In June, the NIH’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Working Group to the Advisory Committee released “BRAIN 2025: A Scientific Vision,” a report on its findings and recommendations. The Group was formed to develop a plan to advance President Obama’s BRAIN Initiative, which was announced last year (see IBO 4/15/13). Last fall, the Group released an interim report (see IBO 9/30/13).

The BRAIN Initiative aims to study neural activity and patterns in the human brain, including neurons’ electrical and chemical activities and biophysical properties. As the report details, the development and integration of technologies are key to this pursuit and will be facilitated by current advancements in molecular, genetic, cellular, anatomical, electrical, optical and computing tools.

The report recommends an investment of $300–$500 million annually over 10 years, starting in fiscal 2016. The initial five-year period will focus on developing and validating technologies and methods. The second five-year period will concentrate on integrating technologies. In fiscal 2014, BRAIN received $40 million in funding, and the Obama Administration has requested $100 million in funding for fiscal 2015.

The report lays out seven scientific goals of BRAIN. For each goal, deliverables and mechanisms as well as time lines and milestones are detailed. The first goal is to “identify and provide experimental access to the different brain cell types to determine their roles in health and disease.” As defined by the report, modalities of interest include transcriptional/protein profiling, electrophysiological recording, cellular anatomy and connectivity, with initial studies using model organisms, mice and nonhuman primates. Technology development will include improvements in cellular phenotyping and measurement of phenotypic marker expression.

The second goal is to “generate circuit diagrams that vary in resolution from synapses to the whole brain.” The diagrams will be used to study patterns of neural-circuit activity and will rely on the mapping of anatomical connectivity on the macro-, meso- and microscale. Areas of technology development will include MRI, electron microscopy and super-resolution light-microscopy techniques.

Production of “a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity” is the third goal. This goal requires the development of new microelectrode and optical-recording techniques and enhanced human neuroimaging to map electrical and chemical activity. Technology development will involve electrodes, optical sensors and MRI.

The fourth scientific goal is to “link brain activity to behavior by developing and applying precise interventional tools that change neural-circuit dynamics.” This goal focuses on the development and application of perturbation techniques, and subsequent measurements and analyses of behavior. Technologies to be developed involve stimulating electrodes, optogenetics, chemogenetics, natural-products biochemistry and synthetic biology.

To “produce conceptual foundations for understanding the biological basis of mental processes through development of new theoretical- and data-analysis tools” is the fifth goal. This goal relies on theory, modeling, computation and statistics, which are used to explore neural activity in relation to cognitive and behavior functions. Areas of development will include analysis of large, complex data and multiscale data integration.

Goal six is to “develop innovative technologies to understand the human brain and treat its disorders; create and support integrated human brain-research networks.” This goal addresses human neuroscience, both at research and clinical levels, including the use of invasive stimulation and recording devices. Issues to be addressed include clinical support networks, data capture and sharing, ethics and the use of human neurotechnology.

The seventh goal is “integrating new technological and conceptual approaches produced in goals #1–6 to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception and action in health and disease.” This goal emphasizes integrated platforms and experimentation. Examples of integrated technologies could include optical stimulation and optical or electrical recording of genetically tagged cells, and the combination of differentially labeled cell types and light or electron microscopy.