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  1. Electrophysiological stimulation has been widely adopted for clinical diagnostic and therapeutic treatments for modulation of neuronal activity. Safety is a primary concern in an interventional design leveraging the effects of electrical charge injection into tissue in the proximity of target neurons. While modalities of tissue damage during stimulation have been extensively investigated for specific electrode geometries and stimulation paradigms, a comprehensive model that can predict the electrochemical safety limits in vivo doesn’t yet exist. Here we develop a model that accounts for the electrode geometry, inter-electrode separation, material, and stimulation paradigm in predicting safe current injection limits. We performed a parametric investigation of the stimulation limits in both benchtop and in vivo setups for flexible microelectrode arrays with low impedance, high geometric surface area platinum nanorods and PEDOT:PSS, and higher impedance, planar platinum contacts. We benchmark our findings against standard clinical electrocorticography and depth electrodes. Using four, three and two contact electrochemical impedance measurements and comprehensive circuit models derived from these measurements, we developed a more accurate, clinically relevant and predictive model for the electrochemical interface potential. For each electrode configuration, we experimentally determined the geometric correction factors that dictate geometry-enforced current spreading effects. We also determined the electrolysis windowmore »from cyclic-voltammetry measurements which allowed us to calculate stimulation current safety limits from voltage transient measurements. From parametric benchtop electrochemical measurements and analyses for different electrode types, we created a predictive equation for the cathodal excitation measured at the electrode interface as a function of the electrode dimensions, geometric factor, material and stimulation paradigm. We validated the accuracy of our equation in vivo and compared the experimentally determined safety limits to clinically used stimulation protocols. Our new model overcomes the design limitations of Shannon’s equation and applies to macro- and micro-electrodes at different density or separation of contacts, captures the breakdown of charge-density based approaches at long stimulation pulse widths, and invokes appropriate power exponents to current, pulse width, and material/electrode-dependent impedance.« less
    Free, publicly-accessible full text available October 6, 2023
  2. A roadmap of the spine During spinal cord surgery, intraoperative neuromonitoring (IONM) is used to reduce the risk of damage. Electrodes on muscles or scalp record the response to large-amplitude electrical stimuli delivered to the spinal cord. However, this method does not allow precise spatiotemporal characterization of spinal cord neurophysiology. Now, Russman et al. developed a microelectrode array that can be placed on the spinal cord during surgery and record with high spatiotemporal definition and high sensitivity the electrophysiological response to low-current stimulation, providing precise maps of spinal cord electrophysiology. These maps can be used during surgery to improve IONM.
    Free, publicly-accessible full text available September 28, 2023
  3. Free, publicly-accessible full text available June 1, 2023
  4. Cortex in high resolution Recording brain cortical activity with high spatial and temporal resolution is critical for understanding brain circuitry in physiological and pathological conditions. In this study, Tchoe et al. developed a reconfigurable and scalable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods, called PtNRGrids, that could record thousands of channels with submillimeter resolution in the rat barrel cortex. In human subjects, PtNRGrids were able to provide high-resolution recordings of large and curvilinear brain areas and to resolve spatiotemporal dynamics of motor and sensory activities. The results suggest that PtNRGrids could be used in the preclinical and clinical setting for high spatial and temporal recording of neural activity.
  5. Abstract Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their “intermediate” microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.