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Detecting connectivity in EEG: A comparative study of data-driven effective connectivity measures.
In this paper, we perform the first comparison of a large variety of effective connectivity measures in detecting causal effects among observed interacting systems based on their statistical significance. Well-known measures estimating direction and strength of interdependence between time series are compared: information theoretic measures, model-based multivariate measures in the time and frequency domains, and phase-based measures. The performance of measures is tested on simulated data from three systems: three coupled Hénon maps; a multivariate autoregressive (MVAR) model with and without EEG as an exogenous input; and simulated EEG. No measure was consistently superior. Measures that model the data as MVAR perform well when the data are drawn from that model. Frequency domain measures perform well when the data have a clearly defined band of interest. When neither of these is true, information theoretic measures perform well. Overall, the measure with the best performance in a variety of situations and with a low computational cost is conditional Granger causality. Partial Granger causality and multivariate Granger causality are also good measures, but their computational cost rises rapidly with the number of channels. Copula Granger causality can also be used reliably, but its computational cost rises rapidly with the number of data.
Detecting synchrony in EEG: A comparative study of functional connectivity measures.
In neuroscience, there is considerable current interest in investigating the connections between different parts of the brain. EEG is one modality for examining brain function, with advantages such as high temporal resolution and low cost. Many measures of connectivity have been proposed, but which is the best measure to use? In this paper, we address part of this question: which measure is best able to detect connections that do exist, in the challenging situation of non-stationary and noisy data from nonlinear systems, like EEG. This requires knowledge of the true relationship between signals, hence we compare 26 measures of functional connectivity on simulated data (unidirectionally coupled Hénon maps, and simulated EEG). To determine whether synchrony is detected, surrogate data were generated and analysed, and a threshold determined from the surrogate ensemble. No measure performed best in all tested situations. The correlation and coherence measures performed best on stationary data with many samples. S-estimator, correntropy, mean-phase coherence (Hilbert), mutual information (kernel), nonlinear interdependence (S) and nonlinear interdependence (N) performed most reliably on non-stationary data with small to medium window sizes. Of these, correlation and S-estimator have execution times that scale slower with the number of channels and the number of samples.
Towards a brain-controlled wheelchair prototype
Copyright 2010 ACM. In this project, a design for a non-invasive, EEG-based brain-controlled wheelchair has been developed for use by completely paralyzed patients. The proposed design includes a novel approach for selecting optimal electrode positions, a series of signal processing algorithms and an interface to a powered wheelchair. In addition, a 3D virtual environment has been implemented for training, evaluating and testing the system prior to establishing the wheelchair interface. Simulation of a virtual scenario replicating the real world gives subjects an opportunity to become familiar with operating the device prior to engaging the wheelchair.
APOE-ε4 Genotype and Dementia Before and After Transient Ischemic Attack and Stroke: Population-Based Cohort Study.
Background and Purpose- APOE-ε4 genotype is a risk factor for sporadic Alzheimer disease and reduced recovery from brain injury. Since data on APOE genotype and dementia associated with transient ischemic attack/stroke are sparse, we determined the associations in a longitudinal population-based cohort. Methods- All patients with transient ischemic attack or stroke (2002-2012) in a defined population of 92 728 OxVASC (Oxford Vascular Study) had follow-up to 5-years. Pre-event and incident postevent dementia were ascertained through direct patient assessment and follow-up, supplemented by review of hospital/primary care records. Associations between pre- and post-event dementia and APOE genotype (ε4/ε4-homozygous and ε4/ε3-heterozygous versus ε3/ε3) were examined using logistic regression and Cox regression models, respectively, adjusted for age, sex, education, cerebrovascular burden (stroke severity, prior stroke, white matter disease), diabetes mellitus, and dysphasia. Results- Among 1767 genotyped patients (mean/SD age, 73.0/13.0 years, 901 [51%] male, 602 [34%] transient ischemic attack), 1058 (59.9%) were APOE-ε3/ε3, 403 (22.8%) were ε4/ε3 and 30 (1.7%) were ε4-homozygous. Homozygosity was associated with both pre-event (adjusted odds ratio, 5.81 [95% CI, 1.93-17.48]; P=0.002) and postevent dementia (adjusted hazard ratio, 3.64 [95% CI, 1.90-7.00]; P<0.0001). Association with postevent dementia was maintained after further adjustment for baseline cognitive impairment (hazard ratio, 2.41 [95% CI, 1.19-4.89]; P=0.01). There were no associations overall between ε4/ε3 and pre-event dementia (adjusted odds ratio, 1.47 [95% CI, 0.88-2.45]; P=0.14) or postevent dementia (hazard ratio, 1.11 [95% CI, 0.84-1.48]; P=0.47). Conclusions- In patients with transient ischemic attack and stroke, APOE-ε4 homozygosity was associated with both pre- and post-event dementia. Associations were independent of cerebrovascular burden and may be mediated through increased neurodegenerative pathology or vulnerability to injury.
Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomised trials
Background: Long-term follow-up of randomised trials of aspirin in prevention of vascular events showed that daily aspirin reduced the incidence of colorectal cancer and several other cancers and reduced metastasis. However, statistical power was inadequate to establish effects on less common cancers and on cancers in women. Observational studies could provide this information if results can be shown to be reliable. We therefore compared effects of aspirin on risk and outcome of cancer in observational studies versus randomised trials. Methods: For this systematic review, we searched for case-control and cohort studies published from 1950 to 2011 that reported associations between aspirin use and risk or outcome of cancer. Associations were pooled across studies by meta-analysis and stratified by duration, dose, and frequency of aspirin use and by stage of cancer. We compared associations from observational studies with the effect of aspirin on 20-year risk of cancer death and on metastasis in the recent reports of randomised trials. Findings: In case-control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled odds ratio [OR] 0·62, 95% CI 0·58-0·67, p sig<0·0001, 17 studies), with little heterogeneity (p het=0·13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk of death due to colorectal cancer from the randomised trials (OR 0·58, 95% CI 0·44-0·78, p sig=0·0002, p het=0·45). Similarly consistent reductions were seen in risks of oesophageal, gastric, biliary, and breast cancer. Overall, estimates of effect of aspirin on individual cancers in case-control studies were highly correlated with those in randomised trials (r 2=0·71, p=0·0006), with largest effects on risk of gastrointestinal cancers (case-control studies, OR 0·62, 95% CI 0·55-0·70, p<0·0001, 41 studies; randomised trials, OR 0·54, 95% CI 0·42-0·70, p<0·0001). Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use, were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics. Although fewer observational studies stratified analyses by the stage of cancer at diagnosis, regular use of aspirin was associated with a reduced proportion of cancers with distant metastasis (OR 0·69, 95% CI 0·57-0·83, p sig<0·0001, p het=0·89, five studies), but not with any reduction in regional spread (OR 0·98, 95% CI 0·88-1·09, p sig=0·71, p het=0·88, seven studies), consistent again with the findings in randomised trials. Interpretation: Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis. Results of methodologically rigorous studies are consistent with those obtained from randomised controlled trials, but sensitivity is particularly dependent on appropriately detailed recording and analysis of aspirin use. Funding: None. © 2012 Elsevier Ltd.
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10 -11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes. © 2012 Nature America, Inc. All rights reserved.