Monitor Neural Activity

Project Summary Parkinson’s disease (PD) is a neurodegenerative disorder that leads to both motor and non-motor symptoms. While there is as yet no cure for PD, medical and surgical therapies have been developed that effectively target the motor symptoms of PD. Non-motor symptoms are far more disabling for patients, precede the onset of motor symptoms by a decade, are more insidious in onset, have been less apparent to clinicians, and are less effectively treated.

SUMMARY ABSTRACT More than 1.2 million people in the United States have a spinal cord injury (SCI), and each year there are 10,000 new cases. In the last few years, we have shown that neuromodulation using epidural stimulation of the lumbosacral spinal cord can activate latent neural circuits and restore voluntary movement, standing and stepping in individuals with chronic SCI. One participant in this study also reported gains in bladder function following training with spinal cord epidural stimulation.

Project Summary Large-field-of-view high-throughput two-photon endoscope to image neuronal activity Development of miniaturized optical endoscopes have enabled visualization and recording of neural activity in freely-behaving animals. Two-photon endoscopes have excellent signal-to-background ratio, and can image deep into the tissue. It has a good optical sectioning and low phototoxicity. However, two-photon endoscopes have a very limited field of view and imaging throughput, and cannot typically perform axial refocusing for 3D imaging.

Abstract There is a growing interest to effectively combine optical approaches with electrophysiology at large scale and with great precision to fully leverage the complementary spatial and temporal resolution advantages of both techniques. It is also widely recognized that device softness and compliance are important attributes to dramatically lower tissue injury and irritation and maintain signal quality over time.

PROJECT SUMMARY/ABSTRACT Respiratory failure after spinal cord injury (SCI) impairs the health of the injured patients, and respiratory failure is the leading cause of death in patients with SCI. Treatment of respiratory failure consists of mechanical ventilation, in which a mechanical pump is used to facilitate air exchange with the lungs. Mechanical ventilation is invasive, costly, limiting, and carries with it a high risk of complications and death.

7. Project Summary Multiple early feasibility trials in humans have demonstrated that implantable Brain-Computer Interfaces (BCIs) can enable people with severe paralysis to use neural signals to control remote and digital communication technologies, including messaging and email. Such studies have demonstrated clearly that BCIs have the potential to improve the quality of life of patients who have physical disability due to paralysis of speech and upper limbs.

The large-scale dynamics of neural circuitry depend on interactions among numerous neurochemical spe- cies that play functionally distinct roles throughout the brain. Understanding the spatial and temporal character- istics of chemical signaling is thus crucial for building mechanistic models of brain function. Our laboratory has introduced paramagnetic neurotransmitter sensors that enable functional analysis of neurochemical phenomena over large fields of view by molecular-level functional magnetic resonance imaging (molecular fMRI).

ABSTRACT Micromagnetic stimulation (µMS) has several advantages over electrical stimulation. First, µMS does not require charge-balanced stimulation waveforms as in electrical stimulation. In µMS, neither sinks nor sources are present when the time-varying magnetic field induces a current. Thus µMS does not suffer from charge buildup as can occur with electrical stimulation. Second, magnetic stimulation via µMS is capable of activating neurons with specific axonal orientations.

PROJECT SUMMARY/ABSTRACT A wealth of new tools can directly control output of specific neurons on fast (e.g., optogenetic) or sustained (e.g., chemogenetic) time scales. In contrast, almost no methods exist for selectively modulating communication between defined cells at the synaptic level, which is key to understanding how functional connectivity creates percepts, engrams and actions. Here, we advance a novel strategy for selectively modulating synaptic transmission, Interluminescence.