White matter matters: a multimodal approach to investigate white matter microstructure and metabolism

White matter connects different brain areas and applies electrical insulation to the neuron’s axons with myelin sheaths in order to enable quick signal transmission. Due to its modulatory properties in signal conduction, white matter plays an essential role in learning, cognition and psychiatric disorders (Fields, 2008a). In respect thereof, the non-invasive investigation of white matter anatomy and function in vivo provides the unique opportunity to explore the most complex organ of our body. Thus, the present thesis aimed to apply a multimodal neuroimaging approach to investigate different white matter properties in psychiatric and healthy populations. On the one hand, white matter microstructural properties were investigated in a psychiatric population; on the other hand, white matter metabolic properties were assessed in healthy adults providing basic information about the brain’s wiring entity. As a result, three research papers are presented here. The first paper assessed the microstructural properties of white matter in relation to a frequent epidemiologic finding in schizophrenia. As a result, reduced white matter integrity was observed in patients born in summer and autumn compared to patients born in winter and spring. Despite the large genetic basis of schizophrenia, accumulating evidence indicates that environmental exposures may be implicated in the development of schizophrenia (A. S. Brown, 2011). Notably, epidemiologic studies have shown a 5–8% excess of births during winter and spring for patients with schizophrenia on the Northern Hemisphere at higher latitudes (Torrey, Miller, Rawlings, & Yolken, 1997). Although the underlying mechanisms are unclear, the seasonal birth effect may indicate fluctuating environmental risk factors for schizophrenia. Thus, exposure to harmful factors during foetal development may result in the activation of pathologic neural circuits during adolescence or young adulthood, increasing the risk of schizophrenia (Fatemi & Folsom, 2009). While white matter development starts during the foetal period and continues until adulthood, its major development is accomplished by the age of two years (Brody, Kinney, Kloman, & Gilles, 1987; Huang et al., 2009). This indicates a vulnerability period of white matter that may coincide with the fluctuating environmental risk factors for schizophrenia. Since microstructural alterations of white matter in schizophrenia are frequently observed, the current study provided evidence for the neurodevelopmental hypothesis of schizophrenia. In the second research paper, the perfusion of white matter showed a positive correlation between white matter microstructure and its perfusion with blood across healthy adults. This finding was in line with clinical studies indicating a tight coupling between cerebral perfusion and WM health across subjects (Amann et al., 2012; Chen, Rosas, & Salat, 2013; Kitagawa et al., 2009). Although relatively little is known about the metabolic properties of white matter, different microstructural properties, such as axon diameter and myelination, might be coupled with the metabolic demand of white matter. Furthermore, the ability to detect perfusion signal in white matter was in accordance with a recent study showing that technical improvements, such as pseudo-continuous arterial spin labeling, enabled the reliable detection of white matter perfusion signal (van Osch et al., 2009). The third paper involved a collaboration within the same department to assess the interrelation between functional connectivity networks and their underlying structural connectivity.

Quantitative microstructure analysis of polymer-modified mortars

Digital light, fluorescence and electron microscopy in combination with wavelength-dispersive spectroscopy were used to visualize individual polymers, air voids, cement phases and filler minerals in a polymer-modified cementitious tile adhesive. In order to investigate the evolution and processes involved in formation of the mortar microstructure, quantifications of the phase distribution in the mortar were performed including phase-specific imaging and digital image analysis. The required sample preparation techniques and imaging related topics are discussed. As a form of case study, the different techniques were applied to obtain a quantitative characterization of a specific mortar mixture. The results indicate that the mortar fractionates during different stages ranging from the early fresh mortar until the final hardened mortar stage. This induces process-dependent enrichments of the phases at specific locations in the mortar. The approach presented provides important information for a comprehensive understanding of the functionality of polymer-modified mortars.

Influence of polymers on microstructure and adhesive strength of cementitious tile adhesive mortars

The impact of polymer modification on the physical properties of cementitious mortars is investigated using a multimethod approach. Special emphasis is put on the identification and quantification of different polymer components within the cementitious matrix. With respect to thin-bed applications, particularly tile adhesives, the spatial distributions of latex, cellulose ether (CE), polyvinyl alcohol (PVA), and cement hydration products can be quantified. It is shown that capillary forces and evaporation induce water fluxes in the interconnected part of the pore system, which transport CE, PVA, and cement ions to the mortar interfaces. In contrast, the distribution of latex remains homogeneous. In combination with results from qualitative experiments, the quantitative findings allow reconstruction of the evolution from fresh to hardened mortar, including polymer film formation, cement hydration, and water migration. The resulting microstructure and the failure modes can be correlated with the final adhesive strength of the tile adhesive. The results demonstrate that skinning prior to tile inlaying can strongly reduce wetting properties of the fresh mortar and lower final adhesive strength.

Neuroanatomy of intergroup bias: A white matter microstructure study of individual differences

Intergroup bias - the tendency to behave more positively towards an ingroup member than an outgroup member - is a powerful social force, for good and ill. And though it is widely demonstrated, intergroup bias is not universal, as it is characterized by significant individual differences. Recently, attention has begun to turn to whether neuroanatomy might explain these individual differences in intergroup bias. However, no research to date has examined whether white matter microstructure could help determine differences in behavior towards ingroup and outgroup members. In the current research, we examine intergroup bias with the third-party punishment paradigm and white matter integrity and connectivity strength as determined by diffusion tensor imaging (DTI). We found that both increased white matter integrity at the right temporal-parietal junction (TPJ) and connectivity strength between the right TPJ and the dorsomedial prefrontal cortex (DMPFC) were associated with increased impartiality in the third-party punishment paradigm, i.e., reduced intergroup bias. Further, consistent with the role that these brain regions play in the mentalizing network, we found that these effects were mediated by mentalizing processes. Participants with greater white matter integrity at the right TPJ and connectivity strength between the right TPJ and the DMPFC employed mentalizing processes more equally for ingroup and outgroup members, and this non-biased use of mentalizing was associated with increased impartiality. The current results help shed light on the mechanisms of bias and, potentially, on interventions that promote impartiality over intergroup bias.

Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis.

BACKGROUND White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. METHODS Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). RESULTS CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. CONCLUSION The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.

Age, Growth and Population Structure of Jumbo Flying Squid, Dosidicus Gigas, Based on Statolith Microstructure Off the Exclusive Economic Zone of Chilean Waters

The jumbo flying squid, Dosidicus gigas, support an important squid fishery off the Exclusive Economic Zone of Chilean waters. However, we only have limited information about their biology. In this study, age, growth and population structure of D. gigas were studied using statoliths from 333 specimens (386 females and 147 males) randomly sampled in the Chinese squid jigging surveys from 2007 to 2008 off the Exclusive Economic Zone of Chile. Mantle lengths (MLs) of the sample ranged from 206 to 702 mm, and their ages were estimated from 150 to 307 days for females and from 127 to 302 days for males. At least two spawning groups were identified, the main spawning peak tended to occur between August and November (austral spring group), and the secondary peak appeared during March to June (austral autumn group). The ML-age relationship was best modelled by a linear function for the austral spring group and a power function for the austral autumn group, and the body weight (BW)-age relationship was best described by an exponential function for both the groups. Instantaneous relative growth rates and absolute growth rates for ML and BW did not differ significantly between the two groups. The growth rate of D. gigas tended to be high at young stages, and then decreased after the sub-adult stage (>180 days old). This study suggests large spatial and temporal variability in key life history parameters of D. gigas, calling for the collection of more data with fine spatial and temporal scales to further improve our understanding of the fishery biology of D. gigas.

Ocean acidification alters the calcareous microstructure of the green macro-alga Halimeda opuntia

Decreases in seawater pH and carbonate saturation state (Omega) following the continuous increase in atmospheric CO2 represent a process termed ocean acidification, which is predicted to become a main threat to marine calcifiers in the near future. Segmented, tropical, marine green macro-algae of the genus Halimeda form a calcareous skeleton that involves biotically initiated and induced calcification processes influenced by cell physiology. As Halimeda is an important habitat provider and major carbonate sediment producer in tropical shallow areas, alterations of these processes due to ocean acidification may cause changes in the skeletal microstructure that have major consequences for the alga and its environment, but related knowledge is scarce. This study used scanning electron microscopy to examine changes of the CaCO3 segment microstructure of Halimedaopuntia specimens that had been exposed to artificially elevated seawater pCO2 of 650 µatm for 45 d. In spite of elevated seawater pCO2, the calcification of needles, located at the former utricle walls, was not reduced as frequent initiation of new needle-shaped crystals was observed. Abundance of the needles was 22 %/µm**2 higher and needle crystal dimensions 14 % longer. However, those needles were 42 % thinner compared with the control treatment. Moreover, lifetime cementation of the segments decreased under elevated seawater pCO2 due to a loss in micro-anhedral carbonate as indicated by significantly thinner calcified rims of central utricles (35-173 % compared with the control treatment). Decreased micro-anhedral carbonate suggests that seawater within the inter-utricular space becomes CaCO3 undersaturated (Omega < 1) during nighttime under conditions of elevated seawater pCO2, thereby favoring CaCO3 dissolution over micro-anhedral carbonate accretion. Less-cemented segments of H. opuntia may impair the environmental success of the alga, its carbonate sediment contribution, and the temporal storage of atmospheric CO2 within Halimeda-derived sediments.