Leigh R. Hochberg - US grants

ABSTRACT

Integration of Dynamic Sensing and Actuating of Neural Microcircuits
PI: Arto V. Nurmikko

The proposed EFRI program aims to develop transformative paradigms in our understanding of the complex nonlinear dynamics of brain microcircuits and their function, by developing and fusing a new generation biosensing (recording) and actuation (neurostimulation) techniques to a potent toolbox. The proposed research engages brain circuits with external photonic and microelectronic interfaces in animal models, in particular for the study of the so-called "working memory" - the brain's "random access memory". At the neuroengineering level, the proposed research integrates new set of neural sensing and actuation tools on the microscale that are applied to engage with specific sensing and planning action by the brain - in particular the dynamics of information processing in the prefrontal cortex. A key experimental driver is the development of a new micro-optical/photonic device technology that will enable precise spatio-temporal targeting through sensory pathways of cortical microcircuitry and the imaging of this circuitry in real time in specific animal models. The unique device technology elements in the sensor/actuator engineering integrate ultracompact multi-element arrays of light emitters and microelectronic chip-scale sensors for excitation and mapping of the brain microcircuitry in real-time, which has been rendered both stimulus responsive and recordable by cellular-level genetic and nanomaterial sensitizing. The goal of the development of sensing/actuation microtools with associated brain science paradigms is to pave way for microdevice interfaces for bidirectional access across a population of neurons in the brain. Bidirectionality requires that both neural recording and neural stimulation can be achieved simultaneously at cellular level for multiple neurons, and ultimately multiple brain sites, spatially and temporally. Development of a class of specific brain-interfaces probes which synergize approaches from contemporary photonics/optoelectronics for "reading" and "writing" neural information from/to brain's microcircuits is the contributing aim of this planned EFRI proposal.

In a broader context, the research aims to facilitate the implementation of a closed-loop feedback compact device technology that offers the promise of entirely new classes of neural interfaces for (i) advancing the understanding of the brain from sensing to actuation- with cellular level resolution of microcircuit dynamics, (ii) aim the application of the technology to potentially therapeutic and prosthetic applications. For example, the study of the working memory function in the brain is closely associated with neurological diseases such as schizophrenia, attention deficit disorder and has been linked to epilepsy. The team aims to leverage the research outcomes from this program in mammalian animal models (in vitro and in vivo) so that key brain science paradigms such as the fundamentally important "working memory" will find translation to human neuroscience and rehabilitative goals. By including within the team a clinical neurology interface, our proposed research is envisioned to contribute to our unraveling of neurological disease, pave way for elucidating and exploring the applicability the nature of the brain-like systems to other technologies, as well as improve U.S. competitiveness in the global economy through advanced technology development in a frontier area at the intersection of physical and life sciences. The research on these topics is also expected to create a generation of "neuroengineering" graduate students with true interdisciplinary education, as well as innovative businesses and entrepreneurs.

Project Summary Conventional augmentative and alternative communication (AAC) devices for people with severe speech and motor impairments (SSMI) rely on residual motor function, inherently limiting communication throughput. Commercially available AAC solutions require daily caregiver setup, need frequent recalibration often from a technically savvy caregiver, are often unable to be used in dark lighting conditions, and can encumber or fatigue important remaining physical abilities. Furthermore, for people with progressive motor dysfunction due to amyotrophic lateral sclerosis (ALS), even the most well-designed AAC devices will eventually fail as movements become unreliable. For people with brainstem stroke, ALS, and other disorders causing locked-in syndrome (LIS) or SSMI, brain-computer interfaces (BCIs) hold promise as a method of enabling communication that does not rely upon speech or voluntary movement. In prior NIDCD-supported research, our BrainGate research team provided early proofs of principle of a powerful intracortical brain-computer interface (iBCI) that decodes movement intentions directly from brain activity. This technology has allowed people to control a cursor on a computer screen for communication simply by imagining movements of their own arm. The proposed NIDCD U01 clinical research will further the development and testing of a fully implanted iBCI that could provide robust, intuitive control of industry-grade communication apps for people with LIS or SSMI. By leveraging the ongoing pilot clinical trials of the investigational BrainGate system, we aim to (1) improve the robustness and accuracy of neurally actuated point-and click, in part through the translation of neuronal activity from human premotor and motor cortex, (2) expand the number of input dimensions to tablet computers available via neural activity, allowing intended hand gesture commands to control communication apps on touch-screen tablet computers, and (3) rigorously compare the performance of the investigational BrainGate system to trial participants? conventional AAC systems with respect to communication competence, information throughput, user preference and outcomes measures. By incorporating the feedback of six individual participants with paralysis, this feasibility trial will optimize a powerful iBCI for communication and will establish the metrics needed for a subsequent pivotal trial of a fully implanted, always-available iBCI communication system for people with SSMI.