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Statistical issues in the analysis of disease mapping data.

In this paper we discuss a number of issues that are pertinent to the analysis of disease mapping data. As an illustrative example we consider the mapping of larynx cancer across electoral wards in the North West Thames region of the U.K. Bayesian hierarchical models are now frequently employed to carry out such mapping. In a typical situation, a three-stage hierarchical model is specified in which the data are modelled as a function of area-specific relative risks at stage one; the collection of relative risks across the study region are modelled at stage two; and at stage three prior distributions are assigned to parameters of the stage two distribution. Such models allow area-specific disease relative risks to be 'smoothed' towards global and/or local mean levels across the study region. However, these models contain many structural and functional assumptions at different levels of the hierarchy; we aim to discuss some of these assumptions and illustrate their sensitivity. When relative risks are the endpoint of interest, it is common practice to assume that, for each of the age-sex strata of a particular area, there is a common multiplier (the relative risk) acting upon each of the stratum-specific risks in that area; we will examine this proportionality assumption. We also consider the choices of models and priors at stages two and three of the hierarchy, the effect of outlying areas, and an assessment of the level of smoothing that is being carried out. For inference, we concentrate on the description of the spatial variability in relative risks and on the association between the relative risks of larynx cancer and an area-level measure of socio-economic status.

Age Factors↗

The effects of synaptic noise on measurements of evoked excitatory postsynaptic response amplitudes.

Spontaneously occurring synaptic events (synaptic noise) recorded intracellularly are usually assumed to be independent of evoked postsynaptic responses and to contaminate measures of postsynaptic response amplitude in a roughly Gaussian manner. Here we derive analytically the expected noise distribution for excitatory synaptic noise and investigate its effects on amplitude histograms. We propose that some fraction of this excitatory noise is initiated at the same release sites that contribute to the evoked synaptic event and develop an analytical model of the interaction between this fraction of the noise and the evoked postsynaptic response amplitude. Recording intracellularly with sharp microelectrodes in the in vitro hippocampal slice preparation, we find that excitatory synaptic noise accounts for up to 70% of the intracellular recording noise, when inhibition is blocked pharmacologically. Up to 20% of this noise shows a significant correlation with the evoked event amplitude, and the behavior of this component of the noise is consistent with a model which assumes that each release site experiences a refractory period of approximately 60 ms after release. In contrast with classical models of quantal variance, our models predict that excitatory synaptic noise can cause the apparent variance of successive peaks in an excitatory synaptic amplitude histogram to decrease from left to right, and in some cases to be less than the variance of the measured noise.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

[Individual variability in the number of stem cells in mammalian tissues].

The distribution of animal groups (3--4 control or gamma-irradiated mice per group) were obtained when analysing published data on the mean number of the CFUs in the femoral bone marrow or stem cells of small intestinal crypt. Almost 50% of such groups have the mean number less than the geometric mean. The mean value for the group of animals deviation from the expected geometric mean for all animal population for more than 2.5 times, both for the larger values and for the smaller, was about 5% in such groups for the marrow CFUs and 20% for intestinal stem cells. The percentage of mice, that died from acute radiation sickness after acute irradiation, was related with the parameter D(0), that characterized the CFUs survivability on the exponential part of the survivability curve. The negative correlation (r = -0.83) was determined between the mean value of the small intestine crypt stem cells and the ability of intestinal stem cells to the radiation damage reparation, evaluated through the parameter D(q) of the stem enterocyte survival curve for this animal groups.

Acute Disease↗

Pregnancy outcomes after abdominal irradiation that included or excluded the pelvis in childhood Wilms tumor survivors: a report from the National Wilms Tumor Study.

