The explanatory power of activity flow models of brain function

Tremendous neuroscientific progress has recently been made by mapping brain connectivity, complementing extensive knowledge of task-evoked brain activation patterns. However, despite evidence that they are related, these connectivity and activity lines of research have mostly progressed separately. Here I review the notable productivity and future promise of combining connectivity and task-evoked activity estimates into activity flow models. These data-driven computational models simulate the generation of task-evoked activations (including those linked to behavior), producing empirically-supported explanations of the origin of neurocognitive functions based on the flow of task-evoked activity over empirical brain connections. Critically, by incorporating causal principles and extensive empirical constraints from brain data, this approach can provide more mechanistic accounts of neurocognitive phenomena than purely predictive (as opposed to explanatory) models or models optimized primarily for task performance (e.g., standard artificial neural networks). The variety of activity-flow-based explanations reported so far are covered here along with important methodological and theoretical considerations when discovering new activity-flow-based explanations. Together, these considerations illustrate the promise of activity flow modeling for the future of neuroscience and ultimately for the development of novel clinical treatments (e.g., using brain stimulation) for brain disorders

Gait characteristics and falls in Parkinson's disease: A systematic review and meta-analysis

Introduction: Given the high rate of falls during walking in people with idiopathic Parkinson's disease (PD), identifying at risk individuals and developing targeted interventions to reduce falls incidence is paramount. Numerous studies have investigated gait-related risk factors for falls in PD, however findings are inconsistent across studies, and thus a synthesis of the current evidence is needed to guide clinical practice and the development of interventions to reduce falls risk. The objective of this study was to systematically review the literature regarding the association between walking biomechanics and falls in people with PD, and where possible, perform meta-analyses. Methods: The study was performed in accordance with the PRISMA guidelines. Databases were searched until January 2018 to identify articles that reported on the association between walking biomechanics and prospective or retrospective falls in people with PD. Results: Twenty-six articles were included (15 prospective studies, 11 retrospective studies). Articles reported on spatiotemporal and kinematic characteristics, and muscle activation patterns. Meta-analyses revealed slower walking speed, lower cadence, shorter strides and more mediolateral head and pelvis motion in those at higher risk of future falls. Findings from prospective and retrospective articles were largely consistent. Conclusion: Our findings identify spatiotemporal and kinematic characteristics of gait that are risk factors for falls in PD. Modification of these characteristics may have the potential to mediate falls risk, and future research to investigate this possibility is merited. The influence of body and ground reaction forces, and muscle activation patterns on falls risk in PD is currently under-researched

Proposal for an IMLS Collection Registry and Metadata Repository

The University of Illinois at Urbana-Champaign proposes to design, implement, and research a collection-level registry and item-level metadata repository service that will aggregate information about digital collections and items of digital content created using funds from Institute of Museum and Library Services (IMLS) National Leadership Grants. This work will be a collaboration by the University Library and the Graduate School of Library and Information Science. All extant digital collections initiated or augmented under IMLS aegis from 1998 through September 30, 2005 will be included in the proposed collection registry. Item-level metadata will be harvested from collections making such content available using the Open Archives Initiative Protocol for Metadata Harvesting (OAI PMH). As part of this work, project personnel, in cooperation with IMLS staff and grantees, will define and document appropriate metadata schemas, help create and maintain collection-level metadata records, assist in implementing OAI compliant metadata provider services for dissemination of item-level metadata records, and research potential benefits and issues associated with these activities. The immediate outcomes of this work will be the practical demonstration of technologies that have the potential to enhance the visibility of IMLS funded online exhibits and digital library collections and improve discoverability of items contained in these resources. Experience gained and research conducted during this project will make clearer both the costs and the potential benefits associated with such services. Metadata provider and harvesting service implementations will be appropriately instrumented (e.g., customized anonymous transaction logs, online questionnaires for targeted user groups, performance monitors). At the conclusion of this project we will submit a final report that discusses tasks performed and lessons learned, presents business plans for sustaining registry and repository services, enumerates and summarizes potential benefits of these services, and makes recommendations regarding future implementations of these and related intermediary and end user interoperability services by IMLS projects.unpublishednot peer reviewe

Long-term storage and age‐biased export of fluvial organic carbon: field evidence from West Iceland

Terrestrial organic carbon (OC) plays an important role in the carbon cycle, but questions remain regarding the controls and timescale(s) over which atmospheric CO₂ remains sequestered as particulate OC (POC). Motivated by observations that terrestrial POC is physically stored within soils and other shallow sedimentary deposits, we examined the role that sediment storage plays in the terrestrial OC cycle. Specifically, we tested the hypothesis that sediment storage impacts the age of terrestrial POC. We focused on the Efri Haukadalsá River catchment in Iceland as it lacks ancient sedimentary bedrock that would otherwise bias radiocarbon‐based determinations of POC storage duration by supplying pre‐aged “petrogenic” POC. Our radiocarbon measurements of riverine suspended sediments and deposits implicated millennial‐scale storage times. Comparison between the sample types (suspended and deposits) suggested an age offset between transported (suspended sediments) and stored (deposits) POC at the time of sampling, which is predicted by theory for the sediment age distribution in floodplains. We also observed that POC in suspended sediments is younger than the predicted mean storage duration generated from independent geomorphological data, which suggested an additional role for OC cycling. Consistent with this, we observed interparticle heterogeneity in the composition of POC by imaging our samples at the microscale using X‐ray absorption spectroscopy. Specifically, we found that particles within individual samples differed in their sulfur oxidation state, which is indicative of multiple origins and/or diagenetic histories. Altogether, our results support recent coupled sediment storage and OC cycling models and indicate that the physical drivers of sediment storage are important factors controlling the cadence of carbon cycling

When planning results in loss of control: intention-based reflexivity and working-memory

In this review, the authors discuss the seemingly paradoxical loss of control associated with states of high readiness to execute a plan, termed “intention-based reflexivity.” The review suggests that the neuro-cognitive systems involved in the preparation of novel plans are different than those involved in preparation of practiced plans (i.e., those that have been executed beforehand). When the plans are practiced, intention-based reflexivity depends on the prior availability of response codes in long-term memory (LTM). When the plans are novel, reflexivity is observed when the plan is pending and the goal has not yet been achieved. Intention-based reflexivity also depends on the availability of working-memory (WM) limited resources and the motivation to prepare. Reflexivity is probably related to the fact that, unlike reactive control (once a plan is prepared), proactive control tends to be relatively rigid

Luminescence complementation technology for the identification of MYC:TRRAP inhibitors

Mechanism-based targeted therapies have exhibited remarkable success in treating otherwise untreatable or unresectable cancers. Novel targeted therapies that correct dysregulated transcriptional programs in cancer are an unmet medical need. The transcription factor MYC is the most frequently amplified gene in human cancer and is overexpressed because of mutations in an array of oncogenic signaling pathways. The fact that many cancer cells cannot survive without MYC - a phenomenon termed MYC addiction - provides a compelling case for the development of MYC-specific targeted therapies. We propose a new strategy to inhibit MYC function by disrupting its essential interaction with TRRAP using small molecules. To achieve our goal, we developed a platform using luminescence complementation for identifying small molecules as inhibitors of the MYC:TRRAP interaction. Here we present validation of this assay by measuring the disruption of TRRAP binding caused by substitutions to the invariant and essential MYC homology 2 region of MYC