Closed-Loop, Open-Source Electrophysiology

Multiple extracellular microelectrodes (multi-electrode arrays, or MEAs) effectively record rapidly varying neural signals, and can also be used for electrical stimulation. Multi-electrode recording can serve as artificial output (efferents) from a neural system, while complex spatially and temporally targeted stimulation can serve as artificial input (afferents) to the neuronal network. Multi-unit or local field potential (LFP) recordings can not only be used to control real world artifacts, such as prostheses, computers or robots, but can also trigger or alter subsequent stimulation. Real-time feedback stimulation may serve to modulate or normalize aberrant neural activity, to induce plasticity, or to serve as artificial sensory input. Despite promising closed-loop applications, commercial electrophysiology systems do not yet take advantage of the bidirectional capabilities of multi-electrodes, especially for use in freely moving animals. We addressed this lack of tools for closing the loop with NeuroRighter, an open-source system including recording hardware, stimulation hardware, and control software with a graphical user interface. The integrated system is capable of multi-electrode recording and simultaneous patterned microstimulation (triggered by recordings) with minimal stimulation artifact. The potential applications of closed-loop systems as research tools and clinical treatments are broad; we provide one example where epileptic activity recorded by a multi-electrode probe is used to trigger targeted stimulation, via that probe, to freely moving rodents

A Low-Cost Multielectrode System for Data Acquisition Enabling Real-Time Closed-Loop Processing with Rapid Recovery from Stimulation Artifacts

Commercially available data acquisition systems for multielectrode recording from freely moving animals are expensive, often rely on proprietary software, and do not provide detailed, modifiable circuit schematics. When used in conjunction with electrical stimulation, they are prone to prolonged, saturating stimulation artifacts that prevent the recording of short-latency evoked responses. Yet electrical stimulation is integral to many experimental designs, and critical for emerging brain-computer interfacing and neuroprosthetic applications. To address these issues, we developed an easy-to-use, modifiable, and inexpensive system for multielectrode neural recording and stimulation. Setup costs are less than US$10,000 for 64 channels, an order of magnitude lower than comparable commercial systems. Unlike commercial equipment, the system recovers rapidly from stimulation and allows short-latency action potentials (<1 ms post-stimulus) to be detected, facilitating closed-loop applications and exposing neural activity that would otherwise remain hidden. To illustrate this capability, evoked activity from microstimulation of the rodent hippocampus is presented. System noise levels are similar to existing platforms, and extracellular action potentials and local field potentials can be recorded simultaneously. The system is modular, in banks of 16 channels, and flexible in usage: while primarily designed for in vivo use, it can be combined with commercial preamplifiers to record from in vitro multielectrode arrays. The system's open-source control software, NeuroRighter, is implemented in C#, with an easy-to-use graphical interface. As C# functions in a managed code environment, which may impact performance, analysis was conducted to ensure comparable speed to C++ for this application. Hardware schematics, layout files, and software are freely available. Since maintaining wired headstage connections with freely moving animals is difficult, we describe a new method of electrode-headstage coupling using neodymium magnets

Improving Impedance of Implantable Microwire Multi-Electrode Arrays by Ultrasonic Electroplating of Durable Platinum Black

Implantable microelectrode arrays (MEAs) have been a boon for neural stimulation and recording experiments. Commercially available MEAs have high impedances, due to their low surface area and small tip diameters, which are suitable for recording single unit activity. Lowering the electrode impedance, but preserving the small diameter, would provide a number of advantages, including reduced stimulation voltages, reduced stimulation artifacts and improved signal-to-noise ratio. Impedance reductions can be achieved by electroplating the MEAs with platinum (Pt) black, which increases the surface area but has little effect on the physical extent of the electrodes. However, because of the low durability of Pt black plating, this method has not been popular for chronic use. Sonicoplating (i.e. electroplating under ultrasonic agitation) has been shown to improve the durability of Pt black on the base metals of macro-electrodes used for cyclic voltammetry. This method has not previously been characterized for MEAs used in chronic neural implants. We show here that sonicoplating can lower the impedances of microwire multi-electrode arrays (MMEA) by an order of magnitude or more (depending on the time and voltage of electroplating), with better durability compared to pulsed plating or traditional DC methods. We also show the improved stimulation and recording performance that can be achieved in an in vivo implantation study with the sonicoplated low-impedance MMEAs, compared to high-impedance unplated electrodes

Infectious agents and colorectal cancer: a review of Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus.

