Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> 1. Neural activity was recorded from cats during locomotion on a treadmill using electrodes in Silastic cuffs placed around the sciatic nerve and the lateral gastrocnemius-soleus, medial gastrocnemius, common peroneal and tibial nerve branches. Each branch gave characteristic patterns of activity which were studied before and after it was cut distal to the recording cuffs. Sensory and motor components were separated and measured using cross-correlation techniques. The amplitude of the cross-correlation peaks was compared with the amplitude of compound action potentials evoked by electrical stimulation and recorded from the same sites in the anaesthetized animal. 2. Sensory activity declined rapidly following axotomy and did not recover unless reinnervation occurred. Sensory activity even 5 months after nerve section and resuture had recovered to only a fraction of the control values. This reduction is attributed to a decline in the evoked compound potentials and to many fibres being unsuccessful in regenerating to appropriate sensory organs. 3. Motor activity declined more than could be accounted for by a decline in evoked potentials over the first month after axotomy. The extra reduction represents a decline in the number of impulses generated by alpha-motoneurones after axotomy. If regeneration was permitted, motor activity recovered to higher levels than did the evoked potentials for the whole nerve. Even if regeneration was prevented by nerve ligation, motoneurones continued to generate activity at a stable level over a period of months during which whole nerve compound potentials continued to decline. 4. The modulation of motor activity in ligated nerves during the step cycle was still appropriate to the required movement. Thus, activity recorded from severed nerves in human amputees may be useful in controlling powered artificial limbs. The persistence of motor activity may be responsible for the lesser degree of atrophy found in motor fibres than in sensory fibres following ligation (Hoffer, Stein & Gordon, 1979b). <s> BIB001 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> We have used a self-curling nerve cuff electrode to record sensory information from a cutaneous nerve. This type of cuffs has previously been used only for stimulation, but its mechanical properties could make it very suitable for recording also, since it can be fitted closer to the nerve than traditional cuffs without compromising the nerve. In this study we show that it is possible to record neural signals with at least the same quality as traditional cuffs. <s> BIB002 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> A comparative study of 5 different designs of nerve cuff electrodes was undertaken to determine their relative merits for stimulating and recording whole-nerve activity over extended periods of chronic implantation on large and small peripheral nerves in 8 cats. Four of the designs represent novel fabrication strategies, including 2 based on flexible, thin-film substrates and 2 based on dip-coating silicone elastomer on a cylindrical mandrel. Various advantages and shortcomings of these materials and designs are discussed in the context of the biophysical factors that influence these electrophysiological interfaces, particularly the problem of recording microvolt-level neurograms in the presence of millivolt-level electromyograms from adjacent muscles in freely behaving subjects. The most effective design was one in which a thin sheath of silicone rubber was wrapped around and intra-operatively sealed to a longitudinally slit, tripolar cuff made by dip-coating silicone over stranded stainless steel leads that were prepositioned on a mandrel using polyvinyl alcohol as a temporary adhesive. When properly installed, these electrodes had stable impedances, recruitment thresholds and relatively interference-free recording properties for the duration of this study (up to 9 weeks). <s> BIB003 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> This paper discusses certain important issues involved in the design of a nerve signal preamplifier for implantable neuroprostheses. Since the electroneurogram signal measured from cuff electrodes is typically on the order of 1 /spl mu/V, a very low-noise interface is essential. We present the argument for the use of BiCMOS technology in this application and then describe the design and evaluation of a complete preamplifier fabricated in a 0.8-/spl mu/m double-metal double-poly process. The preamplifier has a nominal voltage gain of 100, a bandwidth of 15 kHz, and a measured equivalent input-referred noise voltage spectral density of 3.3 nV//spl radic/Hz at 1 kHz. The total input-referred rms noise voltage in a bandwidth 1 Hz-10 kHz is 290 nV, the power consumption is 1.3 mW from /spl plusmn/2.5-V power supplies, and the active area is 0.3 mm/sup 2/. <s> BIB004 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> We examined the recording characteristics of two different types of polymer-based longitudinal intrafascicular electrodes (LIFEs) in peripheral nerve: single-stranded (s-polyLIFEs) and multistranded (m-polyLIFEs). Recordings were also made from Pt-Ir wire-based electrodes (PtIrLIFEs) as a control. The electrodes were implanted in either tibial or medial gastrocnemius branches of the rabbit sciatic nerve, and in the sciatic nerve of rats. Recorded neural activity induced by manually elicited afferent neural activity showed that both polyLIFE versions performed comparably to PtIrLIFEs. <s> BIB005 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> The development and in vivo test of a fully integrated differential CMOS amplifier, implemented with standard 0.7-/spl mu/m CMOS technology (one poly, two metals, self aligned twin-well CMOS process) intended to record extracellular neural signals is described. In order to minimize the flicker noise generated by the CMOS circuitry, a chopper technique has been chosen. The fabricated amplifier has a gain of 74 dB, a bandwidth of 3 kHz, an input noise of 6.6 nV/(Hz)/sup 0.5/, a power dissipation of 1.3 mW, and the active area is 2.7 mm/sup 2/. An ac coupling has been used to adapt the electrode to the amplifier circuitry for the in