UC San Diego

Understanding cognitive processing in intact brains is the subject of intense research efforts that aim to resolve individual and network activity of neuronal cells across different layers of the brain. While efforts to record a large number of individual cellular activity in intact brains are underway, the network-level coordinated activity of neurons result in long-range, low frequency oscillations that carry significant electrophysiological information and is the gold standard for recording neural correlates of cognition from animals and humans. Recently, recording of individual cellular activity, commonly referred to as single units, with high signal-to-noise ratio from the cortical surface was accomplished. Critical to this milestone in electrophysiology was the use of organic microelectrode arrays that (1) possess superior electrochemical junction characteristics enabling them to have contact diameters that are similar to neuronal sizes yet while maintaining low electrochemical impedances and low noise, and (2) enable conformal coverage of thin parylene C device carrier layers to the brain curvature. The small contact diameter, and therefore listening sphere, its low noise, and its intimate contact with the surface of the brain are all attributed as essential conditions to permit the recording of single unit activity from the brain’s surface. This thesis appraises the development of novel microelectrode arrays that record single units from the brain’s surface, and their application in recording brain activity from anesthetized and awake animal models. The first part of the dissertation discusses the application of Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, commonly known as PEDOT:PSS – a semiconductive polymer with excellent electrochemical properties – as well as microelectrode contacts that employ large surface area one-dimensional nanostructures, to the electrophysiological investigations in songbird experiments. Significantly, we observed strong correlation of surface-recorded single units with spectrotemporal features of replayed birdsongs across trials and that were also validated with simultaneously implanted depth electrodes. This finding has implications for minimally destructive brain-machine interfaces that can make use of surface-recorded units. Additionally, we carried out systematic investigations to understand the influence of the electrode contact diameter and the contact material on resolving single unit activity from the surface of the brain. Our initial results suggest that contacts with lower impedances result in higher signal amplitude as well as higher biological noise amplitude, due to their sensitivity and that amplitude of single units generally decreases with diameter. While acute recordings can streamline testing of neurotechnologies, chronic recordings are important for applications in which subjects can ultimately engage in behavioral experiments. To this end, the last part of this dissertation concerns with the development and optimization of a chronically stable device form factor. This device leverages the transparency of the parylene C substrate to perform simultaneous electrophysiological recording and multi-photon imaging of neuronal activity in awake mice. We recorded stimulus-evoked calcium indicator responses that correlated with local field potential (LFP) response and higher frequency multi-and single unit activity. This dissertation encompasses advances in the scalable, monolithic fabrication procedure for high-yield PEDOT:PSS microelectrode arrays on parylene C substrates and their utility of electrocorticography (ECoG) recording capability of neuronal activity from intact brains.