermesC-INI3 system was used to record and telemeter one channel of broadband neural data at 15.7 kSps from a monkey performing routine daily activities in the home cage. <s> BIB006 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> We present an inductively powered 32-channel wireless integrated neural recording (WINeR) system-on-a-chip (SoC) to be ultimately used for one or more small freely behaving animals. The inductive powering is intended to relieve the animals from carrying bulky batteries used in other wireless systems, and enables long recording sessions. The WINeR system uses time-division multiplexing along with a novel power scheduling method that reduces the current in unused low-noise amplifiers (LNAs) to cut the total SoC power consumption. In addition, an on-chip high-efficiency active rectifier with optimized coils help improve the overall system power efficiency, which is controlled in a closed loop to supply stable power to the WINeR regardless of the coil displacements. The WINeR SoC has been implemented in a 0.5-μ m standard complementary metal-oxide semiconductor process, measuring 4.9×3.3 mm2 and consuming 5.85 mW at ±1.5 V when 12 out of 32 LNAs are active at any time by power scheduling. Measured input-referred noise for the entire system, including the receiver located at 1.2 m, is 4.95 μVrms in the 1 Hz~10 kHz range when the system is inductively powered with 7-cm separation between aligned coils. <s> BIB007 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> HermesD is a high-rate, low-power wireless transmission system to aid research in neural prosthetic systems for motor disabilities and basic motor neuroscience. It is the third generation of our "Hermes systems" aimed at recording and transmitting neural activity from brain-implanted electrode arrays. This system supports the simultaneous transmission of 32 channels of broadband data sampled at 30 ks/s, 12 b/sample, using frequency-shift keying modulation on a carrier frequency adjustable from 3.7 to 4.1 GHz, with a link range extending over 20 m. The channel rate is 24 Mb/s and the bit stream includes synchronization and error detection mechanisms. The power consumption, approximately 142 mW, is low enough to allow the system to operate continuously for 33 h, using two 3.6-V/1200-mAh Li-SOCl2 batteries. The transmitter was designed using off-the-shelf components and is assembled in a stack of three 28 mm ? 28-mm boards that fit in a 38 mm ? 38 mm ? 51-mm aluminum enclosure, a significant size reduction over the initial version of HermesD. A 7-dBi circularly polarized patch antenna is used as the transmitter antenna, while on the receiver side, a 13-dBi circular horn antenna is employed. The advantages of using circularly polarized waves are analyzed and confirmed by indoor measurements. The receiver is a stand-alone device composed of several submodules and is interfaced to a computer for data acquisition and processing. It is based on the superheterodyne architecture and includes automatic frequency control that keeps it optimally tuned to the transmitter frequency. The HermesD communications performance is shown through bit-error rate measurements and eye-diagram plots. The sensitivity of the receiver is -83 dBm for a bit-error probability of 10-9. Experimental recordings from a rhesus monkey conducting multiple tasks show a signal quality comparable to commercial acquisition systems, both in the low-frequency (local field potentials) and upper-frequency bands (action potentials) of the neural signals. This system can be easily scaled up in terms of the number of channels and data rate to accommodate future generations of Hermes systems. <s> BIB008 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Mammalian brains generate internal activity independent of environmental stimuli. Internally generated states may bring about distinct cortical processing modes. To investigate how brain state impacts cortical circuitry, we recorded intracellularly from the same neurons, under anesthesia and subsequent wakefulness, in rat barrel cortex. In every cell examined throughout layers 2-6, wakefulness produced a temporal pattern of synaptic inputs differing markedly from those under anesthesia. Recurring periods of synaptic quiescence, prominent under anesthesia, were abolished by wakefulness, which produced instead a persistently depolarized state. This switch in dynamics was unaffected by elimination of afferent synaptic input from thalamus, suggesting that arousal alters cortical dynamics by neuromodulators acting directly on cortex. Indeed, blockade of noradrenergic, but not cholinergic, pathways induced synaptic quiescence during wakefulness. We conclude that global brain states can switch local recurrent networks into different regimes via direct neuromodulation. <s> BIB009 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems. <s> BIB010 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Szuts et al. have developed a wireless neural recording system that outperforms existing rodent telemetry systems in either channel count, weight or transmission range. They show that it can be used to record brain signals in animals outdoors and in tunnels. <s> BIB011 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> This paper reports on a compact, small-scale neural recording system combining state-of-art silicon-based probe arrays with a light-weight 32-channel wireless head stage. The system is equipped with two- and four-shaft, comb-shaped probe arrays connected to highly flexible ribbon cables enabling a reliable and controlled insertion of probe arrays through the intact dura mater into the medial prefrontal cortex and nucleus accumbens of rats. The in vivo experiments applied the 5-choice serial reaction time task (5-CSRTT) using freely behaving rats in order to understand the neural basis of sustained visual attention and impulsivity. The long-term stability of the system allowed local field potential (LFP) activity to be recorded without a significant decrement in signal quality for up to 28 weeks, and similarly, we were able to follow single unit activity for up to 4 weeks. <s> BIB012 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Neural control of movement is typically studied in constrained environments where there is a reduced set of possible behaviors. This constraint may unintentionally limit the applicability of findings to the generalized case of unconstrained behavior. We hypothesize that examining the unconstrained state across multiple behavioral contexts will lead to new insights into the neural control of movement and help advance the design of neural prosthetic decode algorithms. However, to pursue electrophysiological studies in such a manner requires a more flexible framework for experimentation. We propose that head-mounted neural recording systems with wireless data transmission, combined with markerless computer-vision based motion tracking, will enable new, less constrained experiments. As a proof-of-concept, we recorded and wirelessly transmitted broadband neural data from 32 electrodes in premotor cortex while acquiring single-camera video of a rhesus macaque walking on a treadmill. We demonstrate the ability to extract behavioral kinematics using an automated computer vision algorithm without use of markers and to predict kinematics from the neural data. Together these advances suggest that a new class of “freely moving monkey” experiments should be possible and should help broaden our understanding of the neural control of movement. <s> BIB013 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> We have developed miniature telemetry systems that capture neural, EMG, and acceleration signals from a freely moving insect or other small animal and transmit the data wirelessly to a remote digital receiver. The systems are based on custom low-power integrated circuits (ICs) that amplify, filter, and digitize four biopotential signals using low-noise circuits. One of the chips also digitizes three acceleration signals from an off-chip microelectromechanical-system accelerometer. All information is transmitted over a wireless ~ 900-MHz telemetry link. The first unit, using a custom chip fabricated in a 0.6- μm BiCMOS process, weighs 0.79 g and runs for two hours on two small batteries. We have used this system to monitor neural and EMG signals in jumping and flying locusts as well as transdermal potentials in weakly swimming electric fish. The second unit, using a custom chip fabricated in a 0.35-μ m complementary metal-oxide semiconductor CMOS process, weighs 0.17 g and runs for five hours on a single 1.5-V battery. This system has been used to monitor neural potentials in untethered perching dragonflies. <s> BIB014 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> This paper presents a digital neural/EMG telemetry system small enough and lightweight enough to permit recording from insects in flight. It has a measured flight package mass of only 38 mg. This system includes a single-chip telemetry integrated circuit (IC) employing RF power harvesting for battery-free operation, with communication via modulated backscatter in the UHF (902-928 MHz) band. An on-chip 11-bit ADC digitizes 10 neural channels with a sampling rate of 26.1 kSps and 4 EMG channels at 1.63 kSps, and telemeters this data wirelessly to a base station. The companion base station transceiver includes an RF transmitter of +36 dBm (4 W) output power to wirelessly power the telemetry IC, and a digital receiver with a sensitivity of -70 dBm for 10-5 BER at 5.0 Mbps to receive the data stream from the telemetry IC. The telemetry chip was fabricated in a commercial 0.35 μ m 4M1P (4 metal, 1 poly) CMOS process. The die measures 2.36 × 1.88 mm, is 250 μm thick, and is wire bonded into a flex circuit assembly measuring 4.6 × 6.8 mm. <s> BIB015 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> This paper describes a inductively powered multichannel bionic neural link (BNL) system-on-chip (SOC) for peripheral nerve function restoration. The BNL-SOC consists of 8 neural recording and 4 stimulation channels, and is implemented in a 0.35-μm CMOS technology. Full function of the BNL has been demonstrated with in-vivo animal experiments. The entire BNL SOC consumes 1.5mW and operates under a 3V supply with an external +/-9V multichannel stimulation output driver. <s> BIB016 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> The ability to record well-isolated action potentials from individual neurons in naturally behaving animals is crucial for understanding neural mechanisms underlying natural behaviors. Traditional neurophysiology techniques, however, require the animal to be restrained which often restricts natural behavior. An example is the common marmoset (Callithrix jacchus), a highly vocal New World primate species, used in our laboratory to study the neural correlates of vocal production and sensory feedback. When restrained by traditional neurophysiological techniques marmoset vocal behavior is severely inhibited. Tethered recording systems, while proven effective in rodents pose limitations in arboreal animals such as the marmoset that typically roam in a three-dimensional environment. To overcome these obstacles, we have developed a wireless neural recording technique that is capable of collecting single-unit data from chronically implanted multi-electrodes in freely moving marmosets. A lightweight, low power and low noise wireless transmitter (headstage) is attached to a multi-electrode array placed in the premotor cortex of the marmoset. The wireless headstage is capable of transmitting 15 channels of neural data with signal-to-noise ratio (SNR) comparable to a tethered system. To minimize radio-frequency (RF) and electro-magnetic interference (EMI), the experiments were conducted within a custom designed RF/EMI and acoustically shielded chamber. The individual electrodes of the multi-electrode array were periodically advanced to densely sample the cortical layers. We recorded single-unit data over a period of several months from the frontal cortex of two marmosets. These recordings demonstrate the feasibility of using our wireless recording method to study single neuron activity in freely roaming primates. <s> BIB017 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> A power and area efficient sensor interface consumes 6.4 mW from 1.2 V while occupying 5 mm × 5 mm in 0.13 μm CMOS. The interface offers simultaneous access to 96 channels of broadband neural data acquired from cortical microelectrodes as part of a head-mounted wireless recording system, enabling basic neuroscience as well as neuroprosthetics research. Signals are conditioned with a front-end achieving 2.2 μVrms input-referred noise in a 10 kHz bandwidth before conversion at 31.25 kSa/s by 10-bit SAR ADCs with 60.3 dB SNDR and 42 fJ/conv-step. Switched-capacitor filtering provides a well-controlled frequency response and utilizes windowed integrator sampling to mitigate noise aliasing, enhancing noise/power efficiency. <s> BIB018 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses. It has long been thought that individual neurons in the motor and premotor cortex are tuned for parameters of movements such as direction. But despite decades of work, the exact nature of the represented parameters is still unclear, as are the mechanisms through which such representations could support the complex movements made in the course of every day life. Here, Churchland et al. propose an alternative theory — that population dynamics could underlie motor control. They show that reaching movements are associated with oscillatory population activity in the monkey motor cortex, despite there being no periodic component to this behaviour. The amplitude and phase of the oscillation followed naturally from the preceding state, suggesting a role for preparatory neural activity in reaching. <s> BIB019 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1?Hz to 7.8?kHz, 200? gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8?GHz to a receiver 1?m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7?h continuous operation between recharge via an inductive transcutaneous wireless power link at 2?MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions and will advance brain research. <s> BIB020 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> A 100-channel fully implantable wireless broadband neural recording system was developed. It features 100 parallel broadband (0.1 Hz-7.8 kHz) neural recording channels, a medical grade 200 mAh Li-ion battery recharged inductively at 150 kHz , and data telemetry using 3.2 GHz to 3.8 GHz FSK modulated wireless link for 48 Mbps Manchester encoded data. All active electronics are hermetically sealed in a titanium enclosure with a sapphire window for electromagnetic transparency. A custom, high-density configuration of 100 individual hermetic feedthrough pins enable connection to an intracortical neural recording microelectrode array. A 100 MHz bandwidth custom receiver was built to remotely receive the FSK signal and achieved -77.7 dBm sensitivity with 10-8 BER at 48 Mbps data rate. ESD testing on all the electronic inputs and outputs has proven that the implantable device satisfies the HBM Class-1B ESD Standard. In addition, the evaluation of the worst-case charge density delivered to the tissue from each I/O pin verifies the patient safety of the device in the event of failure. Finally, the functionality and reliability of the complete device has been tested on-bench and further validated chronically in ongoing freely moving swine and monkey animal trials for