White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.

Measurement of structural anisotropy in femoral trabecular bone using clinical-resolution CT images

Discrepancies in finite-element model predictions of bone strength may be attributed to the simplified modeling of bone as an isotropic structure due to the resolution limitations of clinical-level Computed Tomography (CT) data. The aim of this study is to calculate the preferential orientations of bone (the principal directions) and the extent to which bone is deposited more in one direction compared to another (degree of anisotropy). Using 100 femoral trabecular samples, the principal directions and degree of anisotropy were calculated with a Gradient Structure Tensor (GST) and a Sobel Structure Tensor (SST) using clinical-level CT. The results were compared against those calculated with the gold standard Mean-Intercept-Length (MIL) fabric tensor using micro-CT. There was no significant difference between the GST and SST in the calculation of the main principal direction (median error=28°), and the error was inversely correlated to the degree of transverse isotropy (r=−0.34, p<0.01). The degree of anisotropy measured using the structure tensors was weakly correlated with the MIL-based measurements (r=0.2, p<0.001). Combining the principal directions with the degree of anisotropy resulted in a significant increase in the correlation of the tensor distributions (r=0.79, p<0.001). Both structure tensors were robust against simulated noise, kernel sizes, and bone volume fraction. We recommend the use of the GST because of its computational efficiency and ease of implementation. This methodology has the promise to predict the structural anisotropy of bone in areas with a high degree of anisotropy, and may improve the in vivo characterization of bone.

Upscaling of anisotropy in unsaturated Miller-similar porous media

Geological and pedological processes rarely form isotropic media as is usually assumed in transport studies. Anisotropy at the Darcy or field scale may be detected directly by measuring flow parameters or may become indirectly evident from movement and shape of solute plumes. Anisotropic behavior of a soil at one scale may, in many cases, be related to the presence of lower-scale directional structures. Miller similitude with different pore-scale geometries of the basic element is used to model macroscopic flow and transport behavior. Analytical expressions for the anisotropic conductivity tensor are derived based on the dynamic law that governs the flow problem at the pore scale. The effects of anisotropy on transport parameters are estimated by numerical modeling.

Effect of Acute Administration of Angiopoietin-1 in Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging and Neurobehavioral Studies

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI. In these studies, angiopoietin-1 (Ang1), an agent known to reduce vascular permeability, was hypothesized to attenuate the severity of secondary injuries of SCI. Using longitudinal magnetic resonance imaging (MRI) studies (dynamic contrast-enhanced [DCE]-MRI for quantification of BSCB permeability, highresolution anatomical MRI for calculation of lesion size, and diffusion tensor imaging for assessment of axonal integrity), the acute, subacute, and chronic effects of Ang1 administration after SCI were evaluated. Neurobehavioral assessments were also performed. These non-invasive techniques have applicability to the monitoring of therapies in patients with SCI. In the acute phase of injury, Ang1 was found to reduce BSCB permeability and improve neuromotor recovery. Dynamic contrast-enhanced MRI revealed a persistent compromise of the BSCB up to two months post-injury. In the subacute phase of injury, Ang1’s effect on reducing BSCB permeability was maintained and it was found to transiently reduce axonal integrity. The SCI lesion burden was assessed with an objective method that compared favorably with segmentations from human raters. In the chronic phase of injury, Ang1 resulted in maintained reduction in BSCB permeability, a decrease in lesion size, and improved axonal integrity. Finally, longitudinal correlations among data from the MRI modalities and neurobehavioral assays were evaluated. Locomotor recovery was negatively correlated with lesion size in the Ang1 cohort and positively correlated with diffusion measures in the vehicle cohort. In summary, the results demonstrate a possible role for Ang1 in mitigating the secondary pathologies of SCI during the acute and chronic phases of injury.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Calculation of crystal optical properties from molecular electron density

We have recently developed a method to obtain distributed atomic polarizabilities adopting a partitioning of the molecular electron density (for example, the Quantum Theory of Atoms in Molecules, [1]), calculated with or without an applied electric field. The procedure [2] allows to obtained atomic polarizability tensors, which are perfectly exportable, because quite representative of an atom in a given functional group. Among the many applications of this idea, the calculation of crystal susceptibility is easily available, either from a rough estimation (the polarizability of the isolated molecule is used) or from a more precise estimation (the polarizability of a molecule embedded in a cluster representing the first coordination sphere is used). Lorentz factor is applied to include the long range effect of packing, which is enhancing the molecular polarizability. Simple properties like linear refractive index or the gyration tensor can be calculated at relatively low costs and with good precision. This approach is particularly useful within the field of crystal engineering of organic/organometallic materials, because it would allow a relatively easy prediction of a property as a function of the packing, thus allowing "reverse crystal engineering". Examples of some amino acid crystals and salts of amino acids [3] will be illustrated, together with other crystallographic or non-crystallographic applications. For example, the induction and dispersion energies of intermolecular interactions could be calculated with superior precision (allowing anisotropic van der Waals interactions). This could allow revision of some commonly misunderstood intermolecular interactions, like the halogen bonding (see for example the recent remarks by Stone or Gilli [4]). Moreover, the chemical reactivity of coordination complexes could be reinvestigated, by coupling the conventional analysis of the electrostatic potential (useful only in the circumstances of hard nucleophilic/electrophilic interaction) with the distributed atomic polarizability. The enhanced reactivity of coordinated organic ligands would be better appreciated. [1] R. F. W. Bader, Atoms in Molecules: A Quantum Theory. Oxford Univ. Press, 1990. [2] A. Krawczuk-Pantula, D. Pérez, K. Stadnicka, P. Macchi, Trans. Amer. Cryst. Ass. 2011, 1-25 [3] A. S. Chimpri1, M. Gryl, L. H.R. Dos Santos1, A. Krawczuk, P. Macchi Crystal Growth & Design, in the press. [4] a) A. J. Stone, J. Am. Chem. Soc. 2013, 135, 7005−7009; b) V. Bertolasi, P. Gilli, G. Gilli Crystal Growth & Design, 2013, 12, 4758-4770.

