Miguel Sancho

Functional Connectivity in Mild Cognitive Impairment During a Memory Task: Implications for the Disconnection Hypothesis

Mild cognitive impairment (MCI) has been considered an intermediate state between healthy aging and dementia. The early damage in anatomical connectivity and progressive loss of synapses that characterize early Alzheimers disease suggest that MCI could also be a disconnection syndrome. Here, we compare the degree of synchronization of brain signals recorded with magnetoencephalography from patients (22) with MCI with that of healthy controls (19) during a memory task. Synchronization Likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. During the memory task patients showed higher interhemispheric synchronization than healthy controls between left and right -anterior temporo-frontal regions (in all studied frequency bands) and in posterior regions in the γ band. On the other hand, the connectivity pattern from healthy controls indicated two clusters of higher synchronization, one among left temporal sensors and another one among central channels. Both of them were found in all frequency bands. In the γ band, controls showed higher Synchronization Likelihood values than MCI patients between central-posterior and frontal-posterior channels and a high synchronization in posterior regions. The inter-hemispheric increased synchronization values could reflect a compensatory mechanism for the lack of efficiency of the memory networks in MCI patients. Therefore, these connectivity profiles support only partially the idea of MCI as a disconnection syndrome, as patients showed increased long distance inter-hemispheric connections but a decrease in antero-posterior functional connectivity.

Analysis of the influence of the cell geometry, orientation and cell proximity effects on the electric field distribution from direct RF exposure.

This paper shows the importance of using a cell model with the proper geometry, orientation and internal structure to study possible cellular effects from direct radiofrequency exposure. For this purpose, the electric field intensity is calculated, using the finite element numerical technique, in single- and multilayer spherical, cylindrical and ellipsoidal mammalian cell models exposed to linearly polarized electromagnetic plane waves of frequencies 900 and 2450 MHz. An extensive analysis is performed on the influence that the cell geometry and orientation with respect to the external field have in the value of the electric field induced in the membrane and cytoplasm. We also show the significant role that the cytoplasmic and extracellular bound water layers play in determining the electric field intensity for the cylindrical and ellipsoidal cell models. Finally, a study of the mutual interactions between cells shows that polarizing effects between cells significantly modify the values of field intensity within the cell.

The Default Mode Network is functionally and structurally disrupted in amnestic mild cognitive impairment — A bimodal MEG-DTI study

Over the past years, several studies on Mild Cognitive Impairment (MCI) and Alzheimers disease (AD) have reported Default Mode Network (DMN) deficits. This network is attracting increasing interest in the AD community, as it seems to play an important role in cognitive functioning and in beta amyloid deposition. Attention has been particularly drawn to how different DMN regions are connected using functional or structural connectivity. To this end, most studies have used functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET) or Diffusion Tensor Imaging (DTI). In this study we evaluated (1) functional connectivity from resting state magnetoencephalography (MEG) and (2) structural connectivity from DTI in 26 MCI patients and 31 age-matched controls. Compared to controls, the DMN in the MCI group was functionally disrupted in the alpha band, while no differences were found for delta, theta, beta and gamma frequency bands. In addition, structural disconnection could be assessed through a decreased fractional anisotropy along tracts connecting different DMN regions. This suggests that the DMN functional and anatomical disconnection could represent a core feature of MCI.

Transverse dipolar chaining in binary suspensions induced by rf fields

The problem of structure formation in colloidal systems composed of polarizable and conducting particles is considered. It is demonstrated that, in certain frequency ranges of the applied field, the dipole interaction leads to patterns whereby particles of different types are connected across field lines. By applying a Monte Carlo simulation, the main characteristics of the chaining process in a mixture of polystyrene beads and yeast cells are analysed. A good correlation between the theoretical model applied and experimental data is achieved. The data show that different aggregation patterns occur as a function of frequency.

Accurate dielectric modelling of shelled particles and cells

Dielectric modelling of shelled particles is usually based on analytical solutions of Laplaces equation, assuming a simplified spherical or ellipsoidal geometry. We propose a boundary element method, derived from an integral equation for the charge density at the interfaces, to overcome the limitations of the analytical approach. It can be applied to a variety of situations involving stress effects or dielectric response of individual particles and colloidal suspensions, with particular reference to biological cells. Effects of particle shape and membrane structure, are analyzed. Polarizabilities of a spheroid with a layer defined by confocal surfaces and different elongated particles with a layer of uniform thickness, are compared. Numerical stability and efficiency of the proposed method are shown to be excellent.

