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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Resource-Related Research Projects (R24)
Project #
1R24MH106075-01
Application #
8828404
Study Section
Special Emphasis Panel (ZMH1-ERB-C (09))
Program Officer
Farber, Gregory K
Project Start
2014-09-26
Project End
2017-06-30
Budget Start
2014-09-26
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$468,000
Indirect Cost
$168,000
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Piatkevich, Kiryl D; Jung, Erica E; Straub, Christoph et al. (2018) A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters. Nat Chem Biol 14:352-360
Oran, Daniel; Rodriques, Samuel G; Gao, Ruixuan et al. (2018) 3D nanofabrication by volumetric deposition and controlled shrinkage of patterned scaffolds. Science 362:1281-1285
Caravaca, A S; Tsaava, T; Goldman, L et al. (2017) A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve. J Neural Eng 14:066005
Rowlands, Christopher J; Park, Demian; Bruns, Oliver T et al. (2017) Wide-field three-photon excitation in biological samples. Light Sci Appl 6:e16255
Wang, Yu; Woehrstein, Johannes B; Donoghue, Noah et al. (2017) Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues. Nano Lett 17:6131-6139
Kodandaramaiah, Suhasa B; Holst, Gregory L; Wickersham, Ian R et al. (2016) Assembly and operation of the autopatcher for automated intracellular neural recording in vivo. Nat Protoc 11:634-54
Chen, Fei; Wassie, Asmamaw T; Cote, Allison J et al. (2016) Nanoscale imaging of RNA with expansion microscopy. Nat Methods 13:679-84
Rodriques, Samuel G; Marblestone, Adam H; Scholvin, Jorg et al. (2016) Multiplexed neural recording along a single optical fiber via optical reflectometry. J Biomed Opt 21:57003