An implantable translational platform enabling clinical investigation of unexplored adaptive stimulation

Abstract

Adaptive stimulation has cultivated growing interest due to its potential for improving the therapeutic efficacy of neuromodulation in a variety of neurorehabilitative applications. In utilizing neuronal activity to drive neuromodulation delivery, adaptive stimulation may induce synaptic plasticity changes that could result in enhanced functional connectivity and potentially towards improved patient outcomes. While advances in sensing and stimulation capabilities of neuromodulation systems have facilitated research thrusts in investigating preliminary adaptive stimulation design, there are still limitations in the types of algorithms that can be explored by current systems. These limitations present a gap in the technological capabilities currently available for investigating novel adaptive paradigms. This technological limitation also impedes investigation into the nature of neuroplasticity and its relationship towards improving therapeutic outcomes from neurological conditions.In this thesis, we address this gap by developing a neuromodulation research platform capable of realizing novel adaptive stimulation algorithms not currently supported by clinical systems. Building around the investigational CorTec Brain Interchange, we develop a research software interface capable of implementing customized neuromodulation therapies and providing full access to the features of the investigational device. This work aims to support continued growth within the adaptive neuromodulation space by expanding the types of adaptive algorithms that can be designed and investigated within the clinical research space. To thoroughly assess this platform, we introduce a benchtop evaluation tool, the NeuroTest, to verify the functionalities and increase confidence in its abilities. We specifically focus on the ability of the platform to sense cortico-cortical evoked potentials, a recognized metric for measuring neural connectivity. With the NeuroTest, we simulate cortico-cortical evoked potential experiments and characterize the platform's behavior under the presence of stimulation. We also assess the efficacy of signal processing techniques to identify cortico-cortical evoked potentials activity and extend this initial verification work by performing cortico-cortical evoked potentials experiments with the proposed platform in vivo. In verifying the platform and processing pipeline for cortico-cortical evoked potentials applications, we develop a comprehensive understanding of the Brain Interchange's capabilities, identifying limitations and ideal configurations to optimize performance with the research platform. Finally, we utilize the proposed research platform to implement and execute a temporally-driven adaptive stimulation paradigm. We establish the platform's ability to perform the adaptive paradigm robustly with the NeuroTest environment and following these promising feasibility outcomes, we demonstrate preliminary plasticity induction via cortico-cortical evoked potentials modulation with the implemented paradigm in vivo. While future efforts will aim to characterize the influence of these plasticity effects on behavior, these outcomes demonstrate the platform's potential to be an effective research tool for supporting clinical neuroplasticity investigations.