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BACKGROUND: Whether recurrent epileptic seizures induce brain damage is debated. Disease progression in epilepsy has been evaluated only in a few community-based studies involving patients with seizures well controlled by medication. These studies concluded that epilepsy does not inevitably lead to global cerebral damage. OBJECTIVE: To track the progression of neocortical atrophy in pharmacoresistant temporal lobe epilepsy (TLE) using longitudinal and cross-sectional designs. METHODS: Using a fully automated measure of cortical thickness on MRI, we studied a homogeneous sample of patients with pharmacoresistant TLE. In the longitudinal analysis (n = 18), fixed-effect models were used to quantify cortical atrophy over a mean interscan interval of 2.5 years (range = 7 to 90 months). In the cross-sectional analysis (n = 121), we correlated epilepsy duration and thickness. To dissociate normal aging from pathologic progression, we compared aging effects in TLE to healthy controls. RESULTS: The longitudinal analysis mapped progression in ipsilateral temporopolar and central and contralateral orbitofrontal, insular, and angular regions. In patients with more than 14 years of disease, atrophy progressed more rapidly in frontocentral and parietal regions that in those with shorter duration. The cross-sectional study showed progressive atrophy in the mesial and superolateral frontal, and parietal cortices. CONCLUSIONS: Our combined cross-sectional and longitudinal analysis in patients with pharmacoresistant temporal lobe epilepsy demonstrated progressive neocortical atrophy over a mean interval of 2.5 years that is distinct from normal aging, likely representing seizure-induced damage. The cumulative character of atrophy underlies the importance of early surgical treatment in this group of patients.
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Anticonvulsivantes/uso terapéutico , Atrofia , Corteza Cerebral/patología , Epilepsia del Lóbulo Temporal , Adolescente , Adulto , Anciano , Atrofia/etiología , Atrofia/patología , Corteza Cerebral/anatomía & histología , Niño , Estudios Transversales , Progresión de la Enfermedad , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/terapia , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The aims of this study were to investigate the pattern of cortical atrophy and the relationships between memory performances and the brain regions in Alzheimer's Disease (AD). optimized voxel-based morphometry (VBM) was applied to the MRI brain images of 18 probable AD and 18 healthy subjects (HS). Patients performed verbal and visuo-spatial episodic and shortterm memory tests. Contrasting of AD group with HS, and anatomobehavioural correlations were carried out in order to identify regional atrophic changes and neuro-cognitive aspects in AD group. We found evidence of gray matter (GM) volume reduction in AD in the medial temporal, parietal and frontal areas bilaterally and in the left anterior thalamic nuclei. Performance on the episodic memory delayed recall tests co-varied with GM volume in the left entorhinal cortex. The pattern of cortical atrophy likely reflects the heterogeneous level of dementia severity in our AD group. The anatomical region affected in the left hemisphere indicates a sufferance at multiple levels of the Polysynaptic Hippocampal Pathway, which is involved in declarative memory. Findings on the entorhinal cortex and the delayed memory scores support the role of the entorhinal cortex in episodic memory. Damage to the entorhinal cortex, deafferenting the hippocampus from neocortical inputs, interferes with episodic memory consolidation in AD patients.
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Enfermedad de Alzheimer/patología , Atrofia/patología , Corteza Entorrinal/patología , Trastornos de la Memoria/patología , Anciano , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/psicología , Atrofia/etiología , Atrofia/fisiopatología , Mapeo Encefálico , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Corteza Entorrinal/fisiopatología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Memoria/fisiología , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Tálamo/patología , Tálamo/fisiopatologíaRESUMEN
We used straightforward linear mixed effects models as described in Worsley et al. together with recent advances in smoothing to control the degrees of freedom, and random field theory based on discrete local maxima. This has been implemented in BRAINSTAT, a Python version of FMRISTAT. Our main novelty is voxel-wise inference for both magnitude and delay (latency) of the hemodynamic response. Our analysis appears to be more sensitive than that of Dehaene-Lambertz et al. Our main findings are greater magnitude (1.08% +/- 0.17%) and delay (0.153 +/- 0.035 s) for different sentences compared to same sentences, together with a smaller but still significantly greater magnitude for different speaker compared to same speaker (0.47% +/- 0.08%).