PURPOSE: This report describes the pregnancy outcomes among 7 survivors of childhood Wilms tumor, who were treated on one of the National Wilms Tumor Studies (NWTS) with radiation therapy (RT) portals that extended beyond the flank. METHODS AND MATERIALS: Pregnancy outcomes among female survivors of childhood Wilms tumor treated with abdominal irradiation in NWTS 1-4 were analyzed as part of the long-term follow-up study. Medical records and maternal questionnaires were used to gather information on pregnancy outcomes. RESULTS: A total of 130 patients received abdominal RT and survived to at least 15 years of age. Seven patients (5.4%) had at least 1 recorded pregnancy. The extent of RT fields was ascertained in 126 patients. For 4 patients, the extent of RT fields could not be determined. Twelve girls received RT using portals that included the upper abdomen but not the entire pelvis. Ten pregnancies were recorded in 5 of these patients; 9 resulted in live births, and 1 resulted in a miscarriage. One hundred fourteen girls received RT using portals that included the entire abdomen and pelvis. The abdominal RT dose distribution among these 114 patients was as follows: 9 received 0-10.49 Gy, 22 patients received 10.5-14.99 Gy, and 83 patients received 15+ Gy. Four pregnancies were recorded in 2 of these patients. After 21 Gy to the abdomen and pelvis in 1 patient, all 3 pregnancies resulted in miscarriages and fetal deaths. However, after 10.5 Gy, a normal live birth was reported in the other patient. Pregnancy-related complications were also more common if the RT portals included the pelvis. CONCLUSIONS: Fertility can be preserved in children with Wilms tumor after upper abdominal RT (10-20 Gy) that does not include the entire pelvis. In rare instances, fertility can be preserved after low-dose whole-abdominal RT (10.5 Gy). The indications and dosages for RT currently used have been greatly refined compared to NWTS-1 and NWTS-2. Childhood Wilms tumor survivors should be considered to be at a high risk for infertility and pregnancy-related complications during their reproductive years. Prompt obstetric evaluation is indicated for optimal prenatal, antenatal, and postnatal care.

Abortion, Spontaneous↗

Air pollution and doctors' house calls for respiratory diseases in the Greater Paris area (2000-3).

This study describes the short-term relationships between the daily levels of PM10, PM2.5, NO2 and the number of doctors' house calls for asthma, upper respiratory diseases (URD) and lower respiratory diseases (LRD) in Greater Paris for the years 2000-3. Doctors' house calls are a relevant health indicator for the study of short-term health effects of air pollution. Indeed, it is potentially more sensitive than indicators such as general hospital admissions due to the severity of diseases motivating the call. In this study, time-series analysis was used. The daily numbers of doctor's house calls were adjusted for time trends, seasonal factors, day of the week, influenza, weather and pollen. Up to 15 days of lag between exposure and health effects was considered using distributed lag models. A total of about 1,760,000 doctors' house calls for all causes occurred during the study period, among which 8027 were for asthma, 52,928 for LRD and 74,845 for URD. No significant increase in risk was found between air pollution and doctors' house calls for asthma. No significant association was found between NO2 and doctors' house calls. An increase of 10 microg/m3 in the mean levels of PM10 and PM2.5 encountered during the 3 previous days was associated with an increase of 3% (0.8% and 5.3%) and 5.9% (2.9% and 9.0%) in the number of doctor's house calls for URD and LRD, respectively. Considering up to 15 days between exposure and health outcomes, effects persist until 4 days after exposure and then decrease progressively. No morbidity displacement was observed. This study shows a significant heath effect of ambient particles (PM2.5 and PM10). When compared to the RRs obtained for mortality or hospital admissions in the same area, the values of the RRs obtained in this study confirm the higher sensibility of doctor's house calls for respiratory diseases as a health indicator.

Air Pollutants↗

[Research protocol for the mortality atlas of the provincial capitals of Andalusia and Catalonia (AMCAC Project)].

The aim of this work is to make known the multicentric project AMCAC, whose objective is to describe the geographical distribution of mortality from all causes in census groups of the provincial capitals of Andalusia and Catalonia during 1992-2002 and 1994-2000 respectively, and to study the relationship between the sociodemographic characteristics of the census groups and mortality. This is an ecological study in which the analytical unit is the census group. The data correspond to 298,731 individuals (152,913 men and 145,818 women) who died during the study periods in the towns of Almeria, Barcelona, Cadiz, Cordoba, Girona, Granada, Huelva, Jaen, Lleida, Malaga, Seville and Tarragona during the study periods. The dependent variable is the number of deaths observed per census group. The independent variables are the percentage of unemployment, illiteracy and manual workers. Estimation of the moderated relative risk and the study of the associations among the sociodemographic characteristics of the census groups and the mortality will be done for each town and each sex using the Besag-York-Mollie model. Dissemination of the results will help to improve and broaden knowledge about the population's health, and will provide an important starting point to establish the influence of contextual variables on the health of urban populations.

