The rapid collection of brain images from healthy and diseased subjects has stimulated the development of powerful mathematical algorithms to compare, pool and average brain data across whole populations. Brain structure is so complex and variable that new approaches in computer vision, partial differential equations, and statistical field theory are being formulated to detect and visualize disease-specific patterns. We present some novel mathematical strategies for computational anatomy, focusing on the creation of population-based brain atlases. These atlases describe how the brain varies with age, gender, genetics, and over time. We review applications in Alzheimer's disease, schizophrenia and brain development, outlining some current challenges in the field.

This paper focuses on extracting the ideal midsagittal plane (iMSP) from three-dimensional (3-D) normal and pathological neuroimages. The main challenges in this work are the structural asymmetry that may exist in pathological brains, and the anisotropic, unevenly sampled image data that is common in clinical practice. We present an edge-based, cross-correlation approach that decomposes the plane fitting problem into discovery of two-dimensional symmetry axes on each slice, followed by a robust estimation of plane parameters. The algorithm's tolerance to brain asymmetries, input image offsets and image noise is quantitatively evaluated. We find that the algorithm can extract the iMSP from input 3-D images with 1) large asymmetrical lesions; 2) arbitrary initial rotation offsets; 3) low signal-to-noise ratio or high bias field. The iMSP algorithm is compared with an approach based on maximization of mutual information registration, and is found to exhibit superior performance under adve...

“Origins of communicative disorders ” to Elizabeth Bates, and by a grant from the John D. and Catherine T. MacArthur Foundation. We are grateful to Larry Juarez and Meiti Opie The effects of focal brain injury are investigated in the first stages of language development, during the passage from first words to grammar. Parent report and/or free speech data are reported for 53 infants and preschool children between 10- 44 months of age. All children had suffered a single, unilateral brain injury to the left or right hemisphere, incurred before six months of age (usually in the pre- or perinatal period). This is the period in which we should expect to see maximal plasticity, but it is also the period in which the initial specializations of particular cortical regions ought to be most evident. In direct contradiction of hypotheses based on the adult aphasia literature, results from 10- 17 months suggest that children with righthemisphere injuries are at greater risk for delays in word comprehension, and in the gestures that normally precede and accompany language onset. Although there were no differences between left- vs. right-hemisphere injury per se on expressive language, children whose lesions include the left temporal lobe did show significantly greater delays in expressive vocabulary and

We present a new method to automatically compute, reorient and recenter the mid-sagittal plane in anatomical and functional 3D brain images. This iterative approach is composed of two steps. At rst, given an initial guess of the mid-sagittal plane (generally, the central plane of the image grid), the computation of local similarity measures between the two sides of the head allows to identify homologous anatomical structures or functional areas, by way of a block matching procedure. The output is a set of point-to-point correspondences: the centers of homologous blocks. Subsequently, we de ne the mid-sagittal plane as the one best superposing the points on one side and their counterparts on the other side by reective symmetry. Practically, the computation of the parameters characterizing the plane is performed by a least trimmed squares estimation. Then, the estimated plane is aligned with the center of the image grid, and the whole process is iterated until convergence. The robust estimation technique we use allows normal or abnormal asymmetrical structures or areas to be treated as outliers, and the plane to be mainly computed from the underlying gross symmetry of the brain. The algorithm is fast and accurate, even for strongly tilted heads, and even in presence of high acquisition noise and bias eld, as shown on a large set of synthetic data. The algorithm has also been visually evaluated on a large set of real MR images. We present a few results on isotropic as well as anisotropic anatomical (MR, CT) and functional (SPECT, PET) real images, for normal and pathological subjects.

We present a general method to study the dissymmetry of anatomical structures such as the human brain. Our method relies on the estimate of 3D dissymmetry fields, the use of 3D vector field operators, and T 2 statistics to compute significance maps. We also present a fully automated implementation of this method which relies mainly on the intensive use of a 3D non-rigid inter-patient matching tool. Such a tool is applied successively between the images and their symmetric versions with respect to an arbitrary plane, both to realign the images with respect to the midplane of the subject and to compute a dense 3D dissymmetry map. Inter-patient matching is also used to fuse the data of a population of subjects. We then describe three main application elds: the study of the normal dissymmetry within a given population, the comparison of the dissymmetry between two populations, and the detection of the significant abnormal dissymmetries of a patient with respect to a reference population. Fina...

