Stefan Eilemann

Reconstruction and Simulation of Neocortical Microcircuitry

UNLABELLED We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies. PAPERCLIP VIDEO ABSTRACT.

Equalizer: A Scalable Parallel Rendering Framework

Continuing improvements in CPU and GPU performances as well as increasing multi-core processor and cluster-based parallelism demand for flexible and scalable parallel rendering solutions that can exploit multipipe hardware accelerated graphics. In fact, to achieve interactive visualization, scalable rendering systems are essential to cope with the rapid growth of data sets. However, parallel rendering systems are non-trivial to develop and often only application specific implementations have been proposed. The task of developing a scalable parallel rendering framework is even more difficult if it should be generic to support various types of data and visualization applications, and at the same time work efficiently on a cluster with distributed graphics cards. In this paper we introduce a novel system called Equalizer, a toolkit for scalable parallel rendering based on OpenGL which provides an application programming interface (API) to develop scalable graphics applications for a wide range of systems ranging from large distributed visualization clusters and multi-processor multipipe graphics systems to single-processor single-pipe desktop machines. We describe the system architecture, the basic API, discuss its advantages over previous approaches, present example configurations and usage scenarios as well as scalability results.

The neocortical microcircuit collaboration portal: a resource for rat somatosensory cortex.

We have established a multi-constraint, data-driven process to digitally reconstruct, and simulate prototypical neocortical microcircuitry, using sparse experimental data. We applied this process to reconstruct the microcircuitry of the somatosensory cortex in juvenile rat at the cellular and synaptic levels. The resulting reconstruction is broadly consistent with current knowledge about the neocortical microcircuit and provides an array of predictions on its structure and function. To engage the community in exploring, challenging, and refining the reconstruction, we have developed a collaborative, internet-accessible facility-the Neocortical Microcircuit Collaboration portal (NMC portal; https://bbp.epfl.ch/nmc-portal). The NMC portal allows users to access the experimental data used in the reconstruction process, download cellular and synaptic models, and analyze the predicted properties of the microcircuit: six layers, similar to 31,000 neurons, 55 morphological types, 11 electrical types, 207 morpho-electrical types, 1941 unique synaptic connection types between neurons of specific morphological types, predicted properties for the anatomy and physiology of similar to 40 million intrinsic synapses. It also provides data supporting comparison of the anatomy and physiology of the reconstructed microcircuit against results in the literature. The portal aims to catalyzee consensus on the cellular and synaptic organization of neocortical microcircuitry (ion channel, neuron and synapse types and distributions, connectivity, etc.). Community feedback will contribute to refined versions of the reconstruction to be released periodically. We consider that the reconstructions and the simulations they enable represent a major step in the development of in silica neuroscience.

Physically-based in silico light sheet microscopy for visualizing fluorescent brain models

BackgroundWe present a physically-based computational model of the light sheet fluorescence microscope (LSFM). Based on Monte Carlo ray tracing and geometric optics, our method simulates the operational aspects and image formation process of the LSFM. This simulated, in silico LSFM creates synthetic images of digital fluorescent specimens that can resemble those generated by a real LSFM, as opposed to established visualization methods producing visually-plausible images. We also propose an accurate fluorescence rendering model which takes into account the intrinsic characteristics of fluorescent dyes to simulate the light interaction with fluorescent biological specimen.ResultsWe demonstrate first results of our visualization pipeline to a simplified brain tissue model reconstructed from the somatosensory cortex of a young rat. The modeling aspects of the LSFM units are qualitatively analysed, and the results of the fluorescence model were quantitatively validated against the fluorescence brightness equation and characteristic emission spectra of different fluorescent dyes.AMS subject classificationModelling and simulation

Parallel Rendering on Hybrid Multi-GPU Clusters

Achieving efficient scalable parallel rendering for interactive visualization applications on medium-sized graphics clusters remains a challenging problem. Framerates of up to 60hz require a carefully designed and fine-tuned parallel rendering implementation that fits all required operations into the 16ms time budget available for each rendered frame. Furthermore, modern commodity hardware embraces more and more a NUMA architecture, where multiple processor sockets each have their locally attached memory and where auxiliary devices such as GPUs and network interfaces are directly attached to one of the processors. Such so called fat NUMA processing and graphics nodes are increasingly used to build cost-effective hybrid shared/distributed memory visualization clusters. In this paper we present a thorough analysis of the asynchronous parallelization of the rendering stages and we derive and implement important optimizations to achieve highly interactive framerates on such hybrid multi-GPU clusters. We use both a benchmark program and a real-world scientific application used to visualize, navigate and interact with simulations of cortical neuron circuit models.

