Kavli Blog

Videocasts will be available for the open sessions of two upcoming BRAIN Initiative workshops on August 24 and September 21, 2018.

As mentioned earlier, the ACD (Advisory Committee to the NIH Director) BRAIN Initiative Working Group 2.0, co-chaired by Dr. Catherine Dulac (Harvard University) and Dr. John Maunsell (University of Chicago) is holding a series of public, cross-country workshops to solicit input and expert consultations from leaders in the field, as well as to hear from stakeholders in the scientific community and the general public.

The first workshop, scheduled to take place in Boston, Massachusetts, on Friday, August 24th, 2018, will broadly address human neuroscience through four sessions that will be videocast and open to the public. The workshop will include presentations and panel discussions by scientific speakers, broader discussion with the working group, and opportunities for public comment. The videocast may be accessed here. Due to a high volume of local community interest in this workshop, the venue for the general session has been changed. For more information and to register, visit: https://palladianpartners.cvent.com/BRAIN_ACDWG1.

The second workshop, scheduled to take place in Chicago, Illinois, on Friday, September 21st, 2018, will broadly address emerging opportunities, including sensitive molecular and cellular methods to circuit analysis, developing and disseminating new technologies, and revolutionizing circuit-to-behavior analyses. As with the first event, this workshop will include presentations and panel discussions by scientific speakers, broader discussion with the working group, and opportunities for public comment. The videocast may be accessed here. For more information and to register, visit: https://palladianpartners.cvent.com/BRAIN_ACDWG2.

For detailed, updated information about these workshops, please visit: https://www.braininitiative.nih.gov/about/acd-wg.htm.

And, to submit input to the ACD WG at any point, please visit the BRAIN Request for Information (RFI) at www.braininitiative.nih.gov/rfi.aspx or provide feedback via email to BRAINFeedback@nih.gov. To assure consideration, your responses must be received by November 15, 2018.

Videocasts will be available for the open sessions of three upcoming BRAIN Initiative events on August 13, August 14, and August 24, 2018.

The NIH BRAIN Initiative Multi-Council Working Group (MCWG), consisting of non-Federal representatives from various NIH Institutes and Centers participating in BRAIN, at-large members, and ex officio representatives from DARPA, FDA, IARPA and NSF, provides ongoing oversight of the long-term scientific vision of the NIH BRAIN Initiative, in the context of the evolving neuroscience landscape. The eleventh meeting of the MCWG will occur on Tuesday, August 14th, 2018, at the NIH Porter Neuroscience Research Center (35 Convent Dr., Bethesda, MD 20892). The videocast may be accessed here.

The Neuroethics Working Group of the MCWG recommends overall approaches for how the NIH BRAIN Initiative might handle issues and problems involving ethics. The sixth meeting of the Neuroethics Working Group will occur on Monday, August 13th, 2018, at the NIH Porter Neuroscience Research Center (35 Convent Dr., Bethesda, MD 20892). The videocast may be accessed here.

The ACD (Advisory Committee to the NIH Director) BRAIN Initiative Working Group 2.0, co-chaired by Dr. Catherine Dulac (Harvard University) and Dr. John Maunsell (University of Chicago) is holding a series of public, cross-country workshops to solicit input and expert consultations from leaders in the field, as well as to hear from stakeholders in the scientific community and the general public. The first workshop, scheduled to take place in Boston, Massachusetts, on Friday, August 24th, 2018, will broadly address human neuroscience through four sessions that will be videocast and open to the public. The workshop will include presentations and panel discussions by scientific speakers, broader discussion with the working group, and opportunities for public comment. The videocast may be accessed here.

NIH BRAIN Initiative seeks input through a Request for Information (RFI) from key stakeholders on how to best accomplish the ambitious scientific vision of the BRAIN 2025 report.

NIH is happy to solicit input on how best to accomplish the ambitious vision for the BRAIN Initiative from all interested stakeholders, including members of the scientific community, trainees, academic institutions, the private sector, health professionals, professional societies, advocacy groups, and patient communities, as well as other interested members of the public.

BRAIN 2025: A Scientific Vision serves as the strategic plan for the BRAIN Initiative at NIH and outlines an overarching vision, seven high level scientific priorities, and many specific goals. As the Initiative approaches its midpoint, NIH seeks feedback on the BRAIN Initiative’s progress and on opportunities moving forward, given the current state of the science.

