Different brain areas require different analysis models: fMRI observations in Parkinson’s disease

Foreseeing how specific brain areas respond in time to a stimulus can be a prerequisite for a successfully conceived fMRI experiment. We demonstrate that in medicated Parkinson’s disease patients, putamen's activation peaks around the onset of tapping but does not persist throughout the tapping block, whereas sustained activation is observed in the motor cortex. Consequently, in the widely used tapping paradigm “On vs. Off L-DOPA”, the drug effect remains undetected if statistical analysis apply a block design instead of an event-related one. Ignoring this information can lead to fallacious conclusions which suggests using different models to investigate different brain regions

Improving brain imaging in Parkinson's disease by accounting for simultaneous motor output

Parkinson's disease leads to a variety of movement impairments. While studying the disease with fMRI, the main motivation for the research becomes one of its major obstacles: the motor output is unpredictable. Therefore it is troublesome to access, inside the scanner, performances of motor tasks and reliably relate them to brain measurements. We proposed to overcome this by expanding the patients’ number and restricting statistical criteria from a previous study which used a glove with non-magnetic sensors during scanning. Our results revealed basal ganglia not observed in the previous study confirming the usefulness of the device in fMRI studies

Modulatory effects of levodopa on cerebellar connectivity in Parkinson’s disease

Levodopa has been the mainstay of symptomatic therapy for Parkinson’s disease (PD) for the last five decades. However, it is associated with the development of motor fluctuations and dyskinesia, in particular after several years of treatment. The aim of this study was to shed light on the acute brain functional reorganization in response to a single levodopa dose. Functional magnetic resonance imaging (fMRI) was performed after an overnight withdrawal of dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group of 24 PD patients. Eigenvector centrality was calculated in both treatment states using resting-state fMRI. This offers a new data-driven and parameter-free approach, similar to Google’s PageRank algorithm, revealing brain connectivity alterations due to the effect of levodopa treatment. In all PD patients, levodopa treatment led to an improvement of clinical symptoms as measured with the Unified Parkinson’s Disease Rating Scale motor score (UPDRS-III). This therapeutic effect was accompanied with a major connectivity increase between cerebellar brain regions and subcortical areas of the motor system such as the thalamus, putamen, globus pallidus, and brainstem. The degree of interconnectedness of cerebellar regions correlated with the improvement of clinical symptoms due to the administration of levodopa. We observed significant functional cerebellar connectivity reorganization immediately after a single levodopa dose in PD patients. Enhanced general connectivity (eigenvector centrality) was associated with better motor performance as assessed by UPDRS-III score. This underlines the importance of considering cerebellar networks as therapeutic targets in PD

Improving fMRI in Parkinson's disease by accounting for realistic motor output

In Parkinson's disease (PD), the motor loop functioning and the patients’ motor output are unpredictable, due to brain compensatory mechanisms initiated up to decades before diagnosis. Consequently, the accuracy of motor tasks during fMRI is impeded, and deviations of the movement performance affect results. Kinematic modeling based on simultaneous measurements with MR-compatible gloves has been previously proposed as means to address this problem and outperform conventional boxcar modeling (Standard). Here, we adopted this approach in a larger cohort along with conservative statistics employing family-wise error (FWE) correction at the voxel level (p< 0.05) to be less prone to produce false positives

Causality in relativistic many body theory

The stability of the nuclear matter system with respect to density fluctuations is examined exploring in detail the pole structure of the electro-nuclear response functions. Making extensive use of the method of dispersion integrals we calculate the full polarization propagator not only for real energies in the spacelike and timelike regime but also in the whole complex energy plane. The latter proved to be necessary in order to identify unphysical causality violating poles which are the consequence of a neglection of vacuum polarization. On the contrary it is shown that Dirac sea effects stabilize the nuclear matter system shifting the unphysical pole from the upper energy plane back to the real axis. The exchange of strength between these real timelike collective excitations and the spacelike energy regime is shown to lead to a reduction of the quasielastic peak as it is seen in electron scattering experiments. Neglecting vacuum polarization one also obtains a reduction of the quasielastic peak but in this case the strength is partly shifted to the causality violating pole mentioned above which consequently cannot be considered as a physical reliable result. Our investigation of the response function in the energy region above the threshold of nucleon anti-nucleon production leads to another remarkable result. Treating the nucleons as point-like Dirac particles we show that for any isospin independent NN-interaction RPA-correlations provide a reduction of the production amplitude for $p\bar p$-pairs by a factor 2.Comment: 19 pages Latex including 12 postscript figure

The characterization of Vicker`s microhardness indentations and pile-up profiles as a strain-hardening microprobe

Microhardness measurements have long been used to examine strength properties and changes in strength properties in metals, for example, as induced by irradiation. Microhardness affords a relatively simple test that can be applied to very small volumes of material. Microhardness is nominally related to the flow stress of the material at a fixed level of plastic strain. Further, the geometry of the pile-up of material around the indentation is related to the strain-hardening behavior of a material; steeper pile-ups correspond to smaller strain-hardening rates. In this study the relationship between pile-up profiles and strain hardening is examined using both experimental and analytical methods. Vickers microhardness tests have been performed on a variety of metal alloys including low alloy, high Cr and austenitic stainless steels. The pile-up topology around the indentations has been quantified using confocal microscopy techniques. In addition, the indentation and pile-up geometry has been simulated using finite element method techniques. These results have been used to develop an improved quantification of the relationship between the pile-up geometry and the strain-hardening constitutive behavior of the test material