50 research outputs found
Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies
The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer’s disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic–ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD
Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology
Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology
Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology:The impact of researchers choices on the selection of treatment targets using the experience sampling methodology
OBJECTIVE: One of the promises of the experience sampling methodology (ESM) is that a statistical analysis of an individual’s emotions, cognitions and behaviors in everyday-life could be used to identify relevant treatment targets. A requisite for clinical implementation is that outcomes of such person-specific time-series analyses are not wholly contingent on the researcher performing them. METHODS: To evaluate this, we crowdsourced the analysis of one individual patient’s ESM data to 12 prominent research teams, asking them what symptom(s) they would advise the treating clinician to target in subsequent treatment. RESULTS: Variation was evident at different stages of the analysis, from preprocessing steps (e.g., variable selection, clustering, handling of missing data) to the type of statistics and rationale for selecting targets. Most teams did include a type of vector autoregressive model, examining relations between symptoms over time. Although most teams were confident their selected targets would provide useful information to the clinician, not one recommendation was similar: both the number (0–16) and nature of selected targets varied widely. CONCLUSION: This study makes transparent that the selection of treatment targets based on personalized models using ESM data is currently highly conditional on subjective analytical choices and highlights key conceptual and methodological issues that need to be addressed in moving towards clinical implementation
Quantitative neuropathology:an update on automated methodologies and implications for large scale cohorts
Consensus Paper: Radiological Biomarkers of Cerebellar Diseases
Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine
Relationship between structural abnormalities in the cerebellum and dementia, posttraumatic stress disorder and bipolar disorder
Neuronal Loss in the Brainstem and Cerebellum--Part of the Normal Aging Process? A Morphometric Study of the Vermis Cerebelli and Inferior Olivary Nucleus
Epigenetic modification of the oxytocin receptor gene is associated with child-parent neural synchrony during competition
Interpersonal neural synchrony (INS) occurs when neural electrical activity temporally aligns between individuals during social interactions. It has been used as a metric for interpersonal closeness, often during naturalistic child-parent interactions. This study evaluated whether other biological correlates of social processing predicted the prevalence of INS during child-parent interactions, and whether their observed cooperativity modulated this association. Child-parent dyads (n = 27) performed a visuospatial tower-building task in cooperative and competitive conditions. Neural activity was recorded using mobile electroencephalogram (EEG) headsets, and experimenters coded video-recordings post-hoc for behavioral attunement. DNA methylation of the oxytocin receptor gene (OXTRm) was measured, an epigenetic modification associated with reduced oxytocin activity and socioemotional functioning. Greater INS during competition was associated with lower child OXTRm, while greater behavioral attunement during competition and cooperation was associated with higher parent OXTRm. These differential relationships suggest that interpersonal dynamics as measured by INS may be similarly reflected by other biological markers of social functioning, irrespective of observed behavior. Children’s self-perceived communication skill also showed opposite associations with parent and child OXTRm, suggesting complex relationships between children’s and their parents’ social functioning. Our findings have implications for ongoing developmental research, supporting the utility of biological metrics in characterizing interpersonal relationships