BRAIN Initiative Research Articles

Manufacturing Processes of Implantable Microelectrode Array for In Vivo Neural Electrophysiological Recordings and Stimulation: A State-Of-the-Art Review.

Electrophysiological recording and stimulation of neuron activities are important for us to understand the function and dysfunction of the nervous system. To record/stimulate neuron activities as voltage fluctuation extracellularly, microelectrode array (MEA) implants are a promising tool to provide high temporal and spatial resolution for neuroscience studies and medical treatments. The design configuration and recording capabilities of the MEAs have evolved dramatically since their invention and manufacturing process development has been a key driving force for such advancement. Over the past decade, since the White House Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative launched in 2013, advanced manufacturing processes have enabled advanced MEAs with increased channel count and density, access to more brain areas, more reliable chronic performance, as well as minimal invasiveness and tissue reaction. In this state-of-the-art review paper, three major types of electrophysiological recording MEAs widely used nowadays, namely, microwire-based, silicon-based, and flexible MEAs are introduced and discussed. Conventional design and manufacturing processes and materials used for each type are elaborated, followed by a review of further development and recent advances in manufacturing technologies and the enabling new designs and capabilities. The review concludes with a discussion on potential future directions of manufacturing process development to enable the long-term goal of large-scale high-density brain-wide chronic recordings in freely moving animals.

The Neuroscience Multi-Omic Archive: a BRAIN Initiative resource for single-cell transcriptomic and epigenomic data from the mammalian brain.

Scalable technologies to sequence the transcriptomes and epigenomes of single cells are transforming our understanding of cell types and cell states. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative Cell Census Network (BICCN) is applying these technologies at unprecedented scale to map the cell types in the mammalian brain. In an effort to increase data FAIRness (Findable, Accessible, Interoperable, Reusable), the NIH has established repositories to make data generated by the BICCN and related BRAIN Initiative projects accessible to the broader research community. Here, we describe the Neuroscience Multi-Omic Archive (NeMO Archive; nemoarchive.org), which serves as the primary repository for genomics data from the BRAIN Initiative. Working closely with other BRAIN Initiative researchers, we have organized these data into a continually expanding, curated repository, which contains transcriptomic and epigenomic data from over 50 million brain cells, including single-cell genomic data from all of the major regions of the adult and prenatal human and mouse brains, as well as substantial single-cell genomic data from non-human primates. We make available several tools for accessing these data, including a searchable web portal, a cloud-computing interface for large-scale data processing (implemented on Terra, terra.bio), and a visualization and analysis platform, NeMO Analytics (nemoanalytics.org).

Electrocorticography During Deep Brain Stimulation Surgery: Safety Experience From 4 Centers Within the National Institute of Neurological Disorders and Stroke Research Opportunities in Human Consortium.

Intraoperative research during deep brain stimulation (DBS) surgery has enabled major advances in understanding movement disorders pathophysiology and potential mechanisms for therapeutic benefit. In particular, over the last decade, recording electrocorticography (ECoG) from the cortical surface, simultaneously with subcortical recordings, has become an important research tool for assessing basal ganglia-thalamocortical circuit physiology. To provide confirmation of the safety of performing ECoG during DBS surgery, using data from centers involved in 2 BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative-funded basic human neuroscience projects. Data were collected separately at 4 centers. The primary endpoint was complication rate, defined as any intraoperative event, infection, or postoperative magnetic resonance imaging abnormality requiring clinical follow-up. Complication rates for explanatory variables were compared using point biserial correlations and Fisher exact tests. A total of 367 DBS surgeries involving ECoG were reviewed. No cortical hemorrhages were observed. Seven complications occurred: 4 intraparenchymal hemorrhages and 3 infections (complication rate of 1.91%; CI=0.77%-3.89%). The placement of 2 separate ECoG research electrodes through a single burr hole (84 cases) did not result in a significantly different rate of complications, compared to placement of a single electrode (3.6%vs 1.5%; P=.4). Research data were obtained successfully in 350 surgeries (95.4%). Combined with the single report previously available, which described no ECoG-related complications in a single-center cohort of 200 cases, these findings suggest that research ECOG during DBS surgery did not significantly alter complication rates.

