Cooperative Agreements

Project Summary Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction, maternal care, and social behavior, as well as various ‘non-social’ aspects of internal state and physiological processes. Although sometimes referred to as a ‘trust’ hormone, a growing body of evidence across species and brain areas indicates that oxytocin can increase social salience, i.e., amplifying or enabling selective attention towards certain social stimuli, such as the sound of a crying infant or the presence of a threatening or high-status individual.

Abstract Humans can rapidly regulate actions according to updated demands of the environment. A key component of action regulation is action inhibition, the failure of which contributes to various neuropsychiatric diseases, such as Parkinson’s disease (PD), obsessive compulsive disorder and Tourette syndrome.

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].

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.

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.

PROJECT SUMMARY / ABSTRACT Functional MRI (fMRI) is today the predominant tool for noninvasive imaging of brain function, which has revolutionized our understanding of the human brain. To date, echo-planar imaging (EPI) has been the standard fMRI acquisition method, but suffers from intrinsic limitations such as static and dynamic distortion, image/contrast blurring, signal voids, suboptimal CNR and physiological noises.

A central goal of neuroscience is to discover how neural circuits control the body’s muscles to produce behavior. However, despite recent advances in tools for studying brain activity, methods for examining the signals that actually control behavior – spiking activity in muscle fibers – have advanced little since the 1950s, fundamentally limiting our understanding of how the brain controls the body. By combining our expertise in electrophysiology (Dr. Sober) and engineering (Dr.