Circuit Diagrams

PROJECT SUMMARY/ABSTRACT Critical advances in the treatment of human brain disorders are hindered by our inability to specifically target dysfunctional circuitry in a safe and noninvasive manner. Existing noninvasive techniques (e.g., transcranial magnetic, electrical, and ultrasound neuromodulation) activate many brain circuit components within the targeted region, and their efficacies are difficult to control.

PROJECT SUMMARY Although genetic tools have dramatically advanced our understanding of brain function, they have largely been confined to mice. While mice are essential models for many areas of neuroscience, there are also many aspects of higher brain function that cannot be adequately modeled in rodents. Similarly, many brain disorders affect higher cognitive functions that have no clear parallels in rodents. Furthermore, recent large- scale single cell transcriptomic analyses have revealed many neuron types, connections and gene expression patterns that are unique to primates.

Primate brains contain cortical areas that exhibit selective engagement in high-level sensory or behavioral operations. The functional specialization of these regions is thought to be central to primate-specific cognitive faculties and to associated disorders. Deciphering the origins of functional specialization in primate brain regions has been an enormously challenging task, however, due in large part to the absence of suitable experimental tools.

Project Summary/Abstract The goal of this work is to facilitate synaptic level analysis of neurons and their interconnecting microcircuits in neurosurgical cerebral cortex biopsies from human patients. These full-thickness human cerebral cortex biopsies will be provided by neurosurgical colleagues from patients undergoing resective surgery or surgical implantation of leads for deep brain stimulation (DBS).

Project Summary/Abstract Over the past decade, there have been transformative advances in three areas of mammalian neuroscience. First, our ability to record from large populations of neurons has dramatically increased with the advent of new electrode technologies and improved multiphoton imaging. Second, the study of brain connections in their entirety, connectomics, has come into its own as a field.

Project Summary The proposed work will address a critical gap in our understanding of neuronal phenotypes and cell types by developing machine learning algorithms and cloud-based software for the integration of multiple modality characterizations large and growing datasets of cortical neurons in mouse and human.

PROJECT SUMMARY/ABSTRACT Modern experimental approaches allow researchers to collect a variety of whole-brain data from the same animal via different anatomical labels, including tracers, genetic markers, and fiducial marks from recording electrodes. Unfortunately, viewing and analysis methods have not kept pace with the complexity of these datasets, which can be as large as several terabytes. This limitation makes it time- and resource-intensive to view and manipulate light-microscopy data or to share these datasets with distant laboratories.

The increasing availability and ease of use of confocal, two-photon, and light-sheet microscopes coupled with rapid developments in fluorescent protein reporters have made 3D and functional imaging and its analysis a central component of modern Neuroscience research. Yet, the ease of acquiring 3D and functional images is creating progressively larger datasets, prompting the need for high-throughput image analysis algorithms and software that can be both rapid and accurate.

Project Summary Neural prosthetic devices for sensorimotor and psychiatric disorders are in development as a priority area of the BRAIN Initiative yet they raise important ethical concerns about human agency.

7. PROJECT SUMMARY/ABSTRACT Mental health disorders cause immense personal suffering and represent a significant societal burden. Recent research emphasizes the potential of psychiatric electroceutical interventions (PEIs) – bioelectronic treatments that employ electrical stimulation to affect and modify brain function – to effectively treat such disorders. Novel PEIs, however, also raise significant ethical concerns. Not uncommonly, they are negatively associated with historically controversial interventions such as electroconvulsive therapy and lobotomy.