vivo testing. Compound muscle action potentials, motor unit action potentials, and compound nerve action potentials have been recorded in acute experiments with rats, in order to validate the amplifier. <s> BIB006 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> This paper describes the design of an adaptive control system for recording neural signals from tripolar cuff electrodes. The control system is based on an adaptive version of the true-tripole amplifier configuration and was developed to compensate for possible errors in the cuff electrode balance by continuously adjusting the gains of the two differential amplifiers. Thus, in the presence of cuff imbalance, the output signal-to-interference ratio is expected to be significantly increased, in turn reducing the requirement for post-filtering to reasonable levels and resulting in a system which is fully implantable. A realization in 0.8-/spl mu/m CMOS technology is described and simulated and preliminary measured results are presented. Gain control is achieved by means of current-mode feedback and many of the system blocks operate in the current-mode domain. The chip has a core area of 0.4 mm/sup 2/ and dissipates 3 mW from /spl plusmn/ 2.5V power supplies. Measurements indicate that the adaptive control system is expected to be capable of compensating for up to /spl plusmn/5% errors in the tripolar cuff electrode balance. <s> BIB007 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> The purpose of this study was to evaluate the value of utilizing longitudinal intrafascicular electrodes (LIFEs) in collecting and analyzing sensory signals from the peripheral nerve. The longitudinal intrafascicular electrodes were made of 25-μm Teflon-insulated Pt/Ir wire and implanted into the fascicle of the superficial peroneal nerves in a feline model. The sensory signals at rest status and induced with various stimulations were recorded. The action potential area, frequency, coefficient of variation (CV) of the peak, and functional spectrum were then analyzed by the MF Lab version 3.01 software package. The results showed that the sensory nerve action potentials (SNAPs) were 0–2 spikes per second at rest state; the count was increased when stimulation was administered. SNAPs were 16–24 spikes per second when scraping stimulation was applied. The pulse intervals and the waveform remained consistent. SNAPs burst and were clustered when stress stimulation was given. The comparison of area, frequency, and CV of the peak showed statistically significant differences between these parameters receiving different stimulations. The functional spectrum analysis showed that the frequency of action potential increased when the stress stimulation was applied. In conclusion, LIFEs can sensitively collect sensory signals and provide a good interface to analyze sensory information from peripheral fasciculi. These data provide useful information for further study of control of electronic prostheses. © 2005 Wiley-Liss, Inc. Microsurgery 25:561–565, 2005. <s> BIB008 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> In this paper the design, fabrication and testing of a 10-channel array of identical amplifiers suitable for velocity selective electroneurogram (ENG) recording is described. The overall gain per channel is 10,000 and the total input-referred rms noise in a bandwidth 1 Hz-5 kHz is 290 nV per channel. The active area is 12 mm/sup 2/ and the power consumption is 24 mW from /spl plusmn/2.5 V power supplies. <s> BIB009 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> We are developing a new type of bipolar recording electrode intended for implantation within individual fascicles of mammalian peripheral nerves. In the experiments reported here we used electrodes fabricated from 25 μm diameter Pt wire, 50 μm 90% Pt-10% Ir wire and 7 μm carbon fibers. The electrodes were implanted in the sciatic nerves of rats and in the ulnar nerves of cats. The signal-to-noise ratio of recorded activity induced by nonnoxious mechanical stimulation of the skin and joints was studied as a function of the type of electrode material used, the amount of insulation removed from the recording zone, and the longitudinal separation of the recording zones of bipolar electrode pairs. Both acute and short term (two day) chronic experiments were performed. <s> BIB010 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> In this paper, we describe the design and testing of a system for recording electroneurographic signals (ENG) from a multielectrode nerve cuff (MEC). This device, which is an extension of the conventional nerve signal recording cuff, enables ENG to be classified by action potential velocity. In addition to electrical measurements, we provide preliminary in vitro data obtained from frogs that demonstrate the validity of the technique for the first time. Since typical ENG signals are extremely small, on the order of 1 1 muV, very low-noise, high-gain amplifiers are required. The ten-channel system we describe was realized in a 0.8 mum CMOS technology and detailed measured results are presented. The overall gain is 10 000 and the total input-referred root mean square (rms) noise in a bandwidth 1 Hz-5 kHZ is 291 nV. The active area is 12 mm2 and the power consumption is 24 mW from plusmn2.5 V power supplies <s> BIB011 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> This paper describes some recent progress in the development of amplifiers and other signal acquisition and signal conditioning systems for biopotential recording. The discussion will be based on two contrasting applications. The first concerns the connection of implantable amplifiers to arrays of nerve cuff electrodes which requires very low noise design due to the inherently poor signal to noise ratio of the interface. The second example deals with the interface between cultured neurones and standard CMOS technology. In this case the interface impedance is difficult to quantify accurately and is potentially time varying, requiring a different approach to amplifier design, which is tolerant to these parameter uncertainties. <s> BIB012 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> The earthworm (Lumbricus terrestris) is presented as an in vitro model of a peripheral