Algorithms↗

Bovine tuberculosis in badgers in four areas in Ireland: does tuberculosis cluster?

We described the distribution of badger populations in four different areas in the Republic of Ireland. The data came from periodic targeted badger-removal and subsequent post-mortem examinations conducted between 1989 and September 1997, and from a formal badger-removal project in the same areas from 1997 through 1999. Records were complete for 2292 badgers regarding the date of capture, tuberculosis status, geographical area and specific sett from where the badgers were snared. Of 3187 setts, 2290 had no badgers recorded against them (i.e. were inactive). The badger-level prevalence of tuberculosis differed among areas (range 13-29%). Badger populations were highly clustered by sett, and this result was similar over the four study areas. The median number of badgers per active sett was 2. Tuberculous badgers also clustered within a sett. The third quartile of tuberculous badgers was 1 per active sett. The prevalence of tuberculous badgers within a sett was not related to the total number of badgers. There was little evidence of spatial clustering with only one local cluster of tuberculous setts in each of three areas, and none in the fourth area. After adjusting for the number of badgers per sett, only one area had spatial clusters identified.

Animals↗

Abundance of correctly folded RNA motifs in sequence space, calculated on computational grids.

Although functional RNA molecules are known to be biased in overall composition, the effects of background composition on the probability of finding a particular active site by chance has received little attention. The probability of finding a particular motif has important implications both for understanding the distribution of functional RNAs in ancient and modern organisms with varying genome compositions and for tuning SELEX pools to optimize the chance of finding specific functions. Here we develop a new method for calculating the probability of finding a modular motif containing base-paired regions, and use a computational grid to fold several hundred million random RNA sequences containing the core elements of the isoleucine aptamer and the hammerhead ribozyme to estimate the probability that a sequence containing these structural elements will fold correctly when isolated from background sequences of different compositions. We find that the two motifs are most likely to be found in distinct regions of compositional space, and that the regions of greatest abundance are influenced by the probability of finding the conserved bases, finding the flanking helices, and folding, in that order of importance. Additionally, we can refine our estimates of the number of random sequences required for a 50% probability of finding an example of each site in unbiased random pools of length 100 to 4.1 x 10(9) for the isoleucine aptamer and 1.6 x 10(10) for the hammerhead ribozyme. These figures are consistent with the facile recovery of these motifs from SELEX experiments.

Base Composition↗

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study.

CONTEXT: Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE: To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN: Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING: Southeast London, Nottingham, and Bristol, England. PARTICIPANTS: One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES: The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis. RESULTS: All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS: There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Adolescent↗

Super- and sub-Poissonian photon statistics for single molecule spectroscopy.

We investigate the distribution of the number of photons emitted by a single molecule undergoing a spectral diffusion process and interacting with a continuous wave laser field. The spectral diffusion is modeled based on a stochastic approach, in the spirit of the Anderson-Kubo line shape theory. Using a generating function formalism we solve the generalized optical Bloch equations and obtain an exact analytical formula for the line shape and Mandel's Q parameter. The line shape exhibits well-known behaviors, including motional narrowing when the stochastic modulation is fast and power broadening. The Mandel parameter, describing the line shape fluctuations, exhibits a transition from a quantum sub-Poissonian behavior in the fast modulation limit to a classical super-Poissonian behavior found in the slow modulation limit. Our result is applicable for weak and strong laser fields, namely, for arbitrary Rabi frequency. We show how to choose the Rabi frequency in such a way so that the quantum sub-Poissonian nature of the emission process becomes strongest. A lower bound on Q is found and simple limiting behaviors are investigated. A nontrivial behavior is obtained in the intermediate modulation limit, when the time scales for spectral diffusion and the lifetime of the excited state become similar. A comparison is made between our results and previous ones derived, based on the semiclassical generalized Wiener-Khintchine formula.

Algorithms↗

Space-time clustering of childhood malaria at the household level: a dynamic cohort in a Mali village.

