Cortical spatio-temporal dimensionality reduction for visual grouping

The visual systems of many mammals, including humans, is able to integrate the geometric information of visual stimuli and to perform cognitive tasks already at the first stages of the cortical processing. This is thought to be the result of a combination of mechanisms, which include feature extraction at single cell level and geometric processing by means of cells connectivity. We present a geometric model of such connectivities in the space of detected features associated to spatio-temporal visual stimuli, and show how they can be used to obtain low-level object segmentation. The main idea is that of defining a spectral clustering procedure with anisotropic affinities over datasets consisting of embeddings of the visual stimuli into higher dimensional spaces. Neural plausibility of the proposed arguments will be discussed

Characterising population variability in brain structure through models of whole-brain structural connectivity

Models of whole-brain connectivity are valuable for understanding neurological function. This thesis seeks to develop an optimal framework for extracting models of whole-brain connectivity from clinically acquired diffusion data. We propose new approaches for studying these models. The aim is to develop techniques which can take models of brain connectivity and use them to identify biomarkers or phenotypes of disease. The models of connectivity are extracted using a standard probabilistic tractography algorithm, modified to assess the structural integrity of tracts, through estimates of white matter anisotropy. Connections are traced between 77 regions of interest, automatically extracted by label propagation from multiple brain atlases followed by classifier fusion. The estimates of tissue integrity for each tract are input as indices in 77x77 ”connectivity” matrices, extracted for large populations of clinical data. These are compared in subsequent studies. To date, most whole-brain connectivity studies have characterised population differences using graph theory techniques. However these can be limited in their ability to pinpoint the locations of differences in the underlying neural anatomy. Therefore, this thesis proposes new techniques. These include a spectral clustering approach for comparing population differences in the clustering properties of weighted brain networks. In addition, machine learning approaches are suggested for the first time. These are particularly advantageous as they allow classification of subjects and extraction of features which best represent the differences between groups. One limitation of the proposed approach is that errors propagate from segmentation and registration steps prior to tractography. This can cumulate in the assignment of false positive connections, where the contribution of these factors may vary across populations, causing the appearance of population differences where there are none. The final contribution of this thesis is therefore to develop a common co-ordinate space approach. This combines probabilistic models of voxel-wise diffusion for each subject into a single probabilistic model of diffusion for the population. This allows tractography to be performed only once, ensuring that there is one model of connectivity. Cross-subject differences can then be identified by mapping individual subjects’ anisotropy data to this model. The approach is used to compare populations separated by age and gender

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

One-Dimensional Radial Diffusion of Small Molecules (376 Da) in Bone Tissue

The flow of nutrients through any biological tissue is important to maintain homeostasis. If the transport process is understood, medical research teams can better design medications, prosthetic implants, and tissue scaffolds. Additionally, transport rates help physicians to better understand disease states and wound healing, including minor injuries such as breaks and sprains, which will aid in better diagnoses. We developed a novel method that measures the rate of diffusion in vitro, of fluorescein sodium salt. Samples were incubated at 37°C in a 5 CO2 atmosphere for various periods of time. Samples were sliced and analyzed using Image-Pro Plus and MATLAB to obtain concentration profiles. The diffusivity was estimated from the data using the model equation for one-dimensional transport in a finite medium. We found that radial diffusivity in canine bone in 1-dimension was 1.27 x 10-7±177 1.96 x 10-8 cm2/s. As a point of reference, the diffusivity of fluorescein sodium salt in PBS is 2.7 x 10-6 cm2/s. Given the average distance between a Haversian canal and an osteon radius is 250 um, our data shows it would take approximately 20 minutes for a nutrient of a weight of 376 Da to travel between the two locations. This indicates that the diffusion time of key nutrients, such as vitamin D, with molecular weight of 384 Da, would be about 20 minute