NeuroEthics and the BRAIN Initiative: Where Are We? Where Are We Going?

From its inception, the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an ambitious project focused on understanding the human brain, has made a concerted effort to integrate neuroethics into its science. In the past five years, the BRAIN Initiative has given rise to powerful tools and neurotechnologies capable of probing deeply into the brain circuits in animal models. As these tools mature and move to human applications they will raise a host of important neuroethical considerations not just for the medical community but for society as a whole. Now marks a pivotal moment to assess the status and consider the future of the BRAIN Initiative’s neuroethics efforts. Here we describe core issues of neuroscience advances, the state of neurotechnologies in human neuroscience, and how ethics will be incorporated into the BRAIN Initiative as this ten-year project enters its second phase. BRAIN Initiative neurotechnologies have immense potential to transform the way we diagnose and treat neurological disease; therefore, they may become more commonplace in research, medicine, and society. We also discuss future global efforts to ensure continued guidance and open dialogue surrounding neuroethics.

BRAIN Initiative: Cutting-Edge Tools and Resources for the Community.

The overarching goal of the NIH BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is to advance the understanding of healthy and diseased brain circuit function through technological innovation. Core principles for this goal include the validation and dissemination of the myriad innovative technologies, tools, methods, and resources emerging from BRAIN-funded research. Innovators, BRAIN funding agencies, and non-Federal partners are working together to develop strategies for making these products usable, available, and accessible to the scientific community. Here, we describe several early strategies for supporting the dissemination of BRAIN technologies. We aim to invigorate a dialogue with the neuroscience research and funding community, interdisciplinary collaborators, and trainees about the existing and future opportunities for cultivating groundbreaking research products into mature, integrated, and adaptable research systems. Along with the accompanying Society for Neuroscience 2019 Mini-Symposium, "BRAIN Initiative: Cutting-Edge Tools and Resources for the Community," we spotlight the work of several BRAIN investigator teams who are making progress toward providing tools, technologies, and services for the neuroscience community. These tools access neural circuits at multiple levels of analysis, from subcellular composition to brain-wide network connectivity, including the following: integrated systems for EM- and florescence-based connectomics, advances in immunolabeling capabilities, and resources for recording and analyzing functional connectivity. Investigators describe how the resources they provide to the community will contribute to achieving the goals of the NIH BRAIN Initiative. Finally, in addition to celebrating the contributions of these BRAIN-funded investigators, the Mini-Symposium will illustrate the broader diversity of BRAIN Initiative investments in cutting-edge technologies and resources.

The NIH BRAIN Initiative: Integrating Neuroethics and Neuroscience

The NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is focused on developing new tools and neurotechnologies to transform our understanding of the brain, and neuroethics is an essential component of this research effort. Coordination with other brain projects around the world will help maximize success.

The NIH BRAIN Initiative: Advancing neurotechnologies, integrating disciplines.

In 2014, the National Institutes of Health (NIH) began funding an ambitious research program, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, with the singular focus of advancing our understanding of brain circuits though development and application of breakthrough neurotechnologies. As we approach the halfway mark of this 10-year effort aimed at revolutionizing our understanding of information processing in the human brain, it is timely to review the progress and the future trajectory of BRAIN Initiative research.

New round of awards announced for cutting‐edge brain research

The National Institutes of Health (NIH) announced Nov. 2 funding of more than 200 new awards, totaling over $220 million, through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an exciting transagency effort to arm researchers with revolutionary tools to fundamentally understand the neural circuits that underlie the healthy and diseased brain, NIH officials stated in a press release. Supported by Congress through both the regular appropriations process and the 21st Century Cures Act, this brings the total 2018 support for the program to more than $400 million, which is 50 percent more than the amount spent last year. Many of the new awards explore the human brain directly. Furthermore, the NIH is trying to leverage some BRAIN Initiative advances to help tackle the pain and opioid crisis. “The BRAIN Initiative is laying the foundation for improved ways to target brain circuits disrupted in brain disorders,” said Joshua A. Gordon, M.D., Ph.D., director of the NIH's National Institute of Mental Health.