BRAIN ACTIVATION AND CONNECTIVITY IN NON-DISABLED MULTIPLE SCLEROSIS PATIENTS

Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. There is no cure for MS and current therapies have limited efficacy. While the majority of individuals with MS develop significant clinical disability, a subset experiences a disease course with minimal impairment even in the presence of significant apparent tissue damage on magnetic resonance imaging (MRI). The current studies combined functional MRI and diffusion tensor imaging (DTI) to elucidate brain mechanisms associated with lack of clinical disability in patients with MS. Recent evidence has implicated cortical reorganization as a mechanism to limit the clinical manifestation of the disease. Functional MRI was used to test the hypothesis that non-disabled MS patients (Expanded Disability Status Scale ≤ 1.5) show increased recruitment of cognitive control regions (dorsolateral prefrontal and anterior cingulate cortex) while performing sensory, motor and cognitive tasks. Compared to matched healthy controls, patients increased activation of cognitive control brain regions when performing non-dominant hand movements and the 2-back working memory task. Using dynamic causal modeling, we tested whether increased cognitive control recruitment is associated with alterations in connectivity in the working memory functional network. Patients exhibited similar network connectivity to that of control subjects when performing working memory tasks. We subsequently investigated the integrity of major white matter tracts to assess structural connectivity and its relation to activation and functional integration of the cognitive control system. Patients showed substantial alterations in callosal, inferior and posterior white matter tracts and less pronounced involvement of the corticospinal tracts and superior longitudinal fasciculi (SLF). Decreased structural integrity within the right SLF in patients was associated with decreased performance, and decreased activation and connectivity of the cognitive control system when performing working memory tasks. These studies suggest that patient with MS without clinical disability increase cognitive control system recruitment across functional domains and rely on preserved functional and structural connectivity of brain regions associated with this network. Moreover, the current studies show the usefulness of combining brain activation data from functional MRI and structural connectivity data from DTI to improve our understanding of brain adaptation mechanisms to neurological disease.

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

(Non)-Dissipative Hydrodynamics on Embedded Surfaces

We construct the theory of dissipative hydrodynamics of uncharged fluids living on embedded space-time surfaces to first order in a derivative expansion in the case of codimension-1 surfaces (including fluid membranes) and the theory of non-dissipative hydrodynamics to second order in a derivative expansion in the case of codimension higher than one under the assumption of no angular momenta in transverse directions to the surface. This construction includes the elastic degrees of freedom, and hence the corresponding transport coefficients, that take into account transverse fluctuations of the geometry where the fluid lives. Requiring the second law of thermodynamics to be satisfied leads us to conclude that in the case of codimension-1 surfaces the stress-energy tensor is characterized by 2 hydrodynamic and 1 elastic independent transport coefficient to first order in the expansion while for codimension higher than one, and for non-dissipative flows, the stress-energy tensor is characterized by 7 hydrodynamic and 3 elastic independent transport coefficients to second order in the expansion. Furthermore, the constraints imposed between the stress-energy tensor, the bending moment and the entropy current of the fluid by these extra non-dissipative contributions are fully captured by equilibrium partition functions. This analysis constrains the Young modulus which can be measured from gravity by elastically perturbing black branes.

Dispersive approach to hadronic light-by-light scattering and the muon ɡ − 2

The largest uncertainties in the Standard Model calculation of the anomalous magnetic moment of the muon (ɡ − 2)μ come from hadronic contributions. In particular, it can be expected that in a few years the subleading hadronic light-by-light (HLbL) contribution will dominate the theory uncertainty. We present a dispersive description of the HLbL tensor. This new, model-independent approach opens up an avenue towards a data-driven determination of the HLbL contribution to the (ɡ − 2)μ.

Image registration for triggered and non-triggered DTI of the human kidney: Reduced variability of diffusion parameter estimation

BACKGROUND: To investigate if non-rigid image-registration reduces motion artifacts in triggered and non-triggered diffusion tensor imaging (DTI) of native kidneys. A secondary aim was to determine, if improvements through registration allow for omitting respiratory-triggering. METHODS: Twenty volunteers underwent coronal DTI of the kidneys with nine b-values (10-700 s/mm2 ) at 3 Tesla. Image-registration was performed using a multimodal nonrigid registration algorithm. Data processing yielded the apparent diffusion coefficient (ADC), the contribution of perfusion (FP ), and the fractional anisotropy (FA). For comparison of the data stability, the root mean square error (RMSE) of the fitting and the standard deviations within the regions of interest (SDROI ) were evaluated. RESULTS: RMSEs decreased significantly after registration for triggered and also for non-triggered scans (P < 0.05). SDROI for ADC, FA, and FP were significantly lower after registration in both medulla and cortex of triggered scans (P < 0.01). Similarly the SDROI of FA and FP decreased significantly in non-triggered scans after registration (P < 0.05). RMSEs were significantly lower in triggered than in non-triggered scans, both with and without registration (P < 0.05). CONCLUSION: Respiratory motion correction by registration of individual echo-planar images leads to clearly reduced signal variations in renal DTI for both triggered and particularly non-triggered scans. Secondarily, the results suggest that respiratory-triggering still seems advantageous.J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc.

Bone Volume Fraction and Fabric Anisotropy Are Better Determinants of Trabecular Bone Stiffness than Other Morphological Variables

As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphologyelasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro-computed tomography reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae and iliac crest were analysed. Their morphology was assessed via 25 variables and their stiffness tensor (inline image) was computed from six independent load cases using micro finite element analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology-elasticity relationships. The statistically admissible morphological variables were included in a multi-linear regression modelling the dependent variable inline image. The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of inline image (inline image=0.889), especially in combination with fabric (inline image=0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (inline image=0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and post-elastic properties.

Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method

OBJECT The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4-2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated. METHODS The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r(2) = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11-20 mA, 13 patients; 6-10 mA, 8 patients; 4-5 mA, 17 patients; and 1-3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST. CONCLUSIONS Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

Nickel(II)-, cobalt(II)-, copper(II)-, and zinc(II)-phthalate and 1-methylimidazole coordination compounds: synthesis, crystal structures and magnetic properties

Three new coordination polymers [M(Pht)(1-MeIm)2]n (where M=Cu (1), Zn (2), Co (3); Pht2−=dianion of o-phthalic acid; 1-MeIm=1-methylimidazole) and two compounds [M(1-MeIm)6](HPht)2 · 2H2O (M=Co (4), Ni (5)) have been synthesized and characterized by X-ray crystallography. The structures of 1–3 (2 is isostructural to 3) consist of [M(1-MeIm)2] building units connected by 1,6-bridging phthalate ions to form infinite chains. In complex 1, each copper(II) center adopts a square coordination mode of N2O2 type by two O atoms from different phthalate ions and two N atoms of 1-MeIm, whereas in 3 two independent metal atoms are tetrahedrally (N2O2) coordinated to a pair of Pht ligands and a pair of 1-MeIm molecules. There are only van der Waals interactions between the chains in 1, while the three-dimensional network in 3 is assembled by C–H⋯O contacts. In contrast to polymers 1–3 the structures of 4 and 5 (complexes are also isostructural) are made up of the [M(1-MeIm)6]2+ cation, two hydrogen phthalate anions (HPht−) and two H2O solvate molecules. The coordination around each metal(II) atom is octahedral with six nitrogen atoms of 1-MeIm. Extended hydrogen bonding networks embracing the solvate water molecules and a phthalate residue as well as the weak C–H⋯O interactions stabilize the three-dimensional structures. Magnetic studies clearly show that the magnetic ions do not interact with each other. Furthermore, in compound 4 we have another example of a highly anisotropic Co2+ ion with a rhombic g-tensor and large zero-field-splitting. The complexes were also characterized by IR and 1H NMR spectroscopy, thermogravimetric analysis, and all data are discussed in the terms of known structures.

The effective Planck mass and the scale of inflation

Observable quantities in cosmology are dimensionless, and therefore independent of the units in which they are measured. This is true of all physical quantities associated with the primordial perturbations that source cosmic microwave background anisotropies such as their amplitude and spectral properties. However, if one were to try and infer an absolute energy scale for inflation—a priori, one of the more immediate corollaries of detecting primordial tensor modes—one necessarily makes reference to a particular choice of units, the natural choice for which is Planck units. In this note, we discuss various aspects of how inferring the energy scale of inflation is complicated by the fact that the effective strength of gravity as seen by inflationary quanta necessarily differs from that seen by gravitational experiments at presently accessible scales. The uncertainty in the former relative to the latter has to do with the unknown spectrum of universally coupled particles between laboratory scales and the putative scale of inflation. These intermediate particles could be in hidden as well as visible sectors or could also be associated with Kaluza–Klein resonances associated with a compactification scale below the scale of inflation. We discuss various implications for cosmological observables.