BACKGROUND: Spatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend fine-scale stratification of the epidemiological situation, making it possible to set up actions and clinical or basic researches targeting high-risk zones. Before initiating such studies it is necessary to define local patterns of malaria transmission and infection (in time and in space) in order to facilitate selection of the appropriate study population and the intervention allocation. The aim of this study was to identify, spatially and temporally, high-risk zones of malaria, at the household level (resolution of 1 to 3 m). METHODS: This study took place in a Malian village with hyperendemic seasonal transmission as part of Mali-Tulane Tropical Medicine Research Center (NIAID/NIH). The study design was a dynamic cohort (22 surveys, from June 1996 to June 2001) on about 1300 children (<12 years) distributed between 173 households localized by GPS. We used the computed parasitological data to analyzed levels of Plasmodium falciparum, P. malariae and P. ovale infection and P. falciparum gametocyte carriage by means of time series and Kulldorff's scan statistic for space-time cluster detection. RESULTS: The time series analysis determined that malaria parasitemia (primarily P. falciparum) was persistently present throughout the population with the expected seasonal variability pattern and a downward temporal trend. We identified six high-risk clusters of P. falciparum infection, some of which persisted despite an overall tendency towards a decrease in risk. The first high-risk cluster of P. falciparum infection (rate ratio = 14.161) was detected from September 1996 to October 1996, in the north of the village. CONCLUSION: This study showed that, although infection proportions tended to decrease, high-risk zones persisted in the village particularly near temporal backwaters. Analysis of this heterogeneity at the household scale by GIS methods lead to target preventive actions more accurately on the high-risk zones identified. This mapping of malaria risk makes it possible to orient control programs, treating the high-risk zones identified as a matter of priority, and to improve the planning of intervention trials or research studies on malaria.

Animals↗

Tissue and electrode capacitance reduce neural activation volumes during deep brain stimulation.

OBJECTIVE: The growing clinical acceptance of neurostimulation technology has highlighted the need to accurately predict neural activation as a function of stimulation parameters and electrode design. In this study we evaluate the effects of the tissue and electrode capacitance on the volume of tissue activated (VTA) during deep brain stimulation (DBS). METHODS: We use a Fourier finite element method (Fourier FEM) to calculate the potential distribution in the tissue medium as a function of time and space simultaneously for a range of stimulus waveforms. The extracellular voltages are then applied to detailed multi-compartment cable models of myelinated axons to determine neural activation. Neural activation volumes are calculated as a function of the stimulation parameters and magnitude of the capacitive components of the electrode-tissue interface. RESULTS: Inclusion of either electrode or tissue capacitance reduces the VTA compared to electrostatic simulations in a manner dependent on the capacitance magnitude and the stimulation parameters (amplitude and pulse width). Electrostatic simulations with typical DBS parameter settings (-3 V or -3 mA, 90 micros, 130 Hz) overestimate the VTA by approximately 20% for voltage- or current-controlled stimulation. In addition, strength-duration time constants decrease and more closely match clinical measurements when explicitly accounting for the effects of voltage-controlled stimulation. CONCLUSIONS: Attempts to quantify the VTA from clinical neurostimulation devices should account for the effects of electrode and tissue capacitance. SIGNIFICANCE: DBS has rapidly emerged as an effective treatment for movement disorders; however, little is known about the VTA during therapeutic stimulation. In addition, the influence of tissue and electrode capacitance has been largely ignored in previous models of neural stimulation. The results and methodology of this study provide the foundation for the quantitative analysis of the VTA during clinical neurostimulation.

Algorithms↗

Segmental analysis of coronary arterial stenoses in patients presenting with angina or first myocardial infarction.

The segmental distribution of stenoses within the coronary arteries was analysed in a population of 258 patients with a first myocardial infarction undergoing coronary angiography to evaluate the effect of thrombolytic therapy, and in a population of 466 patients undergoing elective coronary angiography for stable angina. Mean ages were 53.7 and 56.7 years respectively (P = NS). As judged angiographically, coronary arterial disease was more extensive in the group suffering angina, with a greater proportion of patients with two- or three-vessel disease (odds ratio 2.56, 95% confidence interval 1.87 to 3.52) and more patients having stenoses in two or more coronary arterial segments (odds ratio 1.52, 95% confidence interval 1.12 to 2.08). For each coronary vessel, the probability of finding a stenosis greater than 50% in an individual segment was greater in the group presenting with angina. There was a relative deficiency of stenoses within the main stem of the left coronary artery or its proximal left anterior descending branch among the patients suffering myocardial infarction. Within those having angina, subgroups were identified with "isolated" and "diffuse" coronary arterial disease: the latter patients tended to have a lower concentration of total cholesterol in the serum, but an increased prevalence of diabetes mellitus. Patients presenting clinically with a first myocardial infarction, and patients with severe angina, constitute distinct populations selected by different mechanisms from the overall pool of patients with atheromatous coronary arterial disease.

