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1.
Front Neurosci ; 15: 643740, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803577

RESUMO

Introduction: Functional magnetic resonance imaging (fMRI) often involves long scanning durations to ensure the associated brain activity can be detected. However, excessive experimentation can lead to many undesirable effects, such as from learning and/or fatigue effects, discomfort for the subject, excessive motion artifacts and loss of sustained attention on task. Overly long experimentation can thus have a detrimental effect on signal quality and accurate voxel activation detection. Here, we propose dynamic experimentation with real-time fMRI using a novel statistically driven approach that invokes early stopping when sufficient statistical evidence for assessing the task-related activation is observed. Methods: Voxel-level sequential probability ratio test (SPRT) statistics based on general linear models (GLMs) were implemented on fMRI scans of a mathematical 1-back task from 12 healthy teenage subjects and 11 teenage subjects born extremely preterm (EPT). This approach is based on likelihood ratios and allows for systematic early stopping based on target statistical error thresholds. We adopt a two-stage estimation approach that allows for accurate estimates of GLM parameters before stopping is considered. Early stopping performance is reported for different first stage lengths, and activation results are compared with full durations. Finally, group comparisons are conducted with both early stopped and full duration scan data. Numerical parallelization was employed to facilitate completion of computations involving a new scan within every repetition time (TR). Results: Use of SPRT demonstrates the feasibility and efficiency gains of automated early stopping, with comparable activation detection as with full protocols. Dynamic stopping of stimulus administration was achieved in around half of subjects, with typical time savings of up to 33% (4 min on a 12 min scan). A group analysis produced similar patterns of activity for control subjects between early stopping and full duration scans. The EPT group, individually, demonstrated more variability in location and extent of the activations compared to the normal term control group. This was apparent in the EPT group results, reflected by fewer and smaller clusters. Conclusion: A systematic statistical approach for early stopping with real-time fMRI experimentation has been implemented. This dynamic approach has promise for reducing subject burden and fatigue effects.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34388852

RESUMO

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

3.
J Ment Health ; : 1-9, 2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-33966543

RESUMO

Mental health problems bring substantial individual, community and societal costs and the need for innovation to promote good mental health and to prevent and treat mental health problems has never been greater. However, we know that research findings can take up to 20 years to implement. One way to push the pace is to focus researchers and funders on shared, specific goals and targets. We describe a consultation process organised by the Department of Health and Social Care and convened by the Chief Medical Officer to consider high level goals for future research efforts and to begin to identify UK-specific targets to measure research impact. The process took account of new scientific methods and evidence, the UK context with a universal health care system (the NHS) and the embedded research support from the National Institute for Health Research Clinical Research Network, as well as the views of individual service users and service user organisations. The result of the consultation is a set of four overarching goals with the potential to be measured at intervals of three, five or ten years.

4.
Fem Psychol ; 31(1): 119-139, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33716411

RESUMO

This article explores the relationship between lesbian activists and the "psy professions" (especially psychology and psychiatry) in England from the 1960s to the 1980s. We draw on UK-based LGBTQIA+ archive sources and specifically magazines produced by, and for, lesbians. We use this material to identify three key strategies used within the lesbian movement to contest psycho-pathologisation during this 30-year period: from respectable collaborationist forms of activism during the 1960s; to more liberationist oppositional politics during the early 1970s; to radical feminist separatist activism in the 1980s. Whilst these strategies broadly map onto activist strategies deployed within the wider lesbian and gay movement during this time, this article explores how these politics manifested in particular ways, specifically in relation to the psy disciplines in the UK. We describe these strategies, illustrating them with examples of activism from the archives. We then use this history to problematise a linear, overly reductionist or binary history of liberation from psycho-pathologisation. Finally, we explore some complexities in the relationship between sexuality, activism and the psy professions.

5.
Soc Psychiatry Psychiatr Epidemiol ; 56(1): 13-24, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32804258

RESUMO

PURPOSE: The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. METHODS: We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. RESULTS: We found 872 eligible sources from 28 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. CONCLUSION: Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.


Assuntos
COVID-19 , Transtornos Mentais , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Saúde Mental , Pandemias , SARS-CoV-2
6.
Health Expect ; 24 Suppl 1: 10-19, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31556244

RESUMO

This paper explores the methodological aspects of a user-led study investigating mental health service user experiences of targeted violence and abuse (often called 'hate crime'). 'Keeping Control' was a 16-month qualitative study, undertaken in the context of adult safeguarding reforms in England. By collecting data on service user concepts and experiences, the research sought to address a gap in research and practice knowledge relating to targeted violence, abuse and hostility against people with mental health problems. In this paper, we discuss the significance of the design and methodology used for this study, with a particular focus on the interviews with service users. The research was both user-led and carried out in collaboration with practitioners and academics, a form of research co-production. Our aim is to inform researchers, practitioners and policymakers about the value of user leadership in co-productive research with practitioners, particularly for a highly sensitive and potentially distressing topic.

