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PubMed2000

Selection of an adaptive test statistic for use with multiple comparison analyses of neuroimaging data.

Statistical analysis of neuroimages is commonly approached with intergroup comparisons made by repeated application of univariate or multivariate tests performed on the set of the regions of interest sampled in the acquired images. The use of such large numbers of tests requires application of techniques for correction for multiple comparisons. Standard multiple comparison adjustments (such as the Bonferroni) may be overly conservative when data are correlated and/or not normally distributed. Resampling-based step-down procedures that successfully account for unknown correlation structures in the data have recently been introduced. We combined resampling step-down procedures with the Minimum Variance Adaptive method, which allows selection of an optimal test statistic from a predefined class of statistics for the data under analysis. As shown in simulation studies and analysis of autoradiographic data, the combined technique exhibits a significant increase in statistical power, even for small sample sizes (n = 8, 9, 10).

Algorithms↗
PubMed2001

Consensus inference in neuroimaging.

We introduce model averaging in neuroimaging. We show that model summary images can be directly compared and averaged after histogram equalization. We demonstrate that averaging enhances the ROC curve in a simulation study. The averaging procedure is applied to a fMRI study of motor cortex.

Brain Mapping↗
PubMed2001

Template images for nonhuman primate neuroimaging: 1. Baboon.

Coregistration of functional brain images across many subjects offers several experimental advantages and is widely used for studies in humans. Voxel-based coregistration methods require a high-quality 3-D template image, preferably one that corresponds to a published atlas. Template images are available for human, but we could not find an appropriate template for neuroimaging studies in baboon. Here we describe the formation of a T1-weighted structural MR template image and a PET blood flow template, derived from 9 and 7 baboons, respectively. Custom software aligns individual MR images to the MRI template; human supervision is needed only to initially estimate any gross rotational misalignment. In these aligned individual images, internal subcortical fiducial points correspond closely to a photomicrographic baboon atlas with an average error of 1.53 mm. Cortical test points showed a mean error of 1.99 mm compared to the mean location for each point. Alignment of individual PET blood flow images directly to the PET template was compared to a two-step alignment process via each subject's MR image. The two transformations were identical within 0.41 mm, 0.54 degrees, and 1.0% (translation, rotation, and linear stretch; mean). These quantities provide a check on the validity of the alignment software as well as of the template images. The baboon structural MR and blood flow PET templates are available on the Internet (purl.org/net/kbmd/b2k) and can be used as targets for any image registration software.

Animals↗
PubMed2001

Template images for nonhuman primate neuroimaging: 2. Macaque.

Neuroimaging studies are increasingly performed in macaque species, including the pig-tailed macaque (Macaca nemestrina). At times experimental questions can be answered by analysis of functional images in individual subjects and reference to a structural image in that subject. However, coregistration of functional brain images across many subjects offers the experimental advantage of enabling voxel-based analysis over multiple subjects and is therefore widely used in human studies. Voxel-based coregistration methods require a high-quality 3D template image. We created such templates, derived from T1-weighted MRI and blood-flow PET images from 12 nemestrina monkeys. We designed the macaque templates to be maximally compatible with the baboon template images described in a companion paper, to facilitate cross-species comparison of functional imaging data. Here we present data showing the reliability and validity of automatic image registration to the template. Alignment of selected internal fiducial points was accurate to within 1.9 mm overall (mean) even across species. The template images, along with copies aligned to the UCLA nemestrina brain atlas, are available on the Internet (purl.org/net/kbmd/n2k) and can be used as targets with any image registration software.

Animals↗
PubMed2002

Neuroimaging a single thought: dorsolateral PFC activity associated with refreshing just-activated information.

Neuroimaging studies of human working memory (WM) show conflicting results regarding whether dorsolateral prefrontal cortex (PFC) contributes to maintaining information in consciousness or is recruited primarily when information must be manipulated. Using functional magnetic resonance imaging (fMRI), we looked at a minimal maintenance process--thinking back to a single, just-seen stimulus (refreshing). We found greater activity in left dorsolateral PFC (BA9) when participants refreshed a word compared to reading a word once or a second time. Furthermore, recognition memory was subsequently more accurate and faster for items that had been refreshed, demonstrating that a single thought that maintains activation can have consequences for long-term memory. Our fMRI results call into question any class of models of the functional organization of PFC and WM that associates simple and/or maintenance processes only with ventrolateral PFC or that associates dorsolateral PFC only with more complex processes such as manipulation.

Adult↗
PubMed2002

The quantitative evaluation of functional neuroimaging experiments: mutual information learning curves.

