Neuroethics guiding principles for the NIH Brain Initiative

Neuroscience presents important neuroethical considerations. Human neuroscience demands focused application of the core research ethics guidelines set out in documents such as the Belmont Report. Various mechanisms, including institutional review boards (IRBs), privacy rules, and the Food and Drug Administration, regulate many aspects of neuroscience research and many articles, books, workshops, and conferences address neuroethics. (Farah, 2010; https://bioethicsarchive.georgetown.edu/pcsbi/studies.html; http://www.neuroethicssociety.org/annual-meeting). However, responsible neuroscience research requires continual dialogue among neuroscience researchers, ethicists, philosophers, lawyers, and other stakeholders to help assess its ethical, legal, and societal implications. The Neuroethics Working Group of the National Institutes of Health (NIH) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a group of experts providing neuroethics input to the NIH BRAIN Initiative Multi-Council Working Group, seeks to promote this dialogue by proposing the following Neuroethics Guiding Principles (Table 1)

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

Spinally-mediated hyperalgesia in experimental diabetes

A proportion of diabetic patients experience chronic pain that is frequently refractory to treatment with conventional analgesics. Experimentally diabetic animals exhibit a range of behavioral abnormalities indicative of pain, and can be used to model human painful diabetic neuropathy. Studies suggest that pain during diabetes is not associated with structural damage to the peripheral nerves, and biochemical amplification of nociceptive processing may be of importance. The formalin test is used to measure spinal sensitization in animals. Diabetic rats exhibit exaggerated flinching during this test, in addition to increased constitutive spinal expression of cyclooxygenase-2 (COX-2) protein. Studies were designed to establish causality between increased spinal COX-2 activity and formalin hyperalgesia in diabetic rats. Rats with one, two or four weeks of streptozotocin-induced diabetes exhibited significantly increased levels of spinal COX-2 protein and activity, along with exaggerated paw flinching in response to 0.5% paw formalin injection. Increased flinching of diabetic rats was attenuated by intrathecal pre-treatment with a selective COX-2 inhibitor immediately prior to formalin injection, confirming the involvement of COX-2 activity in formalin hyperalgesia observed in diabetic rats. We hypothesized that glucose flux through the polyol pathway in the central nervous system (CNS) causes elevated spinal COX-2 expression and formalin hyperalgesia in diabetic rats. Chronic treatment with insulin or ICI222155, an aldose reductase inhibitor (ARI) previously shown to cross the blood-brain barrier (BBB) and prevent formalin-evoked hyperalgesia in diabetic rats, prevented elevated spinal COX-2 protein and activity in diabetic rats. In contrast, the ARI IDD676 showed efficacy against AR activity only in the peripheral nervous system, and had no effect on elevated spinal COX-2 or hyperalgesia to paw formalin injection, despite demonstrating efficacy against indices of peripheral nerve dysfunction. In the spinal cord, aldose reductase (AR) expression was observed solely in oligodendrocytes, which also expressed COX-2. These data suggest that activity of AR in spinal oligodendrocytes may be a primary initiating factor linking hyperglycemia with hyperalgesia in diabetic rats. Further, CNS targeting of ARIs may be important in treating painful diabetic neuropathy in patient

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

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