Multiformity of extracellular microelectrode recordings from Aδ neurons in the dorsal root ganglia: a computational modeling study.

Microelectrodes serve as a fundamental tool in electrophysiology research throughout the nervous system, providing a means of exploring neural function with a high resolution of neural firing information. We constructed a hybrid computational model using the finite element method and multicompartment cable models to explore factors that contribute to extracellular voltage waveforms that are produced by sensory pseudounipolar neurons, specifically smaller A-type neurons, and that are recorded by microelectrodes in dorsal root ganglia. The finite element method model included a dorsal root ganglion, surrounding tissues, and a planar microelectrode array. We built a multicompartment neuron model with multiple trajectories of the glomerular initial segment found in many A-type sensory neurons. Our model replicated both the somatic intracellular voltage profile of Aδ low-threshold mechanoreceptor neurons and the unique extracellular voltage waveform shapes that are observed in experimental settings. Results from this model indicated that tortuous glomerular initial segment geometries can introduce distinct multiphasic properties into a neuron's recorded waveform. Our model also demonstrated how recording location relative to specific microanatomical components of these neurons, and recording distance from these components, can contribute to additional changes in the multiphasic characteristics and peak-to-peak voltage amplitude of the waveform. This knowledge may provide context for research employing microelectrode recordings of pseudounipolar neurons in sensory ganglia, including functional mapping and closed-loop neuromodulation. Furthermore, our simulations gave insight into the neurophysiology of pseudounipolar neurons by demonstrating how the glomerular initial segment aids in increasing the resistance of the stem axon and mitigating rebounding somatic action potentials.NEW & NOTEWORTHY We built a computational model of sensory neurons in the dorsal root ganglia to investigate factors that influence the extracellular waveforms recorded by microelectrodes. Our model demonstrates how the unique structure of these neurons can lead to diverse and often multiphasic waveform profiles depending on the location of the recording contact relative to microanatomical neural components. Our model also provides insight into the neurophysiological function of axon glomeruli that are often present in these neurons.

Mapping Spinal Cord Stimulation-Evoked Muscle Responses in Patients With Chronic Spinal Cord Injury.

OBJECTIVES: Epidural spinal cord stimulation (eSCS) has shown promise for restoring some volitional motor control after spinal cord injury (SCI). Maximizing therapeutic response requires effective spatial stimulation generated through careful configuration of anodes and cathodes on the eSCS lead. By exploring the way the spatial distribution of low frequency stimulation affects muscle activation patterns, we investigated the spatial specificity of stimulation-evoked responses for targeted muscle groups for restoration after chronic SCI (cSCI) in participants in the Epidural Stimulation After Neurologic Damage (E-STAND) trial. MATERIALS AND METHODS: Fifteen participants with Abbreviated Injury Scale A cSCI from the E-STAND study were evaluated with a wide range of bipolar spatial patterns. Surface electromyography captured stimulation-evoked responses from the rectus abdominis (RA), intercostal, paraspinal, iliopsoas, rectus femoris (RF), tibialis anterior (TA), extensor hallucis longus (EHL), and gastrocnemius muscle groups bilaterally. Peak-to-peak amplitudes were analyzed for each pulse across muscles. Stimulation patterns with dipoles parallel (vertical configurations), perpendicular (horizontal configurations), and oblique (diagonal configurations) relative to the rostral-caudal axis were evaluated. RESULTS: Cathodic stimulation in the transverse plane indicated ipsilaterally biased activation in RA, intercostal, paraspinal, iliopsoas, RF, TA, EHL, and gastrocnemius muscles (p < 0.05). We found that caudal cathodic stimulation was significantly more activating only in the RF and EHL muscle groups than in the rostral (p < 0.037 and p < 0.006, respectively). Oblique stimulation was found to be more activating in the RA, intercostal, paraspinal, iliopsoas, and TA muscle groups than in the transverse (p < 0.05). CONCLUSIONS: Cathodic stimulation provides uniform specificity for targeting laterality. Few muscle groups responded specifically to variation in rostral/caudal stimulation, and oblique stimulation improved stimulation responses when compared with horizontal configurations. These relations may enable tailored targeting of muscle groups, but the surprising amount of variation observed suggests that monitoring these evoked muscle responses will play a key role in this tailoring process. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03026816.

High-density neural recordings from feline sacral dorsal root ganglia with thin-film array.

Objective. Dorsal root ganglia (DRG) are promising sites for recording sensory activity. Current technologies for DRG recording are stiff and typically do not have sufficient site density for high-fidelity neural data techniques.Approach. In acute experiments, we demonstrate single-unit neural recordings in sacral DRG of anesthetized felines using a 4.5µm thick, high-density flexible polyimide microelectrode array with 60 sites and 30-40µm site spacing. We delivered arrays into DRG with ultrananocrystalline diamond shuttles designed for high stiffness affording a smaller footprint. We recorded neural activity during sensory activation, including cutaneous brushing and bladder filling, as well as during electrical stimulation of the pudendal nerve and anal sphincter. We used specialized neural signal analysis software to sort densely packed neural signals.Main results. We successfully delivered arrays in five of six experiments and recorded single-unit sensory activity in four experiments. The median neural signal amplitude was 55µV peak-to-peak and the maximum unique units recorded at one array position was 260, with 157 driven by sensory or electrical stimulation. In one experiment, we used the neural analysis software to track eight sorted single units as the array was retracted ∼500µm.Significance. This study is the first demonstration of ultrathin, flexible, high-density electronics delivered into DRG, with capabilities for recording and tracking sensory information that are a significant improvement over conventional DRG interfaces.

High-resolution local field potentials measured with deep brain stimulation arrays.

OBJECTIVE: Local field potential (LFP) recordings along a deep brain stimulation (DBS) lead can provide useful feedback for titrating DBS therapy. However, conventional DBS leads with four cylindrical macroelectrodes likely undersample the spatial distribution of sinks and sources in a given brain region. In this study, we investigated the spectral power and spatial feature sizes of LFP activity in non-human primate subthalamic nucleus and globus pallidus using chronically implanted 32-channel directional DBS arrays. APPROACH: Subthalamic nucleus and globus pallidus LFP signals were recorded from directional DBS arrays in the resting state and during a reach-and-retrieval task in two non-human primates in naïve and parkinsonian conditions. LFP recordings were compared amongst bipolar pairs of electrodes using individual and grouped electrode configurations, with the latter mimicking the cylindrical macroelectrode configurations used in current clinical LFP recordings. MAIN RESULTS: Recordings from these DBS arrays showed that (1) beta oscillations have spatial 'fingerprints' in the subthalamic nucleus and globus pallidus, and (2) that these oscillations were muted when grouping electrode contacts together to create cylindrical macroelectrodes similar in relative dimension to those used clinically. Further, these maps depended on parkinsonian condition and whether the subject was resting or performing a motor task. SIGNIFICANCE: Development of future closed-loop DBS therapies that rely on LFP feedback will benefit from implanting DBS arrays with electrode sizes and spacings that are more consistent with the dimensions of oscillatory sinks and sources within the brain.