Ophthalmologic techniques to assess the severity of hyperviscosity syndrome and the effect of plasmapheresis in patients with Waldenström's macroglobulinemia

BACKGROUND: The aim of this study is to determine the serum immunoglobulin (Ig) M and serum viscosity (SV) levels at which retinal changes associated with hyperviscosity syndrome (HVS) as a result of Waldenström's macroglobulinemia (WM) occur. In addition, the effect of plasmapheresis on HVS-related retinopathy was tested. PATIENTS AND METHODS: A total of 46 patients with WM received indirect ophthalmoscopy, laser Doppler retinal blood flow measurements, serum IgM, and SV determinations. A total of 9 patients with HVS were studied before and after plasmapheresis. RESULTS: Mean IgM and SV levels of patients with the earliest retinal changes were 5442 mg/dL and 3.1 cp, respectively. Plasmapheresis improved retinopathy, decreased serum IgM (46.5 +/- 18%; P = .0009), SV (44.7 +/- 17.3%; P = .002), retinal venous diameter (15.3 +/- 5.8%; P = .0001), and increased venous blood speed by +55.2 +/- 22.5% (P = .0004). CONCLUSION: Examination of the retina is useful in identifying the symptomatic threshold of plasma viscosity levels in patients with HVS and can be used to gauge the effectiveness of plasmapheresis treatment.

Optimizing infrared to near infrared upconversion quantum yield of β-NaYF4:Er3+ in fluoropolymer matrix for photovoltaic devices

The present study reports for the first time the optimization of the infrared (1523 nm) to near-infrared (980 nm) upconversion quantum yield (UC-QY) of hexagonal trivalent erbium doped sodium yttrium fluoride (β-NaYF4:Er3+) in a perfluorocyclobutane (PFCB) host matrix under monochromatic excitation. Maximum internal and external UC-QYs of 8.4% ± 0.8% and 6.5% ± 0.7%, respectively, have been achieved for 1523 nm excitation of 970 ± 43 Wm−2 for an optimum Er3+ concentration of 25 mol% and a phosphor concentration of 84.9 w/w% in the matrix. These results correspond to normalized internal and external efficiencies of 0.86 ± 0.12 cm2 W−1 and 0.67 ± 0.10 cm2 W−1, respectively. These are the highest values ever reported for β-NaYF4:Er3+ under monochromatic excitation. The special characteristics of both the UC phosphor β-NaYF4:Er3+ and the PFCB matrix give rise to this outstanding property. Detailed power and time dependent luminescence measurements reveal energy transfer upconversion as the dominant UC mechanism.

Emergency transcatheter aortic valve implantation for decompensated aortic stenosis

We report the case of an 84-year-old male presenting with syncope and dynamic ST-T wave changes due to decompensated severe valvular aortic stenosis undergoing successful emergency transcatheter aortic valve implantation.

Sensory discrimination, working memory and intelligence in 9-year-old and 11-year-old children

More than a century ago, Galton and Spearman suggested that there was a functional relationship between sensory discrimination ability and intelligence. Studies have since been able to confirm a close relationship between general discrimination ability (GDA) and IQ. The aim of the present study was to assess whether this strong relationship between GDA and IQ could be due to working memory (WM) demands of GDA tasks. A sample of 140 children (seventy 9-year-olds and seventy 11-year-olds) was studied. Results showed that there was a significant overlap between WM, GDA and fluid intelligence. Furthermore, results also revealed that WM could not explain the relationship between GDA and fluid intelligence as such, but that it acted as a bottleneck of information processing, limiting the influence of GDA on the prediction of fluid intelligence. Specifically, GDA's influence on the prediction of intelligence was only visible when WM capacity was above a certain level.

Improved cerebellar tissue classification on magnetic resonance images of brain.