7.
Soc Psychiatry Psychiatr Epidemiol ; 56(1): 25-37, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32857218

RESUMO

PURPOSE: The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users. METHODS: We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities, and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data. RESULTS: 2,180 staff from a range of sectors, professions, and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care. CONCLUSION: This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.


Assuntos
COVID-19 , Serviços de Saúde Mental , Humanos , Saúde Mental , Pandemias , SARS-CoV-2 , Reino Unido/epidemiologia
8.
Sci Adv ; 6(47)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33208365

RESUMO

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

10.
Wellcome Open Res ; 5: 166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802967

RESUMO

We argue that predictions of a 'tsunami' of mental health problems as a consequence of the pandemic of coronavirus disease 2019 (COVID-19) and the lockdown are overstated; feelings of anxiety and sadness are entirely normal reactions to difficult circumstances, not symptoms of poor mental health.  Some people will need specialised mental health support, especially those already leading tough lives; we need immediate reversal of years of underfunding of community mental health services.  However, the disproportionate effects of COVID-19 on the most disadvantaged, especially BAME people placed at risk by their social and economic conditions, were entirely predictable. Mental health is best ensured by urgently rebuilding the social and economic supports stripped away over the last decade. Governments must pump funds into local authorities to rebuild community services, peer support, mutual aid and local community and voluntary sector organisations.  Health care organisations must tackle racism and discrimination to ensure genuine equal access to universal health care.  Government must replace highly conditional benefit systems by something like a universal basic income. All economic and social policies must be subjected to a legally binding mental health audit. This may sound unfeasibly expensive, but the social and economic costs, not to mention the costs in personal and community suffering, though often invisible, are far greater.

11.
Brain ; 143(8): 2454-2473, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32814957

RESUMO

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.


Assuntos
Encéfalo/patologia , Síndromes Epilépticas/patologia , Substância Branca/patologia , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade
12.
Lancet Psychiatry ; 7(9): 813-824, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682460

RESUMO

The unpredictability and uncertainty of the COVID-19 pandemic; the associated lockdowns, physical distancing, and other containment strategies; and the resulting economic breakdown could increase the risk of mental health problems and exacerbate health inequalities. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorders. Despite the heterogeneity of worldwide health systems, efforts have been made to adapt the delivery of mental health care to the demands of COVID-19. Mental health concerns have been addressed via the public mental health response and by adapting mental health services, mostly focusing on infection control, modifying access to diagnosis and treatment, ensuring continuity of care for mental health service users, and paying attention to new cases of mental ill health and populations at high risk of mental health problems. Sustainable adaptations of delivery systems for mental health care should be developed by experts, clinicians, and service users, and should be specifically designed to mitigate disparities in health-care provision. Thorough and continuous assessment of health and service-use outcomes in mental health clinical practice will be crucial for defining which practices should be further developed and which discontinued. For this Position Paper, an international group of clinicians, mental health experts, and users of mental health services has come together to reflect on the challenges for mental health that COVID-19 poses. The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery. Thus, the COVID-19 pandemic could be an opportunity to improve mental health services.


Assuntos
Infecções por Coronavirus/epidemiologia , Transtornos Mentais/terapia , Serviços de Saúde Mental/normas , Pneumonia Viral/epidemiologia , Telemedicina/métodos , Betacoronavirus , COVID-19 , Infecções por Coronavirus/psicologia , Pessoal de Saúde/psicologia , Humanos , Transtornos Mentais/virologia , Pandemias , Pneumonia Viral/psicologia , SARS-CoV-2
13.
Animals (Basel) ; 10(6)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503110

RESUMO

Soils with marginal to deficient levels of selenium (Se) are widespread in the northwest, northeast, and southeast US. Supplementation to the diet of forage-grazing beef cattle with a vitamin-mineral mix containing additional Se is recommended in these geographic regions. We have reported that the form of supplemental Se provided to Angus-cross beef cows can affect circulating levels of progesterone (P4) on day 6 of the estrous cycle, a time when increased P4 is known to promote fertility. The objectives of this study were to (1) confirm and expand upon our initial report that the form of Se provided to cows affects early luteal-phase concentrations of systemic P4, (2) determine the effects of the form of Se on concentrations of P4 during gestation, and (3) determine the effects of the form of Se on concentrations of prolactin (PRL) during lactation. Throughout this study, Angus-cross beef cows had ad libitum access to a vitamin-mineral mix containing 35 ppm of Se in either an inorganic form (ISe) or a 1:1 mix of inorganic and organic forms (MIX). We observed a MIX-induced increase (p = 0.006) in systemic concentrations of P4 on day 7 but not on days 4 or 10 of the estrous cycle, consistent with our earlier report. We observed a MIX-induced increase (p = 0.02) in the systemic concentration of P4 at months 1, 3, 5, and 7 of gestation, and a MIX-induced decrease (p < 0.05) in systemic concentrations of PRL at months 5 and 6 of lactation. In summary, the form of Se provided to cows can be manipulated to affect the early luteal phase and gestational concentrations of P4, and postpartum concentrations of PRL.

14.
Hum Brain Mapp ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32468614

RESUMO

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

15.
Health Res Policy Syst ; 18(1): 43, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380998

RESUMO

This article is a response to Oliver et al.'s Commentary 'The dark side of coproduction: do the costs outweigh the benefits for health research?' recently published in Health Research Policy and Systems (2019, 17:33). The original commentary raises some important questions about how and when to co-produce health research, including highlighting various professional costs to those involved. However, we identify four related limitations in their inquiry, as follows: (1) the adoption of a problematically expansive definition of co-production that fails to acknowledge key features that distinguish co-production from broader collaboration; (2) a strong focus on technocratic rationales for co-producing research and a relative neglect of democratic rationales; (3) the transposition of legitimate concerns relating to collaboration between researchers and practitioners onto work with patients, service users and marginalised citizens; and (4) the presentation of bad practice as an inherent flaw, or indeed 'dark side', of co-production without attending to the corrupting influence of contextual factors within academic research that facilitate and even promote such malpractice. The Commentary's limitations can be seen to reflect the contemporary use of the term 'co-production' more broadly. We describe this phenomenon as 'cobiquity' - an apparent appetite for participatory research practice and increased emphasis on partnership working, in combination with the related emergence of a plethora of 'co' words, promoting a conflation of meanings and practices from different collaborative traditions. This phenomenon commonly leads to a misappropriation of the term 'co-production'. Our main motivation is to address this imprecision and the detrimental impact it has on efforts to enable co-production with marginalised and disadvantaged groups. We conclude that Oliver et al. stray too close to 'the problem' of 'co-production' seeing only the dark side rather than what is casting the shadows. We warn against such a restricted view and argue for greater scrutiny of the structural factors that largely explain academia's failure to accommodate and promote the egalitarian and utilitarian potential of co-produced research.


Assuntos
Política de Saúde , Motivação , Humanos , Pesquisadores
17.
Acad Radiol ; 27(3): 409-420, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987872

RESUMO

RATIONALE AND OBJECTIVES: Iodine quantification (IQ) and virtual noncontrast (VNC) images produced by dual-energy CT (DECT) can be used for various clinical applications. We investigate the performance of dual-layer DECT (DLDECT) in different phantom sizes and varying radiation doses and tube voltages, including a low-dose pediatric setting. MATERIALS AND METHODS: Three phantom sizes (simulating a 10-year-old child, an average, and a large-sized adult) were scanned with iodine solution inserts with concentrations ranging 0-32 mg/ml, using the DLDECT. Each phantom size was scanned with CTDIvol 2-15 mGy at 120 and 140 kVp. The smallest phantom underwent additional scans with CTDIvol 0.9-1.8 mGy. All scans were repeated 3 times. Each iodine insert was analyzed using VNC and IQ images for accuracy and precision, by comparison to known values. RESULTS: For scans from 2 to 15 mGy mean VNC attenuation and IQ error in the iodine inserts in the small, medium, and large phantoms was 1.2 HU ± 3.2, -1.2 HU ± 14.9, 2.6 HU ± 23.6; and +0.1 mg/cc ± 0.4, -0.9 mg/cc ± 0.9, and -1.8 mg/cc ± 1.8, respectively. In this dose range, there were no significant differences (p ≥ 0.05) in mean VNC attenuation or IQ accuracy in each phantom size, while IQ was significantly less precise in the small phantom at 2 mGy and 10 mGy (p < 0.05). Scans with CTDIvol 0.9-1.8 mGy in the small phantom showed a limited, but statistically significantly lower VNC attenuation precision and IQ accuracy (-0.5 HU ± 5.3 and -0.3 mg/cc ± 0.5, respectively) compared to higher dose scans in the same phantom size. CONCLUSION: Performance of iodine quantification and subtraction by VNC images in DLDECT is largely dose independent, with the primary factor being patient size. Low-dose pediatric scan protocols have a significant, but limited impact on IQ and VNC attenuation values.


