Neurofibrillary tangles and plaques are not accompanied by white matter pathology in aged triple transgenic-Alzheimer disease mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aging populations. Although senile plaques and neurofibrillary tangles are well-established hallmarks of AD, changes in cerebral white matter correlate with cognitive decline and may increase the risk of the development of dementia. We used the triple transgenic (3xTg)-AD mouse model of AD, previously used to show that white matter changes precede plaque formation, to test the hypothesis that MRI detectable changes occur in the corpus callosum, external capsule and the fornix. T₂-weighted and diffusion tensor magnetic resonance imaging and histological stains were employed to assess white matter in older (11–17 months) 3xTg-AD mice and controls. We found no statistically significant changes in white matter between 3xTg-AD mice and controls, despite well-developed neurofibrillary tangles and beta amyloid immunoreactive plaques. Myelin staining was normal in affected mice. These data suggest that the 3xTg-AD mouse model does not develop MRI detectable white matter changes at the ages we examined.     

Rapid microscopic fractional anisotropy imaging via an optimized linear regression formulation

Water diffusion anisotropy in the human brain is affected by disease, trauma, and development. Microscopic fractional anisotropy (μFA) is a diffusion MRI (dMRI) metric that can quantify water diffusion anisotropy independent of neuron fiber orientation dispersion. However, there are several different techniques to estimate μFA and few have demonstrated full brain imaging capabilities within clinically viable scan times and resolutions. Here, we present an optimized spherical tensor encoding (STE) technique to acquire μFA directly from the 2nd order cumulant expansion of the powder averaged dMRI signal obtained from direct linear regression (i.e. diffusion kurtosis) which requires fewer powder-averaged signals than other STE fitting techniques and can be rapidly computed. We found that the optimal dMRI parameters for white matter μFA imaging were a maximum b-value of 2000 s/mm² and a ratio of STE to LTE tensor encoded acquisitions of 1.7 for our system specifications. We then compared two implementations of the direct regression approach to the well-established gamma model in 4 healthy volunteers on a 3 Tesla system. One implementation used mean diffusivity (D) obtained from a 2nd order fit of the cumulant expansion, while the other used a linear estimation of D from the low b-values. Both implementations of the direct regression approach showed strong linear correlations with the gamma model (ρ = 0.97 and ρ = 0.90) but mean biases of −0.11 and − 0.02 relative to the gamma model were also observed, respectively. All three μFA measurements showed good test-retest reliability (ρ ≥ 0.79 and bias = 0). To demonstrate the potential scan time advantage of the direct approach, 2 mm isotropic resolution μFA was demonstrated over a 10 cm slab using a subsampled data set with fewer powder-averaged signals that would correspond to a 3.3-min scan. Accordingly, our results introduce an optimization procedure that has enabled nearly full brain μFA in only several minutes.     

Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study

Object

Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency.

Materials and Methods

DKI was performed on 18 AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann–Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation.

Results

In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM.

Conclusion

Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.     

In-vivo diffusion MRI protocol optimization for the chimpanzee brain and examination of aging effects on the primate optic nerve at 3T

BackgroundDiffusion MRI (dMRI) data acquisition protocols are well-established on modern high-field clinical scanners for human studies. However, these protocols are not suitable for the chimpanzee (or other large-brained mammals) because of its substantial difference in head geometry and brain volume compared with humans. Therefore, an optimal dMRI data acquisition protocol dedicated to chimpanzee neuroimaging is needed.MethodsA multi-shot (4 segments) double spin-echo echo-planar imaging (MS-EPI) sequence and a single-shot double spin-echo EPI (SS-EPI) sequence were optimized separately for in vivo dMRI data acquisition of chimpanzees using a clinical 3T scanner. Correction for severe susceptibility-induced image distortion and signal drop-off of the chimpanzee brain was performed and evaluated using FSL software. DTI indices in different brain regions and probabilistic tractography were compared. A separate DTI data set from n=34 chimpanzees (13 to 56 years old) was collected using the optimal protocol. Age-related changes in diffusivity indices of optic nerve fibers were evaluated.ResultsThe SS-EPI sequence acquired dMRI data of the chimpanzee brain with approximately doubled the SNR as the MS-EPI sequence given the same scan time. The quality of white matter fiber tracking from the SS-EPI data was much higher than that from MS-EPI data. However, quantitative analysis of DTI indices showed no difference in most ROIs between the SS-EPI and MS-EPI sequences. The progressive evolution of diffusivity indices of optic nerves indicated mild changes in fiber bundles of chimpanzees aged 40 years and above.ConclusionThe single-shot EPI-based acquisition protocol provided better image quality of dMRI for chimpanzee brains and is recommended for in vivo dMRI study or clinical diagnosis of chimpanzees (or other large animals) using a clinical scanner. Also, the tendency of FA decrease or diffusivity increase in the optic nerve of aged chimpanzees was seen but did not show significant age-related changes, suggesting aging may have less impact on optic nerve fiber integrity of chimpanzees, in contrast to previous results for both macaque monkeys and humans.     

Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

Background

Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD)-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD) harbors three AD-related genetic loci: human PS1^M146V, human APP^swe, and human tau^P301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported.

Methods and results

In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation.

Conclusion

These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to examine stage-specific disease mechanisms and/or novel therapeutic interventions for AD.     

Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer’s disease

We report the first application of a novel diffusion-based MRI method, called diffusional kurtosis imaging (DKI), to investigate changes in brain tissue microstructure in patients with mild cognitive impairment (MCI) and AD and in cognitively intact controls. The subject groups were characterized and compared in terms of DKI-derived metrics for selected brain regions using analysis of covariance with a Tukey multiple comparison correction. Receiver operating characteristic (ROC) and binary logistic regression analyses were used to assess the utility of regional diffusion measures, alone and in combination, to discriminate each pair of subject groups. ROC analyses identified mean and radial kurtoses in the anterior corona radiata as the best individual discriminators of MCI from controls, with the measures having an area under the ROC curve (AUC) of 0.80 and 0.82, respectively. The next best discriminators of MCI from controls were diffusivity and kurtosis (both mean and radial) in the prefrontal white matter (WM), with each measure having an AUC between 0.77 and 0.79. Finally, the axial diffusivity in the hippocampus was the best overall discriminator of MCI from AD, having an AUC of 0.90. These preliminary results suggest that non-Gaussian diffusion MRI may be beneficial in the assessment of microstructural tissue damage at the early stage of MCI and may be useful in developing biomarkers for the clinical staging of AD.     

Region-Specific Susceptibilities to Cuprizone-Induced Demyelination of C57BL/6 Mouse: In vivo T2WI and DTI Studies at 7.0T

The cuprizone (CPZ) mouse model of demyelination was recognized and used to explore multiple sclerosis (MS)-like brain lesions. In this study, we assessed CPZ-treated mice using T₂-weighted imaging and diffusion tensor imaging (DTI). C57BL/6 mice treated with 2 weeks of 0.2 % CPZ-containing diet (n = 10) and regular chow diet (n = 10) were scanned with a 7.0 T MRI scanner (Agilent, USA), respectively, using fast spin-echo and fast spin-echo DTI sequences. The normalized T₂ signal intensity (normalized to the cerebrospinal fluid) was calculated and fractional anisotropy (FA value), mean diffusivity, axial diffusivity and radial diffusivity were measured in the brain region of the cerebral cortex (CTX), caudate putamen (CP), hippocampus (HP) and thalamus (TH). Compared with controls, increased normalized T₂ signal intensities and reduced FA values (p < 0.05) were observed in the CTX, HP and CP (p < 0.01), but not in TH in cuprizone-fed mice. In the regions of reduced FA values, an increase in mean diffusivity (p < 0.05) and radial diffusivity (p < 0.05) was also found. Significant decreased axial diffusivity was only observed in CTX (p < 0.05). DTI is sensitive to detecting cuprizone-induced demyelination of C57BL/6 mice. This study suggests that CTX, HP and CP are more susceptible to cuprizone-induced demyelination than TH. Our results also indicate that the decrease of FA value may be more likely due to increased radial diffusivity.     

Diffusion tensor imaging of oral carcinoma: Clinical evaluation and comparison with histopathological findings