Cross-segment load balancing in parallel rendering

With faster graphics hardware comes the possibility to realize even more complicated applications that require more detailed data and provide better presentation. The processors keep being challenged with bigger amount of data and higher resolution outputs, requiring more research in the parallel/distributed rendering domain. Optimizing resource usage to improve throughput is one important topic, which we address in this article for multi-display applications, using the Equalizer parallel rendering framework. This paper introduces and analyzes cross-segment load balancing which efficiently assigns all available shared graphics resources to all display output segments with dynamical task partitioning to improve performance in parallel rendering

Fast compositing for cluster-parallel rendering

The image compositing stages in cluster-parallel rendering for gathering and combining partial rendering results into a final display frame are fundamentally limited by node-to-node image throughput. Therefore, efficient image coding, compression and transmission must be considered to minimize that bottleneck. This paper studies the different performance limiting factors such as image representation, region-of-interest detection and fast image compression. Additionally, we show improved compositing performance using lossy YUV subsampling and we propose a novel fast region-of-interest detection algorithm that can improve in particular sort-last parallel rendering.

Practical parallel rendering of detailed neuron simulations

Parallel rendering of large polygonal models with transparency is challenging due to the need for alpha-correct blending and compositing, which is costly for very large models with high depth complexity and spatial overlap. In this paper we compare the performance of raster-based rendering methods on mesh models of neurons using two applications, one of which is specifically tailored to the neuroscience application domain, the other a general purpose visualization tool with domain specific additions. The first implements both sort-first and sort-last and uses a scene graph style traversal to cull objects, and dual depth peeling for order independent transparency, whilst the other uses a simpler brute force data-parallel approach with sort last composition. The advantages and trade offs of these approaches are discussed. We present the optimized algorithms needed to achieve interactive frame rates for a non-trivial, real-world parallel rendering scenario. We show that a generic data visualization application can provide competitive performance when optimizing its rendering pipeline, with some loss of capability over an optimized domain-specific application.

Bio-physically plausible visualization of highly scattering fluorescent neocortical models for in silico experimentation

BackgroundWe present a visualization pipeline capable of accurate rendering of highly scattering fluorescent neocortical neuronal models. The pipeline is mainly developed to serve the computational neurobiology community. It allows the scientists to visualize the results of their virtual experiments that are performed in computer simulations, or in silico. The impact of the presented pipeline opens novel avenues for assisting the neuroscientists to build biologically accurate models of the brain. These models result from computer simulations of physical experiments that use fluorescence imaging to understand the structural and functional aspects of the brain. Due to the limited capabilities of the current visualization workflows to handle fluorescent volumetric datasets, we propose a physically-based optical model that can accurately simulate light interaction with fluorescent-tagged scattering media based on the basic principles of geometric optics and Monte Carlo path tracing. We also develop an automated and efficient framework for generating dense fluorescent tissue blocks from a neocortical column model that is composed of approximately 31000 neurons.ResultsOur pipeline is used to visualize a virtual fluorescent tissue block of 50 μm3 that is reconstructed from the somatosensory cortex of juvenile rat. The fluorescence optical model is qualitatively analyzed and validated against experimental emission spectra of different fluorescent dyes from the Alexa Fluor family.ConclusionWe discussed a scientific visualization pipeline for creating images of synthetic neocortical neuronal models that are tagged virtually with fluorescent labels on a physically-plausible basis. The pipeline is applied to analyze and validate simulation data generated from neuroscientific in silico experiments.

Reconstruction and visualization of large-scale volumetric models of neocortical circuits for physically-plausible in silico optical studies

BackgroundWe present a software workflow capable of building large scale, highly detailed and realistic volumetric models of neocortical circuits from the morphological skeletons of their digitally reconstructed neurons. The limitations of the existing approaches for creating those models are explained, and then, a multi-stage pipeline is discussed to overcome those limitations. Starting from the neuronal morphologies, we create smooth piecewise watertight polygonal models that can be efficiently utilized to synthesize continuous and plausible volumetric models of the neurons with solid voxelization. The somata of the neurons are reconstructed on a physically-plausible basis relying on the physics engine in Blender.ResultsOur pipeline is applied to create 55 exemplar neurons representing the various morphological types that are reconstructed from the somatsensory cortex of a juvenile rat. The pipeline is then used to reconstruct a volumetric slice of a cortical circuit model that contains ∼210,000 neurons. The applicability of our pipeline to create highly realistic volumetric models of neocortical circuits is demonstrated with an in silico imaging experiment that simulates tissue visualization with brightfield microscopy. The results were evaluated with a group of domain experts to address their demands and also to extend the workflow based on their feedback.ConclusionA systematic workflow is presented to create large scale synthetic tissue models of the neocortical circuitry. This workflow is fundamental to enlarge the scale of in silico neuroscientific optical experiments from several tens of cubic micrometers to a few cubic millimeters.AMS Subject ClassificationModelling and Simulation