Cooperative Agreements

PROJECT SUMMARY Essential tremor (ET) is an incurable, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US (2.2% of the population). While the economic impact of ET is indeterminate, it is surely quite substantial. In one study, 25% of ET patients were forced to change jobs or take early retirement because of tremor. ET is directly linked to progressive functional impairment, social embarrassment, and even depression.

ABSTRACT The proposed work to clinically test an intracortical visual prosthesis under an FDA-approved Early Feasibility Study addresses both health and quality-of-life issues because, without some compensatory strategy for vision loss, over two thirds of individuals with blindness are not gainfully employed, they experience higher rates of depression and social isolation, and experience a reduced quality-of-life.

PROJECT SUMMARY Epilepsy, occurring in 1 percent of the world’s population, is associated with disability, injury, cognitive and neurological dysfunction, depression, loss of productivity, socioeconomic decline and even death. Of this population, 30 percent of epilepsy cases are medically intractable, leaving surgical interventions as the only option for treatment. Whereas open resection, the current surgical standard of treatment, can yield seizure freedom rates as high as 60-80 percent, these are often associated with cognitive dysfunction and focal neurological deficits.

The dominant techniques for brain-wide functional imaging in humans and opaque mammals make use of he- modynamic contrast that results from coupling between neural activity and changes in blood flow and can be detected by noninvasive imaging methods including functional magnetic resonance imaging (fMRI), functional photoacoustic tomography (fPAT), functional ultrasound imaging (fUS), and others.

This is an application in response to RFA-NS-17-00 4 “BRAIN Initiative: Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (U01)”.

To understand how the brain computes, we need to understand how individual neurons in a circuit integrate their numerous inputs into output signals, as well as how they work together to encode a sensory input or execute a motor command in a behaving animal. Circuits and neurons are three-dimensional (3D) and can extend over hundreds or thousands of microns. Therefore, understanding their operations requires monitoring their activity at both synaptic and cellular resolution in 3D at image rates that capture all activity events. Behaving animals present a host of challenges to this goal.

In response to the BRAIN initiative RFA-NS-17-003 “New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (U01)”, in this project we aim at accomplishing selective stimulation and recordings at ultra-high cellular level spatial resolution of distinct axonal b

One of the major challenges in neuroscience is to understand the experience-dependent mechanisms that drive the changes in neural circuits that underlie complex behaviors, and how these mechanisms are altered in disease. Altered synaptic transmission has been implicated in a number of human neurological and psychiatric disorders, including epilepsy, schizophrenia, autism and addiction.

Calcium signaling participates in almost every aspect of cell functioning, specifically in neurons. Genetically encoded calcium indicators (GECIs) developed from fluorescent proteins (FPs) provide a robust reliable readout of neuronal activity including spike number, timing, frequency, and levels of synaptic input.

A significant motivation of the BRAIN Initiative is the desire to understand information processing in neuronal tissues in situ.