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Algoritmos , Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Programas Informáticos/normas , Artefactos , Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Circulación Cerebrovascular/fisiología , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador/normas , Procesamiento de Imagen Asistido por Computador/tendencias , Modelos Lineales , Imagen por Resonancia Magnética/normas , Imagen por Resonancia Magnética/tendencias , Distribución Normal , Lóbulo Parietal/anatomía & histología , Lóbulo Parietal/fisiología , Tiempo de Reacción/fisiología , Procesamiento de Señales Asistido por Computador , Programas Informáticos/tendencias , Percepción del Habla/fisiología , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/fisiologíaRESUMEN
Several authors have suggested allowing for unknown latency of the hemodynamic response by incorporation of hemodynamic derivative terms into the linear model for the statistical analysis of fMRI data. In this paper, we show how to use random field theory to provide a P value for local maxima of two test statistics that have been recently proposed for detecting activation based on this analysis.
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Circulación Cerebrovascular/fisiología , Hemodinámica/fisiología , Imagen por Resonancia Magnética/estadística & datos numéricos , Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos LinealesRESUMEN
We present a new continuity correction to the P value for local maxima of a statistical parametric map that bridges the gap between small FWHM, when the Bonferroni correction is accurate, and large FWHM, when random field theory is accurate. The new method, based on discrete local maxima, is always an upper bound (like the Bonferroni), but lower and hence more accurate for large FWHM, without increasing false positives. It resulted in P values that were approximately 43% lower than the best of Bonferroni or random field theory methods when applied to a typical fMRI data set.
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Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Algoritmos , Simulación por Computador , Humanos , Imagen por Resonancia Magnética , Modelos Estadísticos , Vías Nerviosas/fisiología , Distribución NormalRESUMEN
In the statistical analysis of fMRI data, the parameter of primary interest is the effect of a contrast; of secondary interest is its standard error, and of tertiary interest is the standard error of this standard error, or equivalently, the degrees of freedom (df). In a ReML (Restricted Maximum Likelihood) analysis, we show how spatial smoothing of temporal autocorrelations increases the effective df (but not the smoothness of primary or secondary parameter estimates), so that the amount of smoothing can be chosen in advance to achieve a target df, typically 100. This has already been done at the second level of a hierarchical analysis by smoothing the ratio of random to fixed effects variances (Worsley, K.J., Liao, C., Aston, J.A.D., Petre, V., Duncan, G.H., Morales, F., Evans, A.C., 2002. A general statistical analysis for fMRI data. NeuroImage, 15:1-15); we now show how to do it at the first level, by smoothing autocorrelation parameters. The proposed method is extremely fast and it does not require any image processing. It can be used in conjunction with other regularization methods (Gautama, T., Van Hulle, M.M., in press. Optimal spatial regularisation of autocorrelation estimates in fMRI analysis. NeuroImage.) to avoid unnecessary smoothing beyond 100 df. Our results on a typical 6-min, TR = 3, 1.5-T fMRI data set show that 8.5-mm smoothing is needed to achieve 100 df, and this results in roughly a doubling of detected activations.
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Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética/estadística & datos numéricos , Algoritmos , Simulación por Computador , Interpretación Estadística de Datos , Humanos , Modelos LinealesRESUMEN
We present a simple approach to the analysis of fMRI data collected from several runs, sessions and subjects. We take advantage of the spatial nature of the data to reduce the noise in certain key parameters, achieving an increase in degrees of freedom for a mixed effects analysis. Our main interest is the analysis of the resulting images of test statistics using the geometry of random fields. We show how the Euler characteristic of the excursion set plays a key role in setting the threshold of the image to detect regions of the brain activated by a stimulus.
