Max Hinne

Structurally-informed Bayesian functional connectivity analysis

Functional connectivity refers to covarying activity between spatially segregated brain regions and can be studied by measuring correlation between functional magnetic resonance imaging (fMRI) time series. These correlations can be caused either by direct communication via active axonal pathways or indirectly via the interaction with other regions. It is not possible to discriminate between these two kinds of functional interaction simply by considering the covariance matrix. However, the non-diagonal elements of its inverse, the precision matrix, can be naturally related to direct communication between brain areas and interpreted in terms of partial correlations. In this paper, we propose a Bayesian model for functional connectivity analysis which allows estimation of a posterior density over precision matrices, and, consequently, allows one to quantify the uncertainty about estimated partial correlations. In order to make model estimation feasible it is assumed that the sparseness structure of the precision matrices is given by an estimate of structural connectivity obtained using diffusion imaging data. The model was tested on simulated data as well as resting-state fMRI data and compared with a graphical lasso analysis. The presented approach provides a theoretically solid foundation for quantifying functional connectivity in the presence of uncertainty.

Bayesian inference of structural brain networks

Structural brain networks are used to model white-matter connectivity between spatially segregated brain regions. The presence, location and orientation of these white matter tracts can be derived using diffusion-weighted magnetic resonance imaging in combination with probabilistic tractography. Unfortunately, as of yet, none of the existing approaches provide an undisputed way of inferring brain networks from the streamline distributions which tractography produces. State-of-the-art methods rely on an arbitrary threshold or, alternatively, yield weighted results that are difficult to interpret. In this paper, we provide a generative model that explicitly describes how structural brain networks lead to observed streamline distributions. This allows us to draw principled conclusions about brain networks, which we validate using simultaneously acquired resting-state functional MRI data. Inference may be further informed by means of a prior which combines connectivity estimates from multiple subjects. Based on this prior, we obtain networks that significantly improve on the conventional approach.

Probabilistic clustering of the human connectome identifies communities and hubs.

A fundamental assumption in neuroscience is that brain function is constrained by its structural properties. This motivates the idea that the brain can be parcellated into functionally coherent regions based on anatomical connectivity patterns that capture how different areas are interconnected. Several studies have successfully implemented this idea in humans using diffusion weighted MRI, allowing parcellation to be conducted in vivo. Two distinct approaches to connectivity-based parcellation can be identified. The first uses the connection profiles of brain regions as a feature vector, and groups brain regions with similar connection profiles together. Alternatively, one may adopt a network perspective that aims to identify clusters of brain regions that show dense within-cluster and sparse between-cluster connectivity. In this paper, we introduce a probabilistic model for connectivity-based parcellation that unifies both approaches. Using the model we are able to obtain a parcellation of the human brain whose clusters may adhere to either interpretation. We find that parts of the connectome consistently cluster as densely connected components, while other parts consistently result in clusters with similar connections. Interestingly, the densely connected components consist predominantly of major cortical areas, while the clusters with similar connection profiles consist of regions that have previously been identified as the ‘rich club’; regions known for their integrative role in connectivity. Furthermore, the probabilistic model allows quantification of the uncertainty in cluster assignments. We show that, while most clusters are clearly delineated, some regions are more difficult to assign. These results indicate that care should be taken when interpreting connectivity-based parcellations obtained using alternative deterministic procedures.

Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates.

Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain, which may be studied using functional magnetic resonance imaging (fMRI). This coupled activity is conveniently expressed using covariance, but this measure fails to distinguish between direct and indirect effects. A popular alternative that addresses this issue is partial correlation, which regresses out the signal of potentially confounding variables, resulting in a measure that reveals only direct connections. Importantly, provided the data are normally distributed, if two variables are conditionally independent given all other variables, their respective partial correlation is zero. In this paper, we propose a probabilistic generative model that allows us to estimate functional connectivity in terms of both partial correlations and a graph representing conditional independencies. Simulation results show that this methodology is able to outperform the graphical LASSO, which is the de facto standard for estimating partial correlations. Furthermore, we apply the model to estimate functional connectivity for twenty subjects using resting-state fMRI data. Results show that our model provides a richer representation of functional connectivity as compared to considering partial correlations alone. Finally, we demonstrate how our approach can be extended in several ways, for instance to achieve data fusion by informing the conditional independence graph with data from probabilistic tractography. As our Bayesian formulation of functional connectivity provides access to the posterior distribution instead of only to point estimates, we are able to quantify the uncertainty associated with our results. This reveals that while we are able to infer a clear backbone of connectivity in our empirical results, the data are not accurately described by simply looking at the mode of the distribution over connectivity. The implication of this is that deterministic alternatives may misjudge connectivity results by drawing conclusions from noisy and limited data.

Annotation of URLs: more than the sum of parts

Recently a number of studies have demonstrated that search engine logfiles are an important resource to determine the relevance relation between URLs and query terms. We hypothesized that the queries associated with a URL could also be presented as useful URL metadata in a search engine result list, e.g. for helping to determine the semantic category of a URL. We evaluated this hypothesis by a classification experiment based on the DMOZ dataset. Our method can also annotate URLs that have no associated queries.

Using query logs and click data to create improved document descriptions

Logfiles of search engines are a promising resource for data mining, since they provide raw data associated to users and web documents. In this paper we focus on the latter aspect and explore how the information in logfiles could be used to improve document descriptions. A pilot experiment demonstrated that document descriptors extracted from the queries that are associated with documents by clicks provide useful semantic information about documents in addition to document descriptors extracted from the full text of the web pages.

The missing link: Predicting connectomes from noisy and partially observed tract tracing data

Our understanding of the wiring map of the brain, known as the connectome, has increased greatly in the last decade, mostly due to technological advancements in neuroimaging techniques and improvements in computational tools to interpret the vast amount of available data. Despite this, with the exception of the C. elegans roundworm, no definitive connectome has been established for any species. In order to obtain this, tracer studies are particularly appealing, as these have proven highly reliable. The downside of tract tracing is that it is costly to perform, and can only be applied ex vivo. In this paper, we suggest that instead of probing all possible connections, hitherto unknown connections may be predicted from the data that is already available. Our approach uses a ‘latent space model’ that embeds the connectivity in an abstract physical space. Regions that are close in the latent space have a high chance of being connected, while regions far apart are most likely disconnected in the connectome. After learning the latent embedding from the connections that we did observe, the latent space allows us to predict connections that have not been probed previously. We apply the methodology to two connectivity data sets of the macaque, where we demonstrate that the latent space model is successful in predicting unobserved connectivity, outperforming two baselines and an alternative model in nearly all cases. Furthermore, we show how the latent spatial embedding may be used to integrate multimodal observations (i.e. anterograde and retrograde tracers) for the mouse neocortex. Finally, our probabilistic approach enables us to make explicit which connections are easy to predict and which prove difficult, allowing for informed follow-up studies.

Cutting graphs using competing ant colonies and an edge clustering heuristic

We investigate the usage of Ant Colony Optimization to detect balanced graph cuts. In order to do so we develop an algorithm based on competing ant colonies. We use a heuristic from social network analysis called the edge clustering coefficient, which greatly helps our colonies in local search. The algorithm is able to detect cuts that correspond very well to known cuts on small real-world networks. Also, with the correct parameter balance, our algorithm often outperforms the traditional Kernighan-Lin algorithm for graph partitioning with equal running time complexity. On larger networks, our algorithm is able to obtain low cut sizes, but at the cost of a balanced partition.

Semi-Analytic Nonparametric Bayesian Inference for Spike-Spike Neuronal Connectivity

Estimating causal connectivity between spiking neurons from measured spike sequences is one of the main challenges of systems neuroscience. In this paper we introduce two nonparametric Bayesian methods for spike-membrane and spikespike causal connectivity based on Gaussian process regression. For spike-spike connectivity, we derive a new semi-analytic variational approximation of the response functions of a non-linear dynamical model of interconnected neurons. This semi-analytic method exploits the tractability of GP regression when the membrane potential is observed. The resulting posterior is then marginalized analytically in order to obtain the posterior of the response functions given the spike sequences alone. We validate our methods on both simulated data and real neuronal recordings.

Correction: The missing link: Predicting connectomes from noisy and partially observed tract tracing data

[This corrects the article DOI: 10.1371/journal.pcbi.1005374.].