2018 — 2021 |
Borton, David Allenson (co-PI) Saab, Carl Y |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Spatiotemporal Coding in the Pain Circuit Along the Spine-Brain Continuum
Summary/Abstract Pain is a national health challenge costing our economy more than $600 Billions per year. Faced with ineffective therapies, millions of patients are being over-prescribed opioid-based medications, which is contributing to addiction and lethal overdose. This application is in response to RFA-NS-18-009 ?BRAIN Initiative: Targeted BRAIN Circuits Projects (R01)? which calls for ?Innovative approaches and new paradigms for identifying and understanding nociception and pain in the context of circuit mechanisms of the central nervous system?. We propose AIM 1) tool development to test the hypothesis that Laminae II/III PV neurons inhibit nociceptive relay neurons in vivo, AIM 2) behavioral development to validate a novel model for rapid reporting of sensory stimuli, and AIM 3) combination of real-time neural recording from the spine-brain continuum and ecological behavior to test the hypothesis that distinct rhythms in sensory thalamus and neocortex are temporally correlated with tactile and noxious stimuli. Moreover, excitation of PV neurons inhibits thalamic neurons and modulates thalamocortical rhythms. These aims will be investigated using laboratory animal models of pain and state-of-the-art techniques for simultaneous recording from multiple areas in the spine cord and brain, combined with cell-speci?c stimulation in the periphery using optical methods in awake rodents. Therefore, this application will enhance our scienti?c understanding of pain mechanisms in the central nervous system and potentially lead to novel diagnostic and therapeutic approaches.
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0.888 |
2020 — 2021 |
Borton, David Allenson (co-PI) Denison, Timothy Starr, Philip Andrew [⬀] Worrell, Gregory A |
U24Activity Code Description: To support research projects contributing to improvement of the capability of resources to serve biomedical research. |
Accelerating Dissemination of Implantable Neurotechnology For Clinical Research @ University of California, San Francisco
Summary Invasive neurostimulation is an established technique in the therapy of movement disorders and epilepsy, and shows promise for amelioration of psychiatric and cognitive disorders. Recently, several implantable neurostimulation hardware platforms have begun to incorporate sensing of cortical and subcortical field potential activity, with the capability for wireless streaming from the internal device to external computers over years. These high temporal and spatial resolution signals may be used for discovering the circuit basis of brain disorders, developing new therapies rationally derived from circuit analysis, and developing adaptive (feedback controlled) neurostimulation paradigms in which the device auto-adjusts according to changing brain needs. The most recent ?second generation? implantable devices, such as Summit RC+S (Medtronic), have substantially improved capabilities and offer great flexibility for novel uses, at the expense of increased complexity. However, effective use of this and related platforms requires academic investigators to develop previously unfamiliar capabilities, including programming of the desired device functions using an ?application programming interface?, and documenting the performance and validation of software according to FDA device regulations. While many BRAIN Initiative funded grants intend to use these second generation bidirectional interfaces, the four institutions on this proposal, working together, are the only groups that have surmounted the technical and regulatory barriers to launching clinical protocols with second generation sensing devices. We have formed the ?Open Mind? neural communications consortium to share technical and regulatory infrastructure with each other and with new investigators, and begun to disseminate this knowledge at open meetings for new investigators, at the April 2018 and 2019 Brain Initiative Meetings. Through this proposal, we will greatly expand these technology dissemination activities, to provide investigators with elements critical to the launch of their own clinical studies: A ?turnkey? user interface to get started that includes open source software elements for neural sensing at home and for adaptive stimulation, and a streamlined regulatory pathway for FDA approval of investigational protocols, which we call the ?Open Source Quality Management System?. We will disseminate education and resources through biannual workshops and a web-based library of regulatory documents, software, and the Quality Management System. Our team represents the major clinical areas of interest in neuromodulation: movement disorders (UCSF), epilepsy (Mayo Clinic), and psychiatry (Brown/Baylor), and includes experts in the design and dissemination of implantable devices (Oxford). This consortium will facilitate already funded proposals, as well as entry of new investigators, in the rapidly evolving ecosystem of implantable wireless neural interfaces. Two new clinical teams have already begun to work with our neural sensing interface in preparation for their own clinical trials of adaptive stimulation, demonstrating readiness of tools for dissemination.
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0.966 |
2020 |
Borton, David Allenson (co-PI) Saab, Carl Y |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Large Scale Cortical Laminar Recordings: Novel Instrumentation
SUMMARY We have successfully designed and fabricated the backPack drive for spine recordings in awake mice (AIM I), and fully developed a novel behavioral model AIM II (see Y1 Progress Report and Black et al.). In this SUPPLEMENTAL APPLICATION, we propose new experiments to elucidate the laminar organization of low-frequency oscillations in SI at a much higher level of cellular localization than originally sought. These new experiments will augment the overall impact of our project by localizing oscillations in SI to specific lamina and correlating oscillations with thalamic single-unit firing in the context of ecologically-relevant and ultra-fast nociceptive behavior. They will also generate high dimensional neural data at multiple scales (single units, LFP) which will be available to other investigators upon request.
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0.883 |