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Interpretación Estadística de Datos , Imagen por Resonancia Magnética/estadística & datos numéricos , Modelos Estadísticos , Procesos Estocásticos , Encéfalo/anatomía & histología , Encéfalo/fisiología , Mapeo Encefálico , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética/métodos , Reconocimiento Visual de Modelos , Factores de TiempoRESUMEN
We propose a fast, efficient, general, simple, valid, and robust method of estimating and making inference about the delay of the fMRI response modeled as a temporal shift of the hemodynamic response function (HRF). We estimate the shift unbiasedly using two optimally chosen basis functions for a spectrum of time shifted HRFs. This is done at every voxel, to create an image of estimated delays and their standard deviations. This can be used to compare delays for the same stimulus at different voxels, or for different stimuli at the same voxel. Our method is compared to other alternatives and validated on an fMRI data set from an experiment in pain perception.
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Encéfalo/fisiología , Hemodinámica/fisiología , Imagen por Resonancia Magnética/métodos , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Simulación por Computador , Antebrazo/inervación , Humanos , Modelos Neurológicos , Tiempo de Reacción , Reproducibilidad de los ResultadosRESUMEN
We propose a method for the statistical analysis of fMRI data that seeks a compromise between efficiency, generality, validity, simplicity, and execution speed. The main differences between this analysis and previous ones are: a simple bias reduction and regularization for voxel-wise autoregressive model parameters; the combination of effects and their estimated standard deviations across different runs/sessions/subjects via a hierarchical random effects analysis using the EM algorithm; overcoming the problem of a small number of runs/session/subjects using a regularized variance ratio to increase the degrees of freedom.
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Encéfalo/irrigación sanguínea , Hemodinámica/fisiología , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Imagenología Tridimensional/estadística & datos numéricos , Imagen por Resonancia Magnética/estadística & datos numéricos , Algoritmos , Artefactos , Sesgo , Humanos , Modelos Lineales , Cómputos Matemáticos , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
The use of computational approaches in the analysis of high resolution magnetic resonance images (MRI) of the human brain provides a powerful tool for in vivo studies of brain anatomy. Here, we report results obtained with a voxel-wise statistical analysis of hemispheric asymmetries in regional 'amounts' of gray matter, based on MRI scans obtained in 142 healthy young adults. Firstly, the voxel-wise analysis detected the well-known frontal (right > left) and occipital (left > right) petalias. Secondly, our analysis confirmed the presence of left-greater-than-right asymmetries in several posterior language areas, including the planum temporale and the angular gyrus; no significant asymmetry was detected in the anterior language regions. We also found previously described asymmetries in the cingulate sulcus (right > left) and the caudate nucleus (right > left). Finally, in some brain regions we observed highly significant asymmetries that were not reported before, such as in the anterior insular cortex (right > left). The above asymmetries were observed in men and women. Our results thus provide confirmation of the known structural asymmetries in the human brain as well as new findings that may stimulate further research of hemispheric specialization.
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Corteza Cerebral/anatomía & histología , Lateralidad Funcional , Adolescente , Adulto , Núcleo Caudado/anatomía & histología , Distribución de Chi-Cuadrado , Interpretación Estadística de Datos , Femenino , Giro del Cíngulo/anatomía & histología , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/estadística & datos numéricos , MasculinoRESUMEN
We present a unified statistical framework for analyzing temporally varying brain morphology using the 3D displacement vector field from a nonlinear deformation required to register a subject's brain to an atlas brain. The unification comes from a single model for structural change, rather than two separate models, one for displacement and one for volume changes. The displacement velocity field rather than the displacement itself is used to set up a linear model to account for temporal variations. By introducing the rate of the Jacobian change of the deformation, the local volume change at each voxel can be computed and used to measure possible brain tissue growth or loss. We have applied this method to detecting regions of a morphological change in a group of children and adolescents. Using structural magnetic resonance images for 28 children and adolescents taken at different time intervals, we demonstrate how this method works.
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Atrofia/patología , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Modelos Neurológicos , Adolescente , Niño , HumanosRESUMEN
A methodology for fMRI data analysis confined to the cortex, Cortical Surface Mapping (CSM), is presented. CSM retains the flexibility of the General Linear Model based estimation, but the procedures involved are adapted to operate on the cortical surface, while avoiding to resort to explicit flattening. The methodology is tested by means of simulations and application to a real fMRI protocol. The results are compared with those obtained with a standard, volume-oriented approach (SPM), and it is shown that CSM leads to local differences in sensitivity, with generally higher sensitivity for CSM in two of the three subjects studied. The discussion provided is focused on the benefits of the introduction of anatomical information in fMRI data analysis, and the relevance of CSM as a step toward this goal.