PURPOSE: To develop and implement a method for improved cerebellar tissue classification on the MRI of brain by automatically isolating the cerebellum prior to segmentation. MATERIALS AND METHODS: Dual fast spin echo (FSE) and fluid attenuation inversion recovery (FLAIR) images were acquired on 18 normal volunteers on a 3 T Philips scanner. The cerebellum was isolated from the rest of the brain using a symmetric inverse consistent nonlinear registration of individual brain with the parcellated template. The cerebellum was then separated by masking the anatomical image with individual FLAIR images. Tissues in both the cerebellum and rest of the brain were separately classified using hidden Markov random field (HMRF), a parametric method, and then combined to obtain tissue classification of the whole brain. The proposed method for tissue classification on real MR brain images was evaluated subjectively by two experts. The segmentation results on Brainweb images with varying noise and intensity nonuniformity levels were quantitatively compared with the ground truth by computing the Dice similarity indices. RESULTS: The proposed method significantly improved the cerebellar tissue classification on all normal volunteers included in this study without compromising the classification in remaining part of the brain. The average similarity indices for gray matter (GM) and white matter (WM) in the cerebellum are 89.81 (+/-2.34) and 93.04 (+/-2.41), demonstrating excellent performance of the proposed methodology. CONCLUSION: The proposed method significantly improved tissue classification in the cerebellum. The GM was overestimated when segmentation was performed on the whole brain as a single object.

A Hybrid Model for Multimodal Brain Tumor Segmentation

We present a fully automatic segmentation method for multi-modal brain tumor segmentation. The proposed generative-discriminative hybrid model generates initial tissue probabilities, which are used subsequently for enhancing the classi�cation and spatial regularization. The model has been evaluated on the BRATS2013 training set, which includes multimodal MRI images from patients with high- and low-grade gliomas. Our method is capable of segmenting the image into healthy (GM, WM, CSF) and pathological tissue (necrotic, enhancing and non-enhancing tumor, edema). We achieved state-of-the-art performance (Dice mean values of 0.69 and 0.8 for tumor subcompartments and complete tumor respectively) within a reasonable timeframe (4 to 15 minutes).

The Dissociation of Location and Object Working Memory using fMRI and MEG

Visual working memory (VWM) involves maintaining and processing visual information, often for the purpose of making immediate decisions. Neuroimaging experiments of VWM provide evidence in support of a neural system mainly involving a fronto-parietal neuronal network, but the role of specific brain areas is less clear. A proposal that has recently generated considerable debate suggests that a dissociation of object and location VWM occurs within the prefrontal cortex, in dorsal and ventral regions, respectively. However, re-examination of the relevant literature presents a more robust distribution suggestive of a general caudal-rostral dissociation from occipital and parietal structures, caudally, to prefrontal regions, rostrally, corresponding to location and object memory, respectively. The purpose of the present study was to identify a dissociation of location and object VWM across two imaging methods (magnetoencephalography, MEG, and functional magnetic imaging, fMRI). These two techniques provide complimentary results due the high temporal resolution of MEG and the high spatial resolution of fMRI. The use of identical location and object change detection tasks was employed across techniques and reported for the first time. Moreover, this study is the first to use matched stimulus displays across location and object VWM conditions. The results from these two imaging methods provided convergent evidence of a location and object VWM dissociation favoring a general caudal-rostral rather than the more common prefrontal dorsal-ventral view. Moreover, neural activity across techniques was correlated with behavioral performance for the first time and provided convergent results. This novel approach of combining imaging tools to study memory resulted in robust evidence suggesting a novel interpretation of location and object memory. Accordingly, this study presents a novel context within which to explore the neural substrates of WM across imaging techniques and populations.

Executive functions after pediatric mild traumatic brain injury: A prospective short-term longitudinal study

Traumatic brain injuries (TBIs) occur frequently in childhood and entail broad cognitive deficits, particularly in the domain of executive functions (EF). Concerning mild TBI (mTBI), only little empirical evidence is available on acute and postacute performance in EF. Given that EF are linked to school adaptation and achievement, even subtle deficits in performance may affect children's academic careers. The present study assessed performance in the EF components of inhibition, working memory (WM), and switching in children after mTBI. Regarding both acute and postacute consequences, performance trajectories were measured in 13 patients aged between 5 and 10 years and 13 controls who were closely matched in terms of sex, age, and education. Performance in the EF components of inhibition, switching, and WM was assessed in a short-term longitudinal design at 2, 6, and 12 weeks after the mTBI. Results indicate subtle deficits after mTBI, which became apparent in the longitudinal trajectory in the EF components of switching and WM. Compared with controls, children who sustained mTBI displayed an inferior performance enhancement across testing sessions in the first 6 weeks after the injury in switching and WM, resulting in a delayed deficit in the EF component of WM 12 weeks after the injury. Results are interpreted as mTBI-related deficits that become evident in terms of an inability to profit from previous learning opportunities, a finding that is potentially important for children's mastery of their daily lives.