Based on the high volume of bacteria and viruses that the intestine is exposed to and the importance of infectious agents in some gastrointestinal and anogenital cancers, it is not surprising the many studies have evaluated the association between colorectal cancer and infectious agents. This review highlights investigations of four agents in relation to colorectal cancer. Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus have all been evaluated as possible etiologic agents for colorectal cancer. For each of these agents, a review of possible mechanisms for carcinogenesis and epidemiologic evidence is discussed, and future directions for research are proposed

Quantum spin liquids and the metal-insulator transition in doped semiconductors

We describe a new possible route to the metal-insulator transition in doped semiconductors such as Si:P or Si:B. We explore the possibility that the loss of metallic transport occurs through Mott localization of electrons into a quantum spin liquid state with diffusive charge neutral "spinon" excitations. Such a quantum spin liquid state can appear as an intermediate phase between the metal and the Anderson-Mott insulator. An immediate testable consequence is the presence of metallic thermal conductivity at low temperature in the electrical insulator near the metal-insulator transition. Further we show that though the transition is second order the zero temperature residual electrical conductivity will jump as the transition is approached from the metallic side. However the electrical conductivity will have a non-monotonic temperature dependence that may complicate the extrapolation to zero temperature. Signatures in other experiments and some comparisons with existing data are made.Comment: 4 pages text + 3 pages Appendices, 3 Figures; v2 - References Adde

Ash dieback and other tree pests and pathogens:dispersed risk events and the Social Amplification of Risk Framework

It is widely acknowledged within the risk literature that the mass media play a pivotal role in shaping information about risk events for audiences. Whilst some risk events reflect occurrences specific to particular times and locations, other risk events are more difficult to temporally and spatially situate as they are dispersed across years or months and are not constrained to particular geographic locations. Studies examining the relationship between the social amplification or attenuation of risks and their framing in the media have tended to focus on the former type of event. In this paper we explore the social amplification of risk in relation to ash dieback disease (Hymenoscyphus fraxineus), a tree health issue that attracted intense media attention in the UK in 2012, and characterise what we designate as a dispersed risk event. Drawing on the influential Social Amplification of Risk Framework (SARF), we present a frame analysis of UK national newspaper articles to assess the connection between media coverage of dieback and risk amplification, and the extent to which dieback coverage drew on other tree health issues and objects of media attention. Focusing particularly on the blame frame around dieback, the paper considers the implications of conceptualising dispersed risk events for the SARF and its amplification metaphor. Moreover, given that risk events such as dieback are often associated with policy shifts, we suggest that there is value for risk communicators and policy makers in broadening their focus to incorporate more of the ‘history’ of risk events in order to anticipate likely anchors of public and media attention

How to Culture, Record and Stimulate Neuronal Networks on Micro-electrode Arrays (MEAs)

For the last century, many neuroscientists around the world have dedicated their lives to understanding how neuronal networks work and why they stop working in various diseases. Studies have included neuropathological observation, fluorescent microscopy with genetic labeling, and intracellular recording in both dissociated neurons and slice preparations. This protocol discusses another technology, which involves growing dissociated neuronal cultures on micro-electrode arrays (also called multi-electrode arrays, MEAs)

