Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.

INTRODUCTION:(31)Phosphorous magnetic resonance spectroscopy (2D chemical shift imaging, CSI) allows multiregional study of membrane phospholipids and high-energy phosphates in vivo. Increased membrane lipid turnover and impaired energy supply have repeatedly been shown in first-episode schizophrenia patients, and might be a target of drug actions other than dopamine receptors. Here, we explored differential metabolic effects of a typical vs. an atypical antipsychotic on brain phospholipids. METHODS: We applied 2D-CSI MR spectroscopy in 17 recurrent-episode schizophrenia patients off antipsychotics at baseline and at follow-up after 6weeks, during which 7 patients were treated with haloperidol (10-16mg/d) and 10 with risperidone (4-6mg/d). Psychopathology changes were assessed using PANSS, BPRS and CGI scores. RESULTS: Follow-up analysis using repeated measure ANOVA revealed different effects of both antipsychotic agents: while risperidone generally increased metabolite levels, haloperidol showed a tendency to decrease them. This diverging effect was significant for ATP levels in the left lateral frontal cortex. Furthermore, risperidone increased ATP in the left dorsolateral prefrontal cortex, left anterior temporal cortex and left insular cortex, basal ganglia, and anterior cerebellum, along with left frontal and prefrontal increase of PCr, PDE and PME in these brain regions. CONCLUSION: Risperidone seems to stimulate neuronal and synaptic phospholipid remodeling in left frontal and prefrontal regions, and to a lesser extent also in temporal and insular cortices. We discuss these effects with respect to clinical effects on negative and cognitive symptoms, as well as interaction of phospholipid metabolism with glutamatergic neurotransmission.

INTRODUCTION: Both impaired white matter connectivity and alterations in gray matter morphometry have repeatedly been reported in schizophrenia. Neurodevelopmental models propose a close linkage between gray matter alterations and white matter deficits. However, there are no studies investigating alterations in cortical thickness in relation to white matter connectivity changes. METHODS: This combined diffusion tensor imaging (DTI)- surface based morphometry study examined a potential linkage between disruption in white matter connectivity and alterations in cortical thickness. Cortical thickness was analyzed using the FreeSurfer software package (version 4.0.5, http://surfer.nmr.harvard.edu) in a sample of 19 patients with schizophrenia and 20 healthy controls. RESULTS: Whole brain node-by-node correlational analysis revealed a highly significant association (r=-.8, p<.0001) between disturbed white matter connectivity in the superior temporal cortex and diminished cortical thickness in the posterior part of the cingulate cortex (Brodmann area 23/31). CONCLUSIONS: This result indicates a significant linkage between disturbed white matter connectivity and reduced cortical thickness in a relevant node of the default mode network that is held to be of high pathophysiological relevance in schizophrenia. The result moreover provides support for the assumption of a neurodevelopmental pathogenesis of the disorder.

OBJECT: Referencing metabolite intensities to the tissue water intensity is commonly applied to determine metabolite concentrations from in vivo (1)H-MRS brain data. However, since the water concentration and relaxation properties differ between grey matter, white matter and cerebrospinal fluid (CSF), the volume fractions of these compartments have to be considered in MRS voxels. MATERIALS AND METHODS: The impact of partial volume correction was validated by phantom measurements in voxels containing mixtures of solutions with different NAA and water concentrations as well as by analyzing in vivo (1)H-MRS brain data acquired with various voxel compositions. RESULTS: Phantom measurements indicated substantial underestimation of NAA concentrations when assuming homogeneously composed voxels, especially for voxels containing solution, which simulated CSF (error: ≤92%). This bias was substantially reduced by taking into account voxel composition (error: ≤10%). In the in vivo study, tissue correction reduced the overall variation of quantified metabolites by up to 35% and revealed the expected metabolic differences between various brain tissues. CONCLUSIONS: Tissue composition affects extraction of metabolite concentrations and may cause misinterpretations when comparing measurements performed with different voxel sizes. This variation can be reduced by considering the different tissue types by means of combined analysis of spectroscopic and imaging data.

Chronic granulomatous disease (CGD) is an inherited disorder of phagocytes in which NADPH oxidase is defective in generating reactive oxygen species. In this study, we reprogrammed three normal unrelated patient's fibroblasts (p47(phox) and gp91(phox)) to pluripotency by lentiviral transduction with defined pluripotency factors. These induced pluripotent stem cells (iPSC) share the morphological features of human embryonic stem cells, express the key pluripotency factors, and possess high telomerase activity. Furthermore, all the iPSC lines formed embryoid bodies in vitro containing cells originating from all three germ layers and were capable of teratoma formation in vivo. They were isogenic with the original patient fibroblasts, exhibited normal karyotype, and retained the p47(phox) or gp91(pho)(x) mutations found in the patient fibroblasts. We further demonstrated that these iPSC could be differentiated into monocytes and macrophages with a similar cytokine profile to blood-derived macrophages under resting conditions. Most importantly, CGD-patient-specific iPSC-derived macrophages showed normal phagocytic properties but lacked reactive oxygen species production, which correlates with clinical diagnosis of CGD in the patients. Together these results suggest that CGD-patient-specific iPSC lines represent an important tool for modeling CGD disease phenotypes, screening candidate drugs, and the development of gene therapy.

