Alterations in Multiple Measures of White Matter Integrity in Normal Women at High Risk for Alzheimer\u27s Disease

There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer\u27s disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging data [including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA) and radial diffusivity (DR)] and volumetric comparisons of medial temporal lobe (MTL) structures were conducted. Results indicated equivalent entorhinal cortex and hippocampal volumes between risk groups. Nevertheless, the high risk group showed decreased microstructural integrity in WM tracts with direct and secondary connections to the MTL. The predominant alteration in WM integrity in the high AD-risk group was decreased FA not solely driven by either DA or DR changes alone in regions where no MD changes were observed. A second pattern observed in a smaller number of regions involved decreased FA and increased DR. These results suggest that disconnection of MTL-neocortical fiber pathways represents a very early event in the course of AD and suggest that demyelination may represent one contributing mechanism

Model-based control algorithms for the quadruple tank system: An experimental comparison

We compare the performance of proportional-integral-derivative (PID) control, linear model predictive control (LMPC), and nonlinear model predictive control (NMPC) for a physical setup of the quadruple tank system (QTS). We estimate the parameters in a continuous-discrete time stochastic nonlinear model for the QTS using a prediction-error-method based on the measured process data and a maximum likelihood (ML) criterion. In the NMPC algorithm, we use this identified continuous-discrete time stochastic nonlinear model. The LMPC algorithm is based on a linearization of this nonlinear model. We tune the PID controller using Skogestad's IMC tuning rules using a transfer function representation of the linearized model. Norms of the observed tracking errors and the rate of change of the manipulated variables are used to compare the performance of the control algorithms. The LMPC and NMPC perform better than the PID controller for a predefined time-varying setpoint trajectory. The LMPC and NMPC algorithms have similar performance.Comment: 6 pages, 5 figures, 3 tables, to be published in Foundations of Computer Aided Process Operations / Chemical Process Control (FOCAPO/CPC 2023). Hilton San Antonio Hill Country, San Antonio, Texa

In Situ Detection of Active Edge Sites in Single-Layer MoS2_2 Catalysts

MoS2 nanoparticles are proven catalysts for processes such as hydrodesulphurization and hydrogen evolution, but unravelling their atomic-scale structure under catalytic working conditions has remained significantly challenging. Ambient pressure X-ray Photoelectron Spectroscopy (AP-XPS) allows us to follow in-situ the formation of the catalytically relevant MoS2 edge sites in their active state. The XPS fingerprint is described by independent contributions to the Mo3d core level spectrum whose relative intensity is sensitive to the thermodynamic conditions. Density Functional Theory (DFT) is used to model the triangular MoS2 particles on Au(111) and identify the particular sulphidation state of the edge sites. A consistent picture emerges in which the core level shifts for the edge Mo atoms evolve counter-intuitively towards higher binding energies when the active edges are reduced. The shift is explained by a surprising alteration in the metallic character of the edge sites, which is a distinct spectroscopic signature of the MoS2 edges under working conditions

Dissociation of Automatic and Strategic Lexical-semantics: Functional Magnetic Resonance Imaging Evidence for Differing Roles of Multiple Frontotemporal Regions

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and target being manipulated. Study 1 demonstrated automatic semantic priming in the left mid-fusiform gyrus (mid-FFG) and strategic semantic priming in five regions: left middle temporal gyrus (MTG), bilateral anterior cingulate, anterior left inferior prefrontal cortex (aLIPC), and posterior LIPC (pLIPC). These priming effects were explored in more detail in two subsequent studies. Study 2 replicated the automatic priming effect in mid-FFG and demonstrated that automatic priming in this region is preferential for the semantic domain. Study 3 demonstrated a neural dissociation in regions contributing to the strategic semantic priming effect. Strategic semantic facilitation was observed in the aLIPC and MTG, whereas strategic semantic inhibition was observed in the pLIPC and anterior cingulate. These studies provide reproducible evidence for a neural dissociation between three well established components of the lexical-semantic processing system

White Matter Diffusion Alterations in Normal Women at Risk of Alzheimer\u27s Disease

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer\u27s disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal fasciculi (particularly posteriorly), the splenium of the corpus callosum, subcallosal white matter and the cingulum bundle. These findings demonstrate that specific white matter pathways are altered in normal women at increased risk of AD years before the expected onset of cognitive symptoms

Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

Parkinson\u27s disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients

Dopaminergic Modulation of Memory and Affective Processing in Parkinson Depression

Depression is common in Parkinson\u27s disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson\u27s disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson\u27s disease participated. Ten of these patients were depressed according to DSM IV criteria. Results revealed a statistically significant interaction between depression and medication status on three measures of verbal memory and a facial affect naming task. In all cases, depressed Parkinson\u27s patients performed significantly more poorly while on dopaminergic medication than while off. The opposite pattern emerged for the non-depressed Parkinson\u27s group. The administration of dopaminergic medication to depressed Parkinson patients may carry unintended risks

Brain Structure Changes over Time in Normal and Mildly Impaired Aged Persons

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a cerebrospinal fluid (CSF) expansion rate of 2.97 ± 0.07 ml/year (0.22 ± 0.04%/year). Hippocampal volume loss rate was higher than the GM and CSF global rates, 0.0114 ± 0.0004 ml/year (0.49 ± 0.04%/year). Regions of greatest GM loss were posterior inferior frontal lobe, medial parietal lobe and dorsal cerebellum. Rates of GM loss and CSF expansion were on the low end of the range of other published values, perhaps due to the relatively good health of the elder volunteers in this study. An additional smaller group of 6 subjects diagnosed with MCI at baseline were followed as well, and comparisons were made with the normal group in terms of both global and regional GM loss and CSF expansion rates. An increased rate of GM loss was found in the hippocampus bilaterally for the MCI group

Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

Parkinson’s disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients

Alzheimer\u27s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially During Resting and Task States

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults