Mindboggling morphometry of human brains

Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains ever conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, while more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle’s algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available

Quantitative volumetric study of brain in chronic striatolenticular stroke

Perforating branches of the middle cerebral artery, namely the striato-lenticular arteries provide the majority of blood supply for the striatum and posterior limb of the internal capsules. Occlusions of these arteries cause a small stroke but have a devastating effect on patients’ functions. Previous studies showed that the anterior two thirds of the internal capsule is occupied by the prefrontal tracts with the posterior one third by connection to/from sensorimotor, temporal and posterior parietal cortices. In this study, we aimed to examine the long-term effect of infarction in the striato-capsular region on cerebral cortex thickness and also its association with stroke volume and different functional tests. We hypothesized that because of extensive connections of striatum and internal capsule with the cerebral cortex, infarction of this area results in an extensive cortical thickness degeneration which could in turn cause low fictional measurement scores. High resolution T1 weighted MRI was obtained from 21 patients with ischemic stroke in the striatum/posterior limb of the internal capsule region. Subjects were carefully selected from a pool of 140 stroke cases recruited for the Northstar Stroke Project. 63 healthy volunteers (30 male), matched for age and gender were also chosen to form the control group from the OASIS database. Patients and normal subjects were right handed except for 3 patients who have the stroke in the left side of the brain. Patients were defined as left-sided stroke and right-sided stroke depending on the side of the stroke in brain. MRI scans were done 6 months to 2 years after the stroke. To measure cortical thickness, we used Freesurfer software. Vertexwise group comparison was carried out using General Linear Models (GLM). With the Significance level set at 0.05. Population maps of stroke lesions showed that the majority of strokes were located in the striatum and posterior internal capsule. Cortical thickness reduction was greater in the ipsilateral hemisphere. Vertex-wise group comparison between leftsided stroke patients and controls group showed significant reduction in the cortical II thickness in the dorsal and medial prefrontal, premotor, posterior parietal, precuneus, and temporal cortex which survived after correction for multiple comparison using false discovery rate at Freesurfer. Similar comparison for rightsided stroke showed a similar pattern of cortical thinning, however the extent of cortical thinning was much less than in that of the left-sided stroke patients but the ROI analysis showed the main effect of side was significant (f (1, 19) =6.909, p=0.017), which showed that the left hemisphere stroke side group had a thicker cortex (mean=2.463, sd= 0.020) on average compare to the right hemisphere stroke side (mean=2.372, sd= 0.028). Primary motor cortex was surprisingly spared in both stroke groups. In addition, volume of the corpus callosum increased significantly in the stroke group. The differences between motor cortex (M1) thickness in left-hemispheric stroke patients versus controls (t=1.24, n=14, p>0.05) and right-hemispheric stroke patients versus controls (t=-0.511, n=7, p>0.05) were not significant. There was a negative correlation between the volume of the stroke lesions and the affected M1 thickness. There was no correlation between the stroke volume and functional tests in patients and also no correlation between the motor cortex thickness and functional tests in patients. Regarding normal subjects, comparison between two sides of the brain showed that the both hemispheres are symmetrical. In addition, correlation between age and cortical thickness showed a negative significant correlation (1-tailed, p<0.0007, manual correction for multiple comparisons) in M1, superior frontal, lingual cortex at both side of the brain and also negative significant correlation in superior temporal cortex and isthmus cingulated cortex on the left side of brain and supramarginal cortex on the right side of brain but there was no significant difference in cortical thickness between males and females. The finding from this study suggests that the size of the lesion can be a predictor of further M1 cortex reduction. The correlation of M1 thickness with stroke volume showed that secondary cortical degeneration may be mainly depends on the size of neuronal loss in strital-capsular stroke. From normal subject study it can be concluded that generally cortical thickness will decrease with ageing but gender does not have an effect on the cortical thickness. III Furthermore, the lack of behavioural correlation with M1 thickness and stroke volume and also the non significant M1 cortex reduction versus control group may suggest that the long-term functional disability after capsular-striatal stroke may not be entirely dependent on primary motor cortex and secondary motor cortex and primary somatosensory cortex could have an important role as well. These results may help to understand why relatively small subcortical infarcts often cause severe disability that is relatively resistant to recovery in the long term

Beyond the arcuate fasciculus : consensus and controversy in the connectional anatomy of language

The growing consensus that language is distributed into large-scale cortical and subcortical networks has brought with it an increasing focus on the connectional anatomy of language, or how particular fibre pathways connect regions within the language network. Understanding connectivity of the language network could provide critical insights into function, but recent investigations using a variety of methodologies in both humans and non-human primates have provided conflicting accounts of pathways central to language. Some of the pathways classically considered language pathways, such as the arcuate fasciculus, are now argued to be domain-general rather than specialized, which represents a radical shift in perspective. Other pathways described in the non-human primate remain to be verified in humans. In this review, we examine the consensus and controversy in the study of fibre pathway connectivity for language. We focus on seven fibre pathways—the superior longitudinal fasciculus and arcuate fasciculus, the uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, inferior longitudinal fasciculus and inferior fronto-occipital fasciculus—that have been proposed to support language in the human. We examine the methods in humans and non-human primate used to investigate the connectivity of these pathways, the historical context leading to the most current understanding of their anatomy, and the functional and clinical correlates of each pathway with reference to language. We conclude with a challenge for researchers and clinicians to establish a coherent framework within which fibre pathway connectivity can be systematically incorporated to the study of language

Connectomics across development:towards mapping brain structure from birth to childhood

The brain is probably the most complex system of the human body, composed of numerous neural units interconnected at dierent scales. This highly structured architecture provides the ability to communicate, synthesize information and perform the analytical tasks of human beings. Its development starts during the transition between the embryonic and fetal periods, from a simple tubular to a highly complex folded structure. It is globally organized as early as birth. This developing process is highly vulnerable to antenatal adverse conditions. Indeed, extreme prematurity and intra uterine growth restriction are major risk factors for long-term morbidities, including developmental ailments such as cerebral palsy, mental retardation and a wide spectrum of learning disabilities and behavior disorders. In this context, the characterization of the brainâs normative wiring pattern is crucial for our understanding of its architecture and workings, as the origin of many neurological and neurobehavioral disorders is found in early structural brain development. Diusion magnetic resonance imaging (dMRI) allows the in vivo assessment of biological tissues at the microstructural level. It has emerged as a powerful tool to study brain connectivity and analyse the underlying substrate of the human brain, comprising its structurally integrated and functionally specialized architecture. dMRI has been widely used in adult studies. Nevertheless, due to technical constraints, this mapping at earlier stages of development has not yet been accomplished. Yet, this time period is of extreme importance to comprehend the structural and functional integrity of the brain. This thesis is motivated by this shortfall, and intends to fill the gap between the clinical and neuroscience demands and the methodological developments needed to fulfill them. In our work, we comprehensibly study the brain structural connectivity of children born extremely prematurely and/or with additional prenatal restriction at school-age. We provide evidence that brain systems that mature early in development are the most vulnerable to antenatal insults. Interestingly, the alterations highlighted in these systems correlate with the neurobehavioral and cognitive impairments seen in these children at school-age. The overall brain organization appear also altered after preterm birth and prenatal restriction. Indeed, these children show dierent brain network modular topology, with a reduction in the overall network capacity. What remains unclear is whether the alterations seen at school age are already present at birth and, if yes, to what extent. In this thesis we set the technical basis to enable the connectome analysis as early as at birth. This task is challenging when dealing with neonatal data. Indeed, most of the assumptions used in adult data processing methods do not hold, due to the inverted image contrast and other MRI artefacts such as motion, partial volume and intensity inhomogeneities. Here, we propose a novel technique for surface reconstruction, and provide a fully-automatic procedure to delineate the newborn cortical surface, opening the way to establish the newborn connectome

Craneología funcional y evolución humana: relaciones estructurales y organización espacial en la evolución de las áreas fronto-parietales

Los humanos modernos se caracterizan por la forma globular del neurocráneo y retracción de la cara, atribuidos generalmente a la encefalización. La proximidad entre cara y cerebro podría implicar un conflicto espacial entre órbitas y lóbulos frontal y temporal. El abultamiento parietal puede deberse a cambios en la corteza parietal, por ejemplo, el precúneo. Esta tesis investiga la relación estructural cerebro-orbital y la anatomía del lóbulo parietal utilizando morfometría geométrica aplicada a imágenes biomedicas de humanos modernos y fósiles y de primates no humanos. Los resultados apuntan hacia un mayor conflicto estructural de las órbitas con los lóbulos temporales. Los lóbulos parietales son longitudinal y verticalmente más grandes en humanos modernos que en neandertales. La variación de la proporción longitudinal del precúneo se debe sobre todo a la región superior y es específica de humanos modernos. La dimensión vertical del precúneo está relacionada con la morfología del contorno parietal exterior.Modern humans are characterized by a globular braincase and a reduced face, two features that are generally attributed to encephalization. The anatomical proximity between the face and the brain involves nonetheless spatial conflicts between the orbits and the frontal and temporal lobes. Parietal bulging is likely due to changes in parietal cortical elements, like the precuneus. This thesis investigates the orbit-brain structural relationships and parietal lobe anatomy through geometric morphometrics and biomedical imaging, in modern and fossil humans, as well as in non-human primates. Results point to a greater structural conflict between orbits and temporal lobes. The parietal lobes are longitudinally and vertically larger in modern humans, when compared to those of Neanderthals. The variation in the longitudinal proportions of the precuneus is mostly due to the superior regions, and it is specific to modern humans. Precuneus vertical dimension is related to the morphology of the outer parietal contour