Structural brain changes related to bilingualism: does immersion make a difference?

Abstract Within the field of neuroscientific research on second language learning, considerable attention has been devoted to functional and recently also structural changes related to second language acquisition. The present literature review summarizes studies that investigated structural changes related to bilingualism. Furthermore, as recent evidence has suggested that native-like exposure to a second language (i.e., a naturalistic learning setting or immersion) considerably impacts second language learning, all findings are reflected with respect to the learning environment. Aggregating the existing evidence, we conclude that structural changes in left inferior frontal and inferior parietal regions have been observed in studies on cortical gray matter changes, while the anterior parts of the corpus callosum have been repeatedly found to reflect bilingualism in studies on white matter (WM) connectivity. Regarding the learning environment, no cortical alterations can be attributed specifically to naturalistic or classroom learning. With regard to WM changes, one might tentatively propose that changes in IFOF and SLF are possibly more prominently observed in studies investigating bilinguals with a naturalistic learning experience. However, future studies are needed to replicate and strengthen the existing evidence and to directly test the impact of naturalistic exposure on structural brain plasticity.

Individual differences in working memory capacity explain the relationship between general discrimination ability and psychometric intelligence

The close association between psychometric intelligence and general discrimination ability (GDA), conceptualized as latent variable derived from performance on different sensory discrimination tasks, is empirically well-established but theoretically widely unclear. The present study contrasted two alternative explanations for this association. The first explanation is based on what Spearman (1904) referred to as a central function underlying this relationship in the sense of the g factor of intelligence and becoming most evident in GDA. In this case, correlations between different aspects of cognitive abilities, such as working memory (WM) capacity, and psychometric intelligence should be mediated by GDA if their correlation is caused by g. Alternatively, the second explanation for the relationship between psychometric intelligence and GDA proceeds from fMRI studies which emphasize the role of WM functioning for sensory discrimination. Given the well-known relationship between WM and psychometric intelligence, the relationship between GDA and psychometric intelligence might be attributed to WM. The present study investigated these two alternative explanations at the level of latent variables. In 197 young adults, a model in which WM mediated the relationship between GDA and psychometric intelligence described the data better than a model in which GDA mediated the relationship between WM and psychometric intelligence. Moreover, GDA failed to explain portions of variance of psychometric intelligence above and beyond WM. These findings clearly support the view that the association between psychometric intelligence and GDA must be understood in terms of WM functioning.

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.

Relations among fluid intelligence, sensory discrimination and working memory in middle to late childhood – A latent variable approach

Two factors that have been suggested as key in explaining individual differences in fluid intelligence are working memory and sensory discrimination ability. A latent variable approach was used to explore the relative contributions of these two variables to individual differences in fluid intelligence in middle to late childhood. A sample of 263 children aged 7–12 years was examined. Correlational analyses showed that general discrimination ability (GDA)and working memory (WM) were related to each other and to fluid intelligence. Structural equation modeling showed that within both younger and older age groups and the sample as a whole, the relation between GDA and fluid intelligence could be accounted for by WM. While WM was able to predict variance in fluid intelligence above and beyond GDA, GDA was not able to explain significant amounts of variance in fluid intelligence, either in the whole sample or within the younger or older age group. We concluded that compared to GDA, WM should be considered the better predictor of individual differences in fluid intelligence in childhood. WM and fluid intelligence, while not being separable in middle childhood, develop at different rates, becoming more separable with age.