& The detection of speech in an auditory stream is a requisite first step in processing spoken language. In this study, we used event-related fMRI to investigate the neural substrates mediating detection of speech compared with that of nonspeech auditory stimuli. Unlike previous studies addressing this issue, we contrasted speech with nonspeech analogues that were matched along key temporal and spectral dimensions. In an oddball detection task, listeners heard nonsense speech sounds, matched sine wave analogues (complex nonspeech), or single tones (simple nonspeech). Speech stimuli elicited significantly greater activation than both complex and simple nonspeech stimuli in classic receptive language areas, namely the middle temporal gyri bilaterally and in a locus lateralized to the left posterior superior temporal gyrus. In addition, speech activated a small cluster of the right inferior frontal gyrus. The activation of these areas in a simple detection task, which requires neither identification nor linguistic analysis, suggests they play a fundamental role in speech processing. &

th schizophrenia compared with controls (13.1%) and patients with bipolar mania (16.8%). Conclusions: Compared with controls and patients with bipolar manic psychosis, patients with first-episode schizophrenia showed left planum temporale gray matter volume reduction and bilateral Heschl gyrus gray matter volume reduction. These findings are similar to those reported in patients with chronic schizophrenia and suggest that such abnormalities are present at first episode and are specific to schizophrenia. Arch Gen Psychiatry. 2000;57:692-699 S TRUCTURAL brain abnormalities in schizophrenia have been extensively investigated using magnetic resonance imaging (MRI). 1-5 Several studies have reported abnormalities in portions of the superior temporal gyrus (STG) in patients diagnosed as having schizophrenia, 1-3 including planum temporale (PT) and Heschl gyrus (HG) (primary auditory cortex).<F6.

etric differences of the lateral ventricles, hippocampus, and amygdala indicate regional displacements and shape distortions in several functional systems in schizophrenia. Alterations in these structures as mapped in 3D may provide the foundation for establishing brain abnormalities not previously defined at such a local level. Biol Psychiatry 2001;50: 84 --97 2001 Society of Biological Psychiatry Key Words: MRI, hippocampus, ventricles, amygdala, asymmetry, morphometry Introduction D ecades of imaging research confirm the presence of structural brain abnormalities in schizophrenia. Morphometric findings however, frequently lack consensus, and the regional specificity of cerebral anomalies are difficult to pinpoint, problems that are further complicated by clinical heterogeneity. Structural brain abnormalities reported in schizophrenia appear to include several functional systems, suggesting that different neurobiological me

& Language and arithmetic are both lateralized to the left hemisphere in the majority of right-handed adults. Yet, does this similar lateralization reflect a single overall constraint of brain organization, such an overall ‘‘dominance’ ’ of the left hemisphere for all linguistic and symbolic operations? Is it related to the lateralization of specific cerebral subregions? Or is it merely coincidental? To shed light on this issue, we performed a ‘‘colateralization analysis’ ’ over 209 healthy subjects: We investigated whether normal variations in the degree of left hemispheric asymmetry in areas involved in sentence listening and reading are mirrored in the asymmetry of areas involved in mental arithmetic. Within the language network, a region-of-interest analysis disclosed partially dissociated patterns of lateralization, inconsistent with an overall ‘‘dominance’’ model. Only two of these areas presented a lateralization during sentence listening and reading which correlated strongly with the lateralization of two regions active during calculation. Specifically, the profile of asymmetry in the posterior superior temporal sulcus during sentence processing covaried with the asymmetry of calculation-induced activation in the intraparietal sulcus, and a similar colateralization linked the middle frontal gyrus with the superior posterior parietal lobule. Given recent neuroimaging results suggesting a late emergence of hemispheric asymmetries for symbolic arithmetic during childhood, we speculate that these colateralizations might constitute developmental traces of how the acquisition of linguistic symbols affects the cerebral organization of the arithmetic network. &

Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the `nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain.