Evaluation of Local Field Potentials and Inflammatory Response to Chronic Microelectrode Arrays in Rat Motor Cortex




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Neural interface devices are being developed for applications encompassing communication interfaces between prosthetics and patients and investigative tools for understanding complex neural circuitry. This work investigates encapsulation materials and strategies for chronic recording of neural electrical signals for intracortical electrodes. These devices could be used for brain-computer interfacing in applications related to the recording of volitional intent in conditions such as brainstem stroke, spinal cord injury, and locked-in syndrome. Intracortical microelectrode arrays (MEAs), such as the Utah-style electrode array (UEA) which is currently in clinical trials for neural recording in brain-computer interfacing, suffer from a lack of chronic reliability. A number of abiotic and biotic factors have been identified as contributors to the decline in performance. The primary biotic mechanism for loss of device performance is associated with the inflammatory response that follows implantation and chronic residence in the brain parenchyma. This foreign body response is characterized by glial scarring, loss of viable neurons, and persistent astrogliosis. A significant abiotic failure mechanism involves loss of integrity of polymer encapsulation coatings that may delaminate or become ineffective as barrier coatings resulting in parasitic electrical leakage pathways and corrosion. How adverse tissue reaction and material failure in MEAs interact and affect device performance is yet to be fully understood. This thesis investigates two elements of the chronic performance of neural interfaces: 1) the use of local field potentials (LFPs) as an alternative to single-units as a quantification of recording performance of cortical interfaces, and 2) the adverse foreign body response to amorphous silicon carbide (a-SiC), as an alternative encapsulation material for intracortical devices. The performance of neural electrodes is typically quantified by the capability of the device to measure neuron single-unit activity. However, single-unit activity is challenging to use as a volitional control signal due to an observed variability of recorded action potentials at electrodes during chronic studies. It is known that LFPs represent the sum of the low frequency (<300 Hz) electrical activity surrounding an electrode, and have drawn interest as a signal for brain-computer interface control. However, the long-term stability of LFPs is less well-established. We describe a method of evaluating the trends in LFPs over time and show they reflect the decline in performance as shown by single-unit activity. We identify a time window in which the decline is most prominent, which also correlates with changes in the longitudinal electrochemical properties of the recording electrodes measured in vivo in the same animal preparations. Towards the second goal, we aim to minimize the immune response to intracortical devices. It is known that some encapsulation materials for intracortical devices on the market are not optimal. For example, the current Utah-style MEAs employ Parylene-C, a poly(xylylene) polymer, as an encapsulation material.. This material has been documented to delaminate and therefore result in leakage and shunting of current, reduced signal-to-noise ratio of neural data, and corrosion. Additionally, biocompatibility of the encapsulation influences the extent of the foreign body response. Amorphous SiC is a material with several desirable electrical and material properties as an encapsulation for implanted MEAs, including high electrical resistivity, a low bioreactivity, and extremely low dissolution rate. We compare the foreign body response to a-SiC and Parylene-C encapsulated arrays implanted in rat cortical tissue through progressive histochemical analysis. Our results show that Parylene-C shows a reduced inflammatory response compared to a-SiC or bare Si over a period of 120 days as measured by the spatial distribution of reactive astrocytes, microglial and neurons around implanted electrodes. This thesis discusses alternative methods of evaluating cortical electrode performance and offers insight into a different encapsulation material.



Silicon carbide, Histology, Brain-computer interfaces