Adult↗

A scan statistic for identifying chromosomal patterns of SNP association.

We have developed a single nucleotide polymorphism (SNP) association scan statistic that takes into account the complex distribution of the human genome variation in the identification of chromosomal regions with significant SNP associations. This scan statistic has wide applicability for genetic analysis, whether to identify important chromosomal regions associated with common diseases based on whole-genome SNP association studies or to identify disease susceptibility genes based on dense SNP positional candidate studies. To illustrate this method, we analyzed patterns of SNP associations on chromosome 19 in a large cohort study. Among 2,944 SNPs, we found seven regions that contained clusters of significantly associated SNPs. The average width of these regions was 35 kb with a range of 10-72 kb. We compared the scan statistic results to Fisher's product method using a sliding window approach, and detected 22 regions with significant clusters of SNP associations. The average width of these regions was 131 kb with a range of 10.1-615 kb. Given that the distances between SNPs are not taken into consideration in the sliding window approach, it is likely that a large fraction of these regions represents false positives. However, all seven regions detected by the scan statistic were also detected by the sliding window approach. The linkage disequilibrium (LD) patterns within the seven regions were highly variable indicating that the clusters of SNP associations were not due to LD alone. The scan statistic developed here can be used to make gene-based or region-based SNP inferences about disease association.

Chromosome Mapping↗

Maternal and fetal outcome after invasive cervical cancer in pregnancy.

Invasive carcinoma of the cervix is the most common gynecologic malignancy to occur during the reproductive years. To analyze the effects of pregnancy on the course and survival of invasive cervical cancer, we compared 40 women with invasive cervical cancer to 89 nonpregnant controls matched for age, calendric year of diagnosis, stage, and tumor type. Additionally, we compared the distribution of invasive cervical cancer stages among the 40 pregnant women with that among the 1,963 cases of invasive cervical cancer treated during the same 30 years in women less than 45 years of age registered in the same hospital. To evaluate pregnancy outcome, we compared babies born to women with invasive cervical cancer to babies born of women matched for maternal age and not exposed to known teratogens or reproductive risks during pregnancy. Thirty-year survival of pregnant women with invasive cervical cancer was identical to that of their matched controls. Women having invasive cervical cancer were 3.1 times more likely to be diagnosed with stage I disease (95% confidence interval, 1.6 to 6.2). Additionally, they had a significantly lower chance of being diagnosed with stages III and IV (P = .02). Babies born to women with invasive cervical cancer were similar in gestational age and rates of prematurity but had a lower birth weight than the matched controls. There were two stillbirths among the 24 pregnancies that continued to term (8%), not statistically different from the 1.1% rate for Ontario. Our data suggest that pregnancy per se does not adversely affect the survival of women with invasive cervical cancer. However, this study provides evidence that pregnant women are more likely to present with early disease because of regular, pregnancy-related obstetric exams. Moreover, there is an increased risk for stillbirth, which should lead to follow-up of these patients by a high-risk perinatal unit.

Adult↗

'Clustering'--real or apparent? Probability maps of childhood cancer in the West Midlands Health Authority region.