NIH has established a new BRAIN Initiative Advisory Committee of the NIH Director (ACD) Working Group (WG) who will provide scientific guidance to the ACD on how best to continue to accelerate the ambitious vision for the BRAIN Initiative. The ACD-WG will use the responses to this RFI, along with information gathered through a series of public workshops, to help inform their discussions of the BRAIN Initiative’s progress and potential updates to the plan moving forward. The first workshop takes place on August 24, 2018, in Boston – for more information and to register, visit: https://palladianpartners.cvent.com/BRAIN_ACDWG1.

Please submit ideas and suggestions for new tools and technologies, and/or questions about brain circuit function that could be addressed with novel neurotechnologies. The NIH would also like your input on considerations and approaches on dissemination and training, data sharing infrastructure and policies, ethical implications of BRAIN Initiative-supported research advancements, as well as any other topic relevant to the strategic plan of the BRAIN Initiative.

To assure consideration, your responses must be received by November 15, 2018. Responses to this RFI must be submitted electronically using the web-based form (www.braininitiative.nih.gov/rfi.aspx) or via email to BRAINFeedback@nih.gov.

First demonstration of adaptive DBS for Parkinson’s disease using motor cortex sensing… Coordinated articulator movements discretely encoded in sensorimotor cortex… Ethical considerations for guidelines on continued access to investigational brain implants…

Adaptive DBS for Parkinson’s disease detects and responds to adverse treatment effects

Deep brain stimulation (DBS) can be an effective treatment for Parkinson’s disease, especially for patients whose symptoms remain uncontrolled by medication. However, adverse treatment-related side effects like dyskinesia — abnormal involuntary movements — require patients and physicians to manually adjust settings in response to changing symptoms. This constant re-programming is time consuming and imprecise. To address this issue, Dr. Philip Starr and colleagues at the University of California, San Francisco, developed a technique to automatically detect dyskinesias and adjust DBS stimulation in real-time, an approach called adaptive DBS. The researchers noted that powerful oscillations in the gamma frequency range reliably occur in the motor cortex when dyskinesia is present, independent from other neural signals. In two patients with Parkinson’s disease, the scientists tested a novel DBS system using a stimulation lead in the subthalamic nucleus (STN) and a second electrocorticographic (ECoG) implant over the motor cortex for detecting the gamma signal, both connected to an implantable pulse generator (IPG) capable of recording as well as stimulation. The team first prototyped a control algorithm using an external computer, which sensed when the ECoG gamma signal exceeded a certain threshold — indicating dyskinesia — and implemented changes to the STN stimulation via radio signals. They subsequently implemented this algorithm using the implanted IPG, which recorded ECoG signals and then successfully bilaterally adjusted STN stimulation, increasing or decreasing stimulation if the gamma oscillations fell below or rose above the threshold, respectively. This innovative development resulted in a fully embedded self-tuning DBS device, offering a simple way to continuously manage side-effects while consuming significantly less energy than open-loop DBS. Though the group has yet to compare clinical efficacy of the two methods, this breakthrough in adaptive DBS is highly promising for the future of Parkinson’s disease treatment, especially for patients with severely fluctuating symptoms in the utmost need of DBS. For more information, see the NINDS press release on this work.

 

(A) Illustration of fully implanted, closed loop adaptive DBS system. (B) Top panel: spectrogram of signals recorded from motor cortex. Second panel: classifier state (gold), DBS voltage (blue), and gamma (60-90 Hz) power used as the control signal (red). Lower panels show a zoomed in view to demonstrate that transitions in DBS amplitude correspond appropriately to fluctuations in gamma band power.

Coordinated articulator movements are discretely encoded in sensorimotor cortex to provide the kinematic basis of human speech

To perform the extraordinary feat of speaking, human beings engage almost 100 muscles to power the articulators — our lips, jaw, tongue, and larynx — and rapidly reshape the vocal tract, producing the fluid sounds of speech. Neuroscientists have often wondered how the brain encodes the kinematics of speech. Research points to the ventral sensorimotor cortex (vSMC) as a candidate control region, but it is challenging to investigate the neural representation of articulatory movements during continuous speech, beyond isolated segments or phonemes. To overcome this challenge, Dr. Edward Chang and his team at the University of California, San Francisco, designed an innovative technique to capture vSMC encoding of natural speech kinematics. The researchers used data from 8 speakers reciting sentences to develop a deep learning computer model that then produced standardized estimates of articulator movement for all speech sounds. Next, they performed electrocorticographic (ECoG) recordings from the vSMC while 5 new participants read sentences aloud, using acoustic-to-articulatory inversion (AAI) to infer the associated articulatory kinematics. Subsequently, the team used modelling to obtain a final product of articulatory kinematic trajectories (AKTs), traces that each represent the characteristic vocal tract movement encoded by one electrode’s recorded vSMC activity. This approach culminated in insightful new findings, chiefly that each discrete neuronal population recorded by a single electrode encoded AKTs, a level of complexity that had not been previously observed. AKTs are the result of the coordination of articulator movements, each underlying a particular vocal tract shape — such as an alveolar constriction, which produces similar phonemes like /t/, /d/, and /z/ — rather than simply the movement of one articulator. There were four broad categories of AKTs, each of which represented a group of phonemes requiring similar articulator formation. The vSMC showed topographical organization by these four AKT categories, contrary to theories of a one-to-one mapping between cortical site and articulator. AKTs also encoded co-articulation effects, as electrode activity was dependent on the articulator formations that precede or follow an AKT in successive speech. These new insights, likely overlooked without the team’s pioneering technique, point to coordinated articulatory gestures as the basic cortical units of natural speech. This significantly improved understanding will accelerate new exploration into the realization of speech, sequential motor movement, and executive planning overall.