Comparative evaluation of gene-set analysis methods

<p>Abstract</p> <p>Background</p> <p>Multiple data-analytic methods have been proposed for evaluating gene-expression levels in specific biological pathways, assessing differential expression associated with a binary phenotype. Following Goeman and Bühlmann's recent review, we compared statistical performance of three methods, namely Global Test, ANCOVA Global Test, and SAM-GS, that test "self-contained null hypotheses" Via. subject sampling. The three methods were compared based on a simulation experiment and analyses of three real-world microarray datasets.</p> <p>Results</p> <p>In the simulation experiment, we found that the use of the asymptotic distribution in the two Global Tests leads to a statistical test with an incorrect size. Specifically, p-values calculated by the scaled <it>χ</it>²distribution of Global Test and the asymptotic distribution of ANCOVA Global Test are too liberal, while the asymptotic distribution with a quadratic form of the Global Test results in p-values that are too conservative. The two Global Tests with permutation-based inference, however, gave a correct size. While the three methods showed similar power using permutation inference after a proper standardization of gene expression data, SAM-GS showed slightly higher power than the Global Tests. In the analysis of a real-world microarray dataset, the two Global Tests gave markedly different results, compared to SAM-GS, in identifying pathways whose gene expressions are associated with <it>p53 </it>mutation in cancer cell lines. A proper standardization of gene expression variances is necessary for the two Global Tests in order to produce biologically sensible results. After the standardization, the three methods gave very similar biologically-sensible results, with slightly higher statistical significance given by SAM-GS. The three methods gave similar patterns of results in the analysis of the other two microarray datasets.</p> <p>Conclusion</p> <p>An appropriate standardization makes the performance of all three methods similar, given the use of permutation-based inference. SAM-GS tends to have slightly higher power in the lower <it>α</it>-level region (i.e. gene sets that are of the greatest interest). Global Test and ANCOVA Global Test have the important advantage of being able to analyze continuous and survival phenotypes and to adjust for covariates. A free Microsoft Excel Add-In to perform SAM-GS is available from <url>http://www.ualberta.ca/~yyasui/homepage.html</url>.</p

A prospective study of bowel motility and related factors on breast cancer risk.

BACKGROUND: Estrogen is an established risk factor for breast cancer. Greater bowel motility has been associated with increased estrogen excretion and lower serum estrogen levels, suggesting that it may influence breast cancer risk. However, only one other epidemiologic study thus far, to our knowledge, has examined the relation between bowel motility and breast cancer risk. METHODS: We prospectively examined whether bowel motility, measured by self-reported frequency of bowel movements, and related factors (constipation, laxative use, water consumption, and dietary fiber intake) were associated with incidence of breast cancer among 28,586 postmenopausal women, ages 50 to 76 years, in the Vitamins and Lifestyle study. Cox proportional hazards models were used to estimate multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). From 2000 to 2005, 507 incident invasive breast cancers among the cohort were identified. RESULTS: Women with very frequent (> or =3/d) bowel movements had a 46% decreased risk compared with 1/d women (RR, 0.54; 95% CI, 0.31-0.92), but the test for linear trend was not significant (P(trend) = 0.41). Constipation was nonsignificantly associated with increased risk (RR, 1.30 for > or =1/wk versus <1/y; 95% CI, 0.87-1.95). No statistically significant associations were observed for the other study exposures: 10-year chemical laxative use, 10-year use of fiber laxatives, water consumption, and dietary fiber intake. CONCLUSION: This study adds limited support to the hypothesis that increased bowel motility lowers breast cancer risk

Restoration of Aspen-Dominated Ecosystems in the Lake States

A reserve tree method (RTM) of harvesting was installed in six 70 to 75 year old aspen dominated stands to determine if retaining 10 to 15 dominant aspen per acre would decrease sucker density to facilitate restoration of a conifer component. A reserve shelterwood cut was applied to three additional stands to evaluate performance of white pine planted under 50% crown cover. After the first full growing season following harvest, 96% of the RTM harvested areas were stocked; sucker density averaged 27000 per acre versus 38.2 k per acre on a clearcut control, 41% greater. Basal diameter of dominant suckers averaged 0.45 inch, 28% greater than the control, and mean height was 60 inches, 33% greater. The control site had 3.1k stems per acre of associated commercial species versus 5.8 k on the RTM sites, an 87% difference. Four of the nine stands have been planted; first-year survival ranged from 75% to near 100%. The RTM shows promise for reducing sucker density, increasing their early growth, maintaining species diversity, and providing abundant regeneration of commercial species on a high proportion of the areas harvested. Early results indicate that both the RTM and shelterwood methods can facilitate restoring a component of native conifer species in these ecosystems