Ultra-High Field Magnetic Resonance Imaging for Stereotactic Neurosurgery

Stereotactic neurosurgery is a subspecialty within neurosurgery concerned with accurate targeting of brain structures. Deep brain stimulation (DBS) is a specific type of stereotaxy in which electrodes are implanted in deep brain structures. It has proven therapeutic efficacy in Parkinson’s disease and Essential Tremor, but with an expanding number of indications under evaluation including Alzheimer’s disease, depression, epilepsy, and obesity, many more Canadians with chronic health conditions may benefit. Accurate surgical targeting is crucial with millimeter deviations resulting in unwanted side effects including muscle contractions, or worse, vessel injury. Lack of adequate visualization of surgical targets with conventional lower field strengths (1.5/3 Tesla) has meant that standard-of-care surgical treatment has relied on indirect targeting using standardized landmarks to find a correspondence with a histological ``template\u27\u27 of the brain. For this reason, these procedures routinely require awake testing and microelectrode recording, which increases operating room time, patient discomfort, and risk of complications. Advances in ultra-high field (\u3e= 7 Tesla or 7T) imaging have important potential implications for targeting structures enabling better visualization as a result of its increased (sub-millimeter) spatial resolution, tissue contrast, and signal-to-noise ratio. The work in this thesis explores ways in which ultra-high field magnetic resonance imaging can be integrated into the practice of stereotactic neurosurgery. In Chapter 2, an ultra-high field MRI template is integrated into the surgical workflow to assist with planning for deep brain stimulation surgery cases. Chapter 3 describes a novel anatomical fiducial placement protocol that is developed, validated, and used prospectively to quantify the limits of template-assisted surgical planning. In Chapter 4, geometric distortions at 7T that may impede the ability to perform accurate surgical targeting are characterized in participant data, and generally noted to be away from areas of interest for stereotactic targeting. Finally, Chapter 5 discusses a number of important stereotactic targets that are directly visualized and described for the first time in vivo, paving the way for patient-specific surgical planning using ultra-high field MRI

Cingulate Cortex Networks : Role in learning and memory and Alzheimer's disease related changes

VRIJE UNIVERSITEIT CINGULATE CORTEX NETWORKS Role in learning and memory and Alzheimer’s disease related changesScheltens, P. [Promotor]Witter, M.P. [Promotor

Unique Features and Neuronal Properties in a Multisensory Cortex

UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal cortex (PPr) of ferrets, the present experiments utilized a combination of immunohistological, neuroanatomical and multiple single-channel electrophysiological recording techniques. These experiments produced four main results. First, convergence of extrinsic inputs from unisensory cortical areas predominantly in layers 2-3 in PPr corresponded with the high proportion of multisensory neurons in those layers. This is consistent with multisensory responses in this higher-level multisensory region being driven by cortico-cortical, rather than thalamo-cortical connections. Second, the laminar organization of the PPr differed substantially from the pattern commonly observed in primary sensory cortices. The PPr has a reduced layer 4 compared to primary sensory cortices, which does not receive input from principal thalamic nuclei. Third, the distribution of unisensory and multisensory neurons and properties differs significantly by layer. Given the laminar-dependent input-output relationships, this suggests that unisensory and multisensory signals are processed in parallel as they pass through the circuitry of the PPr. Finally, specific functional properties of bimodal neurons differed significantly from those of their unisensory counterparts. Thus, despite their coextensive distribution within cortex, these results differentiate bimodal from unisensory neurons in ways that have never been examined before. Together these experiments represent the first combined anatomical-electrophysiological examination of the laminar organization of a multisensory cortex and the first systematic comparison of the functional properties of bimodal and unisensory neurons. These results are essential for understanding the neural bases of multisensory processing and carry significant implications for the accurate interpretation of macroscopic studies of multisensory brain regions (i.e. fMRI, EEG), because bimodal and unisensory neurons within a given neural region can no longer be assumed to respond similarly to a given external stimulus

Structures and Connections of the Ccerebral Cortex in Diprotodontid Marsupials and Comparison with Eutherians

This thesis focuses on variation in cortical structure across diprotodontid marsupials and aims to elucidate the archetypal features of the mammalian cortex and those transformations that are of evolutionary importance. The study analysed these features both qualitatively, quantitatively and also compared MRI and DTI derived connectome reconstructions in representatives of the major families of diprotodontids with a representative eutherian (the laboratory mouse). Overall findings suggest that a number of features of the cerebral cortex are retained in all the species examined and have been conserved throughout mammalian evolution and likely represent key aspects of neocortical organization. The differnces observed may be solutions to environmental challenges. For example, a different scaling relationship of hippocampal volume against brain volume has been found amongst the diprotodontids and eutherians. Very small-brained diprotodontids have quite small hippocampal formation volume for their brain size, but the hippocampal formation size increases more steeply with brain size amongst diprotodontids compared to eutherians. The role of the hippocampus in spatial cognition is of direct significance to home range and in species where social behaviour plays an important role, the involvement of the hippocampus in social information processing is also of ecological significance