more than one year to date. <s> BIB021 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> The neural computations underlying sensory-guided behaviors can best be understood in view of the sensory stimuli to be processed under natural conditions. This input is often actively shaped by the movements of the animal and its sensory receptors. Little is known about natural sensory scene statistics taking into account the concomitant movement of sensory receptors in freely moving animals. South American weakly electric fish use a self-generated quasi-sinusoidal electric field for electrolocation and electrocommunication. Thousands of cutaneous electroreceptors detect changes in the transdermal potential (TDP) as the fish interact with conspecifics and the environment. Despite substantial knowledge about the circuitry and physiology of the electrosensory system, the statistical properties of the electrosensory input evoked by natural swimming movements have never been measured directly. Using underwater wireless telemetry, we recorded the TDP of Apteronotus leptorhynchus as they swam freely by themselves and during interaction with a conspecific. Swimming movements caused low-frequency TDP amplitude modulations (AMs). Interacting with a conspecific caused additional AMs around the difference frequency of their electric fields, with the amplitude of the AMs (envelope) varying at low frequencies due to mutual movements. Both AMs and envelopes showed a power-law relationship with frequency, indicating spectral scale invariance. Combining a computational model of the electric field with video tracking of movements, we show that specific swimming patterns cause characteristic spatiotemporal sensory input correlations that contain information that may be used by the brain to guide behavior. <s> BIB022 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> Application of neural amplifiers for brain science <s> Wireless power, when coupled with miniaturized implantable electronics, has the potential to provide a solution to several challenges facing neuroscientists during basic and preclinical studies with freely behaving animals. The EnerCage system is one such solution as it allows for uninterrupted electrophysiology experiments over extended periods of time and vast experimental arenas, while eliminating the need for bulky battery payloads or tethering. It has a scalable array of overlapping planar spiral coils (PSCs) and three-axis magnetic sensors for focused wireless power transmission to devices on freely moving subjects. In this paper, we present the first fully functional EnerCage system, in which the number of PSC drivers and magnetic sensors was reduced to one-third of the number used in our previous design via multicoil coupling. The power transfer efficiency (PTE) has been improved to 5.6% at a 120 mm coupling distance and a 48.5 mm lateral misalignment (worst case) between the transmitter (Tx) array and receiver (Rx) coils. The new EnerCage system is equipped with an Ethernet backbone, further supporting its modular/scalable architecture, which, in turn, allows experimental arenas with arbitrary shapes and dimensions. A set of experiments on a freely behaving rat were conducted by continuously delivering 20 mW to the electronics in the animal headstage for more than one hour in a powered 3538 cm2 experimental area. <s> BIB023
IC neural amplifiers are used by neuroscientists to study the CNS of living organisms. Typical neuroscience studies involve inserting electrodes   BIB001 into specific regions of the cortex to acquire neural electrical activity. IC neural amplifiers then amplify and condition the weak cortical signals for post-processing and analysis. The primary goal of such studies is to understand how the activities of groups of neurons are related to sensation, behavior and cognition BIB002  . Such neurophysiological investigations simultaneously record from dozens of neurons involved in specified behavioral tasks, for example, while an experimental subject performs motor or sensory tasks. Anesthetized and tethered preparations yield invaluable information BIB009 BIB005 BIB003  . Nevertheless, neuroscientists increasingly seek to study animal subjects while naturally behaving. This requires recording systems with a high degree of miniaturization, a small form factor and reduced weight. Often, such systems are powered using miniaturized and light-weight battery packs BIB010 or wireless power transfer systems BIB015 . With continuous improvements in IC design and fabrication technology, IC neural recording systems can be now integrated with wireless telemetry for data and, in some cases, wireless power transfer BIB007 BIB016 . This has enabled many neuroscientific studies that incorporate freely roaming animal models. The following paragraphs summarize recently reported neural recording IC systems that have been successfully used with common animal models. The most common animal model for studying brain is the rodent. Due to their small size, rodents can bear limited weight and, hence, portable neural recording systems for rodent studies must have a small form factor and low weight. For example, Szuts et al. BIB011 reported a 64-channel neural