Learning curves are presented as an unbiased means for evaluating the performance of models for neuroimaging data analysis. The learning curve measures the predictive performance in terms of the generalization or prediction error as a function of the number of independent examples (e.g., subjects) used to determine the parameters in the model. Cross-validation resampling is used to obtain unbiased estimates of a generic multivariate Gaussian classifier, for training set sizes from 2 to 16 subjects. We apply the framework to four different activation experiments, in this case [(15)O]water data sets, although the framework is equally valid for multisubject fMRI studies. We demonstrate how the prediction error can be expressed as the mutual information between the scan and the scan label, measured in units of bits. The mutual information learning curve can be used to evaluate the impact of different methodological choices, e.g., classification label schemes, preprocessing choices. Another application for the learning curve is to examine the model performance using bias/variance considerations enabling the researcher to determine if the model performance is limited by statistical bias or variance. We furthermore present the sensitivity map as a general method for extracting activation maps from statistical models within the probabilistic framework and illustrate relationships between mutual information and pattern reproducibility as derived in the NPAIRS framework described in a companion paper.

Adult↗
PubMed2002

The quantitative evaluation of functional neuroimaging experiments: the NPAIRS data analysis framework.

We introduce a data-analysis framework and performance metrics for evaluating and optimizing the interaction between activation tasks, experimental designs, and the methodological choices and tools for data acquisition, preprocessing, data analysis, and extraction of statistical parametric maps (SPMs). Our NPAIRS (nonparametric prediction, activation, influence, and reproducibility resampling) framework provides an alternative to simulations and ROC curves by using real PET and fMRI data sets to examine the relationship between prediction accuracy and the signal-to-noise ratios (SNRs) associated with reproducible SPMs. Using cross-validation resampling we plot training-test set predictions of the experimental design variables (e.g., brain-state labels) versus reproducibility SNR metrics for the associated SPMs. We demonstrate the utility of this framework across the wide range of performance metrics obtained from [(15)O]water PET studies of 12 age- and sex-matched data sets performing different motor tasks (8 subjects/set). For the 12 data sets we apply NPAIRS with both univariate and multivariate data-analysis approaches to: (1) demonstrate that this framework may be used to obtain reproducible SPMs from any data-analysis approach on a common Z-score scale (rSPM[Z]); (2) demonstrate that the histogram of a rSPM[Z] image may be modeled as the sum of a data-analysis-dependent noise distribution and a task-dependent, Gaussian signal distribution that scales monotonically with our reproducibility performance metric; (3) explore the relation between prediction and reproducibility performance metrics with an emphasis on bias-variance tradeoffs for flexible, multivariate models; and (4) measure the broad range of reproducibility SNRs and the significant influence of individual subjects. A companion paper describes learning curves for four of these 12 data sets, which describe an alternative mutual-information prediction metric and NPAIRS reproducibility as a function of training-set sizes from 2 to 18 subjects. We propose the NPAIRS framework as a validation tool for testing and optimizing methodological choices and tools in functional neuroimaging.

Adult↗
PubMed2002

Classical and Bayesian inference in neuroimaging: applications.

In Friston et al. ((2002) Neuroimage 16: 465-483) we introduced empirical Bayes as a potentially useful way to estimate and make inferences about effects in hierarchical models. In this paper we present a series of models that exemplify the diversity of problems that can be addressed within this framework. In hierarchical linear observation models, both classical and empirical Bayesian approaches can be framed in terms of covariance component estimation (e.g., variance partitioning). To illustrate the use of the expectation-maximization (EM) algorithm in covariance component estimation we focus first on two important problems in fMRI: nonsphericity induced by (i) serial or temporal correlations among errors and (ii) variance components caused by the hierarchical nature of multisubject studies. In hierarchical observation models, variance components at higher levels can be used as constraints on the parameter estimates of lower levels. This enables the use of parametric empirical Bayesian (PEB) estimators, as distinct from classical maximum likelihood (ML) estimates. We develop this distinction to address: (i) The difference between response estimates based on ML and the conditional means from a Bayesian approach and the implications for estimates of intersubject variability. (ii) The relationship between fixed- and random-effect analyses. (iii) The specificity and sensitivity of Bayesian inference and, finally, (iv) the relative importance of the number of scans and subjects. The forgoing is concerned with within- and between-subject variability in multisubject hierarchical fMRI studies. In the second half of this paper we turn to Bayesian inference at the first (within-voxel) level, using PET data to show how priors can be derived from the (between-voxel) distribution of activations over the brain. This application uses exactly the same ideas and formalism but, in this instance, the second level is provided by observations over voxels as opposed to subjects. The ensuing posterior probability maps (PPMs) have enhanced anatomical precision and greater face validity, in relation to underlying anatomy. Furthermore, in comparison to conventional SPMs they are not confounded by the multiple comparison problem that, in a classical context, dictates high thresholds and low sensitivity. We conclude with some general comments on Bayesian approaches to image analysis and on some unresolved issues.

