PENALIZED FUNCTIONAL REGRESSION

We develop fast fitting methods for generalized functional linear models. An undersmooth of the functional predictor is obtained by projecting on a large number of smooth eigenvectors and the coefficient function is estimated using penalized spline regression. Our method can be applied to many functional data designs including functions measured with and without error, sparsely or densely sampled. The methods also extend to the case of multiple functional predictors or functional predictors with a natural multilevel structure. Our approach can be implemented using standard mixed effects software and is computationally fast. Our methodology is motivated by a diffusion tensor imaging (DTI) study. The aim of this study is to analyze differences between various cerebral white matter tract property measurements of multiple sclerosis (MS) patients and controls. While the statistical developments proposed here were motivated by the DTI study, the methodology is designed and presented in generality and is applicable to many other areas of scientific research. An online appendix provides R implementations of all simulations.

NONLINEAR TUBE-FITTING FOR THE ANALYSIS OF ANATOMICAL AND FUNCTIONAL STRUCTURES

We are concerned with the estimation of the exterior surface of tube-shaped anatomical structures. This interest is motivated by two distinct scientific goals, one dealing with the distribution of HIV microbicide in the colon and the other with measuring degradation in white-matter tracts in the brain. Our problem is posed as the estimation of the support of a distribution in three dimensions from a sample from that distribution, possibly measured with error. We propose a novel tube-fitting algorithm to construct such estimators. Further, we conduct a simulation study to aid in the choice of a key parameter of the algorithm, and we test our algorithm with validation study tailored to the motivating data sets. Finally, we apply the tube-fitting algorithm to a colon image produced by single photon emission computed tomography (SPECT)and to a white-matter tract image produced using diffusion tensor `imaging (DTI).

The amygdala in schizophrenia: a trimodal magnetic resonance imaging study

In schizophrenic psychoses, structural and functional alterations of the amygdala have been demonstrated by several neuroimaging studies. However, postmortem examinations on the brains of schizophrenics did not confirm the volume changes reported by volumetric magnetic resonance imaging (MRI) studies. In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed a trimodal MRI design including high-resolution volumetry, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) in a sample of 14 schizophrenic patients and 14 matched controls. Three-dimensional MRI volumetry revealed a significant reduction of amygdala raw volumes in the patient group, while amygdala volumes normalized for intracranial volume did not differ between the two groups. The regional diffusional anisotropy of the amygdala, expressed as inter-voxel coherence (COH), showed a marked and significant reduction in schizophrenics. Assessment of qMTI parameters yielded significant group differences for the T2 time of the bound proton pool and the T1 time of the free proton pool, while the semi-quantitative magnetization transfer ratio (MTR) did not differ between the groups. The application of multimodal MRI protocols is diagnostically relevant for the differentiation between schizophrenic patients and controls and provides a new strategy for the detection and characterization of subtle structural alterations in defined regions of the living brain.

New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study

Postmortem examinations and magnetic resonance imaging (MRI) studies suggest involvement of the entorhinal cortex (EC) in schizophrenic psychoses. However, the extent and nature of the possible pathogenetical process underlying the observed alterations of this limbic key region for processing of multimodal sensory information remains unclear. Three-dimensional high-resolution MRI volumetry and evaluation of the regional diffusional anisotropy based on diffusion tensor imaging (DTI) were performed on the EC of 15 paranoid schizophrenic patients and 15 closely matched control subjects. In schizophrenic patients, EC volumes showed a slight, but not significant, decrease. However, the anisotropy values, expressed as inter-voxel coherences (COH), were found to be significantly decreased by 17.9% (right side) and 12.5% (left side), respectively, in schizophrenics. Reduction of entorhinal diffusional anisotropy can be hypothesized to be functionally related to disturbances in the perforant path, the principal efferent EC fiber tract supplying the limbic system with neuronal input from multimodal association centers. Combinations of different MRI modalities are a promising approach for the detection and characterization of subtle brain tissue alterations.

Reduced hippocampal anisotropy related to anteriorization of alpha EEG in schizophrenia

Dysfunctions of the hippocampus have been suggested to be related to schizophrenia, and reduced connectivity with other brain regions may be a key for the pathophysiology. The aim of this study was to investigate the effect of white matter anomalies in the hippocampus, as a sign of altered connectivity, on the brain electrical activity. We investigated seven first episode schizophrenic patients and seven age, gender and education-matched controls with diffusion tensor imaging and resting EEG. Fractional anisotropy was computed based on diffusion tensor imaging data for the right and left hippocampus for both groups. No group differences were found in hippocampal fractional anisotropy, EEG spectral power and topography. However a significant correlation was found between more anterior alpha activity and lower fractional anisotropy of both hippocampi in schizophrenics, but not in controls. More anterior alpha activity has been described in schizophrenia. We conclude that this feature might depict a group of schizophrenic patients with reduced hippocampal connectivity.

Dissociation of epileptic and inflammatory activity in Rasmussen Encephalitis

SUMMARY: Multimodal imaging was performed in Rasmussen Encephalitis (RE) during episodes of complex-partial and focal motor status epilepticus including independent component analysis of BOLD-fMRI, arterial spin labeling perfusion imaging and diffusion tensor imaging. The active epileptic network and topographically independent brain areas showed regional hyperperfusion and progressive atrophy. The results suggest that hyperperfusion outside of the epileptic network represent active inflammation in RE and the imaging protocol presented here, allows assessing thereby the disease activity non-invasively.

Dynamics and kinematics of eruptive activity at Fuego volcano, Guatemala 2005-2009

Volcanoes are the surficial expressions of complex pathways that vent magma and gasses generated deep in the Earth. Geophysical data record at least the partial history of magma and gas movement in the conduit and venting to the atmosphere. This work focuses on developing a more comprehensive understanding of explosive degassing at Fuego volcano, Guatemala through observations and analysis of geophysical data collected in 2005 – 2009. A pattern of eruptive activity was observed during 2005 – 2007 and quantified with seismic and infrasound, satellite thermal and gas measurements, and lava flow lengths. Eruptive styles are related to variable magma flux and accumulation of gas. Explosive degassing was recorded on broadband seismic and infrasound sensors in 2008 and 2009. Explosion energy partitioning between the ground and the atmosphere shows an increase in acoustic energy from 2008 to 2009, indicating a shift toward increased gas pressure in the conduit. Very-long-period (VLP) seismic signals are associated with the strongest explosions recorded in 2009 and waveform modeling in the 10 – 30 s band produces a best-fit source location 300 m west and 300 m below the summit crater. The calculated moment tensor indicates a volumetric source, which is modeled as a dike feeding a SW-dipping (35°) sill. The sill is the dominant component and its projection to the surface nearly intersects the summit crater. The deformation history of the sill is interpreted as: 1) an initial inflation due to pressurization, followed by 2) a rapid deflation as overpressure is explosively release, and finally 3) a reinflation as fresh magma flows into the sill and degasses. Tilt signals are derived from the horizontal components of the seismometer and show repetitive inflation deflation cycles with a 20 minute period coincident with strong explosions. These cycles represent the pressurization of the shallow conduit and explosive venting of overpressure that develops beneath a partially crystallized plug of magma. The energy released during the strong explosions has allowed for imaging of Fuego’s shallow conduit, which appears to have migrated west of the summit crater. In summary, Fuego is becoming more gas charged and its summit centered vent is shifting to the west - serious hazard consequences are likely.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.

Pathways that make voices - White matter changes in auditory hallucinations

BACKGROUND: The origin of auditory hallucinations, which are one of the core symptoms of schizophrenia, is still a matter of debate. It has been hypothesized that alterations in connectivity between frontal and parietotemporal speech-related areas might contribute to the pathogenesis of auditory hallucinations. These networks are assumed to become dysfunctional during the generation and monitoring of inner speech. Magnetic resonance diffusion tensor imaging is a relatively new in vivo method to investigate the directionality of cortical white matter tracts. OBJECTIVE: To investigate, using diffusion tensor imaging, whether previously described abnormal activation patterns observed during auditory hallucinations relate to changes in structural interconnections between the frontal and parietotemporal speech-related areas. METHODS: A 1.5 T magnetic resonance scanner was used to acquire twelve 5-mm slices covering the Sylvian fissure. Fractional anisotropy was assessed in 13 patients prone to auditory hallucinations, in 13 patients without auditory hallucinations, and in 13 healthy control subjects. Structural magnetic resonance imaging was conducted in the same session. Based on an analysis of variance, areas with significantly different fractional anisotropy values between groups were selected for a confirmatory region of interest analysis. Additionally, descriptive voxel-based t tests between the groups were computed. RESULTS: In patients with hallucinations, we found significantly higher white matter directionality in the lateral parts of the temporoparietal section of the arcuate fasciculus and in parts of the anterior corpus callosum compared with control subjects and patients without hallucinations. Comparing patients with hallucinations with patients without hallucinations, we found significant differences most pronounced in the left hemispheric fiber tracts, including the cingulate bundle. CONCLUSION: Our findings suggest that during inner speech, the alterations of white matter fiber tracts in patients with frequent hallucinations lead to abnormal coactivation in regions related to the acoustical processing of external stimuli. This abnormal activation may account for the patients' inability to distinguish self-generated thoughts from external stimulation.

White matter microstructure alterations of the medial forebrain bundle in melancholic depression

BACKGROUND The medial forebrain bundle (MFB) is a key structure of the reward system and connects the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortex (mOFC, lOFC) and the dorsolateral prefrontal cortex (dlPFC). Previous diffusion tensor imaging (DTI) studies in major depressive disorder point to white matter alterations of regions which may be incorporated in the MFB. Therefore, it was the aim of our study to probe white matter integrity of the MFB using a DTI-based probabilistic fibre tracking approach. METHODS 22 patients with major depressive disorder (MDD) (12 melancholic-MDD patients, 10 non-melancholic-MDD patients) and 21 healthy controls underwent DTI scans. We used a bilateral probabilistic fibre tracking approach to extract pathways between the VTA and NACC, mOFC, lOFC, dlPFC respectively. Mean fractional anisotropy (FA) values were used to compare structural connectivity between groups. RESULTS Mean-FA did not differ between healthy controls and all MDD patients. Compared to healthy controls melancholic MDD-patients had reduced mean-FA in right VTA-lOFC and VTA-dlPFC connections. Furthermore, melancholic-MDD patients had lower mean-FA than non-melancholic MDD-patients in the right VTA-lOFC connection. Mean-FA of these pathways correlated negatively with depression scale rating scores. LIMITATIONS Due to the small sample size and heterogeneous age group comparisons between melancholic and non-melancholic MDD-patients should be regarded as preliminary. CONCLUSIONS Our results suggest that the melancholic subtype of MDD is characterized by white matter microstructure alterations of the MFB. White matter microstructure is associated with both depression severity and anhedonia.

An anisotropic elastic-viscoplastic damage model for bone tissue

A new anisotropic elastic-viscoplastic damage constitutive model for bone is proposed using an eccentric elliptical yield criterion and nonlinear isotropic hardening. A micromechanics-based multiscale homogenization scheme proposed by Reisinger et al. is used to obtain the effective elastic properties of lamellar bone. The dissipative process in bone is modeled as viscoplastic deformation coupled to damage. The model is based on an orthotropic ecuntric elliptical criterion in stress space. In order to simplify material identification, an eccentric elliptical isotropic yield surface was defined in strain space, which is transformed to a stress-based criterion by means of the damaged compliance tensor. Viscoplasticity is implemented by means of the continuous Perzyna formulation. Damage is modeled by a scalar function of the accumulated plastic strain D(κ) , reducing all element s of the stiffness matrix. A polynomial flow rule is proposed in order to capture the rate-dependent post-yield behavior of lamellar bone. A numerical algorithm to perform the back projection on the rate-dependent yield surface has been developed and implemented in the commercial finite element solver Abaqus/Standard as a user subroutine UMAT. A consistent tangent operator has been derived and implemented in order to ensure quadratic convergence. Correct implementation of the algorithm, convergence, and accuracy of the tangent operator was tested by means of strain- and stress-based single element tests. A finite element simulation of nano- indentation in lamellar bone was finally performed in order to show the abilities of the newly developed constitutive model.

Fabric-mechanical property relationships of trabecular bone allografts are altered by supercritical CO2 treatment and gamma sterilization

