1,238 research outputs found

    Normalizing the Abnormal

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    The use of antipsychotic medication to manage psychosis, principally in those with a diagnosis of schizophrenia or bipolar disorder, is well established. Antipsychotics are effective in normalizing positive symptoms of psychosis in the short term (delusions, hallucinations and disordered thought). Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood. In this article, we propose a novel model of the long-term effects of antipsychotic administration focusing on the changes in brain metabolic homeostasis induced by the medication. We propose here that the brain metabolic normalization, that occurs in parallel to the normalization of psychotic symptoms following antipsychotic treatment, may not ultimately be sustainable by the cerebral tissue of some patients; these patients may be characterized by already reduced oxidative metabolic capacity and this may push the brain into an unsustainable metabolic envelope resulting in tissue remodeling. To support this perspective, we will review the existing data on the brain metabolic trajectories of patients with a diagnosis of schizophrenia as indexed using available neuroimaging tools before and after use of medication. We will also consider data from pre-clinical studies to provide mechanistic support for our model

    Supplementary Material, JOP772450_Supplementary_Table – Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits

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    Supplementary Material, JOP772450_Supplementary_Table for Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits by Ulrich Ettinger, Inga Meyhöfer, Mitul A Mehta, Veena Kumari, Philip J Corr, Steven CR Williams and Adam M Perkins in Journal of Psychopharmacology</p

    Brain activation to cues predicting inescapable delay in adolescent Attention Deficit/Hyperactivity Disorder: an fMRI pilot study

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    Abstract: Background: The choice of small immediate over large delayed rewards (i.e., impulsive choice) is a signal marker of motivational style in Attention Deficit/Hyperactivity Disorder (ADHD). The delay aversion model proposes that, in part, this is a conditioned delay avoidance response. Here we test the prediction derived from this model that, in ADHD, cues predicting inescapable delay differentially activate brain regions shown previously to be responsive to motivationally salient, negatively valenced environmental events. Methods: Ten adolescents with ADHD and 10 age matched controls performed a simple speeded reaction time task under two conditions. On Escape Delay trials slow responses only were punished by the imposition of post-response delay periods. On No Escape Delay trials post-response delay occurred on all trials irrespective of response speed. Using functional Magnetic Resonance Imaging (fMRI) BOLD responses were acquired to compare anticipatory brain activation following the two cue types. ROI analyses found significant ADHD-related hyperactivation following No Escape compared to Escape Delay trial cues in the insula, amygdala, ventral striatum and orbito-frontal cortex. Conclusion: The results of this pilot study provide further evidence for the role of altered motivational systems in ADHD and the most direct evidence for a biological basis of delay aversion. (C) 2012 Elsevier B.V. All rights reserved

    Can visual illustrations transform the patient information sheet for PET/MR neuroimaging studies into an engaging and interesting reading?

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    Every research study with human participants requires a participant information sheet (PIS). This is an important document that aims to provide to the study participants, a full description of the study and all procedures, individual risks, and research benefits. But besides its informative use, the PIS also provides the legal basis for an individual to consent to participate and must be agreed and signed prior to participation

    Integration of human whole-brain transcriptome and neuroimaging data

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    The Allen Human Brain Atlas (AHBA) is the first example of human brain transcriptomic mappings and detailed anatomical annotations which, for the first time, has allowed the integration of human brain transcriptomics with neuroimaging. This has been made possible because the AHBA offered an original dataset that contains mRNA expression measures for >20,000 genes covering the whole brain and, critically, in a standard stereotaxic space. In recent years many different methods have been used to integrate this data set with brain imaging data, although this endeavour has lacked harmony in terms of the workflow of data processing and subsequent analyses. In this work we discuss five main issues that experience has highlighted as in need of thorough consideration when integrating the AHBA with neuroimaging. These concerns are corroborated by comparing the performance of three different publicly available methods in correlating the same measures of serotonin receptors density with the correspondent AHBA mRNA maps. In this representative case, we were able to show how these methods can lead to discrepant results, suggesting that processing options are not neutral. We believe that the field should take into serious consideration these issues as they could undermine reproducibility and, in the end, the intrinsic value of the AHBA. We also advise on possible strategies to overcome these discrepancies. Finally, we encourage authors towards practices that will improve reproducibility such as transparency in reporting, algorithm and data sharing, collaboration

