Image processing methods for human brain connectivity analysis from in-vivo diffusion MRI

In this PhD Thesis proposal, the principles of diffusion MRI (dMRI) in its application to the human brain mapping of connectivity are reviewed. The background section covers the fundamentals of dMRI, with special focus on those related to the distortions caused by susceptibility inhomogeneity across tissues. Also, a deep survey of available correction methodologies for this common artifact of dMRI is presented. Two methodological approaches to improved correction are introduced. Finally, the PhD proposal describes its objectives, the research plan, and the necessary resources.

A Three-Dimensional Stereotaxic MRI Brain Atlas of the Cichlid Fish Oreochromis mossambicus

The African cichlid Oreochromis mossambicus (Mozambique tilapia) has been used as a model system in a wide range of behavioural and neurobiological studies. The increasing number of genetic tools available for this species, together with the emerging interest in its use for neurobiological studies, increased the need for an accurate hodological mapping of the tilapia brain to supplement the available histological data. The goal of our study was to elaborate a three-dimensional, high-resolution digital atlas using magnetic resonance imaging, supported by Nissl staining. Resulting images were viewed and analysed in all orientations (transverse, sagittal, and horizontal) and manually labelled to reveal structures in the olfactory bulb, telencephalon, diencephalon, optic tectum, and cerebellum. This high resolution tilapia brain atlas is expected to become a very useful tool for neuroscientists using this fish model and will certainly expand their use in future studies regarding the central nervous system.

Mapping hippocampal and ventricular change in Alzheimer disease

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Fifty-two high-resolution MRI scans were acquired from 12 AD patients (age: 68.4 +/- 1.9 years) and 14 matched controls (age: 71.4 +/- 0.9 years), each scanned twice (2.1 +/- 0.4 years apart). 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials. (C) 2004 Elsevier Inc. All rights reserved.

Mapping dissociations in verb morphology

Substantial behavioural and neuropsychological evidence has been amassed to support the dual-route model of morphological processing, which distinguishes between a rule-based system for regular items (walk–walked, call–called) and an associative system for the irregular items (go–went). Some neural-network models attempt to explain the neuropsychological and brain-mapping dissociations in terms of single-system associative processing. We show that there are problems in the accounts of homogeneous networks in the light of recent brain-mapping evidence of systematic double-dissociation. We also examine the superior capabilities of more internally differentiated connectionist models, which, under certain conditions, display systematic double-dissociations. It appears that the more differentiation models show, the more easily they account for dissociation patterns, yet without implementing symbolic computations.

Combining temporal and spectral information with spatial mapping to identify differences between phonological and semantic networks:a magnetoencephalographic approach

Early, lesion-based models of language processing suggested that semantic and phonological processes are associated with distinct temporal and parietal regions respectively, with frontal areas more indirectly involved. Contemporary spatial brain mapping techniques have not supported such clear-cut segregation, with strong evidence of activation in left temporal areas by both processes and disputed evidence of involvement of frontal areas in both processes. We suggest that combining spatial information with temporal and spectral data may allow a closer scrutiny of the differential involvement of closely overlapping cortical areas in language processing. Using beamforming techniques to analyze magnetoencephalography data, we localized the neuronal substrates underlying primed responses to nouns requiring either phonological or semantic processing, and examined the associated measures of time and frequency in those areas where activation was common to both tasks. Power changes in the beta (14-30 Hz) and gamma (30-50 Hz) frequency bandswere analyzed in pre-selected time windows of 350-550 and 500-700ms In left temporal regions, both tasks elicited power changes in the same time window (350-550 ms), but with different spectral characteristics, low beta (14-20 Hz) for the phonological task and high beta (20-30 Hz) for the semantic task. In frontal areas (BA10), both tasks elicited power changes in the gamma band (30-50 Hz), but in different time windows, 500-700ms for the phonological task and 350-550ms for the semantic task. In the left inferior parietal area (BA40), both tasks elicited changes in the 20-30 Hz beta frequency band but in different time windows, 350-550ms for the phonological task and 500-700ms for the semantic task. Our findings suggest that, where spatial measures may indicate overlapping areas of involvement, additional beamforming techniques can demonstrate differential activation in time and frequency domains. © 2012 McNab, Hillebrand, Swithenby and Rippon.

No gender differences in brain activation during the N-back task:An fMRI study in healthy individuals

Gender differences have been well established in verbal and spatial abilities but few studies have examined if these differences also extend into the domain of working memory in terms of behavioural differences and brain activation. The conclusions that can be drawn from these studies are not clear cut but suggest that even though gender differences might not be apparent from behavioural measures, the underlying neural substrate associated with working memory might be different in men and women. Previous research suggests activation in a network of frontal and parietal regions during working memory tasks. This study aimed to investigate gender differences in patterns of brain activation during a verbal version of the N-back working memory task, which incorporates the effects of increased demands on working memory. A total of 50 healthy subjects, aged 18 to 58 years, that were equally split by gender were recruited matched for age, levels of education and ethnicity. All subjects underwent functional magnetic resonance imaging. We found that men and women performed equally well in terms of accuracy and response times, while using similar brain regions to the same degree. Our observations indicate that verbal working memory is not affected by gender at the behavioural or neural level, and support the findings of a recent meta-analysis by Hyde ([2005]: Sex Roles 53:717-725) that gender differences are generally smaller than intra-gender differences in many cognitive domains. © 2009 Wiley-Liss, Inc.