The West Midlands Regional Children's Tumour Registry collects detailed information on all cases of childhood cancer in the West Midlands Health Authority Region (WMHAR). The distribution by electoral ward of all cases diagnosed in the WMHAR between 1980 and 1984 has been determined. Analysis has also been performed for leukaemias/non-Hodgkin's lymphomas alone. We suggest that this latter grouping should be universally employed, owing to the difficulty of accurately separating out cases of leukaemia. Both spatial analyses showed several wards with significantly excessive rates on the basis of their cumulative Poison probability. Observed/expected ratios of 3-35 were seen for cases in significant wards, which are similar to the ratios seen in analysis of incidence around nuclear installations. However, further detailed consideration of these individual significance levels in the light of the number of statistically significant wards which would occur by chance alone, due to the multiple use of the test, accounted completely for the number of wards obtained in each of the groups considered. Thus, apparent 'clustering' of cases could be mere statistical artefact. In the WMHAR, therefore, using the technique of probability mapping, no true spatial pattern of incidence was found, other than that which would occur by chance alone. This, in a large area without nuclear installations and an even mix of rural and industrialised regions, could be seen as control data for those studies which have considered cases of childhood leukaemia around nuclear facilities, where the observation of single point clusters associated with suspected sites restricts assessments of spatial pattern in the rest of the area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Interpreting neuronal population activity by reconstruction: unified framework with application to hippocampal place cells.

Physical variables such as the orientation of a line in the visual field or the location of the body in space are coded as activity levels in populations of neurons. Reconstruction or decoding is an inverse problem in which the physical variables are estimated from observed neural activity. Reconstruction is useful first in quantifying how much information about the physical variables is present in the population and, second, in providing insight into how the brain might use distributed representations in solving related computational problems such as visual object recognition and spatial navigation. Two classes of reconstruction methods, namely, probabilistic or Bayesian methods and basis function methods, are discussed. They include important existing methods as special cases, such as population vector coding, optimal linear estimation, and template matching. As a representative example for the reconstruction problem, different methods were applied to multi-electrode spike train data from hippocampal place cells in freely moving rats. The reconstruction accuracy of the trajectories of the rats was compared for the different methods. Bayesian methods were especially accurate when a continuity constraint was enforced, and the best errors were within a factor of two of the information-theoretic limit on how accurate any reconstruction can be and were comparable with the intrinsic experimental errors in position tracking. In addition, the reconstruction analysis uncovered some interesting aspects of place cell activity, such as the tendency for erratic jumps of the reconstructed trajectory when the animal stopped running. In general, the theoretical values of the minimal achievable reconstruction errors quantify how accurately a physical variable is encoded in the neuronal population in the sense of mean square error, regardless of the method used for reading out the information. One related result is that the theoretical accuracy is independent of the width of the Gaussian tuning function only in two dimensions. Finally, all the reconstruction methods considered in this paper can be implemented by a unified neural network architecture, which the brain feasibly could use to solve related problems.

Action Potentials↗

Spatiotemporal Bayesian inference dipole analysis for MEG neuroimaging data.

Recently, we described a Bayesian inference approach to the MEG/EEG inverse problem that used numerical techniques to estimate the full posterior probability distributions of likely solutions upon which all inferences were based [Schmidt, D.M., George, J.S., Wood, C.C., 1999. Bayesian inference applied to the electromagnetic inverse problem. Human Brain Mapping 7, 195; Schmidt, D.M., George, J.S., Ranken, D.M., Wood, C.C., 2001. Spatial-temporal bayesian inference for MEG/EEG. In: Nenonen, J., Ilmoniemi, R. J., Katila, T. (Eds.), Biomag 2000: 12th International Conference on Biomagnetism. Espoo, Norway, p. 671]. Schmidt et al. (1999) focused on the analysis of data at a single point in time employing an extended region source model. They subsequently extended their work to a spatiotemporal Bayesian inference analysis of the full spatiotemporal MEG/EEG data set. Here, we formulate spatiotemporal Bayesian inference analysis using a multi-dipole model of neural activity. This approach is faster than the extended region model, does not require use of the subject's anatomical information, does not require prior determination of the number of dipoles, and yields quantitative probabilistic inferences. In addition, we have incorporated the ability to handle much more complex and realistic estimates of the background noise, which may be represented as a sum of Kronecker products of temporal and spatial noise covariance components. This reduces the effects of undermodeling noise. In order to reduce the rigidity of the multi-dipole formulation which commonly causes problems due to multiple local minima, we treat the given covariance of the background as uncertain and marginalize over it in the analysis. Markov Chain Monte Carlo (MCMC) was used to sample the many possible likely solutions. The spatiotemporal Bayesian dipole analysis is demonstrated using simulated and empirical whole-head MEG data.

Algorithms↗