Biology subjects

Eles, J. R.

Publications and source records attributed to Eles, J. R..

4 recordsLinked to original sources

bioRxiv2023

Impact of electrodes design and insertion methods to surrounding cortical tissues from high-density arrays.

ObjectiveOver the past decade, neural electrodes have played a crucial role in bridging biological tissues with electronic and robotic devices. This study focuses on evaluating the optimal tip profile and insertion speed for effectively implanting Paradromics high-density Fine Microwire Arrays (FA) prototypes into the primary visual cortex (V1) of mice and rats, addressing the challenges associated with the "bed-of-nails" effect and tissue dimpling. ApproachTissue response was assessed by investigating the impact of electrodes on the blood-brain barrier (BBB) and cellular damage, with a specific emphasis on tailored insertion strategies to minimize tissue disruption during electrode implantation. Main ResultsElectro-sharpened arrays demonstrated a marked reduction in cellular damage within 50 m of the electrode tip compared to blunt and angled arrays. Histological analysis revealed that slow insertion speeds led to greater BBB compromise than fast and pneumatic methods. Successful single-unit recordings validated the efficacy of the optimized electro-sharpened arrays in capturing neural activity. SignificanceThese findings underscore the critical role of tailored insertion strategies in minimizing tissue damage during electrode implantation, highlighting the suitability of electro-sharpened arrays for long-term implant applications. This research contributes to a deeper understanding of the complexities associated with high-channel-count microelectrode array implantation, emphasizing the importance of meticulous assessment and optimization of key parameters for effective integration and minimal tissue disruption. By elucidating the interplay between insertion parameters and tissue response, our study lays a strong foundation for the development of advanced implantable devices with a reduction in reactive gliosis and improved performance in neural recording applications.

bioengineering↗

bioRxiv2022

In vivo spatiotemporal dynamics of astrocyte reactivity following neural electrode implantation

Brain computer interfaces (BCIs), including penetrating microelectrode arrays, enable both recording and stimulation of neuronal cells. However, device implantation inevitably causes injury to brain tissue and induces a foreign body response, leading to reduced recording performance and stimulation efficacy. Astrocytes in the healthy brain play multiple roles including regulating energy metabolism, homeostatic balance, transmission of neural signals, and neurovascular coupling. Following an insult to the brain, they are activated and observed to gather around the site of injury. These reactive astrocytes have been regarded as one of the main contributors to the formation of a glial scar which affects the performance of microelectrode arrays. This study investigates the dynamics of astrocytes within the first 2 weeks after implantation of an intracortical microelectrode into the mouse brain using two-photon microscopy. From our observation astrocytes are highly dynamic during this period, exhibiting patterns of process extension, soma migration, morphological activation, and device encapsulation that are spatiotemporally distinct from other glial cells, such as microglia or oligodendrocyte precursor cells. This detailed characterization of astrocyte reactivity will help to better understand the tissue response to intracortical devices and lead to the development of more effective intervention strategies to improve the functional performance neural interfacing technology.

bioengineering↗

bioRxiv2022

Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation.

BackgroundNeural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz). ObjectiveWe hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent. MethodsWe quantified how asymmetric stimulation waveforms delivered at 10 Hz or 100 Hz for 30s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the leading phase to the return phase of charge-balanced cathodal- and anodal-first waveforms. ResultsNeurons within 40-60m of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and the preferential activation of 20-90 % of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity increased over time for some waveforms at 10 Hz, but decreased more at 100 Hz than other waveforms. ConclusionThese data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation.

neuroscience↗

bioRxiv2019

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons.

Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e. increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10 Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics. Significance StatementElectrical stimulation has promise to restore sensation and motor function, as well as treat the symptoms of several neurological disorders. However, the mechanisms responsible for the beneficial effects of stimulation are not fully understood. This work supports modeling predictions by demonstrating that modulation of the stimulation waveform dramatically affects the spatial recruitment and activity level of neurons in vivo. These findings suggest that stimulation waveform symmetry represents a parameter that may be able to increase the dynamic range of stimulation applications. Further characterization of these parameters with frequency, and amplitude could provide further insight into the mechanisms of electrical stimulation.

bioengineering↗