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Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Imagen por Resonancia Magnética/métodos , Simulación por Computador , Humanos , Modelos Neurológicos , Reproducibilidad de los ResultadosRESUMEN
A method for voxel by voxel statistical inference of PET radioligand receptor studies is presented. This method is aimed at detecting differences in radioligand binding between baseline and activation scans. It uses nonlinear least squares theory to estimate the ligand-receptor model parameters and utilizes the residuals to calculate their associated variance. The approach both increases the degrees of freedom for statistical testing and produces more accurate estimates of the standard deviation of the parameters. This technique is applicable to any ligand with a validated compartmental model, whether reversibly or irreversibly bound. The method was investigated and compared with a simple voxel-wise t test. Both simulated and real PET data for the dopamine D(1) receptor ligand [(11)C]SCH 23390 were used to assess the method. The assumptions implicit in the residuals methods were validated. The residuals method was found to be more sensitive than a simple t test, while not producing false-positive results. In addition, we showed that this method reliably differentiates changes in radioligand binding from the effects of changes in cerebral blood flow.
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Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Células Receptoras Sensoriales/fisiología , Tomografía Computarizada de Emisión/estadística & datos numéricos , Adulto , Benzazepinas , Encéfalo/diagnóstico por imagen , Química Encefálica , Simulación por Computador , Humanos , Ligandos , Imagen por Resonancia Magnética , Modelos Biológicos , RadiofármacosRESUMEN
PURPOSE: To determine the evolution of magnetization transfer (MT) in white matter regions before and after plaque development in patients with multiple sclerosis (MS). MATERIALS AND METHODS: In a 5-year longitudinal evaluation, 30 patients with MS underwent conventional magnetic resonance (MR) imaging, MT MR imaging, and clinical assessment. Cross-sectional data in 12 healthy subjects were also collected. Semiautomated lesion classification with use of T2-weighted MR images was used to measure the time course of the MT ratio (calculated with MR data acquired without and with MT saturation) in every voxel and to help analyze the relationship with the status of lesions depicted on T2-weighted images. RESULTS: There was a significant (P <.001) temporal decline in lesion MT ratio after lesion appearance on T2-weighted images. A significant (P <. 001) progressive decline in MT ratio was also present in voxels that later became lesions, prior to initial detection on T2-weighted images. Even 1(1/2) years prior to lesion appearance, the MT ratio (33.3%) in regions destined to become such lesions was significantly (P <.001) lower than that in both white matter in healthy subjects (41.3%) and other normal-appearing white matter in patients with MS (38.1%). CONCLUSION: The MT ratio reveals progressive focal abnormalities in MS that antedate by up to 2 years the appearance of lesions on T2-weighted MR images.
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Encéfalo/patología , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Adulto , Análisis de Varianza , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The assessment of significant activations in functional imaging using voxel-based methods often relies on results derived from the theory of Gaussian random fields. These results solve the multiple comparison problem and assume that the spatial correlation or smoothness of the data is known or can be estimated. End results (i. e., P values associated with local maxima, clusters, or sets of clusters) critically depend on this assessment, which should be as exact and as reliable as possible. In some earlier implementations of statistical parametric mapping (SPM) (SPM94, SPM95) the smoothness was assessed on Gaussianized t-fields (Gt-f) that are not generally free of physiological signal. This technique has two limitations. First, the estimation is not stable (the variance of the estimator being far from negligible) and, second, physiological signal in the Gt-f will bias the estimation. In this paper, we describe an estimation method that overcomes these drawbacks. The new approach involves estimating the smoothness of standardized residual fields which approximates the smoothness of the component fields of the associated t-field. Knowing the smoothness of these component fields is important because it allows one to compute corrected P values for statistical fields other than the t-field or the Gt-f (e.g., the F-map) and eschews bias due to deviation from the null hypothesis. We validate the method on simulated data and demonstrate it using data from a functional MRI study.