Are there theory of mind regions in the brain? A review of the neuroimaging literature

There have been many functional imaging studies of the brain basis of theory of mind (ToM) skills, but the findings are heterogeneous and implicate anatomical regions as far apart as orbitofrontal cortex and the inferior parietal lobe. The functional imaging studies are reviewed to determine whether the diverse findings are due to methodological factors. The studies are considered according to the paradigm employed (e.g., stories vs. cartoons and explicit vs. implicit ToM instructions), the mental state(s) investigated, and the language demands of the tasks. Methodological variability does not seem to account for the variation in findings, although this conclusion may partly reflect the relatively small number of studies. Alternatively, several distinct brain regions may be activated during ToM reasoning, forming an integrated functional "network." The imaging findings suggest that there are several "core" regions in the network-including parts of the prefrontal cortex and superior temporal sulcus-while several more "peripheral" regions may contribute to ToM reasoning in a manner contingent on relatively minor aspects of the ToM task. © 2008 Wiley-Liss, Inc.

MEASURING HEAD IMPACT CONTACT PRESSURE IN COLLEGIATE FOOTBALL GAMES TO CORRELATE HEAD KINEMATICS TO BRAIN KINETICS ELUCIDATING BRAIN INJURY DYNAMICS

Does a brain store thoughts and memories the way a computer saves its files? How can a single hit or a fall erase all those memories? Brain Mapping and traumatic brain injuries (TBIs) have become widely researched fields today. Many researchers have been studying TBIs caused to adult American football players however youth athletes have been rarely considered for these studies, contradicting to the fact that American football enrolls highest number of collegiate and high-school children than adults. This research is an attempt to contribute to the field of youth TBIs. Earlier studies have related head kinematics (linear and angular accelerations) to TBIs. However, fewer studies have dealt with brain kinetics (impact pressures and stresses) occurring during head-on collisions. The National Operating Committee on Standards for Athletic Equipment (NOCSAE) drop tests were conducted for linear impact accelerations and the Head Impact Contact Pressures (HICP) calculated from them were applied to a validated FE model. The results showed lateral region of the head as the most vulnerable region to damage from any drop height or impact distance followed by posterior region. The TBI tolerance levels in terms of Von-Mises and Maximum Principal Stresses deduced for lateral impact were 30 MPa and 18 MPa respectively. These levels were corresponding to 2.625 feet drop height. The drop heights beyond this value will result in TBI causing stress concentrations in human head without any detectable structural damage to the brain tissue. This data can be utilized for designing helmets that provide cushioning to brain along with providing a resistance to shear.

Structural brain connectivity and cognitive ability differences: A multivariate distance matrix regression analysis

Neuroimaging research involves analyses of huge amounts of biological data that might or might not be related with cognition. This relationship is usually approached using univariate methods, and, therefore, correction methods are mandatory for reducing false positives. Nevertheless, the probability of false negatives is also increased. Multivariate frameworks have been proposed for helping to alleviate this balance. Here we apply multivariate distance matrix regression for the simultaneous analysis of biological and cognitive data, namely, structural connections among 82 brain regions and several latent factors estimating cognitive performance. We tested whether cognitive differences predict distances among individuals regarding their connectivity pattern. Beginning with 3,321 connections among regions, the 36 edges better predicted by the individuals' cognitive scores were selected. Cognitive scores were related to connectivity distances in both the full (3,321) and reduced (36) connectivity patterns. The selected edges connect regions distributed across the entire brain and the network defined by these edges supports high-order cognitive processes such as (a) (fluid) executive control, (b) (crystallized) recognition, learning, and language processing, and (c) visuospatial processing. This multivariate study suggests that one widespread, but limited number, of regions in the human brain, supports high-level cognitive ability differences. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

Structural Connectivity Of The Default Mode Network And Cognition In Alzheimer׳s Disease.

Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer׳s disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60°) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. Structural connectivity within the DMN is important to the execution of high-complexity tasks, probably due to its relevant role in the integration of the network.

Whole Cortical And Default Mode Network Mean Functional Connectivity As Potential Biomarkers For Mild Alzheimer's Disease.

