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Kozai T.D.Y.,University of Pittsburgh | Kozai T.D.Y.,Center for Neural Basis of Cognition | Kozai T.D.Y.,McGowan Institute for Regenerative Medicine | Catt K.,University of Pittsburgh | And 8 more authors.
Biomaterials | Year: 2015

Penetrating intracortical electrode arrays that record brain activity longitudinally are powerful tools for basic neuroscience research and emerging clinical applications. However, regardless of the technology used, signals recorded by these electrodes degrade over time. The failure mechanisms of these electrodes are understood to be a complex combination of the biological reactive tissue response and material failure of the device over time. While mechanical mismatch between the brain tissue and implanted neural electrodes have been studied as a source of chronic inflammation and performance degradation, the electrode failure caused by mechanical mismatch between different material properties and different structural components within a device have remained poorly characterized. Using Finite Element Model (FEM) we simulate the mechanical strain on a planar silicon electrode. The results presented here demonstrate that mechanical mismatch between iridium and silicon leads to concentrated strain along the border of the two materials. This strain is further focused on small protrusions such as the electrical traces in planar silicon electrodes. These findings are confirmed with chronic invivo data (133-189 days) in mice by correlating a combination of single-unit electrophysiology, evoked multi-unit recordings, electrochemical impedance spectroscopy, and scanning electron microscopy from traces and electrode sites with our modeling data. Several modes of mechanical failure of chronically implanted planar silicon electrodes are found that result in degradation and/or loss of recording. These findings highlight the importance of strains and material properties of various subcomponents within an electrode array. © 2014 Elsevier Ltd.

Fisher L.E.,University of Pittsburgh | Fisher L.E.,Center for Neural Basis of Cognition | Ayers C.A.,Center for Neural Basis of Cognition | Ayers C.A.,University of Pittsburgh | And 6 more authors.
Journal of Neural Engineering | Year: 2014

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/Aβ 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/Aβ) 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/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ 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. © 2014 IOP Publishing Ltd.

Kozai T.D.Y.,University of Pittsburgh | Kozai T.D.Y.,Center for Neural Basis of Cognition | Kozai T.D.Y.,McGowan Institute for Regenerative Medicine | Li X.,University of Pittsburgh | And 8 more authors.
Biomaterials | Year: 2014

Chronic implantation of microelectrodes into the cortex has been shown to lead to inflammatory gliosis and neuronal loss in the microenvironment immediately surrounding the probe, a hypothesized cause of neural recording failure. Caspase-1 (aka Interleukin 1β converting enzyme) is known to play a key role in both inflammation and programmed cell death, particularly in stroke and neurodegenerative diseases. Caspase-1 knockout (KO) mice are resistant to apoptosis and these mice have preserved neurologic function by reducing ischemia-induced brain injury in stroke models. Local ischemic injury can occur following neural probe insertion and thus in this study we investigated the hypothesis that caspase-1 KO mice would have less ischemic injury surrounding the neural probe. In this study, caspase-1 KO mice were implanted with chronic single shank 3mm Michigan probes into V1m cortex. Electrophysiology recording showed significantly improved single-unit recording performance (yield and signal to noise ratio) of caspase-1 KO mice compared to wild type C57B6 (WT) mice over the course of up to 6 months for the majority of the depth. The higher yield is supported by the improved neuronal survival in the caspase-1 KO mice. Impedance fluctuates over time but appears to be steadier in the caspase-1 KO especially at longer time points, suggesting milder glia scarring. These findings show that caspase-1 is a promising target for pharmacologic interventions. © 2014 Elsevier Ltd.

Kozai T.D.Y.,University of Pittsburgh | Kozai T.D.Y.,Center for Neural Basis of Cognition | Kozai T.D.Y.,McGowan Institute for Regenerative Medicine | Gugel Z.,University of Pittsburgh | And 9 more authors.
Biomaterials | Year: 2014

Implantable neural electrodes must drastically improve chronic recording stability before they can be translated into long-term human clinical prosthetics. Previous studies suggest that sub-cellular sized and mechanically compliant probes may result in improved tissue integration and recording longevity. However, currently these design features are restricted by the opposing mechanical requirements needed for minimally damaging insertions. We designed a non-cytotoxic, carboxymethylcellulose (CMC) based dissolvable delivery vehicle (shuttle) to provide the mechanical support for insertion of ultra-small, ultra-compliant microfabricated neural probes. Stiff CMC-based shuttles rapidly soften immediately after being placed ~1mm above an open craniotomy as they absorb vapors from the brain. To address this, we developed a sophisticated targeting, high speed insertion (~80mm/s), and release system to implant these shuttles. After implantation, the goal is for the shuttle to dissolve away leaving only the electrodes behind. Here we show the histology of chronically implanted shuttles of large (300μm×125μm) and small (100μm×125μm) size at discrete time points over 12 weeks. Early time points show the CMC shuttle expanded after insertion as it absorbed moisture from the brain and slowly dissolved. At later time points neuronal cell bodies populate regions within the original shuttle tract. The large CMC shuttles show that the CMC expansion can cause extended secondary damage. On the other hand, the smaller CMC shuttles show limited secondary damage, wound closure by 4 weeks, absence of activated microglia at 12 weeks, as well as evidence suggesting neural regeneration at the implant site. This shuttle, therefore, shows great promise facilitating the implantation of nontraditional ultra-small, and ultra-compliant probes. © 2014 Elsevier Ltd.

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