NIMH Director Describes What’s Next for Institute

NIMH Director Describes What’s Next for Institute

Oquendo Recounts Past Year’s Victories, Coming Year’s Challenges

Oquendo Recounts Past Year’s Victories, Coming Year’s Challenges

Congress Rejects White House Proposal to Cut NIH Funding

Back to table of contents Previous article Next article Government NewsFull AccessCongress Rejects White House Proposal to Cut NIH FundingHarriet EdlesonHarriet EdlesonSearch for more papers by this authorPublished Online:26 May 2017https://doi.org/10.1176/appi.pn.2017.6a7AbstractAgencies that support mental health research and programs are given a $2 billion boost.When the U.S. House of Representatives and U.S. Senate voted in favor of passing a $1.1 trillion federal spending package last month, it signaled significant good news for medicine in general and mental health and psychiatry in particular.NIHIn a rejection of the White House proposal to cut $1.2 billion from the budget of the National Institutes of Health (NIH), Congress pushed through a bipartisan deal that increased funding for NIH. Passage of the legislation, which was signed by President Trump on May 5, averted a government shutdown and provides funding through September, the end of Fiscal 2017.Overall, the Department of Health and Human Services (HHS) was appropriated $2.8 billion more than in Fiscal 2016, mostly due to the $2 billion increase for NIH. With that increase, the total appropriated to NIH through September is $34 billion, a 6.2 percent increase. The mental health institutes under NIH are also winners in the budget: the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) all received funding increases (see table).Among the research areas benefiting from passage of the package are Alzheimer’s disease, the Precision Medicine Initiative, and the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. They received increases of, respectively, $400 million, $120 million, and $110 million. The Substance Abuse and Mental Health Services Administration was given a total budget of $3.6 billion, including $650 million over Fiscal 2016 to address the opioid crisis. This represents an increase of $150 million for prevention and treatment programs for opioid and heroin use disorders, as well as $500 million in funding authorized by the 21st Century Cures Act. The funding level for the Substance Abuse Prevention and Treatment Block Grant has been maintained at $1.8 billion, while the Mental Health Block Grant funding was increased from $533 million to $563 million. “The federal government and the Congress play a vital role in advancing research into the causes of, and new treatments for, mental health and substance use disorders,” said CEO and Medical Director Saul Levin, M.D., M.P.A. “The increased funding that Congress has appropriated this year gives us renewed hope that people with mental illness and substance use disorders will one day benefit from the growing understanding of mental disorders and new, personalized health and treatment options. We sincerely appreciate Congress considering our requests for additional funding for those governmental entities helping those with mental illness and substance use disorders get the best treatment and care through research.”Ariel Gonzalez, APA’s chief of government affairs, agreed. “We were pleased to see that the budget for HHS has been increased $2.8 billion above the Fiscal 2016 level. We will continue to advocate for additional funding to address the needs of those impacted by mental health issues and those in need of substance use disorders treatment.” ■ ISSUES NewArchived

The BRAIN Initiative: Building, Strengthening, and Sustaining

Successful federal initiatives share a focus on tangible success stories, constant input and guidance from scientists, participation by a wide range of funders, ongoing interest from policy makers, and a broad and effective communications network. By comparing these elements of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative with other initiatives, we look at what needs to be done to sustain the BRAIN Initiative in the years to come.

Neurology Advocacy 2.0: After Sustainable Growth Rate Repeal.

Neurology Advocacy 2.0: After Sustainable Growth Rate Repeal.

What cell biologists should know about the National Institutes of Health BRAIN Initiative.

The BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is an ambitious project to develop innovative tools for a deeper understanding of how the brain functions in health and disease. Early programs in the National Institutes of Health BRAIN Initiative focus on tools for next-generation imaging and recording, studies of cell diversity and cell census, and integrative approaches to circuit function. In all of these efforts, cell biologists can play a leading role.

Trouble in Mind

The article focuses on the European Union big science Human Brain Project (HBP) and problems it is facing. It states the HBP was conceived by professor Henry Markram to craft a mathematical brain model simulating the entire brain and mentions that a lack of transparency and managerial problems have resulted in a massive overhaul of the HBP. It contrasts HBP with the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative in the U.S. and its outreach to neuroscientists.