Algorithms↗
PubMed2002

A model of the coupling between brain electrical activity, metabolism, and hemodynamics: application to the interpretation of functional neuroimaging.

In order to improve the interpretation of functional neuroimaging data, we implemented a mathematical model of the coupling between membrane ionic currents, energy metabolism (i.e., ATP regeneration via phosphocreatine buffer effect, glycolysis, and mitochondrial respiration), blood-brain barrier exchanges, and hemodynamics. Various hypotheses were tested for the variation of the cerebral metabolic rate of oxygen (CMRO(2)): (H1) the CMRO(2) remains at its baseline level; (H2) the CMRO(2) is enhanced as soon as the cerebral blood flow (CBF) increases; (H3) the CMRO(2) increase depends on intracellular oxygen and pyruvate concentrations, and intracellular ATP/ADP ratio; (H4) in addition to hypothesis H3, the CMRO(2) progressively increases, due to the action of a second messenger. A good agreement with experimental data from magnetic resonance imaging and spectroscopy (MRI and MRS) was obtained when we simulated sustained and repetitive activation protocols using hypotheses (H3) or (H4), rather than hypotheses (H1) or (H2). Furthermore, by studying the effect of the variation of some physiologically important parameters on the time course of the modeled blood-oxygenation-level-dependent (BOLD) signal, we were able to formulate hypotheses about the physiological or biochemical significance of functional magnetic resonance data, especially the poststimulus undershoot and the baseline drift.

Adenosine Triphosphate↗
PubMedDate not supplied

On the relations among priming, conscious recollection, and intentional retrieval: evidence from neuroimaging research.

Neurobiological distinctions among forms of memory have been investigated mainly from the perspective of lesion studies in nonhuman animals and experiments with human neurological patients. We consider recent neuroimaging studies of healthy human volunteers using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) that provide new information concerning the neural correlates of particular forms of memory retrieval. More specifically, we consider evidence indicating that priming, a form of implicit retrieval, is associated with decreased activity in various cortical regions. We also consider evidence suggesting that two components of explicit retrieval-intentional or effortful search and successful conscious recollection-are preferentially associated with increased activity in prefrontal and medial temporal regions, respectively.

Brain↗
PubMed1985

Neuroimaging of mass lesions of the pineal region in infancy and childhood.

Mass lesions of the pineal gland, quadrigeminal plate, posterior third ventricle and midbrain are grouped together as pineal region lesions. The various methods of neuroimaging should not only help to localise and circumscribe these lesions, but should also suggest their quality and nature, i.e. cystic parts, delineation and possible histology. Also, the pathomorphological pattern with respect to the position of the aqueduct and the direction of growth towards the third ventricle and trigone of the lateral ventricle plays an important role in deciding which approach is possible and most suitable. Of major importance are the deep vascular structures and the vasculature of the lesion itself. The study is based on 24 cases of the pediatric age group from a total of 52 observed cases.

Adolescent↗
PubMed1992

The role of anatomic information in quantifying functional neuroimaging data.

When using modern neuroimaging tools, such as CT, PET, SPECT, MRI and MEG, in brain research and brain diagnostics, there is a common need for including external anatomical information into the interpretation and analysis of data. This information may be used to aid the interpretation of structures in images from low resolution imaging tools. With high resolution tools it can help to identify resolved structures. It can also facilitate the merging of data from different modalities, or from different individuals. The anatomical information is often given as regions of interests (ROIs), which may be manually created from an anatomy rich image or automatically created from a standard template collection or from an atlas data base. Automatic methods will lead to a substantial reduction in bias and in size of the systematic errors. Functional ROIs can correspondingly be derived from functional images (usually PET or SPECT). Different aspects of these processes are discussed in the report.

Brain↗
PubMed1996

The child with a cephalocele: etiology, neuroimaging, and outcome.