One-Dimensional Radial Diffusion of Small Molecules (376 Da) in Bone Tissue

The flow of nutrients through any biological tissue is important to maintain homeostasis. If the transport process is understood, medical research teams can better design medications, prosthetic implants, and tissue scaffolds. Additionally, transport rates help physicians to better understand disease states and wound healing, including minor injuries such as breaks and sprains, which will aid in better diagnoses. We developed a novel method that measures the rate of diffusion in vitro, of fluorescein sodium salt. Samples were incubated at 37°C in a 5 CO2 atmosphere for various periods of time. Samples were sliced and analyzed using Image-Pro Plus and MATLAB to obtain concentration profiles. The diffusivity was estimated from the data using the model equation for one-dimensional transport in a finite medium. We found that radial diffusivity in canine bone in 1-dimension was 1.27 x 10-7±177 1.96 x 10-8 cm2/s. As a point of reference, the diffusivity of fluorescein sodium salt in PBS is 2.7 x 10-6 cm2/s. Given the average distance between a Haversian canal and an osteon radius is 250 um, our data shows it would take approximately 20 minutes for a nutrient of a weight of 376 Da to travel between the two locations. This indicates that the diffusion time of key nutrients, such as vitamin D, with molecular weight of 384 Da, would be about 20 minute

Local and global gestalt laws: A neurally based spectral approach

A mathematical model of figure-ground articulation is presented, taking into account both local and global gestalt laws. The model is compatible with the functional architecture of the primary visual cortex (V1). Particularly the local gestalt law of good continuity is described by means of suitable connectivity kernels, that are derived from Lie group theory and are neurally implemented in long range connectivity in V1. Different kernels are compatible with the geometric structure of cortical connectivity and they are derived as the fundamental solutions of the Fokker Planck, the Sub-Riemannian Laplacian and the isotropic Laplacian equations. The kernels are used to construct matrices of connectivity among the features present in a visual stimulus. Global gestalt constraints are then introduced in terms of spectral analysis of the connectivity matrix, showing that this processing can be cortically implemented in V1 by mean field neural equations. This analysis performs grouping of local features and individuates perceptual units with the highest saliency. Numerical simulations are performed and results are obtained applying the technique to a number of stimuli.Comment: submitted to Neural Computatio

Multimodal image analysis of the human brain

Gedurende de laatste decennia heeft de snelle ontwikkeling van multi-modale en niet-invasieve hersenbeeldvorming technologieën een revolutie teweeg gebracht in de mogelijkheid om de structuur en functionaliteit van de hersens te bestuderen. Er is grote vooruitgang geboekt in het beoordelen van hersenschade door gebruik te maken van Magnetic Reconance Imaging (MRI), terwijl Elektroencefalografie (EEG) beschouwd wordt als de gouden standaard voor diagnose van neurologische afwijkingen. In deze thesis focussen we op de ontwikkeling van nieuwe technieken voor multi-modale beeldanalyse van het menselijke brein, waaronder MRI segmentatie en EEG bronlokalisatie. Hierdoor voegen we theorie en praktijk samen waarbij we focussen op twee medische applicaties: (1) automatische 3D MRI segmentatie van de volwassen hersens en (2) multi-modale EEG-MRI data analyse van de hersens van een pasgeborene met perinatale hersenschade. We besteden veel aandacht aan de verbetering en ontwikkeling van nieuwe methoden voor accurate en ruisrobuuste beeldsegmentatie, dewelke daarna succesvol gebruikt worden voor de segmentatie van hersens in MRI van zowel volwassen als pasgeborenen. Daarenboven ontwikkelden we een geïntegreerd multi-modaal methode voor de EEG bronlokalisatie in de hersenen van een pasgeborene. Deze lokalisatie wordt gebruikt voor de vergelijkende studie tussen een EEG aanval bij pasgeborenen en acute perinatale hersenletsels zichtbaar in MRI

Statistics of Weighted Brain Networks Reveal Hierarchical Organization and Gaussian Degree Distribution

Whole brain weighted connectivity networks were extracted from high resolution diffusion MRI data of 14 healthy volunteers. A statistically robust technique was proposed for the removal of questionable connections. Unlike most previous studies our methods are completely adapted for networks with arbitrary weights. Conventional statistics of these weighted networks were computed and found to be comparable to existing reports. After a robust fitting procedure using multiple parametric distributions it was found that the weighted node degree of our networks is best described by the normal distribution, in contrast to previous reports which have proposed heavy tailed distributions. We show that post-processing of the connectivity weights, such as thresholding, can influence the weighted degree asymptotics. The clustering coefficients were found to be distributed either as gamma or power-law distribution, depending on the formula used. We proposed a new hierarchical graph clustering approach, which revealed that the brain network is divided into a regular base-2 hierarchical tree. Connections within and across this hierarchy were found to be uncommonly ordered. The combined weight of our results supports a hierarchically ordered view of the brain, whose connections have heavy tails, but whose weighted node degrees are comparable

