Diego Sona

Chronic and Acute Intranasal Oxytocin Produce Divergent Social Effects in Mice

Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a ‘healthy’ oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors.

Automatic Visual Tracking and Social Behaviour Analysis with Multiple Mice

Social interactions are made of complex behavioural actions that might be found in all mammalians, including humans and rodents. Recently, mouse models are increasingly being used in preclinical research to understand the biological basis of social-related pathologies or abnormalities. However, reliable and flexible automatic systems able to precisely quantify social behavioural interactions of multiple mice are still missing. Here, we present a system built on two components. A module able to accurately track the position of multiple interacting mice from videos, regardless of their fur colour or light settings, and a module that automatically characterise social and non-social behaviours. The behavioural analysis is obtained by deriving a new set of specialised spatio-temporal features from the tracker output. These features are further employed by a learning-by-example classifier, which predicts for each frame and for each mouse in the cage one of the behaviours learnt from the examples given by the experimenters. The system is validated on an extensive set of experimental trials involving multiple mice in an open arena. In a first evaluation we compare the classifier output with the independent evaluation of two human graders, obtaining comparable results. Then, we show the applicability of our technique to multiple mice settings, using up to four interacting mice. The system is also compared with a solution recently proposed in the literature that, similarly to us, addresses the problem with a learning-by-examples approach. Finally, we further validated our automatic system to differentiate between C57B/6J (a commonly used reference inbred strain) and BTBR T+tf/J (a mouse model for autism spectrum disorders). Overall, these data demonstrate the validity and effectiveness of this new machine learning system in the detection of social and non-social behaviours in multiple (>2) interacting mice, and its versatility to deal with different experimental settings and scenarios.

Contextual processing of structured data by recursive cascade correlation

This paper propose a first approach to deal with contextual information in structured domains by recursive neural networks. The proposed model, i.e., contextual recursive cascade correlation (CRCC), a generalization of the recursive cascade correlation (RCC) model, is able to partially remove the causality assumption by exploiting contextual information stored in frozen units. We formally characterize the properties of CRCC showing that it is able to compute contextual transductions and also some causal supersource transductions that RCC cannot compute. Experimental results on controlled sequences and on a real-world task involving chemical structures confirm the computational limitations of RCC, while assessing the efficiency and efficacy of CRCC in dealing both with pure causal and contextual prediction tasks. Moreover, results obtained for the real-world task show the superiority of the proposed approach versus RCC when exploring a task for which it is not known whether the structural causality assumption holds.

Clustering documents into a web directory for bootstrapping a supervised classification

The management of hierarchically organized data is starting to play a key role in the knowledge management community due to the proliferation of topic hierarchies for text documents. The creation and maintenance of such organized repositories of information requires a great deal of human intervention.The machine learning community has partially addressed this problem by developing hierarchical supervised classifiers that help people categorize new resources within given hierarchies. The worst problem of hierarchical supervised classifiers, however, is their high demand in terms of labeled examples. The number of examples required is related to the number of topics in the taxonomy. Bootstrapping a huge hierarchy with a proper set of labeled examples is therefore a critical issue.This paper proposes some solutions for the bootstrapping problem, that implicitly or explicitly use taxonomy definition: a baseline approach that classifies documents according to the class terms, and two clustering approaches, whose training is constrained by the a priori knowledge encoded in the taxonomy structure, which consists of both terminological and relational aspects. In particular, we propose the Tax-SOM model, that clusters a set of documents in a predefined hierarchy of classes, directly exploiting the knowledge of both their topological organization and their lexical description. Experimental evaluation was performed on a set of taxonomies taken from the GoogleTM and LookSmartTM web directories, obtaining good results.

Bootstrapping for hierarchical document classification

Managing the hierarchical organization of data is starting to play a key role in the knowledge management community due to the great amount of human resources needed to create and maintain these organized repositories of information. Machine learning community has in part addressed this problem by developing hierarchical supervised classifiers that help maintainers to categorize new resources within given hierarchies. Although such learning models succeed in exploiting relational knowledge, they are highly demanding in terms of labeled examples, because the number of categories is related to the dimension of the corresponding hierarchy. Hence, the creation of new directories or the modification of existing ones require strong investments.This paper proposes a semi-automatic process (interleaved with human suggestions) whose aim is to minimize (simplify) the work required to the administrators when creating, modifying, and maintaining directories. Within this process, bootstrapping a taxonomy with examples represents a critical factor for the effective exploitation of any supervised learning model. For this reason we propose a method for the bootstrapping process that makes a first hypothesis of categorization for a set of unlabeled documents, with respect to a given empty hierarchy of concepts. Based on a revision of Self-Organizing Maps, namely TaxSOM, the proposed model performs an unsupervised classification, exploiting the a-priori knowledge encoded in a taxonomy structure both at the terminological and topological level. The ultimate goal of TaxSOM is to create the premise for successfully training a supervised classifier.

