Brain structure in movement disorders: a neuroimaging perspective.

Purpose of review: An overview of recent advances in structural neuroimaging and their impact on movement disorders research is presented. Recent findings: Novel developments in computational neuroanatomy and improvements in magnetic resonance image quality have brought further insight into the pathophysiology of movement disorders. Sophisticated automated techniques allow for sensitive and reliable in-vivo differentiation of phenotype/genotype related traits and their interaction even at presymptomatic stages of disease. Summary: Voxel-based morphometry consistently demonstrates well defined patterns of brain structure changes in movement disorders. Advanced stages of idiopathic Parkinson's disease are characterized by grey matter volume decreases in basal ganglia. Depending on the presence of cognitive impairment, volume changes are reported in widespread cortical and limbic areas. Atypical Parkinsonian syndromes still pose a challenge for accurate morphometry-based classification, especially in early stages of disease progression. Essential tremor has been mainly associated with thalamic and cerebellar changes. Studies on preclinical Huntington's disease show progressive loss of tissue in the caudate and cortical thinning related to distinct motor and cognitive phenotypes. Basal ganglia volume in primary dystonia reveals an interaction between genotype and phenotype such that brain structure changes are modulated by the presence of symptoms under the influence of genetic factors. Tics in Tourette's syndrome correlate with brain structure changes in limbic, motor and associative fronto-striato-parietal circuits. Computational neuroanatomy provides useful tools for in-vivo assessment of brain structure in movement disorders, allowing for accurate classification in early clinical stages as well as for monitoring therapy effects and/or disease progression.

Multi-modal assessment of long-term erythropoietin treatment after neonatal hypoxic-ischemic injury in rat brain.

Erythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury. Timing, dose and length of treatment in preterm brain damage remain to be defined. We have evaluated the effects of high dose and long-term EPO treatment in hypoxic-ischemic (HI) injury in 3 days old (P3) rat pups using histopathology, magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as functional assessment with somatosensory-evoked potentials (SEP). After HI, rat pups were assessed by MRI for initial damage and were randomized to receive EPO or vehicle. At the end of treatment period (P25) the size of resulting cortical damage and white matter (WM) microstructure integrity were assessed by MRI and cortical metabolism by MRS. Whisker elicited SEP were recorded to evaluate somatosensory function. Brains were collected for neuropathological assessment. The EPO treated animals did not show significant decrease of the HI induced cortical loss at P25. WM microstructure measured by diffusion tensor imaging was improved and SEP response in the injured cortex was recovered in the EPO treated animals compared to vehicle treated animals. In addition, the metabolic profile was less altered in the EPO group. Long-term treatment with high dose EPO after HI injury in the very immature rat brain induced recovery of WM microstructure and connectivity as well as somatosensory cortical function despite no effects on volume of cortical damage. This indicates that long-term high-dose EPO induces recovery of structural and functional connectivity despite persisting gross anatomical cortical alteration resulting from HI.

Dynamic properties of human brain structure: learning-related changes in cortical areas and associated fiber connections.

Recent findings in neuroscience suggest that adult brain structure changes in response to environmental alterations and skill learning. Whereas much is known about structural changes after intensive practice for several months, little is known about the effects of single practice sessions on macroscopic brain structure and about progressive (dynamic) morphological alterations relative to improved task proficiency during learning for several weeks. Using T1-weighted and diffusion tensor imaging in humans, we demonstrate significant gray matter volume increases in frontal and parietal brain areas following only two sessions of practice in a complex whole-body balancing task. Gray matter volume increase in the prefrontal cortex correlated positively with subject's performance improvements during a 6 week learning period. Furthermore, we found that microstructural changes of fractional anisotropy in corresponding white matter regions followed the same temporal dynamic in relation to task performance. The results make clear how marginal alterations in our ever changing environment affect adult brain structure and elucidate the interrelated reorganization in cortical areas and associated fiber connections in correlation with improvements in task performance.

Growth, optical characterization, and laser operation of a stoichiometric crystal KYb(WO4)(2)

We present our recent achievements in the growing and optical characterization of KYb(WO4)2 (hereafter KYbW) crystals and demonstrate laser operation in this stoichiometric material. Single crystals of KYbW with optimal crystalline quality have been grown by the top-seeded-solution growth slow-cooling method. The optical anisotropy of this monoclinic crystal has been characterized, locating the tensor of the optical indicatrix and measuring the dispersion of the principal values of the refractive indices as well as the thermo-optic coefficients. Sellmeier equations have been constructed valid in the visible and near-IR spectral range. Raman scattering has been used to determine the phonon energies of KYbW and a simple physical model is applied for classification of the lattice vibration modes. Spectroscopic studies (absorption and emission measurements at room and low temperature) have been carried out in the spectral region near 1 µm characteristic for the ytterbium transition. Energy positions of the Stark sublevels of the ground and the excited state manifolds have been determined and the vibronic substructure has been identified. The intrinsic lifetime of the upper laser level has been measured taking care to suppress the effect of reabsorption and the intrinsic quantum efficiency has been estimated. Lasing has been demonstrated near 1074 nm with 41% slope efficiency at room temperature using a 0.5 mm thin plate of KYbW. This laser material holds great promise for diode pumped high-power lasers, thin disk and waveguide designs as well as for ultrashort (ps/fs) pulse laser systems.