Hitting the right target : noninvasive localization of the subthalamic nucleus motor part for specific deep brain stimulation

Deep brain stimulation of the subthalamic nucleus (STN) has gained momentum as a therapy for advanced Parkinson’s disease. The stimulation effectively alleviates the patients’ typical motor symptoms on a long term, but can give rise to cognitive and psychiatric adverse effects as well. Based on primate studies, the STN has been divided into three functionally different parts, which were distinguished by their afferent and efferent connections. The largest part is the motor area, followed by an associative and a limbic area. The serious adverse effects on cognition and behavior occurring after deep brain stimulation are assumed to be caused by electrical current spread to the associative and limbic areas of the STN. Therefore, selective stimulation of the motor part of the STN seems crucial, both to obtain the best possible therapeutic effect on the motor symptoms and to minimize the debilitating effects on cognition and behavior. However, current medical imaging techniques do not yet facilitate the required accurate identification of the STN itself, let alone its different functional areas. The final target for DBS is still often adjusted using intraoperative electrophysiology. Therefore, in this thesis we aimed to improve imaging for deep brain stimulation using noninvasive MRI protocols, in order to identify the STN and its motor part. We studied the advantages and drawbacks of already available noninvasive methods to target the STN. This review did not lead to a straightforward conclusion; identification of the STN motor part remained an open question. In follow-up on this question, we investigated the possibility to distinguish the different functional STN parts based on their connectivity information. Three types of information were carefully analyzed in this thesis. First, we looked into the clustering of local diffusion information within the STN region. We visually inspected the complex diffusion profiles, derived from postmortem rat brain data with high angular resolution, and augmented this manual segmentation method using k-means and graph cuts clustering. Because the weighing of different orders of diffusion information in the traditionally used L2 norm on the orientation distribution functions (ODFs) remained an open issue, we developed a specialized distance measure, the so-called Sobolev norm. This norm does not only take into account the amplitudes of the diffusion profiles, but also their extrema. We showed it to perform better than the L2 norm on synthetic phantom data and real brain (thalamus) data. The research done on this topic facilitates better classification by clustering of gray matter structures in the (deep) brain. Secondly, we were the first to analyze the STN’s full structural connectivity, based on probabilistic fiber tracking in diffusion MRI data of healthy volunteers. The results correspond well to topical literature on STN projections. Furthermore, we assessed the structural connectivity per voxel of the STN seed region and discovered a gradient in connectivity to the premotor cortex within the STN. While going from the medial to the lateral part of the STN, the connectivity increases, confirming the expected lateral location of the STN motor part. Finally, the connectivity analysis produced evidence for the existence of a "hyperdirect" pathway between the motor cortex and the STN in humans, which is very useful for future research into stimulation targets. The results of these experiments indicate that it is possible to find the motor part of the STN as specific target for deep brain stimulation using structural connectivity information acquired in a noninvasive way. Third and last, we studied functional connectivity using resting state functional MRI data of healthy volunteers. The resulting significant clusters provided us with the first complete description of the STN’s resting state functional connectivity, which corresponds with the expectations based on available literature. Moreover, we performed a reverse regression procedure with the average time series signals in motor and limbic areas as principal regressors. The results were analyzed for each STN voxel separately and also showed mediolateral gradients in functional connectivity within the STN. The lateral STN part exhibited more motor connectivity, while the medial part seemed to be more functionally connected to limbic brain areas, as described in neuronal tracer studies. These results show that functional connectivity analysis also is a viable noninvasive method to find the motor part of the STN. The work on noninvasive MRI methods for identification of the STN and its functional parts, as presented in this thesis, thus contributes to future specific stimulation of the motor part of the STN for deep brain stimulation in patients with Parkinson’s disease. This may help to maximize the motor effects and minimize severe cognitive and psychiatric side effects