The thalamus as a putative biomarker in neurodegenerative disorders

Objective: This review provides a brief account of the clinically relevant functional neuroanatomy of the thalamus, before considering the utility of various modalities utilised to image the thalamus and technical challenges therein, and going on to provide an overview of studies utilising structural imaging techniques to map thalamic morphology in the spectrum of neurodegenerative disorders. Methods: A systematic search was conducted for peer-reviewed studies involving structural neuroimaging modalities investigating the morphology (shape and/ or size) of the thalamus in the spectrum of neurodegenerative disorders. Results: Whilst the precise role of the thalamus in the healthy brain remains unclear, there is a large body of knowledge accumulating which defines more precisely its functional connectivity within the connectome, and a burgeoning literature implicating its involvement in neurodegenerative disorders. It is proposed that correlation of clinical features with thalamic morphology (as a component of a quantifiable subcortical connectome) will provide a better understanding of neuropsychiatric dysfunction in various neurodegenerative disorders, potentially yielding clinically useful endophenotypes and disease biomarkers. Conclusions: Thalamic biomarkers in the neurodegenerative disorders have great potential to provide clinically meaningful knowledge regarding not only disease onset and progression, but may yield targets of and perhaps a way of gauging response to future disease-modifying modalities

Reviewing the preclinical curriculum in a problem based learning driven medical program: Challenges and strategies

In order for medical curricula to remain progressive and contemporary, continuous review is critical to ensure that the learners are directed to achieve the intended goals and become workforce ready. We developed a framework for continuous curriculum review at the School of Medicine Fremantle (The University of Notre Dame Australia), taking the key aspects of a curriculum review process into consideration. In planning and implementing the review process we identified several challenges, including management of metadata, work load on staff members, and evaluation. These challenges were addressed successfully by applying necessary strategies using limited resources. The framework we have developed provides a guide to key stakeholders who are involved in medical curriculum review and development

Boys interrupted : sex between men in post-Franco Spanish cinema.

The synthesis and characterization of a stable, acyclic two-coordinate silylene, Si­(SAr^Me₆)₂ [Ar^Me₆ = C₆H₃-2,6­(C₆H₂-2,4,6-Me₃)₂], by reduction of Br₂Si­(SAr^Me₆)₂ with a magnesium­(I) reductant is described. It features a V-shaped silicon coordination with a S–Si–S angle of 90.52(2)° and an average Si–S distance of 2.158(3) Å. Although it reacts readily with an alkyl halide, it does not react with hydrogen under ambient conditions, probably as a result of the ca. 4.3 eV energy difference between the frontier silicon lone pair and 3p orbitals

The predictive validity of parent and teacher reports of ADHD symptoms

The objectives were to evaluate the ability of the Inattention and Hyperactivity-Impulsivity factors of the ADHD Rating Scale-IV to differentiate children with ADHD from a control group and to discriminate children with different subtypes of ADHD. Also, we sought to determine optimal cutoff scores on the teacher and parent versions of this scale for making diagnostic decisions about ADHD. In a sample of 92 boys and girls 6 to 14 years of age referred to a regional ADHD program, we assessed ADHD diagnostic status using categorical and dimensional approaches as well as parent- and teacher-report measures. Logistic regression analyses showed that the Inattention and Hyperactivity-Impulsivity factors of the ADHD Rating Scale-IV were effective in discriminating children with ADHD from a control group and differentiating children with ADHD, Combined Type from ADHD, Inattentive Type. Although both teacher and parent ratings were significantly predictive of diagnostic status, teacher ratings made a stronger contribution to the prediction of subtype membership. Using symptom utility estimates, optimal cutoff scores on the Inattention and Hyperactivity-Impulsivity scales for predicting subtypes of ADHD were determined

Regional structural hypo- and hyperconnectivity of frontal-striatal and frontal-thalamic pathways in behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty‐four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.Miller Family Bridgewater Illawarra Health and Medical Research Initiative Summer Scholarship; The Swedish Alzheimer foundation; Thureus foundation; The Swedish Society for Medical Research; The Bente Rexed Gersteds Foundation for Brain Researc

Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

Background: Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD. Objective: To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD. Methods: Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated. Results: Hypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes. Conclusions: This exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings

AUSSIE – the Australian United States Scandinavian Imaging Exchange: an innovative virtual integrated health research network embedded in health care

To describe the development, design and function of an innovative international clinical research network for neuroimaging research based in Australia within a joint state health service/medical school. This network focuses upon identifying neuroimaging biomarkers for neuropsychiatric and neurodegenerative disease

DNA methylation predicts age and provides insight into exceptional longevity of bats

This work was supported by a Paul G. Allen Frontiers Group grant to S.H., the University of Maryland, College of Computer, Mathematical and Natural Sciences to G.S.W., an Irish Research Council Consolidator Laureate Award to E.C.T., a UKRI Future Leaders Fellowship (MR/T021985/1) to S.C.V. and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to P.A.F. S.C.V. and P.D. were supported by a Max Planck Research Group awarded to S.C.V. by the Max Planck Gesellschaft, and S.C.V. and E.Z.L. were supported by a Human Frontiers Science Program Grant (RGP0058/2016) awarded to S.C.V. L.J.G. was supported by an NSERC PGS-D scholarship.Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.Publisher PDFPeer reviewe