amplifier chip (Neuroplat64) that was mounted onto the head of a rat. The analog output is wirelessly transmitted to a base system for digitization followed by archival and post-processing. This device consumed 645 mW and weighted 52 g. Subsequently, both Ruther et al. BIB012 and Fan et al. BIB010 reported a system using a commercially available, wireless neurorecording amplifier head-stage BIB004 136] that consisted of a 15-channel neurorecording IC packaged with a radio frequency (RF) IC for wireless data transfer (Fig. 8a) . The total power consumption of both the amplifier and the RF IC was only 21 mW. Having integrated all the necessary components onto 2 chips and powered by smaller-sized batteries, this integrated system weighed just 9 g. The reported system-on-chip solutions require a battery as a power supply. This adds additional weight that the rodent subjects must bear, which often leads to animal fatigue and limits the duration of experiments. Recently, the chip implementation reported by Lee et al. BIB007 eliminated the need for a battery by integrating an on-chip inductive wireless power harvester in addition to 32 neural recording amplifiers and an RF transceiver. With intelligent neural amplifier power scheduling, the total chip consumed 5.85 mW and could be powered by a near-field wireless harvesting scheme BIB023 . Non-human primates (NHPs) are also extensively used for neuroscience studies. Due to the large roaming space required by NHPs, the short-range wireless power harvesting methods described for rodents, such as in BIB007 and BIB023 , are not sufficient to wirelessly power neural recording systems for NHP studies. All current wireless recording systems for primate studies therefore require a light-weight battery pack, which is often head mounted. For example, Roy and Wang reported a battery-powered neural recording setup BIB017 based on the same system used in [136] to study the auditory cortex of free-ranging Marmosets over a 5-hour period on a single battery charge. Nurmikko's group has reported two battery-powered, wireless neural recording systems encased in biocompatible titanium casings BIB020 BIB021 . In their first version, as shown in Fig. 8b [12] , the casing held a 100-channel neural recording IC, digitizers and a 24-Mbps wireless data link module. Both systems contained an inductively powered battery charger to wirelessly charge the implanted battery, and the second system BIB021 mitigated charging-induced heating. Weighing only 44.5 g and consuming only 90 mW, the system in BIB020 has successfully acquired neural recordings from free-ranging Rhesus macaques and swine models for up to 7 h on a single charge. Shenoy's group has developed four generations of the "Hermes" family of portable wireless neural recording systems BIB006 BIB018 BIB008 120] that were successfully applied in recent NHP studies BIB019 BIB013  . Their latest implementation is the HermesE system, which is composed of a 96-channel neural recording chip with on-chip digitizers and an off-chip UWB transmitter. The HermesE chip was fabricated in an advanced CMOS 0.13-µm process, measured 25 mm 2 and consumed only 6.5 mW. Wireless recording instrumentation designed for small subjects, such as insects, requires very aggressive reductions in size, weight and power consumption. Harrison et al. BIB014 reported integrating 2 channels of neural amplifiers, 2 channels of EMG amplifiers, a shared digitizer and Fig. 8 a A neural recording system with an RF transceiver for brain studies in a rodent model, as reported by Fan et al. BIB010 . b A similar system for performing CNS studies in a macaque model reported by Borton et al. BIB020 . (a) Reproduced with permission from IEEE (b) © IOP Publishing. Reproduced with permission. All rights reserved Fig. 9 Neural recording systems for very small subjects, such as a a locust BIB014 and b a dragonfly BIB015 . Reproduced with permission from IEEE a 920-MHz radio onto a single chip. As this design required an operating voltage of 3 V, it was powered by two watch batteries, consumed only 3.6 mW and had a total run time of 2 h. The chip package, batteries and the PCB weighed 0.79 g and were used to perform wireless neural recording from an untethered locust (Fig. 9a) and swimming electric fish BIB022 . Also reported in the same paper, a second version of the chip was implemented in a finer CMOS 0.35-µm process technology, which allowed the chip to operate at only 1.5 V and hence required only a single watch (button) battery. This chip consumed only 1 mW and had a longer run time of 5 h compared to the first version. The chip was also directly bonded to a thinner flexible PCB, reducing the total weight of the system to 0.17 g, and was used to record action potentials from the target-selective descending neuron in the nerve cord of a free-flying dragonfly (Fig. 9b) . A similar chip reported by Fotowat et al. BIB015 included 10 neural recording channels and an RF wireless power harvesting circuit. Compared to the chips reported in BIB014 , the chip reported in BIB015 consumed only 1.23 mW due to the use of more power-efficient neural amplifiers. Without the need for any battery, it weighed 38 mg and had no run-time restrictions.