nerve containing only two fibers each with distinctly different conduction velocities, the median and lateral giant fibers (MGF and LGF). The worm model is used with a multi-contact cuff electrode to validate the spatial-temporal filtering effect of different electrode contact configurations and the effect of applying a delay adder and matched filter tuned to either the MGF or LGF action potential (AP) to extract conduction direction and velocity from the recording. The results confirmed the known effect of inter-electrode spacing and bipolar and tripolar recording configuration on the AP amplitude. It also demonstrates a crossover point where the amplitude of the tripolar recording is larger than the monopolar recording, an effect of the slower action potential conduction velocities in the worm. The delay adder was found to be an effective velocity sensitive filter, able to discriminate units based on conduction velocity. The matched filter to be an effective means to eliminate artifact and increase signal to noise ratios, however was not found to improve selectivity. <s> BIB013 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> Objectives: The principle underlying this project is that, despite nervous reorganization following upper limb amputation, original pathways and CNS relays partially maintain their function and can be exploited for interfacing prostheses. <s> BIB014 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> A single cuff electrode with multiple-contacts permits fibre selective recording from peripheral nerves. This has been demonstrated in frog nerve in vitro and earth worm before. In this paper we apply this method successfully to the peripheral median nerve of pig in vivo. Compound action potentials (CAPs) were electrically excited at the median nerve close to the wrist of the forelimb. The CAPs were recorded by a recording nerve cuff located proximal to the stimulation cuff. Applying simple mathematical routines allowed for generating a profile of nerve fibre activation as a function of propagation velocity. <s> BIB015 </s> Implantable neurotechnologies: a review of integrated circuit neural amplifiers <s> PNS neural amplifier design and considerations <s> Objective. We investigate the ability of the method of velocity selective recording (VSR) to determine the fibre types that contribute to a compound action potential (CAP) propagating along a peripheral nerve. Real-time identification of the active fibre types by determining the direction of action potential propagation (afferent or efferent) and velocity might allow future neural prostheses to make better use of biological sensor signals and provide a new and simple tool for use in fundamental neuroscience. Approach. Fibre activity was recorded from explanted Xenopus Laevis frog sciatic nerve using a single multi-electrode cuff that records whole nerve activity with 11 equidistant ring-shaped electrodes. The recorded signals were amplified, delayed against each other with variable delay times, added and band-pass filtered. Finally, the resulting amplitudes were measured. Main Result. Our experiments showed that electrically evoked frog CAP was dominated by two fibre populations, propagating at around 20 and 40 m/s, respectively. The velocity selectivity, i.e. the ability of the system to discriminate between individual populations was increased by applying band-pass filtering. The method extracted an entire velocity spectrum from a 10 ms CAP recording sample in real time. Significance. Unlike the techniques introduced in the 1970s and subsequently, VSR requires only a single nerve cuff and does not require averaging to provide velocity spectral information. This makes it potentially suitable for the generation of highly-selective real-time control-signals for future neural prostheses. In our study, electrically evoked CAPs were analysed and it remains to be proven whether the method can reliably classify physiological nerve traffic. <s> BIB016
Neural amplifiers are also used to acquire signals from the peripheral nervous system. Signals acquired by nerve electrodes, either extrafascicularly or intrafascicularly, generally have extremely small amplitudes. For example, intrafascicular electrodes, such as the transverse intrafascicular multichannel electrode (TIME) and the longitudinal intrafascicular electrode (LIFE), transduce signals that have amplitudes less than 100 µV pp  BIB005 BIB008 BIB010 82, BIB014 . In addition, the signals transduced by extrafascicular electrodes, such as nerve cuff electrodes, have amplitudes less than 20 µV pp BIB001 BIB003 BIB002  . Hence, to maintain a signal-to-noise ratio of more than 1.5, the peripheral neural amplifiers that are coupled with extracellular electrodes are typically designed with a much lower inputreferred noise (<12 µV pp ) than normal CNS-based neural amplifiers. Due to the noise constraints placed on recording instrumentation, electrophysiological recordings from the PNS are largely performed using commercial bench-top lownoise amplifier setups BIB003 82, BIB014 that require subjects to be tethered to the equipment. Until now, there have been limited reports of IC-based PNS amplifier implementations, and existing technologies have generally only been applied to acute experiments. In general, the reported PNS neural amplifiers consume higher power per channel to achieve a much lower noise level for maintaining at least a signal-to noise ratio (SNR) of 2. Uranga et al. BIB006 reported a neural amplifier chip for the PNS based on CMOS chopperstabilized amplifiers with a bandwidth of 3 kHz. Donaldson et al. reported successive generations of very low-noise amplifier chips suitable for interfacing with extrafascicular electrodes (e.g., nerve cuff electrodes) BIB007 BIB004 BIB011 BIB012 . Recent studies have reported neural amplifiers BIB011 BIB012 that employ the velocity selection recording (VSR) technique, first proposed in BIB009 , to selectively amplify weak PNS signals with differing conduction velocities. The ability of VSR to discriminate recorded activity based on fiber type has been validated in several acute in vivo studies BIB015 BIB016 BIB013 ; demonstrating this technique in a chronically implanted model would represent a major advancement.