PURPOSE Neurological and smelling disorders (e.g. Alzheimer's disease, sinonasal disease) negatively affect the microstructural integrity of the olfactory bulb's (OB) cortical layers. Recovery processes depend on active restoration of this microstructural integrity enabled by neuroneogenesis in the OB. The aim of this study was to evaluate lamination patterns of the OB and adjacent tract (OT) using high resolution MRI at 3 Tesla (T) as well as MR microscopy at 9.4 T in comparison with histological sections. MATERIAL AND METHODS Twenty-four human OBs were imaged in vitro using standard (2mm slice thickness) and high resolution (0.2mm slice thickness) T1w and T2w MR imaging at 3T. Based on signal intensity differences, the number of OB layers and the OB lamination patterns were assessed by two observers in consensus. Results were compared using Wilcoxon test. Signal intensity profiles were compared to reference Nissl stained histological sections and imaging results of MR microscopy. OT lamination patterns were assessed and different configurations of cross sectional areas were compared to macroscopic results and OB/OT lamination patterns. RESULTS Standard resolution at 3T identified three layers in 8.3%, two layers in 83.3%, and one layer in 8.3%. High resolution at 3T (4 layers in 91.7%, 3 layers in 8.3%) significantly performed better (P<0.001). Signal intensity profile analysis at 3T and 9.4 T (yielding up to 6 different signal intensities) correlated with histological sections and enabled quantitative evaluation of OB lamination patterns. 3T MRI of the OT revealed two separate signal intensities in T2w in 73%, a hyperintense core and a hypointense sheath, and the number of OT signal intensities positively correlated (ρ=0.541, P=0.006) with the increasing complexity of the OTs' cross sectional area configurations. Additionally, cross sectional area configurations correlated with macroscopic results (ρ=0.558, P=0.002) and OB lamination patterns (ρ=0.446, P=0.022). CONCLUSIONS 3T MRI and MR-microscopy indicate the possibility to identify the lamination pattern of the human OB/OT and to reflect the histological status. If further development will be able to provide technical equipment that complies with the condition of human in vivo high resolution imaging achieving a good enough signal noise ratio, the method of signal intensity profile analysis could prospectively enable scientists to assess the OB's microstructural status in neurological and smelling disorders.

The magnetic properties of tissues affect MR images and differences in magnetic susceptibility can be utilized to provide impressive image contrast. Specifically, phase images acquired with gradient echo MRI provide unique and superb contrast which reflects variations in the underlying tissue composition. There is great interest in extracting tissue susceptibility from image data since magnetic susceptibility is an intrinsic tissue property that reflects tissue composition much more closely than MRI phase. Still, this major tissue contrast mechanism is largely unexplored in magnetic resonance imaging because non-conventional reconstruction and dipole deconvolution are required to quantitatively map tissue susceptibility properly. This short review summarizes the current state of susceptibility contrast and susceptibility mapping and aims to identify future directions.

OBJECTIVE The authors investigated how human performance consequences of automated decision aids are affected by the degree of automation and the operator's functional state. BACKGROUND As research has shown, decision aids may not only improve performance but also lead to new sorts of risks.Whereas knowledge exists about the impact of system characteristics (e.g., reliability) on human performance, little is known about how these performance consequences are moderated by the functional state of operators. METHOD Participants performed a simulated supervisory process control task with one of two decision aids providing support for fault identification and management. One session took place during the day, and another one took place during the night after a prolonged waking phase of more than 20 hr. RESULTS Results showed that decision aids can support humans effectively in maintaining high levels of performance, even in states of sleep loss, with more highly automated aids being more effective than less automated ones. Furthermore, participants suffering from sleep loss were found to be more careful in interaction with the aids, that is, less prone to effects of complacency and automation bias. However, cost effects arose that included a decline in secondary-task performance and an increased risk of return-to-manual performance decrements. CONCLUSION Automation support can help protect performance after a period of extended wakefulness. In addition, operators suffering from sleep loss seem to compensate for their impaired functional state by reallocating resources and showing a more attentive behavior toward possible automation failures. APPLICATION Results of this research can inform the design of automation, especially decision aids.

In light of bottom-up models of disrupted cognition in schizophrenia, visual processing deficits became a key feature for the pathophysiology of schizophrenia. However, morphometric studies focusing on the visual cortex are limited. Thus, the present study sought to provide a combined cortical shape analysis (cortical thickness, folding) of visual areas, which were implicated to be involved in disturbed visual processing in schizophrenia. A group of 72 patients with schizophrenia according to DSM-IV and 72 age- and gender-matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5-T scanner. Cortical thickness and mean curvature of the V1, V2 and V5/MT+ visual cortex were estimated using an automated computerized algorithm (Freesurfer Software). A GLM controlling for the effect of age was used to estimate differences of cortical shape parameters between the study groups. Significantly increased gyrification of the V1, V2 and the V5/MT+ visual area bilaterally was detected. Conversely, cortical thickness was reduced in patients with schizophrenia only for the V5/MT+ area. This study is the first providing direct in vivo evidence for a disturbed cortical shape of central visual areas in schizophrenia. The present findings of hypergyria are highly indicative for a disrupted corticogenesis of these visual key regions and might constitute a relevant anatomical basis for visual processing deficits in schizophrenia.

Periodically rotated overlapping parallel lines with enhanced reconstruction-echo-planar imaging (PROPELLER-EPI) is a multishot technique that samples k-space by acquisition of narrow blades, which are subsequently rotated until the entire k-space is filled. It has the unique advantage that the center of k-space, and thus the area containing the majority of functional MRI signal changes, is sampled with each shot. This continuous refreshing of the k-space center by each acquired blade enables not only sliding-window but also keyhole reconstruction. Combining PROPELLER-EPI with a fast gradient-echo readout scheme allows for high spatial resolutions to be achieved while maintaining a temporal resolution, which is suitable for functional MRI experiments. Functional data acquired with a novel interlaced sequence that samples both single-shot EPI and blades in an alternating fashion suggest that PROPELLER-EPI can achieve comparable functional MRI results. PROPELLER-EPI, however, features different spatiotemporal characteristics than single-shot EPI, which not only enables keyhole reconstruction but also makes it an interesting alternative for many functional MRI applications. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.