    Associations between dimensions of behaviour, personality traits, and mental-health during the COVID-19 pandemic in the United Kingdom

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    Abstract: The COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples’ perceptions, both positive and negative, of the pandemic’s impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic

    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

    A prospective study of the impact of severe childhood deprivation on brain white matter in adult adoptees: Widespread localized reductions in volume but unaffected microstructural organization

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    Background: Early childhood neglect can impact brain development across the lifespan. Using voxel-based approaches we recently reported that severe and time-limited institutional deprivation in early childhood was linked to substantial reductions in total brain volume in adulthood, more than twenty years later. Here we extend this analysis to explore deprivation-related regional white matter volume and microstructural organization using diffusion-based techniques. Methods: A combination of tensor-based morphometry analysis and tractography was conducted on diffusion weighted imaging data from 59 young adults who spent between 3 and 41 months in the severely depriving Romanian institutions of the 1980’s before being adopted into UK families, and 20 non-deprived age-matched UK controls.Results: Independent of total volume, institutional deprivation was associated with smaller volumes in localized regions across a range of white matter tracts including (1) long-ranging association fibers such as bilateral inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, left superior longitudinal fasciculi, and left arcuate fasciculus; (2) tracts of the limbic circuitry including fornix and cingulum; and (3) projection fibers with the corticospinal tract particularly affected. Tractographic analysis found no evidence of altered microstructural organization of any tract in terms of hindrance modulated orientational anisotropy (HMOA), fractional anisotropy (FA) or mean diffusivity (MD). Discussion: We provide further evidence for the effects of early neglect on brain development and their persistence in adulthood despite many years of environmental enrichment associated with successful adoption. Localized white matter effects appear limited to volumetric changes with microstructural organization unaffected.<br/

    Tracking emotions in the brain - Revisiting the Empathic Accuracy Task

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    Many empathy tasks lack ecological validity due to their use of simplistic stimuli and static analytical approaches. Empathic accuracy tasks overcome these limitations by using autobiographical emotional video clips. Usually, a single measure of empathic accuracy is computed by correlating the participants' continuous ratings of the narrator's emotional state with the narrator's own ratings.In this study, we validated a modified empathic accuracy task. A valence-independent rating of the narrator's emotional intensity was added to provide comparability between videos portraying different primary emotions and to explore changes in neural activity related to variations in emotional intensity over time. We also added a new neutral control condition to investigate general emotional processing. In the scanner, 34 healthy participants watched 6 video clips of people talking about an autobiographical event (2 sad, 2 happy and 2 neutral clips) while continuously rating the narrator's emotional intensity.Fluctuation in perceived emotional intensity correlated with activity in brain regions previously implicated in cognitive empathy (bilateral superior temporal sulcus, temporoparietal junction, and temporal pole) and affective empathy (right anterior insula and inferior frontal gyrus). When emotional video clips were compared to neutral video clips, we observed higher activity in similar brain regions. Empathic accuracy, on the other hand, was only positively related to activation in regions that have been implicated in cognitive empathy.Our modified empathic accuracy task provides a new method for studying the underlying components and dynamic processes involved in empathy. While the task elicited both cognitive and affective empathy, successful tracking of others' emotions relied predominantly on the cognitive components of empathy. The fMRI data analysis techniques developed here may prove valuable in characterising the neural basis of empathic difficulties observed across a range of psychiatric conditions

    The impact of childhood deprivation on adult neuropsychological functioning is associated with ADHD symptom persistence

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    Background: Institutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment – the large-scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s –we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation- related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Methods: Adult neuropsychological functioning was assessed across five domains (inhibitory control, emotion recognition, decision-making, prospective memory and IQ) in 70 previously-institutionalized adoptees (mean age= 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age= 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires. Results: Early institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotion recognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory. Conclusions: These results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair long-term neuropsychological functioning across the lifespan – effects that are linked specifically to deprivation-related adult ADHD symptoms
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