TDP-43-immunoreactive pathology in frontotemporal lobar degeneration with TDP proteinopathy (FTLD-TDP) with and without associated motor neuron disease (MND)

A proportion of patients with motor neuron disease (MND) exhibit frontotemporal dementia (FTD) and some patients with FTD develop the clinical features of MND. Frontotemporal lobar degeneration (FTLD) is the pathological substrate of FTD and some forms of this disease (referred to as FTLD-U) share with MND the common feature of ubiquitin-immunoreactive, tau-negative cellular inclusions in the cerebral cortex and hippocampus. Recently, the transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) has been found to be a major protein of the inclusions of FTLD-U with or without MND and these cases are referred to as FTLD with TDP-43 proteinopathy (FTLD-TDP). To clarify the relationship between MND and FTLD-TDP, TDP-43 pathology was studied in nine cases of FTLD-MND and compared with cases of familial and sporadic FTLD-TDP without associated MND. A principal components analysis (PCA) of the nine FTLD-MND cases suggested that variations in the density of surviving neurons in the frontal cortex and neuronal cytoplasmic inclusions (NCI) in the dentate gyrus (DG) were the major histological differences between cases. The density of surviving neurons in FTLD-MND was significantly less than in FTLD-TDP cases without MND, and there were greater densities of NCI but fewer neuronal intranuclear inclusions (NII) in some brain regions in FTLD-MND. A PCA of all FTLD-TDP cases, based on TDP-43 pathology alone, suggested that neuropathological heterogeneity was essentially continuously distributed. The FTLD-MND cases exhibited consistently high loadings on PC2 and overlapped with subtypes 2 and 3 of FTLD-TDP. The data suggest: (1) FTLD-MND cases have a consistent pathology, variations in the density of NCI in the DG being the major TDP-43-immunoreactive difference between cases, (2) there are considerable similarities in the neuropathology of FTLD-TDP with and without MND, but with greater neuronal loss in FTLD-MND, and (3) FTLD-MND cases are part of the FTLD-TDP 'continuum' overlapping with FTLD-TDP disease subtypes 2 and 3. © 2012 Nova Science Publishers, Inc. All rights reserved.

The visual cortex in alzheimer's disease:laminar distribution of the pathological changes in visual areas V1 and V2

Alzheimer's disease (AD) is an important neurodegenerative disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary responses to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances in complex visual tasks such as reading, visuospatial function, and in the naming and identification of objects. In addition, pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. To better understand degeneration of the visual cortex in AD, the laminar distribution of the SP and NFT was studied in visual areas V1 and V2 in 18 cases of AD which varied in disease onset and duration. In area V1, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In V2, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. The densities of SP in laminae I of V1 and NFT in lamina IV of V2 were negatively correlated with patient age. No significant correlations were observed in any cortical lamina between the density of NFT and disease onset or duration. However, in area V2, the densities of SP in lamina II and lamina V were negatively correlated with disease duration and disease onset respectively. In addition, there were several positive correlations between the densities of SP and NFT in V1 with those in area V2. The data suggest: (1) NFT pathology is greater in area V2 than V1, (2) laminae II/III of V1 and V2 are most affected by the pathology, (3) the formation of SP and NFT in V1 and V2 are interconnected, and (4) the pathology may spread between visual areas via the feed-forward short cortico-cortical connections. © 2012 by Nova Science Publishers, Inc. All rights reserved.

Design and analysis of a 2-DoF split-stator induction motor

A two degrees of freedom (2-DOF) actuator capable of producing linear translation, rotary motion, or helical motion would be a desirable asset to the fields of machine tools, robotics, and various apparatuses. In this paper, a novel 2-DOF split-stator induction motor was proposed and electromagnetic structure pa- rameters of the motor were designed and optimized. The feature of the direct-drive 2-DOF induction motor lies in its solid mover ar- rangement. In order to study the complex distribution of the eddy current field on the ferromagnetic cylinder mover and the motor’s operating characteristics, the mathematical model of the proposed motor was established, and characteristics of the motor were ana- lyzed by adopting the permeation depth method (PDM) and finite element method (FEM). The analytical and numerical results from motor simulation clearly show a correlation between the PDM and FEM models. This may be considered as a fair justification for the proposed machine and design tools.

Deconvolution of magnetic acoustic change complex (mACC)

Objective: The aim of this study was to design a novel experimental approach to investigate the morphological characteristics of auditory cortical responses elicited by rapidly changing synthesized speech sounds. Methods: Six sound-evoked magnetoencephalographic (MEG) responses were measured to a synthesized train of speech sounds using the vowels /e/ and /u/ in 17 normal hearing young adults. Responses were measured to: (i) the onset of the speech train, (ii) an F0 increment; (iii) an F0 decrement; (iv) an F2 decrement; (v) an F2 increment; and (vi) the offset of the speech train using short (jittered around 135. ms) and long (1500. ms) stimulus onset asynchronies (SOAs). The least squares (LS) deconvolution technique was used to disentangle the overlapping MEG responses in the short SOA condition only. Results: Comparison between the morphology of the recovered cortical responses in the short and long SOAs conditions showed high similarity, suggesting that the LS deconvolution technique was successful in disentangling the MEG waveforms. Waveform latencies and amplitudes were different for the two SOAs conditions and were influenced by the spectro-temporal properties of the sound sequence. The magnetic acoustic change complex (mACC) for the short SOA condition showed significantly lower amplitudes and shorter latencies compared to the long SOA condition. The F0 transition showed a larger reduction in amplitude from long to short SOA compared to the F2 transition. Lateralization of the cortical responses were observed under some stimulus conditions and appeared to be associated with the spectro-temporal properties of the acoustic stimulus. Conclusions: The LS deconvolution technique provides a new tool to study the properties of the auditory cortical response to rapidly changing sound stimuli. The presence of the cortical auditory evoked responses for rapid transition of synthesized speech stimuli suggests that the temporal code is preserved at the level of the auditory cortex. Further, the reduced amplitudes and shorter latencies might reflect intrinsic properties of the cortical neurons to rapidly presented sounds. Significance: This is the first demonstration of the separation of overlapping cortical responses to rapidly changing speech sounds and offers a potential new biomarker of discrimination of rapid transition of sound.