PurposeThis study aims to assess the usefulness of diffusion tensor imaging (DTI) as a noninvasive method for the evaluation of histological grade and lymph node metastasis in patients with oral carcinoma (OC).Materials and methodsThirty-six consecutive patients with histologically confirmed OC underwent examination by 3-T MRI. DTI was performed using a single-shot echo-planar imaging sequence with b values of 0 and 1000 s/mm² and motion-probing gradients in 12 noncollinear directions. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were compared with histopathological findings. The DTI parameters were correlated with the histological grade of the OCs based on the World Health Organization grading criteria and the presence or absence of lymph node metastasis.ResultsThe FA values (0.275 ± 0.058) of OC were significantly lower than those of normal tongue, muscle, and parotid glands (P < 0.001 for all), and the MD, AD, and RD values (1.220 ± 0.149, 1.434 ± 0.172, and 1.019 ± 0.165 × 10⁻³ mm²/s, respectively) were significantly higher than their respective normal values (P < 0.001 for all). Significant inverse correlations with histological grades were shown for FA, MD, AD, and RD values in OC patients (r = −0.862, r = −0.797, r = −0.747, and r = −0.844, respectively; P < 0.001 for all). In addition, there was a significant difference in the FA values of metastatic and nonmetastatic lymph nodes (0.186 vs. 0.276), MD (0.923 vs. 1.242 × 10⁻³ mm²/s), AD (1.246 vs. 1.621 × 10⁻³ mm²/s), and RD (0.792 vs. 1.100 × 10⁻³ mm²/s; P < 0.001 for all).ConclusionsDTI may be clinically useful for the noninvasive evaluation of histological grade and lymph node metastasis in OC patients.     

Diffusivity mapping of the ovaries: Variability of apparent diffusion and kurtosis variables over the menstrual cycle and influence of oral contraceptives

PurposeWe aimed to investigate whether quantitative diffusivity variables of healthy ovaries vary during the menstrual cycle and to evaluate alterations in women using oral contraceptives (OC).MethodsThis prospective study (S-339/2016) included 30 healthy female volunteers, with (n = 15) and without (n = 15) intake of OC between 07/2017 and 09/2019. Participants underwent 3T diffusion-weighted MRI (b-values 0–2000 s/mm²) three times during a menstrual cycle (T1 = day 1–5; T2 = day 7–12; T3 = day 19–24). Both ovaries were manually three-dimensionally segmented on b = 1500 s/mm²; apparent diffusion coefficient (ADC) calculation and kurtosis fitting (D_app, K_app) were performed. Differences in ADC, D_app and K_app between time points and groups were compared using repeated measures ANOVA and t-test after Shapiro-Wilk and Brown-Forsythe test for normality and equal variance.ResultsIn women with a natural menstrual cycle, ADC and kurtosis variables showed significant changes in ovaries with the dominant follicle between T1 vs T2 and T1 vs T3, whilst no differences were observed between T2 vs T3: ADC ± SD for T1 1.524 ± 0.160, T2 1.737 ± 0.160, and T3 1.747 ± 0.241 μm²/ms (p = 0.01 T2 vs T1; p = 1.0 T2 vs T3, p = 0.003 T3 vs T1); D_app ± SD for T1 2.018 ± 0.140, T2 2.272 ± 0.189, and T3 2.230 ± 0.256 μm²/ms (p = 0.003 T2 vs T1, p = 1.0 T2 vs T3, p = 0.02 T3 vs T1); K_app ± SD for T1 0.614 ± 0.0339, T2 0.546 ± 0.0637, and T3 0.529 ± 0.0567 (p < 0.001 T2 vs T1, p = 0.86 T2 vs T3, p < 0.001 T3 vs T1). No significant differences were found in the contralateral ovaries or in females taking OC.ConclusionPhysiological cycle-dependent changes in quantitative diffusivity variables of ovaries should be considered especially when interpreting radiomics analyses in reproductive women.     

Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response

Background  

The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease) is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1), and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7–9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis.     

Anti-PrP<Superscript>C</Superscript> monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse

Background  

Alzheimer's Disease (AD) is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ) forms oligomers and fibrils which assemble into neuritic plaques. The most toxic form of Aβ is thought to be oligomeric. A recent study reveals the cellular prion protein, PrP^C, to be a receptor for Aβ oligomers. Aβ oligomers suppress LTP signal in murine hippocampal slices but activity remains when pretreated with the PrP monoclonal anti-PrP antibody, 6D11. We hypothesized that targeting of PrP^C to prevent Aβ oligomer-related cognitive deficits is a potentially novel therapeutic approach. APP/PS1 transgenic mice aged 8 months were intraperitoneally (i.p.) injected with 1 mg 6D11 for 5 days/week for 2 weeks. Two wild-type control groups were given either the same 6D11 injections or vehicle solution. Additional groups of APP/PS1 transgenic mice were given either i.p. injections of vehicle solution or the same dose of mouse IgG over the same period. The mice were then subjected to cognitive behavioral testing using a radial arm maze, over a period of 10 days. At the conclusion of behavioral testing, animals were sacrificed and brain tissue was analyzed biochemically or immunohistochemically for the levels of amyloid plaques, PrP^C, synaptophysin, Aβ40/42 and Aβ oligomers.     