 

(A) Clustering of encoded AKTs for all 108 electrodes across 5 participants. Each column represents one electrode. AKT kinematics were described by maximal articulator displacement (purple to green) along their principal movement axis. Electrodes were clustered by their kinematic descriptions, resulting in four primary clusters. (B) Kinematically clustered electrodes also encoded four clusters of encoded phonemes differentiated by place of articulation (alveolar, bilabial, velar, and vowels). (C) Average AKTs across all electrodes in each cluster. Each trace represents kinematic trajectory of an articulator with a line that becomes thicker with time.

Ethical considerations demonstrate need for guidelines on post-trial access to investigational brain implants for clinical trial participants

Brain implant technologies like deep brain stimulation (DBS), brain-computer interfaces, and neuroprosthetics hold immense promise for treatment-resistant conditions, such as Parkinson’s disease and depression, and for restoring function, such as in traumatic brain injury and vision loss. Existing regulations mandate protections for participants during these high-risk and invasive procedures. However, there are currently no clear guidelines for post-trial maintenance and adjustment of brain implant devices when a device clearly benefits a patient participant. Dr. Gabriel Lázaro-Muñoz and colleagues from Baylor University raise this issue, noting the overall absence of guidelines concerning continued participant access to experimental brain implants. Citing recent examples, the authors explain that research sponsors and health insurers often deny coverage for maintenance or removal costs beyond trial completion, imposing the near-impossible burden on participants whose symptoms improve to rely on personal funds or advocacy. Urging prompt adoption of guidance for continued implant access, the group uses ethical grounds to argue that researchers enter into a relationship of trust with patients and thus owe a limited duty of care. First, they note, compassion requires assisting participants for whom the implant is the best and only treatment option. Second, the Belmont Report research ethics principle of “respect for persons” implies that research participants deserve recognition beyond research usefulness, and it is disrespectful to inflict costs that essentially deny further treatment. Finally, they posit that participants are research partners and merit reciprocation in the form of continued access to the brain implant that brings relief. The team proposes coordination between sponsors, Institutional Review Boards, and scientists to outline plans for continued device access, duration, and steps for determining whether to provide for individuals. These stipulations depend on costs, patient vulnerability, and the protection of future research, but the authors argue that it is ethically imperative to anticipate and build assurances for trial participants who benefit from brain implants. This group has importantly highlighted the necessity of neuroethics in informing responsible human neuroscience research, especially as brain implant devices blossom into a common medical and ethical reality.

Program for BRAIN Initiative K99/R00 Career Transition Award to Promote Diversity announces funding opportunities and webinar.

NIH is proud to release a pair of funding opportunity announcements (PAR-18-813 and PAR-18-814) for the BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) program. The purpose of this program is to enhance workforce diversity in neuroscience and maintain a strong cohort of new and talented, NIH-supported, independent investigators from diverse backgrounds in BRAIN Initiative research areas. This program is designed to facilitate a timely transition of outstanding postdoctoral researchers with a research and/or clinical doctorate degree from mentored, postdoctoral research positions to independent, tenure-track or equivalent faculty positions. The program will provide independent NIH research support during this transition in order to help awardees to launch competitive, independent research careers.

