Cooperative Agreements

Understanding the cerebral cortex requires data-based theoretical models that can yield in- sight into the circuit mechanisms of cortical computation, and reproduce detailed cortical dynamics across stimuli and brain states. The primary visual cortex (V1) is the best-studied cortical area by both theorists and experimen- talists, yet current models - whether statistical or circuit based – only poorly capture how V1 neurons respond to complex stimuli, such as natural scenes.

Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction and maternal behavior. Recent studies have tagged oxytocin as a “trust” hormone, promising to improve social deficits in various mental disorders, such as autism. Despite the enthusiasm for oxytocin, contradictory results in the efficacy of oxytocin in improving human social behaviors have been reported. Such inconsistency in literature is likely due to our poor understanding of complexity of oxytocin action, which likely varies with behavioral state, experience and brain structures.

Project Abstract Background/Description. Given our mutual interest in direct brain stimulation as an effective treatment for non-adherent eating disorders associated with refractory obesity, our multidisciplinary team at Stanford University has developed a collaboration with NeuroPace, Inc, a company that recently received FDA approval for a responsive neurostimulator. We previously found that electrically stimulating the nucleus accumbens (NAc) of mice attenuates binge-like eating.

ABSTRACT The proposed project will build and evaluate the safety and design needs of a new type of intracranial auditory prosthesis that targets the auditory nerve between the cochlea and the brainstem (auditory nerve implant, ANI) in order to substantially improve hearing performance over the current standard of care, the cochlear implant (CI). Current CIs provide crucial speech information to many recipients, but do not restore normal hearing, and are particularly challenged in noisy or complex acoustic environments.

ABSTRACT The goal of this U44 proposal is to develop and test CranialProgrammer, an image-guided programming tool for 2D/3D mapping of disease-related neural signals over patient and device data for more efficient and effective programming of directional deep brain stimulation (DBS) systems. DBS is an established treatment for advanced, refractory movement disorders used in over 150,000 patients.

Project Summary/Abstract Action initiation and withholding are key parts of everyday behavior, and underlying these is action suppression. This includes (1) suppressing competing actions when selecting one action from alternatives (2) suppressing all responses when presented with conflicting information until a proper decision can be made and (3) suppressing a response when the environment rapidly changes indicating a pre-planned response must be stopped. The literature suggests that these three functions are supported by distinct fronto-basal ganglia (BG) circuits.

ABSTRACT In the course of a day we naturally make multiple shifts in our overall cognitive state and in our aims and intents. We go from sleep to awake, from internal dialogue to external communication, from relative immobility to planned complex movements. The neural activity which distinguishes these different high-level states is unknown and yet is a fundamental aspect to understanding overall cognitive processes. It is also a baseline substrate that is adversely impacted by a wide range of neuropsychiatric diseases.

Speech production and control is disrupted in a number of neurological diseases that involve the basal ganglia. Notably, hypophonia and hypokinetic dysarthria (characterized by decreased motor gain) are prevalent in patients with Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces predictable improvements in other motor symptoms of PD but does not result in consistent improvement in speech and can negatively impact language function. These observations and other accumulating evidence indicate an important role for the basal ganglia in speech.

PROJECT SUMMARY Speaking is one of the most complex actions that we perform, yet nearly all of us learn do it effortlessly. The ability to communicate through speech is often described as the unique and defining trait of human behavior. Despite its importance, the basic neural mechanisms that govern our ability to speak fluently remain unresolved.

Project summary/abstract Reach-to-grasp and hand manipulation will be studied in tetraplegic humans with neural recordings from multielectrode arrays (MEAs) and intracortical microstimulation (ICMS) of somatosensory cortex. Recordings will be performed within the cortical grasp circuit with MEAs implanted in two grasp-related areas, the ventral premotor cortex (PMv) and the anterior intraparietal area (AIP) of the posterior parietal cortex (PPC). ICMS will be delivered to Brodmann's area 1 (BA1) of somatosensory cortex.