Implications of single-neuron gain scaling for information transmission in networks

Summary: 

Many neural systems are equipped with mechanisms to efficiently encode sensory information. To represent natural stimuli with time-varying statistical properties, neural systems should adjust their gain to the inputs' statistical distribution. Such matching of dynamic range to input statistics has been shown to maximize the information transmitted by the output spike trains (Brenner et al., 2000, Fairhall et al., 2001). Gain scaling has not only been observed as a system response property, but also in single neurons in developing somatosensory cortex stimulated with currents of different amplitude (Mease et al., 2010). While gain scaling holds for cortical neurons at the end of the first post-natal week, at birth these neurons lack this property. The observed improvement in gain scaling coincides with the disappearance of spontaneous waves of activity in cortex (Conheim et al., 2010).

We studied how single-neuron gain scaling affects the dynamics of signal transmission in networks, using the developing cortex as a model. In a one-layer feedforward network, we showed that the absence of gain control made the network relatively insensitive to uncorrelated local input fluctuations. As a result, these neurons selectively and synchronously responded to large slowly-varying correlated input--the slow build up of synaptic noise generated in pacemaker circuits which most likely triggers waves. Neurons in gain scaling networks were more sensitive to the small-scale input fluctuations, and responded asynchronously to the slow envelope. Thus, gain scaling both increases information in individual neurons about private inputs and allows the population average to encode the slow fluctuations in the input. Paradoxically, the synchronous firing that corresponds to wave propagation is associated with low information transfer. We therefore suggest that the emergence of gain scaling may help the system to increase information transmission on multiple timescales as sensory stimuli become important later in development. 

Methods:

Networks with one and two layers consisting of hundreds of model neurons were constructed. The ability of single neurons to gain scale was controlled by changing the ratio of sodium to potassium conductances in Hodgkin-Huxley neurons (Mainen et al., 1995). The response of single layer networks was studied with ramp-like stimuli with slopes that varied over several hundreds of milliseconds. Fast fluctuations were superimposed on this slowly-varying mean. Then the response to these networks was tested with continuous stimuli. Gain scaling networks captured the slow fluctuations in the inputs, while non-scaling networks simply thresholded the input. Quantifying information transmission confirmed that gain scaling neurons transmit more information about the stimulus. With the two-layer networks we simulated a cortical network where waves could spontaneously emerge, propagate and degrade, based on the gain scaling properties of the neurons in the network

Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis

Objective. To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). Methods. ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age 18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as 40% improvement from baseline (20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and 40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. Results. In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. Conclusion. Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases

Interview with Thelma Shinliver

An interview with Thelma Shinliver regarding her experiences in a one-room school house.https://scholars.fhsu.edu/ors/1197/thumbnail.jp

Asset, liability, possibility: Metaphors of human difference and the business case for diversity

Purpose – This analysis draws on interviews with 19 self-identified US diversity consultants and 94 diversity statements posted on corporate websites. The findings challenge existing literature that characterizes the business case for diversity as monolithic and wholly problematic for the way it constructs understandings of human difference. The authors accomplish this using metaphor analysis to demonstrate how business case arguments incorporate three metaphorical systems for thinking and speaking about human differences – as asset, as liability and as possibility. Given this diversity of metaphors, the business case does not construct human difference in a monolithic way, but in a variety of ways that both challenge and sustain problematic treatments of difference. The authors argue scholars and practitioners should attend to these nuanced difference within the discourse of the business case, and more carefully consider how these metaphorical systems both enable and constrain the design and execution of diversity work in organizations. The paper aims to discuss these issues. Design/methodology/approach – The analysis draws on two data sets: initial interviews with 19 self-identified US diversity consultants analyzed using metaphor analysis. To triangulate findings, the metaphorical framework was applied to 94 diversity statements posted on corporate websites. Findings – Business case arguments operate according to three root metaphors of human difference: human difference as asset, human difference as liability and human difference as possibility. This challenges existing literature that treats the business case as a monolithic discourse. Research limitations/implications – This analysis offers the three metaphorical system and highlights the “constrained capacity” of each. This framework offers an analytical and practical tool for scholars and practitioners, enabling them to more thoroughly understand and respond to their unique organizational and socio-historical context. It also provides a way to analyze how concepts of difference are mobilized across social and historical contexts. Practical implications – The findings offer the “constrained capacity” that is, the strategic limitations and possibilities for practitioners who use the business case in their diversity work. This enables more skilled and ethically informed diversity initiatives. Social implications – The findings offer insight into the subtle ways that hierarchies of human difference embedded in US history are subtly reinforced and made present through language. This enables social justice workers to better challenge problematic constructions of human difference and create new understandings when needed. Originality/value – This piece makes two significant original contributions to existing literature. It offers more nuance to both critical and uncritical analyses of the business case by showing the diversity of business case assumptions about human difference as demonstrated in three different metaphorical systems and highlighting the constrained capacity of three different metaphorical systems. It offers unique analysis grounded in contemporary discourses, but correlated to historical systems of thought. This enables empirical identification of how certain types of thinking about human difference move across socio-historical contexts

Durability of Therapeutic Response to Milnacipran Treatment for Fibromyalgia. Results of a Randomized, Double-Blind, Monotherapy 6-Month Extension Study

To evaluate the durability of improvement and long-term efficacy of milnacipran treatment in fibromyalgia, to assess efficacy in patients re-randomized from placebo to milnacipran, and to collect additional information on the tolerability and efficacy of long-term treatment with milnacipran.A total of 449 patients who successfully completed a 6-month lead-in study enrolled in this 6-month extension study (87.7% of eligible subjects). Patients initially receiving milnacipran 200 mg/day during the lead-in study were maintained at 200 mg/day (n = 209); patients initially assigned to placebo or milnacipran 100 mg/day were re-randomized (1:4) to either 100 mg/day (n = 48) or 200 mg/day (n = 192) of milnacipran for an additional 6 months of treatment. Efficacy assessments included visual analog scale pain ratings, Fibromyalgia Impact Questionnaire (FIQ) total score, and Patient Global Impression of Change (PGIC).Patients continuing on milnacipran demonstrated a sustained reduction in pain over the full 12-month period. Additional beneficial effects were also maintained, as indicated by the PGIC and FIQ. Patients initially assigned to either placebo or milnacipran 100 mg/day in the lead-in study and subsequently re-randomized to milnacipran 200 mg/day in the extension study experienced further improvements in their mean pain scores, FIQ total scores, and PGIC ratings at 1 year. Milnacipran treatment was generally well tolerated. The most commonly reported newly emergent adverse event was nausea.In addition to confirming that milnacipran safely and effectively improves the multiple symptoms of fibromyalgia, these data indicate that milnacipran provides 1-year durable efficacy in this patient population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78636/1/j.1526-4637.2009.00755.x.pd

Intrinsic Neuronal Properties Switch the Mode of Information Transmission in Networks

Diverse ion channels and their dynamics endow single neurons with complex biophysical properties. These properties determine the heterogeneity of cell types that make up the brain, as constituents of neural circuits tuned to perform highly specific computations. How do biophysical properties of single neurons impact network function? We study a set of biophysical properties that emerge in cortical neurons during the first week of development, eventually allowing these neurons to adaptively scale the gain of their response to the amplitude of the fluctuations they encounter. During the same time period, these same neurons participate in large-scale waves of spontaneously generated electrical activity. We investigate the potential role of experimentally observed changes in intrinsic neuronal properties in determining the ability of cortical networks to propagate waves of activity. We show that such changes can strongly affect the ability of multi-layered feedforward networks to represent and transmit information on multiple timescales. With properties modeled on those observed at early stages of development, neurons are relatively insensitive to rapid fluctuations and tend to fire synchronously in response to wave-like events of large amplitude. Following developmental changes in voltage-dependent conductances, these same neurons become efficient encoders of fast input fluctuations over few layers, but lose the ability to transmit slower, population-wide input variations across many layers. Depending on the neurons' intrinsic properties, noise plays different roles in modulating neuronal input-output curves, which can dramatically impact network transmission. The developmental change in intrinsic properties supports a transformation of a networks function from the propagation of network-wide information to one in which computations are scaled to local activity. This work underscores the significance of simple changes in conductance parameters in governing how neurons represent and propagate information, and suggests a role for background synaptic noise in switching the mode of information transmission

Rings of real functions in pointfree topology

AbstractThis paper deals with the algebra F(L) of real functions on a frame L and its subclasses LSC(L) and USC(L) of, respectively, lower and upper semicontinuous real functions. It is well known that F(L) is a lattice-ordered ring; this paper presents explicit formulas for its algebraic operations which allow to conclude about their behaviour in LSC(L) and USC(L).As applications, idempotent functions are characterized and previous pointfree results about strict insertion of functions are significantly improved: general pointfree formulations that correspond exactly to the classical strict insertion results of Dowker and Michael regarding, respectively, normal countably paracompact spaces and perfectly normal spaces are derived.The paper ends with a brief discussion concerning the frames in which every arbitrary real function on the α-dissolution of the frame is continuous

Designing a solution to enable agency-academic scientific collaboration for disasters

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ecology and Society 22 (2017): 18, doi:10.5751/ES-09246-220218.As large-scale environmental disasters become increasingly frequent and more severe globally, people and organizations that prepare for and respond to these crises need efficient and effective ways to integrate sound science into their decision making. Experience has shown that integrating nongovernmental scientific expertise into disaster decision making can improve the quality of the response, and is most effective if the integration occurs before, during, and after a crisis, not just during a crisis. However, collaboration between academic, government, and industry scientists, decision makers, and responders is frequently difficult because of cultural differences, misaligned incentives, time pressures, and legal constraints. Our study addressed this challenge by using the Deep Change Method, a design methodology developed by Stanford ChangeLabs, which combines human-centered design, systems analysis, and behavioral psychology. We investigated underlying needs and motivations of government agency staff and academic scientists, mapped the root causes underlying the relationship failures between these two communities based on their experiences, and identified leverage points for shifting deeply rooted perceptions that impede collaboration. We found that building trust and creating mutual value between multiple stakeholders before crises occur is likely to increase the effectiveness of problem solving. We propose a solution, the Science Action Network, which is designed to address barriers to scientific collaboration by providing new mechanisms to build and improve trust and communication between government administrators and scientists, industry representatives, and academic scientists. The Science Action Network has the potential to ensure cross-disaster preparedness and science-based decision making through novel partnerships and scientific coordination.The authors thank the David and Lucile Packard Foundation for a grant to undertake this project and enable participation of a wide range of participants and interviewees. We thank the Center for Ocean Solutions and ChangeLabs for their oversight and support