Functional Magnetic Resonance Imaging Blood Oxygenation Level-Dependent Signal and Magnetoencephalography Evoked Responses Yield Different Neural Functionality in Reading

It is often implicitly assumed that the neural activation patterns revealed by hemodynamic methods, such as functional magnetic resonance imaging (fMRI), and electrophysiological methods, such as magnetoencephalography (MEG) and electroencephalography (EEG), are comparable. In early sensory processing that seems to be the case, but the assumption may not be correct in high-level cognitive tasks. For example, MEG and fMRI literature of single-word reading suggests differences in cortical activation, but direct comparisons are lacking. Here, while the same human participants performed the same reading task, analysis of MEG evoked responses and fMRI blood oxygenation level-dependent (BOLD) signals revealed marked functional and spatial differences in several cortical areas outside the visual cortex. Divergent patterns of activation were observed in the frontal and temporal cortex, in accordance with previous separate MEG and fMRI studies of reading. Furthermore, opposite stimulus effects in the MEG and fMRI measures were detected in the left occipitotemporal cortex: MEG evoked responses were stronger to letter than symbol strings, whereas the fMRI BOLD signal was stronger to symbol than letter strings. The EEG recorded simultaneously during MEG and fMRI did not indicate neurophysiological differences that could explain the observed functional discrepancies between the MEG and fMRI results. Acknowledgment of the complementary nature of hemodynamic and electrophysiological measures, as reported here in a cognitive task using evoked response analysis in MEG and BOLD signal analysis in fMRI, represents an essential step toward an informed use of multimodal imaging that reaches beyond mere combination of location and timing of neural activationPeer reviewe

Functional Brain Organization in Space and Time

The brain is a network functionally organized at many spatial and temporal scales. To understand how the brain processes information, controls behavior and dynamically adapts to an ever-changing environment, it is critical to have a comprehensive description of the constituent elements of this network and how relationships between these elements may change over time. Decades of lesion studies, anatomical tract-tracing, and electrophysiological recording have given insight into this functional organization. Recently, however, resting state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for whole-brain non-invasive measurement of spontaneous neural activity in humans, giving ready access to macroscopic scales of functional organization previously much more difficult to obtain. This thesis aims to harness the unique combination of spatial and temporal resolution provided by functional MRI to explore the spatial and temporal properties of the functional organization of the brain. First, we establish an approach for defining cortical areas using transitions in correlated patterns of spontaneous BOLD activity (Chapter 2). We then propose and apply measures of internal and external validity to evaluate the credibility of the areal parcellation generated by this technique (Chapter 3). In chapter 4, we extend the study of functional brain organization to a highly sampled individual. We describe the idiosyncratic areal and systems-level organization of the individual relative to a standard group-average description. Further, we develop a model describing the reliability of BOLD correlation estimates across days that accounts for relevant sources of variability. Finally, in Chapter 5, we examine whether BOLD correlations meaningfully vary over the course of single resting-state scans

Magnetic resonance imaging and surface-based analysis techniques to quantify growth of the developing brain

Human brains, and those of most higher mammals, are gyrencephalic: folded) to accommodate a large cortical surface within the limited volume of the skull. Abnormal folding of the cerebral cortex in humans is associated with a number of neurological dysfunctions and diseases such as schizophrenia and Williams syndrome. To understand the mechanism of gyrification, and to illuminate the underlying causes of abnormal folding, objective, quantitative methods to characterize normal and abnormal development must be developed. The ferret is an excellent model in which to study the development of convolutions in the brain because folding occurs post-natally over a period of several weeks, and the brain can be imaged conveniently in small-animal magnetic resonance: MR) scanners. Here, MR imaging was used to acquire three-dimensional image volumes of the ferret brain in vivo at different stages during the period of cortical folding. Through segmentation of these volumes, surface representations of the cortex are generated at each time point. A novel intra-subject registration algorithm: LAndmark Correspondence and Relaxation Of Surface Strain: LACROSS), which provides a point-to-point correspondence between two surfaces, is applied to the cortical surfaces from two ferret kits. The resulting calculations of growth show regional patterns within the cortex, and temporal variations over this period of early brain development

The Microvascular System of the Striate and Extrastriate Visual Cortex of the Macaque

In functional neuroimaging, neurovascular coupling is used to generate maps of hemodynamic changes that are assumed to be surrogates of regional neural activation. The aim of this study was to characterize the microvascular system of the primate cortex as a basis for understanding the constraints imposed on a region's hemodynamic response by the vascular architecture, density, as well as area- and layer-specific variations. In the macaque visual cortex, an array of anatomical techniques has been applied, including corrosion casts, immunohistochemistry, and cytochrome oxidase (COX) staining. Detailed measurements of regional vascular length density, volume fraction, and surface density revealed a similar vascularization in different visual areas. Whereas the lower cortical layers showed a positive correlation between the vascular and cell density, this relationship was very weak in the upper layers. Synapse density values taken from the literature also displayed a very moderate correlation with the vascular density. However, the vascular density was strongly correlated with the steady-state metabolic demand as measured by COX activity. This observation suggests that although the number of neurons and synapses determines an upper bound on an area's integrative capacity, its vascularization reflects the neural activity of those subpopulations that represent a "default” mode of brain steady stat

Developmental MRI markers cosegregate juvenile patients with myoclonic epilepsy and their healthy siblings

OBJECTIVE: MRI studies of genetic generalized epilepsies have mainly described group-level changes between patients and healthy controls. To determine the endophenotypic potential of structural MRI in juvenile myoclonic epilepsy (JME), we examined MRI-based cortical morphologic markers in patients and their healthy siblings. METHODS: In this prospective, cross-sectional study, we obtained 3T MRI in patients with JME, siblings, and controls. We mapped sulco-gyral complexity and surface area, morphologic markers of brain development, and cortical thickness. Furthermore, we calculated mean geodesic distance, a surrogate marker of cortico-cortical connectivity. RESULTS: Compared to controls, patients and siblings showed increased folding complexity and surface area in prefrontal and cingulate cortices. In these regions, they also displayed abnormally increased geodesic distance, suggesting network isolation and decreased efficiency, with strongest effects for limbic, fronto-parietal, and dorsal-attention networks. In areas of findings overlap, we observed strong patient-sibling correlations. Conversely, neocortical thinning was present in patients only and related to disease duration. Patients showed subtle impairment in mental flexibility, a frontal lobe function test, as well as deficits in naming and design learning. Siblings' performance fell between patients and controls. CONCLUSION: MRI markers of brain development and connectivity are likely heritable and may thus serve as endophenotypes. The topography of morphologic anomalies and their abnormal structural network integration likely explains cognitive impairments in patients with JME and their siblings. By contrast, cortical atrophy likely represents a marker of disease