Two Years Since the BRAIN Initiative: Update on Current Scientific and Technological Neuroscience Advancements

On April 2, 2013, President Obama announced the commencement of the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, as part of a presidential focus on further understanding the human brain . Many neurosciences view this as a long-awaited relief, as funding rates for research grants reached an all-time nadir. The focus of the initiative was aimed at accelerating both the development and application of technology in the field of neuroscience, with an ultimate goal of providing new methods to diagnose, treat, and prevent neurologic disorders. The charge of the BRAIN Initiative, as summarized by National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D., is “to accelerate the development and application of innovative technologies to construct a dynamic picture of brain function that integrates neuronal and circuit activity over time and space .” One of the most substantial changes has been the announcement of dozens of leading technological firms, academic institutions, scientists, and other key contributors to the field of neuroscience, who have made commitments to advancing the initiative, with a 12-year research strategy for NIH to achieve the goals of the BRAIN Initiative . The gaps in knowledge that will be the target of the BRAIN Initiative include: “forming a comprehensive, rigorous inventory of different brain cell types, developing the technology to map circuits of the brain, improving methods for large-scale mapping of neural activity, developing and applying interventional tools that can change neural circuit dynamics to link brain activity to behavior, identifying new tools to understand the biological basis of mental processes, and finally discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception and action in health and disease .” Two years since the launch of the BRAIN Initiative, there has been some early progress in the development of novel technologies. Published in the May 2015 issue of Neuron, scientists have described a new method to turn behaviors both on and off in rodents. Using a technique known as DREADDs (designer receptors exclusively activated by designer drugs), Bryan Roth et al. were able to control neuronal circuitry and behavior in rodents , selectively turning them both on and off. This is in contrast to the field of optogenetics, which is a bulky, labor-intensive technique that allows scientists to label neurons with a light-sensitive protein (e.g., channelrhodopsin-2, then use pulses of light to turn genes on and off) . They developed a new DREADD (Designer Receptors Exclusively Activated by Designer Drugs) using the kopioid receptor (KOR), which is activated by the inert ligand SALB (salvinorin B), then expressed KORD in several neuronal contexts (including cells in the substantia nigra [SN], ventral tegmental area [VTA], arcuate nucleus [ARC], and paraventricular hypothalamus [PVH]) to selectively modify distinct neuronal populations and their respective circuits. By silencing via KORD of VTA/SN neurons, they were able to

Mental Health Reform Bill Reintroduced Into House

Mental Health Reform Bill Reintroduced Into House

Brain stimulation and memory.

This scientific commentary refers to ‘Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases’, by Miller et al. (doi:10.1093/brain/awv095). Loss of memory is one of the most devastating afflictions of the human condition. With ageing of the population, the looming spectre of neurological disorders affecting cognition in huge numbers of individuals is a critical societal concern. While major efforts are being directed toward prevention of degenerative diseases such as Alzheimer’s disease and Parkinson’s disease, notable success has already been achieved in the treatment of motor symptoms in Parkinson’s disease and other movement disorders using direct stimulation of specific brain centres. The extension of this therapeutic modality known as deep brain stimulation (DBS) to neuropsychiatric conditions such as severe major depression or refractory obsessive-compulsive disorder is underway. The ultimate frontier may well be the application of neuromodulation to the cognitive domain in general and to memory specifically. Several studies have explored the effect of DBS on memory in humans, focusing on the medial temporal lobe with its efferent and afferent associated pathways. In this issue of Brain , Miller et al. (2015) provide intriguing preliminary data on the effect of fornix stimulation on spatial memory, in patients implanted with intracranial depth electrodes for the treatment of refractory epilepsy. The transition from basic science to clinical application is complex and highly challenging. In a much publicized article, Alivisatos et al. (2012) proposed the Brain Activity Map Project, a large-scale recording effort to map brains in a stepwise progression from Caenorhabditis elegans with its 302 neurons, through various species including the …

The BRAIN Initiative: developing technology to catalyse neuroscience discovery.

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.

Simulating the human brain: Scientists have started various major projects to simulate and understand the brain, but many neuroscientists remain sceptical about their scope and aims.

Simulating the human brain: Scientists have started various major projects to simulate and understand the brain, but many neuroscientists remain sceptical about their scope and aims.