DESCRIPTION (provided by applicant): Functional MRI (fMRI), EEG, and other completely noninvasive modalities for large-scale imaging of human brain activity have pioneeringly revealed many human brain functions, but cannot reach the single-neuron, single-spike level of neural code analysis possible in animals obtained using electrodes. This is partly due to the indirect methods of observation employed (e.g., blood flow for fMRI) and due to blurring of signals over distance by the skull (e.g., for EEG). In contrast, invasive approaches such as trans-cranially implanted multi- electrode arrays can achieve single-cell, single-spike resolution, but they necessitate opening of the skull - and, for implanted arrays, damage of the brain tissue - limiting utility to a small fraction of the population, those undergoing neurosurgery for some intractable brain disorder that justifies the risk. Trans-cranially implanted arrays also degrade i performance over time due to gliosis and other brain reactions, and create vulnerabilities to infection. Vascular access offers a less-invasive, safer and more scalable means - in comparison to trans-cranial electrodes - to deliver recording devices to the vicinity of neurons buried inside the brain parenchyma. We here propose to create a vascular platform for brain imaging, stimulation, electrical recording, and molecular access, aiming for devices that will work at least in large blood vessels, and also paving the way towards capillary-resolution neural access through vasculature. Specifically, we propose to initiate a multi-institutional, collaboratie effort to design a human-applicable vascular neural interface for multiplexed neural recording and stimulation, and to carry out preliminary pilot theoretical and experimental projects to validate the basic parameters of the resulting concepts.

PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because it promises to lead to safer, less invasive and more programmable forms of neural and muscular stimulation, via the vascular system, which permeates the entire body. For example, deep brain stimulation has been shown to be therapeutically effective in brain disorders such as Parkinson's disease, yet highly invasive surgeries are necessary. Our proposed vascular brain interface platform could greatly extend the capability and reach of therapeutic brain machine interfaces.