Monitor Neural Activity

SUMMARY We are proposing a new approach to a hybrid imaging modality that has been called “b+g” or “pamma-positron” Imaging [Gri07] that promises to simultaneously overcome 1) the sensitivity limits of single-gamma-ray-photon emission imaging, 2) the challenge of distinguishing between two different positron-emitting isotopes, and 3) the physics-based spatial resolution limits inherent in radioisotope imaging based on detection of positron- annihilation photons alone [Lan14].

Project Summary Public and private research funders have heavily invested in the application of implantable neurotechnologies to improve the management of treatment-resistant conditions and loss of function (e.g., deep brain stimulation (DBS) systems for recovery after traumatic brain injury (TBI), stroke, disorders of consciousness, movement disorders, and psychiatric disorders such as obsessive-compulsive disorder (OCD) and depression). These devices are trialed with people who have had severe impairments and treatment-resistant disorders for many years.

Project Summary/Abstract The BRAIN Initiative is supporting a broad portfolio of neuroscience research aimed at revolutionizing our understanding of the brain.

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.

Project Summary/Abstract: The field of optogenetics — utilizing light to engage biological systems — is widely used for the dissection of neural circuits, cellular signaling and manipulating neurophysiological systems in awake, behaving animals. However, while many new opsins have been developed and are actively used, challenges still remain, and the current technology lacks a full toolbox for sub-cellular, spatiotemporal control of signaling — the predominant means for neuromodulator communication in the brain.

Project Summary Plasticity is a fundamental aspect of neuronal circuits across all species. It is at the base of learning and memory, sensory adaption, and many disease-related processes such as addiction, chronic pain or regeneration. On the molecular level biochemical mechanisms have been well described, but little is known on how these are coordinated in space and time within neuronal circuits of living brains.

ABSTRACT BRAIN Initiative-funded, large-scale approaches to classify neurons based on transcriptomic, morphological and electrical properties have unveiled dozens of unique cell classes in the mouse brain.

There is a substantial need to understand the fundamental biological mechanisms of neuromodulation therapies in order to improve clinical delivery and outcomes (RFA-NS-20-006). Intractable chronic pain of the back and limbs continues to be challenging to treat clinically, and spinal cord stimulation (SCS) devices have experienced tremendous market growth despite a lack of an accepted mechanistic basis.

PROJECT SUMMARY / ABSTRACT. Research Project: Spatial memory – memory of where an event happened or an object was located – depends on the hippocampus in a wide range of vertebrate species, including mammals and birds. In humans, most spatial memories are formed through visual experience. However, it is unclear how visual information is processed by hippocampal memory circuits to support spatial memory formation.