Diffusion kurtosis imaging for the assessment of renal fibrosis of chronic kidney disease: A preliminary study

Purpose: To investigate the potential of diffusion kurtosis imaging (DKI) for the assessment of renal fibrosis in chronic kidney disease (CKD), using histopathology as the reference standard.Methods: Eighty-nine CKD patients and twenty healthy volunteers were recruited in this study. DKI was performed in all participants and all CKD patients received renal biopsy. The values of mean diffusivity (MD) and mean kurtosis (MK) in the renal cortex and medulla were compared between CKD patients and healthy volunteers. The Spearman correlation coefficient was calculated to assess the relationship between MD, MK values and the estimated glomerular filtration rate (eGFR), serum creatinine (SCr), 24 h urinary protein (24 h-UPRO), histopathological fibrosis score.Results: The medullary MD values were significantly lower than cortex, while the cortical MK values were significantly lower than medulla for all participants. Renal parenchymal MD values were significantly lower in the CKD patients than healthy controls, whereas MK values were significantly higher in the CKD patients than healthy controls. In the CKD patients, the significantly negative correlation was observed between the renal parenchymal MD values and the 24 h-UPRO, SCr, histopathological fibrosis score, as well as between the renal parenchymal MK values and the eGFR, while the significantly positive correlation was found between the renal parenchymal MD values and the eGFR, as well as between the renal parenchymal MK values and the 24 h-UPRO, SCr, histopathological fibrosis score.Conclusion: DKI shows great potential in the noninvasive assessment of renal fibrosis in CKD.     

Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory

Background  

Although a large body of knowledge about both brain structure and function has been gathered over the last decades, we still have a poor understanding of their exact relationship. Graph theory provides a method to study the relation between network structure and function, and its application to neuroscientific data is an emerging research field. We investigated topological changes in large-scale functional brain networks in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) by means of graph theoretical analysis of resting-state EEG recordings. EEGs of 20 patients with mild to moderate AD, 15 FTLD patients, and 23 non-demented individuals were recorded in an eyes-closed resting-state. The synchronization likelihood (SL), a measure of functional connectivity, was calculated for each sensor pair in 0.5–4 Hz, 4–8 Hz, 8–10 Hz, 10–13 Hz, 13–30 Hz and 30–45 Hz frequency bands. The resulting connectivity matrices were converted to unweighted graphs, whose structure was characterized with several measures: mean clustering coefficient (local connectivity), characteristic path length (global connectivity) and degree correlation (network 'assortativity'). All results were normalized for network size and compared with random control networks.     

Broadband Hybridly Polarized Vector Vortex Raman Microchip Laser

Hybridly polarized (HP) vector vortex Raman lasers dramatically extend their applications on optical microscopy, optical communication, and quantum information. Spatial light modulators and waveplates are widely used for generating HP vector vortex lasers, however, the performance and beam quality of HP vector vortex lasers are restricted by diffraction loss and low damage threshold of these optical elements. Here, HP vector vortex Raman microchip lasers constructed with Yb³⁺:Y₃Al₅O₁₂ (Yb:YAG) and vanadate (YVO₄) crystals is demonstrated. The states of polarization (SoP) of HP vector vortex lasers are combination of radial and anti-radial polarizations (RP-ARP), azimuthal and anti-azimuthal polarizations (AP-AAP). The SoP of HP vector vortex lasers can be controlled by adjusting the length of YVO₄ crystal and applying pump power. Maximum output powers are 456 and 586 mW with optical efficiency of 7.1% and 9.2% for HP vector vortex lasers with SoP of RP-ARP and AP-AAP. The HP vector vortex Raman lasers with SoP of RP-ARP and AP-AAP oscillate ≈1076 nm with bandwidths of 11.4 and 10.8 nm. High beam quality is achieved for HP vector vortex lasers with measured M² nearly equal to theoretical value. The broadband HP vector vortex Raman lasers with high beam quality extend applications on optical trapping, and quantum information processing.     