On the use of spatially discrete data to compute energy and mass balance

In many practical applications the state of field soils is monitored by recording the evolution of temperature and soil moisture at discrete depths. We theoretically investigate the systematic errors that arise when mass and energy balances are computed directly from these measurements. We show that, even with no measurement or model errors, large residuals might result when finite difference approximations are used to compute fluxes and storage term. To calculate the limits set by the use of spatially discrete measurements on the accuracy of balance closure, we derive an analytical solution to estimate the residual on the basis of the two key parameters: the penetration depth and the distance between the measurements. When the thickness of the control layer for which the balance is computed is comparable to the penetration depth of the forcing (which depends on the thermal diffusivity and on the forcing period) large residuals arise. The residual is also very sensitive to the distance between the measurements, which requires accurately controlling the position of the sensors in field experiments. We also demonstrate that, for the same experimental setup, mass residuals are sensitively larger than the energy residuals due to the nonlinearity of the moisture transport equation. Our analysis suggests that a careful assessment of the systematic mass error introduced by the use of spatially discrete data is required before using fluxes and residuals computed directly from field measurements.

High-momentum proton removal from 16 O and the (e,e'p) cross section

The cross section for the removal of high-momentum protons from 16O is calculated for high missing energies. The admixture of high-momentum nucleons in the 16O ground state is obtained by calculating the single-hole spectral function directly in the finite nucleus with the inclusion of short-range and tensor correlations induced by a realistic meson-exchange interaction. The presence of high-momentum nucleons in the transition to final states in 15N at 60¿100 MeV missing energy is converted to the coincidence cross section for the (e,e¿p) reaction by including the coupling to the electromagnetic probe and the final state interactions of the outgoing proton in the same way as in the standard analysis of the experimental data. Detectable cross sections for the removal of a single proton at these high missing energies are obtained which are considerably larger at higher missing momentum than the corresponding cross sections for the p-wave quasihole transitions. Cross sections for these quasihole transitions are compared with the most recent experimental data available.

Ultra-High Field (7 Tesla) MRI for Gamma Knife Surgery Targeting of the Ventro-Intermediate Nucleus: A Pilot in Vivo Study

Aim: Gamma Knife surgery (GKS) is a non-invasive neurosurgical stereotactic procedure, increasingly used as an alternative to open functional procedures. This includes the targeting of the ventro-intermediate (Vim) nucleus of the thalamus for tremor. We currently perform an indirect targeting, using the "quadrilatere of Guyot," as the Vim nucleus is not visible on current 3 Tesla (T) MRI acquisitions. The primary objective of the current study was to enhance anatomic imaging for Vim GKS using high-field (7 T) MRI, with the aim of refining the visualization and precision of anatomical targeting. Method: Five young healthy subjects (mean age 23 years) were scanned both on 3 and 7 T MRI in Lausanne University Hospital (CHUV) and Center for Biomedical Imaging (CIBM). Classical T1-weighted MPRAGE, T2 CISS sequences (replacing former ventriculography) and diffusion tensor imaging were acquired at 3T. We obtained high-resolution susceptibility weighted images (SWI) at 7T for the visualization of thalamic subparts. SWI was further integrated for the first time into Leksell Gamma Plan® (LGP) software and co-registered with the 3T images. A simulation of targeting of the Vim was done using the "quadrilatere of Guyot" methodology on the 3T images. Furthermore, a correlation with the position of the found target on SWI was performed. The atlas of Morel et al. was used to confirm the findings on a detailed computer analysis outside LGP. Also, 3T and 7T MRI of one patient undergoing GKS Vim thalamotomy, were obtained before and 2 years after the procedure, and studied similarly. Results: The use of SWI provided a superior resolution and improved image contrast within the central gray matter. This allowed visualization and direct delineation of groups of thalamic nuclei in vivo, including the Vim. The position of the target, as assessed with the "quadrilatere of Guyot" method on 3 T, perfectly matched with the supposed one of the Vim on the SWI. Furthermore, a 3-dimensional model of the Vim target area was created on the basis of 3T and 7T images. Conclusion: This is the first report of the integration of SWI high-field MRI into the LGP in healthy subjects and in one patient treated GKS Vim thalamotomy. This approach aims at the improvement of targeting validation and further direct targeting of the Vim in tremor. The anatomical correlation between the direct visualization on 7T and the current targeting methods on 3T seems to show a very good anatomical matching.

Exotic nonrelativistic string

We construct a classical nonrelativistic string model in 3+1 dimensions. The model contains a spurion tensor field that is responsible for the noncommutative structure of the model. Under double-dimensional reduction the model reduces to the exotic nonrelativistic particle in 2+1 dimensions.

Invariant decomposition of the retarded electromagnetic field.

The integral representation of the electromagnetic two-form, defined on Minkowski space-time, is studied from a new point of view. The aim of the paper is to obtain an invariant criteria in order to define the radiative field. This criteria generalizes the well-known structureless charge case. We begin with the curvature two-form, because its field equations incorporate the motion of the sources. The gauge theory methods (connection one-forms) are not suited because their field equations do not incorporate the motion of the sources. We obtain an integral solution of the Maxwell equations in the case of a flow of charges in irrotational motion. This solution induces us to propose a new method of solving the problem of the nature of the retarded radiative field. This method is based on a projection tensor operator which, being local, is suited to being implemented on general relativity. We propose the field equations for the pair {electromagnetic field, projection tensor J. These field equations are an algebraic differential first-order system of oneforms, which verifies automatically the integrability conditions.

Semiclassical back reaction in the formation of a straight cosmic string

We derive the back reaction on the gravitational field of a straight cosmic string during its formation due to the gravitational coupling of the string to quantum matter fields. A very simple model of string formation is considered. The gravitational field of the string is computed in the linear approximation. The vacuum expectation value of the stress tensor of a massless scalar quantum field coupled to the string gravitational field is computed to one loop order. Finally, the back-reaction effect is obtained by solving perturbatively the semiclassical Einsteins equations.

Stochastic semiclassical equations for weakly inhomogeneous cosmologies

Semiclassical Einstein-Langevin equations for arbitrary small metric perturbations conformally coupled to a massless quantum scalar field in a spatially flat cosmological background are derived. Use is made of the fact that for this problem the in-in or closed time path effective action is simply related to the Feynman-Vernon influence functional which describes the effect of the ``environment,'' the quantum field which is coarse grained here, on the ``system,'' the gravitational field which is the field of interest. This leads to identify the dissipation and noise kernels in the in-in effective action, and to derive a fluctuation-dissipation relation. A tensorial Gaussian stochastic source which couples to the Weyl tensor of the spacetime metric is seen to modify the usual semiclassical equations which can be veiwed now as mean field equsations. As a simple application we derive the correlation functions of the stochastic metric fluctuations produced in a flat spacetime with small metric perturbations due to the quantum fluctuations of the matter field coupled to these perturbations.

Stochastic semiclassical cosmological models

We consider the classical stochastic fluctuations of spacetime geometry induced by quantum fluctuations of massless nonconformal matter fields in the early Universe. To this end, we supplement the stress-energy tensor of these fields with a stochastic part, which is computed along the lines of the Feynman-Vernon and Schwinger-Keldysh techniques; the Einstein equation is therefore upgraded to a so-called Einstein-Langevin equation. We consider in some detail the conformal fluctuations of flat spacetime and the fluctuations of the scale factor in a simple cosmological model introduced by Hartle, which consists of a spatially flat isotropic cosmology driven by radiation and dust.

Proposed gravitational wave observatory based on solid elastic spheres

Spherical gravitational wave (GW) detectors offer a wealth of so far unexplored possibilities to detect gravitational radiation. We find that a sphere can be used as a powerful testbed for any metric theory of gravity, not only general relativity as considered so far, by making use of a deconvolution procedure for all the electric components of the Riemann tensor. We also find that the spheres cross section is large at two frequencies, and advantageous at higher frequencies in the sense that a single antenna constitutes a real xylophone in its own. Proposed GW networks will greatly benefit from this. The main features of a two large sphere observatory are reported.

Cross section of a resonant-mass detector for scalar gravitational waves

Gravitationally coupled scalar fields, originally introduced by Jordan, Brans and Dicke to account for a non-constant gravitational coupling, are a prediction of many non-Einsteinian theories of gravity not excluding perturbative formulations of string theory. In this paper, we compute the cross sections for scattering and absorption of scalar and tensor gravitational waves by a resonant-mass detector in the framework of the Jordan-Brans-Dicke theory. The results are then specialized to the case of a detector of spherical shape and shown to reproduce those obtained in general relativity in a certain limit. Eventually we discuss the potential detectability of scalar waves emitted in a spherically symmetric gravitational collapse.

Stochastic semiclassical fluctuations in Minkowski spacetime

The semiclassical Einstein-Langevin equations which describe the dynamics of stochastic perturbations of the metric induced by quantum stress-energy fluctuations of matter fields in a given state are considered on the background of the ground state of semiclassical gravity, namely, Minkowski spacetime and a scalar field in its vacuum state. The relevant equations are explicitly derived for massless and massive fields arbitrarily coupled to the curvature. In doing so, some semiclassical results, such as the expectation value of the stress-energy tensor to linear order in the metric perturbations and particle creation effects, are obtained. We then solve the equations and compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. In the conformal field case, explicit results are obtained. These results hint that gravitational fluctuations in stochastic semiclassical gravity have a non-perturbative behavior in some characteristic correlation lengths.