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Mapeo Encefálico/métodos , Encéfalo/fisiología , Modelos Lineales , Modelos Neurológicos , Simulación por Computador , Humanos , Imagen por Resonancia MagnéticaRESUMEN
If the noise component of image data is nonisotropic, i.e., if it has nonconstant smoothness or effective point spread function, then theoretical results for the P value of local maxima and the size of suprathreshold clusters of a statistical parametric map (SPM) based on random field theory are not valid. This assumption is reasonable for PET or smoothed fMRI data, but not if these data are projected onto an unfolded, inflated, or flattened 2D cortical surface. Anatomical data such as structure masks, surface displacements, and deformation vectors are also highly nonisotropic. The solution offered here is to suppose that the image can be warped or flattened (in a statistical sense) into a space where the data are isotropic. The subsequent corrected P values do not depend on finding this warping; it is sufficient only to know that such a warping exists.
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Encéfalo/anatomía & histología , Procesamiento de Imagen Asistido por Computador , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada de EmisiónRESUMEN
In this paper we present an approach to making inferences about generic activations in groups of subjects using fMRI. In particular we suggest that activations common to all subjects reflect aspects of functional anatomy that may be "typical" of the population from which that group was sampled. These commonalities can be identified by a conjunction analysis of the activation effects in which the contrasts, testing for an activation, are specified separately for each subject. A conjunction is the joint refutation of multiple null hypotheses, in this instance, of no activation in any subject. The motivation behind this use of conjunctions is that fixed-effect analyses are generally more "sensitive" than equivalent random-effect analyses. This is because fixed-effect analyses can harness the large degrees of freedom and small scan-to-scan variability (relative to the variability in responses from subject to subject) when assessing the significance of an estimated response. The price one pays for the apparent sensitivity of fixed-effect analyses is that the ensuing inferences pertain to, and only to, the subjects studied. However, a conjunction analysis, using a fixed-effect model, allows one to infer: (i) that every subject studied activated and (ii) that at least a certain proportion of the population would have shown this effect. The second inference depends upon a meta-analytic formulation in terms of a confidence region for this proportion. This approach retains the sensitivity of fixed-effect analyses when the inference that only a substantial proportion of the population activates is sufficient.
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Mapeo Encefálico/métodos , Encéfalo/fisiología , Imagen por Resonancia Magnética/métodos , Atención , Encéfalo/anatomía & histología , Fijación Ocular , Humanos , Modelos Estadísticos , Percepción de Movimiento/fisiología , Probabilidad , Reproducibilidad de los ResultadosRESUMEN
In fMRI there are two classes of inference: one aims to make a comment about the "typical" characteristics of a population, and the other about "average" characteristics. The first pertains to studies of normal subjects that try to identify some qualitative aspect of normal functional anatomy. The second class necessarily applies to clinical neuroscience studies that want to make an inference about quantitative differences of a regionally specific nature. The first class of inferences is adequately serviced by conjunction analyses and fixed-effects models with relatively small numbers of subjects. The second requires random-effect analyses and larger cohorts.
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Estudios de Cohortes , Interpretación Estadística de Datos , Imagen por Resonancia Magnética/métodos , Modelos Estadísticos , Proyectos de Investigación , Humanos , Selección de PacienteRESUMEN
Functional connectivity between two voxels or regions of voxels can be measured by the correlation between voxel measurements from either PET CBF or BOLD fMRI images in 3D. We propose to look at the entire 6D matrix of correlations between all voxels and search for 6D local maxima. The main result is a new theoretical formula based on random field theory for the p-value of these local maxima, which distinguishes true correlations from background noise. This can be applied to crosscorrelations between two different sets of images--such as activations under two different tasks, as well as autocorrelations within the same set of images.
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Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada de Emisión/métodos , Humanos , Modelos Lineales , Distribución Normal , Distribución AleatoriaRESUMEN
The current study was designed to determine the relative distribution of decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA:Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA:Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA:Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.