Zachariah Sperry

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

OBJECTIVE Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. APPROACH Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. MAIN RESULTS LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. SIGNIFICANCE This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

Quantitative models of feline lumbosacral dorsal root ganglia neuronal cell density

BACKGROUND Dorsal root ganglia (DRG) are spinal root components that contain the cell bodies of converging primary sensory neurons. DRG are becoming a therapeutic target for electrical neural interfaces. Our purpose was to establish methods for quantifying the non-random nature and distribution of neuronal cell bodies within DRG. NEW METHOD We identified neuronal cell body locations in 26 feline lumbosacral DRG cross-section histological images and used computational tools to quantify spatial trends. We first analyzed spatial randomness using the nearest-neighbor distance method. Next we overlaid a 6×6 grid, modeling neuronal cellular density in each grid square and comparing regions statistically. Finally we transformed DRG onto a polar map and calculated neuronal cellular density in annular sectors. We used a recursive partition model to determine regions of high and low density, and validated the model statistically. RESULTS We found that the arrangement of neuronal cell bodies at the widest point of DRG is distinctly non-random with concentration in particular regions. The grid model suggested a radial trend in density, with increasing density toward the outside of the DRG. The polar transformation model showed that the highest neuronal cellular density is in the outer 23.9% radially and the dorsal ±61.4° angularly. COMPARISON WITH EXISTING METHODS To our knowledge, DRG neuronal cell distribution has not been previously quantified. CONCLUSIONS These results confirm and expand quantitatively on the existing understanding of DRG anatomy. Our methods can be useful for analyzing the distribution of cellular components of other neural structures or expanding to three-dimensional models.

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

The ability to deliver flexible biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural engineering. Bioelectronic devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of interest. We demonstrate that a three-dimensional diamond shuttle can be easily made with a vertical support to deliver ultra-compliant polymer microelectrodes (4.5 μm thick) in-vivo through dura mater and thick epineurium. The diamond shuttle has 54% less cross-sectional area than an equivalently stiff silicon shuttle, which we simulated will result in a 37% reduction in blood vessel damage. We also discovered that higher frequency oscillation of the shuttle (200 Hz) significantly reduced tissue compression regardless of the insertion speed, while slow speeds also independently reduced tissue compression. Insertion and recording performance are demonstrated in rat and feline models, but the large design space of these tools are suitable for research in a variety of animal models and nervous system targets.

Flexible microelectrode array for interfacing with the surface of neural ganglia

OBJECTIVE The dorsal root ganglia (DRG) are promising nerve structures for sensory neural interfaces because they provide centralized access to primary afferent cell bodies and spinal reflex circuitry. In order to harness this potential, new electrode technologies are needed which take advantage of the unique properties of DRG, specifically the high density of neural cell bodies at the dorsal surface. Here we report initial in vivo results from the development of a flexible non-penetrating polyimide electrode array interfacing with the surface of ganglia. APPROACH Multiple layouts of a 64-channel iridium electrode (420 µm2) array were tested, with pitch as small as 25 µm. The buccal ganglia of invertebrate sea slug Aplysia californica were used to develop handling and recording techniques with ganglionic surface electrode arrays (GSEAs). We also demonstrated the GSEAs capability to record single- and multi-unit activity from feline lumbosacral DRG related to a variety of sensory inputs, including cutaneous brushing, joint flexion, and bladder pressure. MAIN RESULTS We recorded action potentials from a variety of Aplysia neurons activated by nerve stimulation, and units were observed firing simultaneously on closely spaced electrode sites. We also recorded single- and multi-unit activity associated with sensory inputs from feline DRG. We utilized spatial oversampling of action potentials on closely-spaced electrode sites to estimate the location of neural sources at between 25 µm and 107 µm below the DRG surface. We also used the high spatial sampling to demonstrate a possible spatial sensory map of one felines DRG. We obtained activation of sensory fibers with low-amplitude stimulation through individual or groups of GSEA electrode sites. SIGNIFICANCE Overall, the GSEA has been shown to provide a variety of information types from ganglia neurons and to have significant potential as a tool for neural mapping and interfacing.