Assuntos
Iodo , Adulto , Criança , Humanos , Imagens de Fantasmas , Doses de Radiação , Tomografia Computadorizada por Raios X
18.
Front Integr Neurosci ; 14: 491403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33510622

RESUMO

A key area of research in epilepsy neurological disorder is the characterization of epileptic networks as they form and evolve during seizure events. In this paper, we describe the development and application of an integrative workflow to analyze functional and structural connectivity measures during seizure events using stereotactic electroencephalogram (SEEG) and diffusion weighted imaging data (DWI). We computed structural connectivity measures using electrode locations involved in recording SEEG signal data as reference points to filter fiber tracts. We used a new workflow-based tool to compute functional connectivity measures based on non-linear correlation coefficient, which allows the derivation of directed graph structures to represent coupling between signal data. We applied a hierarchical clustering based network analysis method over the functional connectivity data to characterize the organization of brain network into modules using data from 27 events across 8 seizures in a patient with refractory left insula epilepsy. The visualization of hierarchical clustering values as dendrograms shows the formation of connected clusters first within each insulae followed by merging of clusters across the two insula; however, there are clear differences between the network structures and clusters formed across the 8 seizures of the patient. The analysis of structural connectivity measures showed strong connections between contacts of certain electrodes within the same brain hemisphere with higher prevalence in the perisylvian/opercular areas. The combination of imaging and signal modalities for connectivity analysis provides information about a patient-specific dynamical functional network and examines the underlying structural connections that potentially influences the properties of the epileptic network. We also performed statistical analysis of the absolute changes in correlation values across all 8 seizures during a baseline normative time period and different seizure events, which showed decreased correlation values during seizure onset; however, the changes during ictal phases were varied.

19.
Front Neurol ; 10: 976, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572291

RESUMO

Background: The presence of brain amyloid-beta positivity is associated with cognitive impairment and dementia, but whether there are specific aspects of cognition that are most linked to amyloid-beta is unclear. Analysis of neuropsychological test data presents challenges since a single test often requires drawing upon multiple cognitive functions to perform well. It can thus be imprecise to link performance on a given test to a specific cognitive function. Our objective was to provide insight into how cognitive functions are associated with brain amyloid-beta positivity among samples consisting of cognitively normal and mild cognitively impaired (MCI) subjects, by using partially ordered set models (POSETs). Methods: We used POSET classification models of neuropsychological test data to classify samples to detailed cognitive profiles using ADNI2 and AIBL data. We considered 3 gradations of episodic memory, cognitive flexibility, verbal fluency, attention and perceptual motor speed, and performed group comparisons of cognitive functioning stratified by amyloid positivity (yes/no) and age (<70, 70-80, 81-90 years). We also employed random forest methods stratified by age to assess the effectiveness of cognitive testing in predicting amyloid positivity, in addition to demographic variables, and APOE4 allele count. Results: In ADNI2, differences in episodic memory and attention by amyloid were found for <70, and 70-80 years groups. In AIBL, episodic memory differences were found in the 70-80 years age group. In both studies, no cognitive differences were found in the 81-90 years group. The random forest analysis indicates that variable importance in classification depends on age. Cognitive testing that targets an intermediate level of episodic memory and delayed recall, in addition to APOE4 allele count, are the most important variables in both studies. Conclusions: In the ADNI2 and AIBL samples, the associations between specific cognitive abilities and brain amyloid-beta positivity depended on age, but in general episodic memory was most consistently predictive of brain amyloid-beta positivity. Random forest methods and OOB error rates establish the feasibility of predicting the presence of brain beta-amyloid using cognitive testing, APOE4 genotyping and demographic variables.

20.
Physiol Rep ; 7(16): e14202, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31466137

RESUMO

Obesity during gestation adversely affects maternal and infant health both during pregnancy and for long afterwards. However, recent work suggests that a period of maternal exercise during pregnancy can improve metabolic health of the obese mother and her offspring. This study aimed to identify the physiological and molecular impact of exercise on the obese mother during pregnancy that may lead to improved metabolic outcomes. To achieve this, a 20-min treadmill exercise intervention was performed 5 days a week in diet-induced obese female mice from 1 week before and up to day 17 of pregnancy. Biometric, biochemical and molecular analyses of maternal tissues and/or plasma were performed on day 19 of pregnancy. We found exercise prevented some of the adverse changes in insulin signaling and lipid metabolic pathways seen in the liver, skeletal muscle and white adipose tissue of sedentary-obese pregnant dams (p110ß, p110α, AKT, SREBP). Exercise also induced changes in the insulin and lipid signaling pathways in obese dams that were different from those observed in control and sedentary-obese dams. The changes induced by obesity and exercise were tissue-specific and related to alterations in tissue lipid, protein and glycogen content and plasma insulin, leptin and triglyceride concentrations. We conclude that the beneficial effects of exercise on metabolic outcomes in obese mothers may be related to specific molecular signatures in metabolically active maternal tissues during pregnancy. These findings highlight potential metabolic targets for therapeutic intervention and the importance of lifestyle in reducing the burden of the current obesity epidemic on healthcare systems.


Assuntos
Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/metabolismo , Condicionamento Físico Animal/fisiologia , Complicações na Gravidez/metabolismo , Adiposidade/fisiologia , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Camundongos , Gravidez
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