Cytoarchitectonic and Dynamic Origins of Giant Positive Local Field Potentials in the Dentate Gyrus

To determine why some pathways but not others produce sizable local field potentials (LFPs) and how far from the source can these be recorded, complementary experimental analyses and realistic modeling of specific brain structures are required. In the present study, we combined multiple in vivo linear recordings in rats and a tridimensional finite element model of the dentate gyrus, a curved structure displaying abnormally large positive LFPs. We demonstrate that the polarized dendritic arbour of granule cells (GCs), combined with the curved layered configuration of the population promote the spatial clustering of GC currents in the interposed hilus and project them through the open side at a distance from cell domains. LFPs grow up to 20 times larger than observed in synaptic sites. The dominant positive polarity of hilar LFPs was only produced by the synchronous activation of GCs in both blades by either somatic inhibition or dendritic excitation. Moreover, the corresponding anatomical pathways must project to both blades of the dentate gyrus as even a mild decrease in the spatial synchronization resulted in a dramatic reduction in LFP power in distant sites, yet not in the GC domains. It is concluded that the activation of layered structures may establish sharply delimited spatial domains where synaptic currents from one or another input appear to be segregated according to the topology of afferent pathways and the cytoarchitectonic features of the target population. These also determine preferred directions for volume conduction in the brain, of relevance for interpretation of surface EEG recordings.

Brain-wide slowing of spontaneous alpha rhythms in mild cognitive impairment.

The neurophysiological changes associated with Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10−2 for controls and (2.70 ± 0.49)·10−2 for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.

Influence of the APOE ε4 Allele and Mild Cognitive Impairment Diagnosis in the Disruption of the MEG Resting State Functional Connectivity in Sources Space

The apolipoprotein E (APOE) ε4 allele constitutes the major genetic risk for the development of late onset Alzheimers disease (AD). However, its influence on the neurodegeneration that occurs in early AD remains unresolved. In this study, the resting state magnetoencephalography(MEG) recordings were obtained from 27 aged healthy controls and 36 mild cognitive impairment (MCI) patients. All participants were divided into carriers and non-carriers of the ε4 allele. We have calculated the functional connectivity (FC) in the source space along brain regions estimated using the Harvard-Oxford atlas and in the classical bands. Then, a two way ANOVA analysis (diagnosis and APOE) was performed in each frequency band. The diagnosis effect consisted of a diminished FC within the high frequency bands in the MCI patients, affecting medial temporal and parietal regions. The APOE effect produced a decreased long range FC in delta band in ε4 carriers. Finally, the interaction effect showed that the FC pattern of the right frontal-temporal region could be reflecting a compensatory/disruption process within the ε4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE ε4 allele and MCI status affect the brains functional organization by analyzing the FC patterns in MEG resting state in the sources space. Therefore a combination of genetic, neuropsychological, and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration.

A study of the electric field distribution in erythrocyte and rod shape cells from direct RF exposure.

This paper shows the importance of using realistic cell shapes with the proper geometry and orientation to study the mechanisms of direct cellular effects from radiofrequency (RF) exposure. For this purpose, the electric field distribution within erythrocyte, rod and ellipsoidal cell models is calculated by using a finite element technique with adaptive meshing. The three cell models are exposed to linearly polarized electromagnetic plane waves of frequencies 900 and 2450 MHz. The results show that the amplification of the electric field within the membrane of the erythrocyte shape cell is more significant than that observed in other cell geometries. The results obtained show the dependence of the induced electric field distribution on frequency, electrical properties of membrane and cytoplasm and the orientation of the cell with respect to the applied field. The analysis of the transition of an erythrocyte shape to an ellipsoidal one shows that a uniformly shelled ellipsoid model is a rough approximation if a precise simulation of bioeffects in cells is desired.

The dynamic evolution of cell chaining in a biological suspension induced by an electrical field

The behaviour of biological cells in a suspension under the effect of an alternating electrical field was numerically simulated by solving the Langevin equation for each particle in the suspension. Cells were modelled as lossy dielectric shelled spheres and their interaction was treated in the dipole approximation. Using electrical parameters taken from the literature, viable and non-viable Saccharomices cerevisiae and Neurospora crassa cells immersed in a uniform field were studied. The aggregation into linear chains was effective only above a critical value of the external field. The obtained connectivity spectra matched the effective polarizability versus frequency curves, showing the possibility of using the study of aggregation patterns to investigate the physical properties of the various cellular components. A relevant difference among the types of cells studied was that we found very low connectivities for dead yeast compared with live yeast and Neurospora cells. For the last we could observe a two-regime aggregation: first, cells formed linear chains and then the chains condensed into columnar structures. These results demonstrate that the Brownian dynamics simulations can be used as a predictive tool in the study of the influences of various physical and biological conditions on the manipulation of cells using electrical fields.