DRG microstimulation evokes postural responses in awake, standing felines.

OBJECTIVE: We have demonstrated previously that microstimulation in the dorsal root ganglia (DRG) can selectively evoke activity in primary afferent neurons in anesthetized cats. This study describes the results of experiments focused on characterizing the postural effects of DRG microstimulation in awake cats during quiet standing. APPROACH: To understand the parameters of stimulation that can affect these postural shifts, we measured changes in ground reaction forces (GRF) while varying stimulation location and amplitude. Four animals were chronically implanted at the L6 and L7 DRG with penetrating multichannel microelectrode arrays. During each week of testing, we identified electrode channels that recruited primary afferent neurons with fast (80-120 m s-1) and medium (30-75 m s-1) conduction velocities, and selected one channel to deliver current-controlled biphasic stimulation trains during quiet standing. MAIN RESULTS: Postural responses were identified by changes in GRFs and were characterized based on their magnitude and latency. During DRG microstimulation, animals did not exhibit obvious signs of distress or discomfort, which could be indicative of pain or aversion to a noxious sensation. Across 56 total weeks, 13 electrode channels evoked behavioral responses, as detected by a significant change in GRF. Stimulation amplitude modulated the magnitude of the GRF responses for these 13 channels (p  < 0.001). It was not possible to predict whether or not an electrode would drive a behavioral response based on information including conduction velocity, recruitment threshold, or the DRG in which it resided. SIGNIFICANCE: The distinct and repeatable effects on the postural response to low amplitude (<40 µA) DRG microstimulation support that this technique may be an effective way to restore somatosensory feedback after neurological injuries such as amputation.

Selectivity of afferent microstimulation at the DRG using epineural and penetrating electrode arrays.

OBJECTIVE: We have shown previously that microstimulation of the lumbar dorsal root ganglia (L5-L7 DRG) using penetrating microelectrodes, selectively recruits distal branches of the sciatic and femoral nerves in an acute preparation. However, a variety of challenges limit the clinical translatability of DRG microstimulation via penetrating electrodes. For clinical translation of a DRG somatosensory neural interface, electrodes placed on the epineural surface of the DRG may be a viable path forward. The goal of this study was to evaluate the recruitment properties of epineural electrodes and compare their performance with that of penetrating electrodes. Here, we compare the number of selectively recruited distal nerve branches and the threshold stimulus intensities between penetrating and epineural electrode arrays. APPROACH: Antidromically propagating action potentials were recorded from multiple distal branches of the femoral and sciatic nerves in response to epineural stimulation on 11 ganglia in four cats to quantify the selectivity of DRG stimulation. Compound action potentials (CAPs) were recorded using nerve cuff electrodes implanted around up to nine distal branches of the femoral and sciatic nerve trunks. We also tested stimulation selectivity with penetrating microelectrode arrays implanted into ten ganglia in four cats. A binary search was carried out to identify the minimum stimulus intensity that evoked a response at any of the distal cuffs, as well as whether the threshold response selectively occurred in only a single distal nerve branch. MAIN RESULTS: Stimulation evoked activity in just a single peripheral nerve through 67% of epineural electrodes (35/52) and through 79% of the penetrating microelectrodes (240/308). The recruitment threshold (median = 9.67 nC/phase) and dynamic range of epineural stimulation (median = 1.01 nC/phase) were significantly higher than penetrating stimulation (0.90 nC/phase and 0.36 nC/phase, respectively). However, the pattern of peripheral nerves recruited for each DRG were similar for stimulation through epineural and penetrating electrodes. SIGNIFICANCE: Despite higher recruitment thresholds, epineural stimulation provides comparable selectivity and superior dynamic range to penetrating electrodes. These results suggest that it may be possible to achieve a highly selective neural interface with the DRG without penetrating the epineurium.

Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee.

Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia.

OBJECTIVE: This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. APPROACH: A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aß primary afferent fibers. MAIN RESULTS: Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aß) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aß responses at threshold, but the relative proportion of Group II/Aß responses decreased over time. SIGNIFICANCE: These results suggest that it is possible to activate Group I or Group II/Aß primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets for sensory neuroprostheses with potential to achieve recruitment of a range of sensory fiber types over multiple months after implantation.

Limb-state information encoded by peripheral and central somatosensory neurons: implications for an afferent interface.

A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches.

Effects of spatial and temporal parameters of primary afferent microstimulation on neural responses evoked in primary somatosensory cortex of an anesthetized cat.

Patterned microstimulation of muscle and cutaneous afferent neurons may provide tactile and proprioceptive feedback to users of advanced prosthetic limbs. However, it is unclear what types of stimulation patterns will be effective, and the parameter space for creating these patterns is prohibitively large to explore systematically using only psychophysics paradigms. In this study, we used an array of microelectrodes in primary somatosensory cortex (S1) of an isoflurane anesthetized cat to measure responses in a population of neurons evoked by various patterns of primary afferent microstimulation delivered to the L6 and L7 dorsal root ganglia (DRG). Each pattern consisted of a 300 ms train of microstimulation pulses having a fixed amplitude, pulse rate, and location in the array of DRG electrodes. Evoked responses were detectable on many S1 channels at the lowest amplitude tested (5 µA) and pulse rate (10 pulses per second). Increasing the pulse rate lowered the threshold amplitude for evoking a response on some S1 channels. Location effects were also observed. Adjacent stimulation sites evoked discriminable responses at low but not high (20 µA) amplitudes. In summary, we observed interactions between stimulation pulse rate, pulse amplitude, and location. Such interactions must be considered when designing stimulation patterns for transmitting sensory feedback by primary afferent microstimulation.