• Neuroinformatics

How can we decipher the hidden structure of a network based on limited observations? This question arises in many scenarios ranging from social to wireless and to neural networks. In such settings, we typically observe the nodes’ behaviors (e.g., the time a node learns about a piece of information, or the time a node gets infected by a disease), and we are interested in inferring the true network over which the diffusion takes place. In this paper, we consider this problem over a neural network where our aim is to reconstruct the connectivity between neurons merely by observing their firing activity. We develop an iterative NEUral INFerence algorithm NEUINF to identify the type of effective neural connections (i.e. excitatory/inhibitory) based on the Perceptron learning rule. We provide theoretical bounds on the average performance of NEUINF as well as numerical analysis to compare the performance of the proposed approach to some previous art.

Experimentally mapping synaptic connections, in terms of the numbers and locations of their synapses and estimating connection probabilities, is still not a tractable task, even for small volumes of tissue. In fact, the six layers of the neocortex contain thousands of unique types of synaptic connections between the many different types of neurons, of which only a handful have been characterized experimentally. Here we present a theoretical framework and a data-driven algorithmic strategy to digitally reconstruct the complete synaptic connectivity between the different types of neurons in a small well-defined volume of tissue the micro scale connectome of a neural microcircuit. By enforcing a set of established principles of synaptic connectivity, and leveraging interdependencies between fundamental properties of neural microcircuits to constrain the reconstructed connectivity, the algorithm yields three parameters per connection type that predict the anatomy of all types of biologically viable synaptic connections. The predictions reproduce a spectrum of experimental data on synaptic connectivity not used by the algorithm. We conclude that an algorithmic approach to the connectome can serve as a tool to accelerate experimental mapping, indicating the minimal dataset required to make useful predictions, identifying the datasets required to improve their accuracy, testing the feasibility of experimental measurements, and making it possible to test hypotheses of synaptic connectivity.

Brain networks, localized or brain-wide, exist only at the cellular level, i.e., between specific pre- and post-synaptic neurons, which are connected through functionally diverse synapses located at specific points of their cell membranes. “Connectomics” is the emerging subfield of neuroanatomy explicitly aimed at elucidating the wiring of brain networks with cellular resolution and a quantified accuracy. Such data are indispensable for realistic modeling of brain circuitry and function. A connectomic analysis, therefore, needs to identify and measure the soma, dendrites, axonal path, and branching patterns together with the synapses and gap junctions of the neurons involved in any given brain circuit or network. However, because of the submicron caliber, 3D complexity, and high packing density of most such structures, as well as the fact that axons frequently extend over long distances to make synapses in remote brain regions, creating connectomic maps is technically challenging and requires multi-scale approaches, Such approaches involve the combination of the most sensitive cell labeling and analysis methods available, as well as the development of new ones able to resolve individual cells and synapses with increasing high-throughput. In this review, we provide an overview of recently introduced high-resolution methods, which researchers wanting to enter the field of connectomics may consider. It includes several molecular labeling tools, some of which specifically label synapses, and covers a number of novel imaging tools such as brain clearing protocols and microscopy approaches. Apart from describing the tools, we also provide an assessment of their qualities. The criteria we use assess the qualities that tools need in order to contribute to deciphering the key levels of circuit organization. We conclude with a brief future outlook for neuroanatomic research, computational methods, and network modeling, where we also point out several outstanding issues like structure–function relations and the complexity of neural models.

Abstract Deciphering the massive volume of complex electronic data that has been compiled by hospital systems over the past decades has the potential to revolutionize modern medicine, as well as present significant challenges. Deep learning is uniquely suited to address these challenges, and recent advances in techniques and hardware have poised the field of medical machine learning for transformational growth. The clinical neurosciences are particularly well positioned to benefit from these advances given the subtle presentation of symptoms typical of neurologic disease. Here we review the various domains in which deep learning algorithms have already provided impetus for change—areas such as medical image analysis for the improved diagnosis of Alzheimer’s disease and the early detection of acute neurologic events; medical image segmentation for quantitative evaluation of neuroanatomy and vasculature; connectome mapping for the diagnosis of Alzheimer’s, autism spectrum disorder, and attention deficit hyperactivity disorder; and mining of microscopic electroencephalogram signals and granular genetic signatures. We additionally note important challenges in the integration of deep learning tools in the clinical setting and discuss the barriers to tackling the challenges that currently exist.

Experimentally mapping synaptic connections, in terms of the numbers and locations of their synapses and estimating connection probabilities is still not a tractable task, even for small volumes of tissue, In fact, the 6 layers of the neocortex contain thousands of unique types of synaptic connections between the many different types of neurons, of which only a handful have been characterized experimentally. Here we present a theoretical framework and a data-driven algorithmic strategy to digitally reconstruct the complete synaptic connectivity between the different types of neuron in a in a small well-defined volume of tissue – the micro scale connectome of a neural microcircuit. By enforcing a set of established principles of synaptic connectivity and leveraging interdependencies between fundamental properties of neural microcircuits to constrain the reconstructed connectivity, the algorithm yields three parameters per connection type that predict the anatomy of all types of biologically viable synaptic connections. The predictions reproduce a spectrum of experimental data on synaptic connectivity not used by the algorithm. We conclude that an algorithmic approach to the connectome can serve as a tool to accelerate experimental mapping, indicating the minimal dataset required to make useful predictions, identifying the datasets required to improve their accuracy, testing the feasibility of experimental measurements, and making it possible to test hypotheses of synaptic connectivity.

Abstract Advanced neuroinformatics tools are required for methods of connectome mapping, analysis and visualization. The inherent multi-modality of connectome datasets poses new challenges for data organization, integration and sharing. We have designed and implemented the Connectome Viewer Toolkit --- a set of free and extensible open-source neuroimaging tools written in Python. The key components of the toolkit are as follows: 1. The Connectome File Format is an XML-based container format to standardize multi-modal data integration and structured metadata annotation. 2. The Connectome File Format Library enables management and sharing of connectome files. 3. The Connectome Viewer is an integrated research and development environment for visualization and analysis of multi-modal connectome data. The Connectome Viewer's plugin architecture supports extensions with network analysis packages and an interactive scripting shell, to enable easy development and community contributions. Integration with tools from the scientific Python community allows the leveraging of numerous existing libraries for powerful connectome data mining, exploration and comparison. We demonstrate the applicability of the Connectome Viewer Toolkit using Diffusion MRI datasets processed by the Connectome Mapper. The Connectome Viewer Toolkit is available from http://www.cmtk.org/.