The brain’s default state interacts with working memory processes in a complex and load-dependent manner

Recently, many studies about a network active during rest and deactivated during tasks emerged in the literature: the default mode network (DMN). Spatial and temporal DMN features are important markers for psychiatric diseases. Another prominent indicator of cognitive functioning, yielding information about the mental condition in health and disease, is working memory (WM) processing. In EEG studies, frontal-midline theta power has been shown to increase with load during WM retention in healthy subjects. From these findings, the conclusion can be drawn that an increase in resting state DMN activity may go along with an increase in theta power in high-load WM conditions. We followed this hypothesis in a study on 17 healthy subjects performing a visual Sternberg WM task. The DMN was obtained by a BOLD-ICA approach and its dynamics represented by the percent-strength during pre-stimulus periods. DMN dynamics were temporally correlated with EEG theta spectral power from retention intervals. This so-called covariance mapping yielded the spatial distribution of the theta EEG fluctuations associated with the dynamics of the DMN. In line with previous findings, theta power was increased at frontal-midline electrodes in high- versus low-load conditions during early WM retention. However, load-dependent correlations of DMN with theta power resulted in primarily positive correlations in low-load conditions, while during high-load conditions negative correlations of DMN activity and theta power were observed at frontal-midline electrodes. This DMN-dependent load effect reached significance during later retention. Our results show a complex and load-dependent interaction of pre-stimulus DMN activity and theta power during retention, varying over the course of the retention period. Since both, WM performance and DMN activity, are markers of mental health, our results could be important for further investigations of psychiatric populations.

The brain’s pre-stimulus default state interacts with working memory in a load-dependent manner

Recently, multiple studies showed that spatial and temporal features of a task-negative default mode network (DMN) (Greicius et al., 2003) are important markers for psychiatric diseases (Balsters et al., 2013). Another prominent indicator of cognitive functioning, yielding information about the mental condition in health and disease, is working memory (WM) processing. In EEG and MEG studies, frontal-midline theta power has been shown to increase with load during WM retention in healthy subjects (Brookes et al., 2011). Negative correlations between DMN activity and theta amplitude have been found during resting state (Jann et al., 2010) as well as during WM (Michels et al., 2010). Likewise, WM training resulted in higher resting state theta power as well as increased small-worldness of the resting brain (Langer et al., 2013). Further, increased fMRI connectivity between nodes of the DMN correlated with better WM performance (Hampson et al., 2006). Hence, the brain’s default state might influence it’s functioning during task. We therefore hypothesized correlations between pre-stimulus DMN activity and EEG-theta power during WM maintenance, depending on the WM load. 17 healthy subjects performed a Sternberg WM task while being measured simultaneously with EEG and fMRI. Data was recorded within a multicenter-study: 12 subjects were measured in Zurich with a 64-channels MR-compatible system (Brain Products) in a 3T Philips scanner, 5 subjects with a 96-channel MR-compatible system (Brain Products) in a 3T Siemens Scanner in Bern. The DMN components was obtained by a group BOLD-ICA approach over the full task duration (figure 1). The subject-wise dynamics were obtained by back-reconstructed onto each subject’s fMRI data and normalized to percent signal change values. The single trial pre-stimulus-DMN activation was then temporally correlated with the single trial EEG-theta (3-8 Hz) spectral power during retention intervals. This so-called covariance mapping (Jann et al., 2010) yielded the spatial distribution of the theta EEG fluctuations during retention associated with the dynamics of the pre-stimulus DMN. In line with previous findings, theta power was increased at frontal-midline electrodes in high- versus low-load conditions during early WM retention (figure 2). However, correlations of DMN with theta power resulted in primarily positive correlations in low-load conditions, while during high-load conditions negative correlations of DMN activity and theta power were observed at frontal-midline electrodes. This DMN-dependent load effect reached significance in the middle of the retention period (TANOVA, p<0.05) (figure 3). Our results show a complex and load-dependent interaction of pre-stimulus DMN activity and theta power during retention, varying over time. While at a more global, load-independent view pre-stimulus DMN activity correlated positively with theta power during retention, the correlation was inversed during certain time windows in high-load trials, meaning that in trials with enhanced pre-stimulus DMN activity theta power decreases during retention. Since both WM performance and DMN activity are markers of mental health our results could be important for further investigations of psychiatric populations.