Research Projects

Great discoveries in neuroscience hold promise for reducing the burden of many of the most disabling conditions that threaten human health on a global scale, including mental illnesses and addictions. Increasingly, exceptionally innovative science inspires hope that these devastating brain-based disorders may be prevented, treated, and even cured but, as the

PROJECT SUMMARY/ABSTRACT New technologies that modulate brain function have tremendous potential for alleviating the persistent burden of depression and other neuropsychiatric disorders, but also raise challenging ethical and societal questions regarding self-ownership and control over our thoughts, emotions and actions. For these reasons, the President’s Bioethics Commission and other experts have called for the integration of ethics and neuroscience from the earliest stages of research.

Project Summary The goal of the proposed project is to test in macaques a technique for non-invasive, safe, reversible, modulation of neuronal activity in small targeted regions of the primate brain. We have developed and tested in macaques a technique for transiently opening the blood-brain barrier (BBB) in targeted brain regions without causing any damage, using a clinically available focused ultrasound device in conjunction with circulating microbubbles.

PROJECT SUMMARY/ABSTRACT Fast microscopy techniques, coupled with recent advances in tissue clearing, are now able to efficiently produce cellular-resolution images of intact brain samples. These technologies have generated three- dimensional (3D) images of entire intact brains from model organisms and large sections of human brain samples, enabling mapping of neuronal circuits from synapse to systems levels. Going forward, it will be essential to share data across laboratories to replicate findings, perform cross-study analyses, and develop robust new analysis tools.

PROJECT SUMMARY Technology for recording from the brain is developing at a breakneck pace. But the digital integration of data acquired from different recording technologies is an impediment to the rapid adoption of these technologies across labs, and also makes analysis by interested 3rd parties, such as theorists, difficult. This lack of integration is a major barrier to scientific inquiry, as labs cannot easily analyze each other's data.

ABSTRACT Despite the increasing use of transcranial magnetic stimulation (TMS) in both research and clinical practice, the field nonetheless lacks a theoretical framework to predict the impact of TMS on circuits. In this application, we propose to test the over-arching hypothesis that brain responses to TMS are governed by both the network control properties of the stimulation site and the functional context of the network during stimulation.

Project Summary/Abstract Brain function is produced by the coordinated activity of multiple neuronal types that are widely distributed across many brain regions. Neuronal signals are acquired using extra- and intracellular recordings, and increasingly optical imaging, during sensory, motor, and cognitive tasks. Neurophysiology research generates large, complex, heterogeneous datasets at terabyte scale. The data size and complexity is expected to continue to grow with the increasing sophistication of experimental apparatus.

Project Abstract Completely noninvasive neuromodulation using focused ultrasound (FUS) offers the promise of precisely stimulating specific targets deep in the brain, at power levels commonly used for diagnostic imaging studies. Having a working mouse model to study neuromodulation with ultrasound is a critical need. The mouse model has a much wider array of immunohistochemical staining antibodies and known genetic markers to answer basic science questions than do larger animals.

PROJECT SUMMARY/ABSTRACT Although neurotechnologies are rapidly advancing, we lack a noninvasive, cell-type specific, and spatiotemporally regulated neuromodulation tool, which would radically change neuroscience research and enable clinically noninvasive brain stimulation with high spatiotemporal precision.

Non-invasive neuromodulation, such as transcranial direct current stimulation (tDCS), is emerging as an important therapeutic tool with documented effects on brain circuitry, yet little is understood about how it changes cognition. In particular, the challenge of how learning, or training, in one domain generalizes to unlearned or unpracticed domains has long been a focus of educational psychology.