369 research outputs found

    Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life

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    Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous group of maltreated individuals has confirmed the presence of abnormalities in the basal ganglia. Based on these studies and known dopaminergic abnormalities from studies in experimental animals using social isolation, we used a task of monetary reward anticipation to examine the functional integrity of brain regions previously shown to be implicated in reward processing. Our sample included a group of adolescents (n = 12) who had experienced global deprivation early in their lives in Romania prior to adoption into UK families. In contrast to a nonadopted comparison group (n = 11), the adoptees did not recruit the striatum during reward anticipation despite comparable performance accuracy and latency. These results show, for the first time, an association between early institutional deprivation and brain reward systems in humans and highlight potential neural vulnerabilities resulting from such exposure

    Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees study

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    The adoption into the UK of children who have been reared in severely deprived conditions provides an opportunity to study possible association between very early negative experiences and subsequent brain development. This cross-sectional study was a pilot for a planned larger study quantifying the effects of early deprivation on later brain structure. We used magnetic resonance imaging (MRI) to measure the sizes of three key brain regions hypothesized to be sensitive to early adverse experiences. Our sample was a group of adoptee adolescents (N = 14) who had experienced severe early institutional deprivation in Romania and a group of non-institutionalised controls (N = 11). The total grey and white matter volumes were significantly smaller in the institutionalised group compared with a group of non-deprived, non-adopted UK controls. After correcting for difference in brain volume, the institutionalised group had greater amygdala volumes, especially on the right, but no differences were observed in hippocampal volume or corpus callosum mid-sagittal area. The left amygdala volume was also related to the time spent in institutions, with those experiencing longer periods of deprivation having a smaller left amygdala volume. These pilot findings highlight the need for future studies to confirm the sensitivity of the amygdala to early deprivation

    Book Reviews

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    Conventions, the Australian Constitution and the future by L.J.M. Cooray, reviewed by James Crawford. Family law and social policy by J. Eekelaar, reviewed by Rebecca J. Bailey. Evidence, Proof and Probability by Sir Richard Eggleston, reviewed by A.L.C. Ligertwood. Family law in Australia by H.A. Finlay, reviewed by Rebecca J. Bailey. Law and legal science by J.W. Harris, reviewed by M.J. Detmold. Barwick by David Marr, reviewed by Steven Churches. A constitutional History of Australia by W.G. McMinn, reviewed by James Crawford. Lawyers and their work in New South Wales : preliminary report by Roman Tomasic and Cedric Bullard, Lawyers in commerce? by Rosemary Hoskins, reviewed by J. Doyle. Cases and materials on evidence by P.K. Waight and C.R. Williams, reviewed by Philip McNamara

    Integrating neuroimaging and gene expression data using the imaging transcriptomics toolbox

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    The integration of neuroimaging and transcriptomics data, Imaging Transcriptomics, is becoming increasingly popular but standardized workflows for its implementation are still lacking. We describe the Imaging Transcriptomics toolbox, a new package that implements a full imaging transcriptomics pipeline using a user-friendly, command line interface. This toolbox allows the user to identify patterns of gene expression which correlates with a specific neuroimaging phenotype and perform gene set enrichment analyses to inform the biological interpretation of the findings using up-to-date methods. For complete details on the use and execution of this protocol, please refer to Martins et al. (2021)

    Transcriptional and cellular signatures of cortical morphometric remodelling in chronic pain

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    Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. Although the development of chronic pain is moderately heritable, how disease-related alterations at the microscopic genetic architecture drive macroscopic brain abnormalities is currently largely unknown. Here, we examined alterations in morphometric similarity (MS) and applied an integrative imaging transcriptomics approach to identify transcriptional and cellular correlates of these MS changes, in 3 independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain, and fibromyalgia) and age-matched and sex-matched pain-free controls. We uncover a novel pattern of cortical MS remodelling involving mostly small-to-medium MS increases in the insula and limbic cortex (none of these changes survived stringent false discovery rate correction for the number of regions tested). This pattern of changes is different from that observed in patients with major depression and cuts across the boundaries of specific pain syndromes. By leveraging transcriptomic data from Allen Human Brain Atlas, we show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes related to pain and broadly involved in the glial immune response and neuronal plasticity. Our findings bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of chronic pain. Although correlational, our data suggest that cortical remodelling in chronic pain might be shaped by multiple elements of the cellular architecture of the brain and identifies several pathways that could be prioritized in future genetic association or drug development studies

    Segregating the Cerebral Mechanisms of Antidepressants and Placebo in Fibromyalgia

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    Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology

    Overlapping Structural and Functional Brain Changes in Patients With Long‐Term Exposure to Fibromyalgia Pain

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    Objective—There is vast evidence for brain aberrations in patients with fibromyalgia (FM) and it is possible that central plasticity is critical for the transition from acute to chronic pain. However, the relationship between brain structure and function is poorly investigated. Methods—The present study, including 26 FM patients and 13 age- and gender-matched healthy controls, investigated the differences between patients and controls regarding functional connectivity during intermittent pressure pain and measures of brain structure. Magnetic resonance imaging (MRI) was used to obtain high-resolution anatomical images and functional MRI scans for measures of pain-evoked brain activity. Results—FM patients displayed a distinct overlap between decreased cortical thickness, brain volumes and measures of functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, we found associations between structural and functional changes in the mesolimbic areas of the brain and comorbid depressive symptoms in FM patients. Conclusion—The combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. Our data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers to predict the development of FM and other pain disorders

    The use of natural site derived materials as concrete aggregate.

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    Includes abstract.Includes bibliographical references.This thesis focuses on the use of site-derived fine material, in its natural form, as aggregate in concrete construction. It is proposed that the utilisation of this type of concrete aggregate will lead to; the preservation of natural materials that would otherwise have to be beneficiated off site, the reduction of waste material produced on a construction site, and an overall energy saving
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