Public-Private Partnerships

Abstract Currently, the brain-computer interface (BCI) field has demonstrated two distinct device strategies - macroelectrodes (e.g., surface grids and depth) versus microelectrode arrays, and some are even pushing the field to smaller, higher density arrays hoping to address the general signal degradation. Both approaches have been in development for decades. However, BCI devices to treat aphasia, dysarthria, or locked-in syndrome also need to access deeper brain regions given the very large, parallel networks involved in speech.

PROJECT SUMMARY This UH3 application seeks to address the major public health burden of treatment-resistant major depression (trMDD) by developing a novel form of Deep Brain Stimulation (DBS). This approach is unique among recent approaches toward DBS optimization in that it incorporates individualized stimulation target location selection and a closed-loop stimulation strategy where a personalized circuit activity biomarker of the pathologic state is identified and used to trigger therapeutic stimulation only when needed.

DBS therapy for Parkinson Disease [PD], the primary, FDA-approved surgical approach, has proven efficacious in clinical trials. However, this continuous stimulation therapy is limited to treatment of a subset of motor symptoms (i.e., tremor, rigidity, bradykinesia and dyskinesias) and requires considerable postoperative clinical adjustment to treat symptoms. Improvements to DBS for PD are being tested, including changes in patterns of stimulation, additional targets, and multiple electrodes.

Essential tremor (ET) is a common neurologic disorder affecting over 10 million people in the United States. Pathologic synchrony in the cerebello-thalamo-cortical (CTC) network has been considered to underlie the development of ET. Traditional high frequency isochronal deep brain stimulation (T-DBS) in the ventral intermediate nucleus (VIM) of the thalamus has been an effective treatment for ET, however, stimulation related side effects such as dysarthria and ataxia occur in at least 30% of patients.

The goal of this project is to develop a Wireless, fully Implantable, bidirectional Cortical Neuroprosthetic System (W-ICONS) for restoring sensorimotor function through an interface with intact upper limb areas of primary motor and sensory cortex. Technologies that enable direct communication to and from the brain have increasingly shown promise for restoring independence to people affected by high spinal cord injuries.

Project Abstract Current common methods for measuring somatosensory function in preclinical rodent models generally rely on withdrawal responses to uncomfortable or painful stimuli. These tests can be stressful to the animal, while also yielding a high variability in measured responses, and repetitive testing in longitudinal models may even result in chronic pain states. To better understand the connection between physiology and perception of touch and proprioception, researchers need a modern, off-the-shelf assessment system to administer and quantify trained, volitional behaviors.

Over the past 15 years, new microscope technologies and methods for high throughput imaging have revolutionized structural biology by extending the resolution and scale of datasets in 3 dimensions. The resulting image volumes are more typically hundreds of GB to even tens of TB and for large volume electron microscope images of brain, can approach PB sizes. These file sizes pose challenges for image analysis, and communication of a representative set of raw data and quantification.

Non-invasive brain stimulation (NIBS) has attracted considerable interest in the cognitive neuroscience community, providing an important basic research tool to study brain function, with emerging clinical applications to enhance function in individuals with neurological disorders. Despite this potential, an emerging literature has highlighted concerns regarding the reliability and robustness of transcranial electric stimulation (tES), the primary NIBS method used to induce changes in brain plasticity through the application of subthreshold stimulation.

Cardiac arrest in infants is a medical emergency requiring rapid resuscitation to restore circulation. However, resuscitation often results in significant brain injury, caused by ischemia/reperfusion injury. Only 36% of infants (<1yr old) treated for out-of-hospital cardiac arrest and 69% of infants that suffer in-hospital cardiac arrest are successfully resuscitated. These infants currently have no therapeutic options to limit brain injury. The current standard treatment for post-cardiac arrest brain injury is therapeutic hypothermia.

Histone modifications carry rich information of cellular memory and gene regulatory mechanisms. Single cell analysis of histone modification in conjunction with transcriptome could recover this critical layer of cell identity and help to dissect the cellular and molecular composition of complex tissues such as the brain. We recently developed an ultra-high throughput single cell multi-omics assay, Paired-Tag, that can jointly map transcriptome and histone modifications from up to a million single cells in parallel.