The search for an Alzheimer's disease (AD) biomarker is one of the most relevant contemporary research topics due to the high prevalence and social costs of the disease. Functional connectivity (FC) of the default mode network (DMN) is a plausible candidate for such a biomarker. We evaluated 22 patients with mild AD and 26 age- and gender-matched healthy controls. All subjects underwent resting functional magnetic resonance imaging (fMRI) in a 3.0 T scanner. To identify the DMN, seed-based FC of the posterior cingulate was calculated. We also measured the sensitivity/specificity of the method, and verified a correlation with cognitive performance. We found a significant difference between patients with mild AD and controls in average z-scores: DMN, whole cortical positive (WCP) and absolute values. DMN individual values showed a sensitivity of 77.3% and specificity of 70%. DMN and WCP values were correlated to global cognition and episodic memory performance. We showed that individual measures of DMN connectivity could be considered a promising method to differentiate AD, even at an early phase, from normal aging. Further studies with larger numbers of participants, as well as validation of normal values, are needed for more definitive conclusions.

The cerebral sulci and gyri

The aim of this study was to describe in detail the microanatomy of the cerebral sulci and gyri, clarifying the nomenclature for microneurosurgical purposes. An extensive review of the literature regarding the historical, evolutionary, embryological, and anatomical aspects pertinent to human cerebral sulci and gyri was conducted, with a special focus on microneuroanatomy issues in the field of neurosurgery. An intimate knowledge of the cerebral sulci and gyri is needed to understand neuroimaging studies, as well as to plan and execute current microneurosurgical procedures. (DOI: 10.3171/2009.11.FOCUS09245)

Frequency Domain Connectivity Identification: An Application of Partial Directed Coherence in fMRI

Functional magnetic resonance imaging (fMRI) has become an important tool in Neuroscience due to its noninvasive and high spatial resolution properties compared to other methods like PET or EEG. Characterization of the neural connectivity has been the aim of several cognitive researches, as the interactions among cortical areas lie at the heart of many brain dysfunctions and mental disorders. Several methods like correlation analysis, structural equation modeling, and dynamic causal models have been proposed to quantify connectivity strength. An important concept related to connectivity modeling is Granger causality, which is one of the most popular definitions for the measure of directional dependence between time series. In this article, we propose the application of the partial directed coherence (PDC) for the connectivity analysis of multisubject fMRI data using multivariate bootstrap. PDC is a frequency domain counterpart of Granger causality and has become a very prominent tool in EEG studies. The achieved frequency decomposition of connectivity is useful in separating interactions from neural modules from those originating in scanner noise, breath, and heart beating. Real fMRI dataset of six subjects executing a language processing protocol was used for the analysis of connectivity. Hum Brain Mapp 30:452-461, 2009. (C) 2007 Wiley-Liss, Inc.

An fMRI Normative Database for Connectivity Networks Using One-Class Support Vector Machines

The application of functional magnetic resonance imaging (fMRI) in neuroscience studies has increased enormously in the last decade. Although primarily used to map brain regions activated by specific stimuli, many studies have shown that fMRI can also be useful in identifying interactions between brain regions (functional and effective connectivity). Despite the widespread use of fMRI as a research tool, clinical applications of brain connectivity as studied by fMRI are not well established. One possible explanation is the lack of normal pattern, and intersubject variability-two variables that are still largely uncharacterized in most patient populations of interest. In the current study, we combine the identification of functional connectivity networks extracted by using Spearman partial correlation with the use of a one-class support vector machine in order construct a normative database. An application of this approach is illustrated using an fMRI dataset of 43 healthy Subjects performing a visual working memory task. In addition, the relationships between the results obtained and behavioral data are explored. Hum Brain Mapp 30:1068-1076, 2009. (C) 2008 Wiley-Liss. Inc.

The Cholinergic System in Mild Cognitive Impairment and Alzheimer`s Disease: An In Vivo MRI and DTI study

Few studies have investigated in vivo changes of the cholinergic basal forebrain in Alzheimer`s disease (AD) and amnestic mild cognitive impairment (MCI), an at risk stage of AD. Even less is known about alterations of cortical projecting fiber tracts associated with basal forebrain atrophy. In this study, we determined regional atrophy within the basal forebrain in 21 patients with AD and 16 subjects with MCI compared to 20 healthy elderly subjects using deformation-based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on fiber tracts derived from high-resolution diffusion tensor imaging (DTI) using tract-based spatial statistics. We localized significant effects relative to a map of cholinergic nuclei in MRI standard space as determined from a postmortem brain. Patients with AD and MCI subjects showed reduced volumes in basal forebrain areas corresponding to anterior medial and lateral, intermediate and posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially more restricted than in AD, but occurred at similar locations. The volume of the right antero-lateral NbM nucleus was correlated with intracortical projecting fiber tract integrity such as the corpus callosum, cingulate, and the superior longitudinal, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest that a multimodal MRI-DTI approach is supportive to determine atrophy of cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD. Hum Brain Mapp 32: 1349-1362, 2011. (C) 2010 Wiley-Liss, Inc.