Tissue grafts are implanted in orthopedic surgery every day. In order to minimize infection risk, bone allografts are often delipidated with supercritical CO2 and sterilized prior to implantation. This treatment may, however, impair the mechanical behavior of the bone graft tissue. The goal of this study was to determine clinically relevant mechanical properties of treated/sterilized human trabecular bone grafts, e.g. the apparent modulus, strength, and the ability to absorb energy during compaction. They were compared with results of identical experiments performed previously on untreated/fresh frozen human trabecular bone from the same anatomical site (Charlebois, 2008). We tested the hypothesis that the morphology–mechanical property relationships of treated cancellous allografts are similar to those of fresh untreated bone. The morphology of the allografts was determined by μCT. Subsequently, cylindrical samples were tested in unconfined and confined compression. To account for various morphologies, the experimental data was fitted to phenomenological mechanical models for elasticity, strength, and dissipated energy density based on bone volume fraction (BV/TV) and the fabric tensor determined by MIL. The treatment/sterilization process does not appear to influence bone graft stiffness. However, strength and energy dissipation of the bone grafts were found to be significantly reduced by 36% to 47% and 66% to 81%, respectively, for a broad range of volume fraction (0.14 < BV/TV < 0.39) and degree of anisotropy (1.24 < DA < 2.18). Since the latter properties are strongly dominated by BV/TV, the clinical consequences of this reduction can be compensated by using grafts with lower porosity. The data of this study suggests that an increase of 5–10% in BV/TV is sufficient to compensate for the reduced post-yield mechanical properties of treated/sterilized bone in monotonic compression. In applications where graft stiffness needs to be matched and strength is not a concern, treated allograft with the same BV/TV as an appropriate fresh bone graft may be used.

On new maximal supergravity and its BPS domain-walls

We revise the SU(3)-invariant sector of N  = 8 supergravity with dyonic SO(8) gaugings. By using the embedding tensor formalism, analytic expressions for the scalar potential, superpotential(s) and fermion mass terms are obtained as a function of the electromagnetic phase ω and the scalars in the theory. Equipped with these results, we explore non-supersymmetric AdS critical points at ω ≠ 0 for which perturbative stability could not be analysed before. The ω-dependent superpotential is then used to derive first-order flow equations and obtain new BPS domain-wall solutions at ω ≠ 0. We numerically look at steepest-descent paths motivated by the (conjectured) RG flows.

Null-wave giant gravitons from thermal spinning brane probes

We construct and analyze thermal spinning giant gravitons in type II/M-theory based on spherically wrapped black branes, using the method of thermal probe branes originating from the blackfold approach. These solutions generalize in different directions recent work in which the case of thermal (non-spinning) D3-brane giant gravitons was considered, and reveal a rich phase structure with various new properties. First of all, we extend the construction to M-theory, by constructing thermal giant graviton solutions using spherically wrapped M2- and M5-branes. More importantly, we switch on new quantum numbers, namely internal spins on the sphere, which are not present in the usual extremal limit for which the brane world volume stress tensor is Lorentz invariant. We examine the effect of this new type of excitation and in particular analyze the physical quantities in various regimes, including that of small temperatures as well as low/high spin. As a byproduct we find new stationary dipole-charged black hole solutions in AdS m × S n backgrounds of type II/M-theory. We finally show, via a double scaling extremal limit, that our spinning thermal giant graviton solutions lead to a novel null-wave zero-temperature giant graviton solution with a BPS spectrum, which does not have an analogue in terms of the conventional weakly coupled world volume theory.

How fluids bend: the elastic expansion for higher-dimensional black holes

Hydrodynamics can be consistently formulated on surfaces of arbitrary co-dimension in a background space-time, providing the effective theory describing long-wavelength perturbations of black branes. When the co-dimension is non-zero, the system acquires fluid-elastic properties and constitutes what is called a fluid brane. Applying an effective action approach, the most general form of the free energy quadratic in the extrinsic curvature and extrinsic twist potential of stationary fluid brane configurations is constructed to second order in a derivative expansion. This construction generalizes the Helfrich-Canham bending energy for fluid membranes studied in theoretical biology to the case in which the fluid is rotating. It is found that stationary fluid brane configurations are characterized by a set of 3 elastic response coefficients, 3 hydrodynamic response coefficients and 1 spin response coefficient for co-dimension greater than one. Moreover, the elastic degrees of freedom present in the system are coupled to the hydrodynamic degrees of freedom. For co-dimension-1 surfaces we find a 8 independent parameter family of stationary fluid branes. It is further shown that elastic and spin corrections to (non)-extremal brane effective actions can be accounted for by a multipole expansion of the stress-energy tensor, therefore establishing a relation between the different formalisms of Carter, Capovilla-Guven and Vasilic-Vojinovic and between gravity and the effective description of stationary fluid branes. Finally, it is shown that the Young modulus found in the literature for black branes falls into the class predicted by this approach - a relation which is then used to make a proposal for the second order effective action of stationary blackfolds and to find the corrected horizon angular velocity of thin black rings.