Denoising Two-Photon Calcium Imaging Data

Two-photon calcium imaging is now an important tool for in vivo imaging of biological systems. By enabling neuronal population imaging with subcellular resolution, this modality offers an approach for gaining a fundamental understanding of brain anatomy and physiology. Proper analysis of calcium imaging data requires denoising, that is separating the signal from complex physiological noise. To analyze two-photon brain imaging data, we present a signal plus colored noise model in which the signal is represented as harmonic regression and the correlated noise is represented as an order autoregressive process. We provide an efficient cyclic descent algorithm to compute approximate maximum likelihood parameter estimates by combing a weighted least-squares procedure with the Burg algorithm. We use Akaike information criterion to guide selection of the harmonic regression and the autoregressive model orders. Our flexible yet parsimonious modeling approach reliably separates stimulus-evoked fluorescence response from background activity and noise, assesses goodness of fit, and estimates confidence intervals and signal-to-noise ratio. This refined separation leads to appreciably enhanced image contrast for individual cells including clear delineation of subcellular details and network activity. The application of our approach to in vivo imaging data recorded in the ferret primary visual cortex demonstrates that our method yields substantially denoised signal estimates. We also provide a general Volterra series framework for deriving this and other signal plus correlated noise models for imaging. This approach to analyzing two-photon calcium imaging data may be readily adapted to other computational biology problems which apply correlated noise models.National Institutes of Health (U.S.) (DP1 OD003646-01)National Institutes of Health (U.S.) (R01EB006385-01)National Institutes of Health (U.S.) (EY07023)National Institutes of Health (U.S.) (EY017098

e3 service: A Critical Reflection and Future Research

Commercial services are of utmost importance for the economy. Due to the widespread use of information and communication technologies, many of these services may be delivered online by means of service value networks. To automate this delivery, however, issues such as composition, integration, and operationalization need to be addressed. In this paper, the authors share their long-term vision on composition of service value networks and describe relationships with fields such as cloud computing and enterprise computing. As a demonstration of the state of the art, capabilities and limitations of e 3 service are described and research challenges are defined

A framework for analysing learning health systems: Are we removing the most impactful barriers?

Objective: Learning Health Systems (LHS) are one of the major computing advances in healthcare. However, no prior research has systematically analysed barriers and facilitators for LHS. This paper presents an investigation into the barriers, benefits and facilitating factors for LHS in order to create a basis for their successful implementation and adoption. Method: First, the ITPOSMO-BBF framework was developed based on the established ITPOSMO (Information, Technology, Processes, Objectives, Staffing, Management and Other factors) framework, extending it for analysing barriers, benefits and facilitators. Second, the new framework was applied to LHS. Results: We found that LHS shares similar barriers and facilitators with Electronic Health Records (EHR); in particular, most facilitator effort in implementing EHR and LHS goes towards barriers categorised as human factors, even though they were seen to carry fewer benefits. Barriers whose resolution would bring significant benefits in safety, quality and health outcomes remain. Discussion: LHS envisage constant generation of new clinical knowledge and practice based on the central role of collections of EHR. Once LHS are constructed and operational, they trigger new data streams into the EHR. So LHS and EHR have a symbiotic relationship. The implementation and adoption of EHRs has proved and continues to prove challenging and there are many lessons for LHS arising from these challenges. Conclusion: Successful adoption of LHS should take account of the framework proposed in this paper, especially with respect to its focus on removing barriers that have the most impact

Neural network model of the primary visual cortex: From functional architecture to lateral connectivity and back

The role of intrinsic cortical dynamics is a debatable issue. A recent optical imaging study (Kenet et al., 2003) found that activity patterns similar to orientation maps (OMs), emerge in the primary visual cortex (V1) even in the absence of sensory input, suggesting an intrinsic mechanism of OM activation. To better understand these results and shed light on the intrinsic V1 processing, we suggest a neural network model in which OMs are encoded by the intrinsic lateral connections. The proposed connectivity pattern depends on the preferred orientation and, unlike previous models, on the degree of orientation selectivity of the interconnected neurons. We prove that the network has a ring attractor composed of an approximated version of the OMs. Consequently, OMs emerge spontaneously when the network is presented with an unstructured noisy input. Simulations show that the model can be applied to experimental data and generate realistic OMs. We study a variation of the model with spatially restricted connections, and show that it gives rise to states composed of several OMs. We hypothesize that these states can represent local properties of the visual scene

On the Origin of the Functional Architecture of the Cortex

The basic structure of receptive fields and functional maps in primary visual cortex is established without exposure to normal sensory experience and before the onset of the critical period. How the brain wires these circuits in the early stages of development remains unknown. Possible explanations include activity-dependent mechanisms driven by spontaneous activity in the retina and thalamus, and molecular guidance orchestrating thalamo-cortical connections on a fine spatial scale. Here I propose an alternative hypothesis: the blueprint for receptive fields, feature maps, and their inter-relationships may reside in the layout of the retinal ganglion cell mosaics along with a simple statistical connectivity scheme dictating the wiring between thalamus and cortex. The model is shown to account for a number of experimental findings, including the relationship between retinotopy, orientation maps, spatial frequency maps and cytochrome oxidase patches. The theory's simplicity, explanatory and predictive power makes it a serious candidate for the origin of the functional architecture of primary visual cortex

Visualization to understand ecosystems

Mapping relationships between stakeholders in an ecosystem to increase understanding and make better-informed strategic decisions.</jats:p