We report a series of 46 children who were treated for one of the diverse forms of cranium bifidum during a period of 22 years. The purpose of the survey was to investigate pathogenetic factors involved in the development of cranial dysraphism and to analyze clinical and pathological factors that influence the patients' outcome. We also investigated the existence of associated intracranial anomalies, in a systematic way, using modern methods of neuroimaging, and related the findings to the patients' final results. The lesions were classified as encephalocele (n = 15), cranial meningocele (n = 3), atretic cephalocele (n = 26), cranium bifidum occultum (n = 1), and exencephaly (n = 1). There was an excess of the atretic form of cephaloceles in our series, a fact that probably reflects geographical variations described for cephaloceles in general. The location of the lesions was occipital in 29 children, parietal in 16, and temporal and frontobasal in one case each. In seven cases there was parental consanguinity. A familial history of malformations of the central nervous system was encountered in eight instances. Associated systemic abnormalities were present in 23 patients, while central nervous system anomalies were found in 36 children. Cephalocele repair was undertaken on 35 occasions. There were no surgical fatalities in the series. The mean follow-up time was of 7 years. Overall mortality for the whole group was of 17/46 or 36%. Twenty of the 29 survivors had no neurological sequelae, but only 18 children exhibited a competitive intelligence level. A good outcome was found to correlate well with: an average head size at birth, a normal initial neurological condition, operability of the lesions, and an absence of disorders of the neuronal migration. Neurological outcome depended also on the occurrence or not of hydrocephalus, while the intelligence level was mainly related to the absence of cerebral tissue within the sac of the malformation.

Abnormalities, Multiple↗
PubMed1995

Neuroimaging and functional examination in hydrocephalus: a comment.

All the papers were of a high scientific standard, giving us clearly defined information that will be applicable in the diagnosis and further management of infantile hydrocephalus. Particularly interesting subjects were the comparison of CT and MRI in the evaluation of hydrocephalus and cine MRI, which allows evaluation of the CSF dynamic flows. CBF measurements with xenon CT/CBF imaging or transcranial Doppler examinations of CBF velocity are used much more for evaluation of the shunt indications for shunting and also for definition of the outcome of shunting procedures. Although measurements of physiological CSF parameters are important, studies on the pathophysiology of hydrocephalus should be focused on the changes in CBF in hydrocephalus patients. The key points and conclusions presented by each author are discussed and the prospects mentioned for the future in neuroimaging and functional examination in hydrocephalus.

Blood Flow Velocity↗
PubMed1996

Oculodental digital dysplasia: neuroimaging in a kindred.

Oculodental digital dysplasia (ODDD) is an uncommon inherited disorder with characteristic facial abnormalities, defects in dentition and syndactyly; previous reports have described neurologic dysfunction. We present neuroimaging features of a mother and daughter with ODDD; despite only the mother having neurologic dysfunction, the MRI findings in both are strikingly similar.

Adolescent↗
PubMed1991

Neuroimaging findings (ultrasonography, CT, MRI) in 3 infants with congenital rubella syndrome.

Neuroimaging observations of three infants with congenital rubella syndrome are reported. We have observed congenital rubella syndrome lesions in the subependymal area, the basal ganglia and the deep white matter. Cranial ultrasonography defines subependymal cysts, calcification and possible vascular changes in the basal ganglia while MRI is the most sensitive to minor atrophic changes and white matter lesions. Although CT defines calcification, it is less sensitive than MRI to white matter changes and does not demonstrate subependymal cysts.

Female↗
PubMed1997

Functional neuroimaging in the assessment of cerebral ischaemia.

Cerebral infarct causes over 170, 000 deaths per year in the United States. Recent developments in neuroimaging are providing an insight into focal cerebral ischaemia, including its pathophysiology and the area of brain at risk. Perfusion-weighted magnetic resonance (MR) allows evaluation of the blood supply to the ischaemic area, and diffusion-weighted MR permits assessment of tissue damage. Although both functional imaging techniques require some refinement, it is likely that they will soon become part of the normal clinical routine and allow accurate characterisation of pathology. It is expected that this may eventually lead to the development of new treatments.

Animals↗
PubMed2000

Correlation of EEG, neuroimaging and histopathology in an epilepsy patient with diffuse cortical dysplasia.

The correlation between scalp EEG, intraoperative electrocorticogram, neuroimaging and histopathology was examined in an epileptic child with diffuse cortical dysplasia. The 6-year-old girl with moderate mental retardation had suffered from intractable complex partial and generalized epilepsies since the age of 2 years. MR images demonstrated unilateral large macrogyria/polymicrogyria and schizencephaly in the right occipital lobe. The epileptic focus was detected on the macrogyria by EEG and single photon emission tomography. However, the intraoperative electrocorticogram showed frequent spikes from the polymicrogyria and no paroxysmal activity in the macrogyria. The polymicrogyria and the macrogyric lesion were resected, using an image-guided system. The histological findings revealed that the macrogyria was covered with and separated by glial bundles. It has been reported that epileptogenicity is produced from abnormal neurons and their arrangement in cortical dysplasia; in this case, however, the major dysplastic lesion had no epileptogenicity; rather the focus might be in the polymicrogyria around the lesion.

Cerebral Cortex↗