Applicants must have no more than 5 years of postdoctoral research experience at the time of the initial or the subsequent resubmission application. Eligible individuals for this program will be U.S. citizens or permanent residents who fall in one of the categories defined in the Notice of NIH’s Interest in Diversity. Women have been shown to be underrepresented in doctorate-granting research institutions at senior faculty levels in most biomedical-relevant disciplines by the National Science Foundation. For the purposes of these funding opportunity announcements, we consider women underrepresented in the disciplines pertinent to the BRAIN Initiative (underrepresented in the neurosciences/biomedical sciences). PAR-18-813 is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary study to an existing trial, as part of their research and career development. PAR-18-814 is designed specifically for applicants proposing research that does not involve leading a clinical trial, a clinical trial feasibility study, or ancillary clinical trial. The first due date is August 1, 2018, and standard dates apply after that.

NIH is hosting a pre-application webinar on Tuesday, June 12, 2018, from 1:00-2:00PM (EDT) to assist participants in putting together their application. Please register here!

Two re-issued Requests for Applications (RFAs) support innovative methodologically-integrated approaches and multi-PI, team science exploratory approaches within a broader suite of RFAs on brain circuits and integrated approaches.

The NIH Institutes and Centers participating in the BRAIN Initiative are happy to announce two re-issued RFAs that support research on targeted circuit projects and exploratory team-research circuit programs. These RFAs sit within a larger family of funding mechanisms that collectively seek to address long-standing neuroscience issues through an integrated experimental approach, as outlined in the BRAIN 2025 report.

RFA-NS-18-030 (Targeted Brain Circuits Projects) utilizes an R01 mechanism and supports research projects utilizing methodologically-integrated approaches to understand how circuit activity gives rise to mental experience and behavior. These targeted Brain Circuit Project awards will support individual laboratories or small multi-PD/PI groups. The RFA seeks proposals that reflect the NIH BRAIN Initiative interests in the application of cutting-edge methodologies for understanding brain circuit function at cellular and sub-second levels of resolution in ethologically relevant behaviors. Applications should offer specific, feasible research goals as endpoints within a 5-year term. Individual budget requests are not limited but must reflect project needs. The next receipt date is July 3, 2018. Subsequent upcoming receipt dates are: November 6, 2018; July 3, 2019; November 6, 2019; July 1, 2020; November 10, 2020.

RFA-NS-18-029 (Exploratory Team-Research BRAIN Circuit Programs) utilizes a U01 mechanism and will support multi-PI, interdisciplinary team science programs to establish overarching principles of circuit function. This RFA seeks applications that build teams of experts for exploratory studies that integrate theory and modeling with new and emerging methods for recording and manipulating neural circuits across multiple brain regions. Funded projects are expected to elucidate a specific behavioral or neural system in terms of dynamic circuit activity. Successful exploratory studies may lead to subsequent, competing applications for support of multi-component, team-research projects (RFA-NS-17-018). Individual budget requests are not limited but must reflect project needs. The upcoming receipt dates are July 23, 2018 and June 10, 2019.

These RFAs sit within a family of funding opportunities that emphasize the use of cutting-edge methods for activation and recording to understand the behavior of circuits at cellular and sub-second levels of spatial and temporal resolution; that is, at the level of functional units of circuits. For more information about the goals and scope of work for these funding opportunities, please visit our list of active funding opportunities, or contact the BRAIN Team for Integrative and Quantitative Neuroscience.

New administrative supplements integrate neuroethics perspectives and approaches into existing BRAIN Initiative awards.

The NIH Institutes and Centers participating in the BRAIN Initiative are pleased to announce support for administrative supplements to embed ethicists into BRAIN Initiative supported research. Over the course of the last several years, NIH has issued a variety of funding opportunity announcements to support projects that develop and apply technologies towards understanding neural circuit function. As a result, the BRAIN portfolio of awards represents diverse approaches focused on better understanding the fundamental biology of nervous system function. Importantly, the BRAIN 2025 report highlights that this scientific research must be of the utmost value to the public it intends to serve.

The NIH is therefore encouraging applications to PA-18-591 to incorporate neuroethics perspectives and approaches into existing BRAIN Initiative awards. Supplement applications are encouraged from ongoing BRAIN Initiative projects that can readily incorporate core ethical issues associated with research focused on the human brain and also projects developing emerging technologies and advancements in research and development supported by the BRAIN Initiative. The intent of this administrative supplement is to support efforts that would be both complementary and integrative with the transformative, breakthrough neuroscience discoveries supported through the BRAIN Initiative.

As an administrative supplement, the proposal must be within the scope of the research that is already supported. Research proposed in supplement applications should have clear relevance to the BRAIN Initiative. The proposed work may cover pilot projects, resource development, or personnel costs for embedding neuroethics into the research project. Individual requests can be no more than $100,000 in direct costs and may be for one year only. Requests must be received by June 15, 2018 for funding in fiscal year 2018.