Hierarchical Dirichlet model for document classification

The proliferation of text documents on the web as well as within institutions necessitates their convenient organization to enable efficient retrieval of information. Although text corpora are frequently organized into concept hierarchies or taxonomies, the classification of the documents into the hierarchy is expensive in terms human effort. We present a novel and simple hierarchical Dirichlet generative model for text corpora and derive an efficient algorithm for the estimation of model parameters and the unsupervised classification of text documents into a given hierarchy. The class conditional feature means are assumed to be inter-related due to the hierarchical Bayesian structure of the model. We show that the algorithm provides robust estimates of the classification parameters by performing smoothing or regularization. We present experimental evidence on real web data that our algorithm achieves significant gains in accuracy over simpler models.

Discriminant Pattern Recognition Using Transformation-Invariant Neurons

To overcome the problem of invariant pattern recognition, Simard, LeCun, and Denker (1993) proposed a successful nearest-neighbor approach based on tangent distance, attaining state-of-the-art accuracy. Since this approach needs great computational and memory effort, Hastie, Simard, and Sckinger (1995) proposed an algorithm (HSS) based on singular value decomposition (SVD), for the generation of nondiscriminant tangent models. In this article we propose a different approach, based on a gradient-descent constructive algorithm, called TD-Neuron, that develops discriminant models. We present as well comparative results of our constructive algorithm versus HSS and learning vector quantization (LVQ) algorithms. Specifically, we tested the HSS algorithm using both the original version based on the two-sided tangent distance and a new version based on the one-sided tangent distance. Empirical results over the NIST-3 database show that the TD-Neuron is superior to both SVD- and LVQ-based algorithms, since it reaches a better trade-off between error and rejection.

Inferring cognition from fMRI brain images

Over the last few years, functional Magnetic Resonance Imaging (fMRI) has emerged as a new and powerful method to map the cognitive states of a human subject to specific functional areas of the subject brain. Although fMRI has been widely used to determine average activation in different brain regions, the problem of automatically decoding the cognitive state from instantaneous brain activations has received little attention. In this paper, we study this prediction problem on a complex time-series dataset that relates fMRI data (brain images) with the corresponding cognitive states of the subjects while watching three 20 minute movies. This work describes the process we used to reduce the extremely high-dimensional feature space and a comparison of the models used for prediction. To solve the prediction task we explored a standard linear model frequently used by neuroscientists, as well as a k-nearest neighbor model, that now are the state-of-art in this area. Finally, we provide experimental evidence that non-linear models such as multi-layer perceptron and especially recurrent neural networks are significantly better.

Functional connectivity estimation over large networks at cellular resolution based on electrophysiological recordings and structural prior.

Despite many structural and functional aspects of the brain organization have been extensively studied in neuroscience, we are still far from a clear understanding of the intricate structure-function interactions occurring in the multi-layered brain architecture, where billions of different neurons are involved. Although structure and function can individually convey a large amount of information, only a combined study of these two aspects can probably shade light on how brain circuits develop and operate at the cellular scale. Here, we propose a novel approach for refining functional connectivity estimates within neuronal networks using the structural connectivity as prior. This is done at the mesoscale, dealing with thousands of neurons while reaching, at the microscale, an unprecedented cellular resolution. The High-Density Micro Electrode Array (HD-MEA) technology, combined with fluorescence microscopy, offers the unique opportunity to acquire structural and functional data from large neuronal cultures approaching the granularity of the single cell. In this work, an advanced method based on probabilistic directional features and heat propagation is introduced to estimate the structural connectivity from the fluorescence image while functional connectivity graphs are obtained from the cross-correlation analysis of the spiking activity. Structural and functional information are then integrated by reweighting the functional connectivity graph based on the structural prior. Results show that the resulting functional connectivity estimates are more coherent with the network topology, as compared to standard measures purely based on cross-correlations and spatio-temporal filters. We finally use the obtained results to gain some insights on which features of the functional activity are more relevant to characterize actual neuronal interactions.

Kernel-based classification for brain connectivity graphs on the Riemannian manifold of positive definite matrices

An important task in connectomics studies is the classification of connectivity graphs coming from healthy and pathological subjects. In this paper, we propose a mathematical framework based on Riemannian geometry and kernel methods that can be applied to connectivity matrices for the classification task. We tested our approach using different real datasets of functional and structural connectivity, evaluating different metrics to describe the similarity between graphs. The empirical results obtained clearly show the superior performance of our approach compared with baseline methods, demonstrating the advantages of our manifold framework and its potential for other applications.