Thermal conductivity and thermal diffusivity of SiO<Subscript>2</Subscript> nanopowder

A 3ω approach for the simultaneous determination of the effective thermal conductivity and thermal diffusivity of nanopowder materials was developed. A 3ω experimental system was established, and the thermal properties of water and alcohol were measured to validate and estimate the accuracy of the current experimental system. The effective thermal conductivity and thermal diffusivity of the SiO₂ nanopowder with 375, 475, and 575 nm diameters were measured at 290–490 K and at different densities. At room temperature, the effective thermal conductivity and thermal diffusivity of the SiO₂ nanopowder increased with temperature; however, both values decreased as the particle diameter was reduced. An optimum SiO₂ powder density that decreased with decreasing diameter was also observed within the measurement range. The minimum effective thermal conductivity and maximum effective thermal diffusivity were obtained at 85 × 10⁻³ kg/L, when the particle diameter was 575 nm. The optimum densities of the particles with 375 and 475 nm diameters were less than 50.23 × 10⁻³ and 64.82 × 10⁻³ kg/L, respectively.     

Microstructure abnormity in the optic nerve of type 1 diabetic rats revealed by diffusion tensor imaging study

Diabetic retinopathy (DR) is one of a major complication of type 1 diabetes mellitus (T1DM) and a leading cause of blindness. Evidence of animal study has shown that it is not only a microvasucular lesion of the eye, but also a neurodegeneration disease of the visual system. However, the in vivo imaging evidence of axonal degeneration in the diabetic optic nerve is scarce. Diffusion tensor imaging (DTI) technique has been proved to be an effective tool to track the integrity of the nerve fibers in the central nervous system. In this study, type 1 diabetes was induced by intraperitoneally injecting a single dose of streptozotocin (STZ) into Sprague-Dawley rats. DTI combined with histological assessments was carried out on the optic nerve to clarify the microstructural alterations underlying DTI indices changes at 4 weeks (4 w), 8 weeks (8 w) and 12 weeks (12 w) after STZ induction. The retinal changes were analyzed by pathological evaluations at 4 weeks (4 w) and 12 weeks (12 w) after STZ induction. DTI results showed significantly decreased mean diffusivity (MD) and axial diffusivity (Da) in diabetic optic nerve compared to controls at 12 w. Atrophy in diabetic nerves was monitored by high resolution T₂-weighted images. Axonal degeneration without myelin loss of the optic nerve was confirmed by histological examination. Moreover, there are positive correlations between decreased diffusivities (MD and Da) in the optic nerve and reduced total axolemmal area. The diabetic rats showed intense glial activity since 4 w and thinning of the thickness in inner plexiform layer and nerve fiber layer at 12 w in the retina. In conclusion, DTI could in vivo monitor the progression of optic nerve degeneration in diabetes and the findings in our study would help supply axonal protection for DR in preclinical practice.     

Chronologically overlapping occurrences of nicotine-induced anxiety- and depression-related behavioral symptoms: effects of anxiolytic and cannabinoid drugs

Background  

Anxiety and depression are among the most frequently-observed psychiatric symptoms associated with nicotine (NC). In addition to the similarity to other addictive drugs, these NC-induced symptoms are characteristic in that the opposite behavioral effects, i.e. anxiolytic and antidepressant effects, which may reinforce the habitual use of NC, have also been reported. In the present study, the time course of anxiety- and depression-related behavioral alterations was examined in mice. Furthermore, based on the reported similarity in the mechanisms responsible for NC-induced anxiety- and depression-related symptoms, as well as the contribution of brain cannabinoid (CB) receptors to these behavioral symptoms, the effects of anxiolytics and CB receptor ligands (CBs) against these behavioral symptoms were investigated.     

Usefulness of event-related potentials in the assessment of mild cognitive impairment

Background  

The aim of this study was to determine if changes in latencies and amplitudes of the major waves of Auditory Event-Related Potentials (AERP), correlate with memory status of patients with mild cognitive impairment (MCI) and conversion to Alzheimer's disease (AD).     

QEPAS methane sensor performance for humidified gases

A trace gas sensor based on quartz enhanced photoacoustic spectroscopy (QEPAS) was evaluated using humidified nitrogen samples and ambient air. Relaxation processes following vibrational excitation of 2ν₃ state of CH₄ were investigated. Sensor performance at different gas pressures could be predicted based on a developed kinetic model. The experimentally determined normalized detection sensitivity for CH₄ in humid gas is 1.0×10^-8 cm^-1 W/Hz^1/2. PACS  82.80.Kq; 42.62.Fi     

Dynamic changes in GABA<Subscript>A</Subscript>receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery

Background  

The basal forebrain (BF) cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABA_A receptors (Rs) and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABA_ARs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep.