Monitor Neural Activity

New tools to selectively regulate neurons have revolutionized causal experimentation. Optogenetics provides an array of elements for specific biophysical control, while designer chemogenetic receptors provide a minimally invasive method to control circuits in vivo by peripheral injection. We have developed a strategy for selective regulation of activity in specific cells that integrates opto- and chemo-genetic approaches, and thus allows manipulation of neuronal activity over a range of spatial and temporal scales in the same experimental animal.

This project will place into the hands of many experimental neuroscientists validated, massively-multiplexed tools for recording of neuronal activity, for chemical sensing of neuromodulators, and for highly-patterned optogenetic stimulation with concurrent electrical recording – in any region of the brain. This will be accomplished by making use of both PIs' decades-long working relationship with microchip foundries, to enable mass production of neural nanoprobes, of VLSI application-specific integrated circuits (“microchips”), and of supporting instrumentation for read-out and control.

PROJECT SUMMARY/ABSTRACT Stroke is a disease of epidemiological proportions in the industrialized world and a leading cause of long-term disabilities. One third of stroke patients maintain long-term motor deficits severe enough to be disabling, despite rehabilitative efforts. We have proposed dentate nucleus deep brain stimulation (DN-DBS) as a therapy to facilitate motor recovery for patients with chronic upper extremity hemiparesis due to ischemic stroke.

Abstract Deep brain stimulation (DBS) has a major role in the management of movement disorders, and is under investigation for the treatment of disorders of mood and memory. In Parkinson's disease (PD), DBS of basal ganglia nuclei can improve motor signs and reduce medication-induced motor fluctuations and dyskinesia, characterized by frequent transitions between a hypokinetic state (too little movement) and a hyperkinetic state (too much movement). However, since the introduction of DBS for PD 25 years ago, there have been no major improvements in this therapy.

Project Abstract This project is a pilot clinical trial of a new brain stimulation treatment for obsessive-compulsive disorder. OCD is a mental illness that affects 4-7 million people in the US. Of those, 50-70% still have substantial symptoms after being treated with medication or talk therapy. Recently, clinicians have started trying to treat OCD with deep brain stimulation (DBS). DBS involves surgically placing electrodes into the brain, then sending electrical stimulation currents through those electrodes.

In patients with intractable Obsessive-Compulsive Disorder (OCD), ventral striatum (VS) deep brain stimulation (DBS) effectively reduces symptom severity in about 60% of cases. However, there is room for improvement in both clinical benefits and reduction of DBS-induced behavioral side effects, especially hypomania. A critical factor may be failure to adaptively adjust DBS in response to phasic changes in negatively and positively valenced states (i.e., OCD-related distress and hypomania, respectively).

ABSTRACT It is easy to underestimate the importance of normal movement in daily life, until that ability is altered or taken away by disease. Used in more than 150,000 patients worldwide, deep brain stimulation (DBS) is often an effective therapy for Parkinson's disease and other movement disorders, however symptomatic improvement varies substantially in individuals, across clinical trials, and over time.

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.