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Porter, T. S.

Publications and source records attributed to Porter, T. S..

2 recordsLinked to original sources

Adaptive Charge Modulation Enables Focal, Selective Spinal Cord Stimulation

Clinical neuromodulation primarily employs near-field low frequency electrical stimulation to activate neurons in the immediate vicinity of the electrode. We introduce Adaptive Charge Modulation (ACM), a spatiotemporal, charge-balanced stimulation strategy that focuses activation at deep tissue sites distant from the stimulating contacts. We apply ACM to stimulate deep regions of the spinal cord, distant from dorsal root entry zones which are preferentially activated during low frequency stimulation (LFS). ACM applies multipolar, biphasic rectangular pulses to exceed activation thresholds in deeper neuronal populations, with reduced surface activation, potentially due to high-frequency suppression of neural activity. In epidural spinal cord stimulation in rats, ACM achieved single-muscle selectivity among fourteen monitored muscles with minimal co-activation of other muscles. Using simultaneous, high spatiotemporal resolution, 2,112-channel brain-spine recordings, we characterized the response latencies and pathways consistent with focal recruitment at depth. We observed chronic stability of the electrode and ACM in freely behaving animals over 68 days post-implantation. By enabling focal activation with epidural surface electrodes, ACM may expand the reach and precision of neuromodulation and neural interfaces.

bioengineering↗

Single-Molecule Orientation Imaging Reveals the Nano-Architecture of Amyloid Fibrils Undergoing Growth and Decay

Amyloid-beta (A{beta}42) aggregates are characteristic signatures of Alzheimers disease, but probing how their nanoscale architectures influence their growth and decay remains challenging using current technologies. Here, we apply time-lapse single-molecule orientation-localization microscopy (SMOLM) to measure the orientations and rotational "wobble" of Nile blue (NB) molecules transiently binding to A{beta}42 fibrils. We quantify correlations between fibril architectures, measured by SMOLM, and their growth and decay visualized by single-molecule localization microscopy (SMLM). We discover that stable A{beta}42 fibrils tend to be well-ordered, signified by well-aligned NB orientations and small wobble. SMOLM also shows that increasing order and disorder are signatures of growing and decaying A{beta}42 fibrils, respectively. We also observe SMLM-invisible fibril remodeling, including steady growth and decay patterns that conserve {beta}-sheet organization. SMOLM reveals that increased heterogeneity in fibril architectures is correlated with more dynamic remodeling and that large-scale fibril remodeling tends to originate from local regions that exhibit strong heterogeneity.

biophysics↗