Theory & Data Analysis Tools

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.

Project Summary – Abstract Neuroscientists are getting close to building realistic bioengineered ex vivo human brain models by: (1) introducing perfusable vascular networks to maintain tissue viability and promote 3D brain model growth; (2) generating the full complement of currently missing cell types; (3) building particular brain regions and exploring specific input and output signals.

Abstract More than 500,000 children in the USA and Canada suffer from epilepsy today. Unmanaged, epilepsy can result in cognitive decline, social isolation and poor quality of life, and has substantial economic impact on families and society. 30% of children with epilepsy continue to have seizures while on anti-seizure medication, a condition known as drug resistant epilepsy (DRE). Properly selected, up to 70% of DRE patients become seizure-free after surgery. Nevertheless, epilepsy surgery carries with it risks proportional to its level of invasiveness.

TOWARD 3D HUMAN BRAIN-LIKE TISSUES FOR TARGETING DYSREGULATED SYNAPSE AND PROTEOSTASIS MECHANISMS IN AUTISM SPECTRUM DISORDER Autism spectrum disorder (ASD) is a neurodevelopmental disease affecting nearly 1/50 children in US with an estimated $268 billion in annual costs. The disease is characterized by significant behavioral abnormalities that are often devastating to the quality of life for these patients. Behavior is directly related to the underlying changes of the central nervous system (CNS) brain tissue.

Project Summary/Abstract The BRAIN initiative has put forth the development of a neuronal cell-type census as the first step towards mapping the structure and components of neuronal circuits.

Project Summary When learning new skills, experience with previously-learned skills can facilitate faster learning by constraining behavioral exploration and shaping, a concept known as “structural learning”3,4. The motor cortex plays an essential role in learning new skills5,6, and its initially variable activity is shaped and consolidated over learning7–10. However, how previous experience modulates exploration and shaping of cortical network activity to facilitate new skill learning is not well understood.

PROJECT SUMMARY ABSTRACT The lateral cerebellum (Crus I/II) interacts with two dissociable large-scale brain networks — the executive control (ECN) and default mode networks (DMN), which support distinct cognitive functions (e.g., prediction versus episodic memory, respectively). The proposed research aims to identify noninvasive brain stimulation parameters that cause this area of the cerebellum to interact more heavily with either network, thereby biasing lateral cerebellar participation in network-specific cognitive functions critical to adult humans.