Comparison of functional activation foci in children and adults using a common stereotactic space

The development of methods allowing direct comparisons between child and adult neuroimaging data is an important prerequisite for studying the neural bases of cognitive development. Several issues arise when attempting to make such direct comparisons, including the comparability of anatomical localization of functional responses and the magnitude and time course of the hemodynamic responses themselves. Previous results suggest that, after transformation into a common stereotactic space, anatomical differences between children (ages 7 and 8) and adults are small relative to the resolution of fMRI data. Here, we investigate whether time courses (BOLD responses) and locations of functional activation foci show similarities as well. Event-related fMRI was performed on 16 children (ages 7 and 8) and 16 adults, who pressed buttons in response to a visual stimulus. After transforming images into Talairach space, the coordinates of four consistent activations in each hemisphere were determined for each subject: two foci in the sensorimotor cortex, one focus in the visual cortex, and one focus in the supplementary motor area (eight activations in total). In seven foci, time courses were similar between children and adults, and peak amplitudes of time courses were comparable in all eight foci. There were negligible between-group differences in location of all foci. Variability of activation location was statistically similar in the two groups. In voxelwise group comparison images, minimal differences were found between children and adults in visual and motor cortex regions. The small differences in time courses and locations of activation foci between child and adult brains validate the feasibility of direct statistical comparison of these groups within a common space.     

Intersubject variability in cortical activations during a complex language task

Intersubject variability in the functional organization of the human brain has theoretical and practical importance for basic and clinical neuroscience. In the present study, positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI) were used to study the functional anatomy of language processes. Intersubject variability in task-induced activations in six brain regions was assessed in 20 normal subjects (10 men and 10 women) for frequency of occurrence, location, intensity, and extent. A complex, but well-studied task (overt verb generation) was compared to a simple baseline (visual fixation) to induce activations in brain areas serving perceptual, motoric, and cognitive functions. The frequency of occurrence was high for all selected brain areas (80-95%). The variability in response location in Talairach space, expressed as the standard deviation along each axis (x, y, z), ranged from 5.2 to 9.9 mm. This variability appears to be uniformly distributed across the brain, uninfluenced by regional differences in the complexity of gyral anatomy or mediated behavior. The variability in response location, expressed as the average Euclidean distances (averaged across subjects) about mean locations of activations, varied from 9.40 to 13.36 mm and had no significant differences by region (P>0.05, beta = 0.20). Intensity variability was also relatively small and homogenous across brain regions. In contrast, response extent was much more variable both across subjects and across brain regions (0.79 to 1.77, coefficient of variation). These findings are in good agreement with previous PET studies of intersubject variability and bode well for the possibility of using functional neuroimaging to study neural plasticity subsequent to congenital and acquired brain lesions.     

A neonatal atlas template for spatial normalization of whole-brain magnetic resonance images of newborns: preliminary results

Commonly used brain templates are based on adults' or children's brains. In this study, we create a neonatal brain template. This becomes necessary because of the pronounced differences not only in size but even more importantly in geometrical proportions of the brains of adults and children as compared to the ones of newborns. The template is created based on high resolution T1 magnetic resonance images of 7 individuals with gestational ages between 39 and 42 weeks at the dates of examination. As usual, the created template presents two characteristics in a single image: an average intensity and an average shape. The normalization process to map subjects to the same space is done using SPM2 (Statistical Parametric Mapping) and its deformation toolbox. It consists of two steps: an affine and a nonlinear registration for global and local alignments, respectively. The template was evaluated by (i) study of anatomical local deviations and (ii) amount of local deformations of brain tissues in normalized neonatal images. The extracted results were compared with the ones obtained by normalization using adult and pediatric templates. It was shown that the application of our neonatal brain template for alignment of neonatal images results in a pronounced increase in performance of the normalization procedure as indicated by reduction of deviation of anatomical equivalent structures. The neonatal atlas template is freely downloadable from http://www.u-picardie.fr/labo/GRAMFC.     

Application of MR/PET in Oncologic Imaging

The present review aims to depict the possibilities offered by hybrid imaging with magnetic resonance positron emission tomography (MR/PET). Recently, new whole-body MR/PET scanners were introduced allowing for the combination of both modalities outside the brain. This is a challenge for both modalities: For MRI, it is essential to provide anatomical images with high resolution. Additionally, diffusion-weighted imaging (DWI), proton spectroscopy, but also dynamic contrast-enhanced imaging plays an important role. With regard to PET, the technical challenge mainly consists of obtaining an appropriate MR-based attenuation correction for the PET data. Using MR/PET, it is possible to acquire morphological and functional data in one examination. In particular, children and young adults will benefit from this new hybrid technique, especially in oncologic imaging with multiple follow-up examinations. However, it is expected that PET/CT will not be replaced completely by MR/PET because PET/CT is less cost-intensive and more widely available. Moreover, in lung imaging, MRI limitations still have to be accepted. Concerning research, simultaneous MR/PET offers a variety of new possibilities, for example cardiac imaging, functional brain studies or the evaluation of new tracers in correlation with specific MR techniques.     

Population-averaged standard template brain atlas for the common marmoset (Callithrix jacchus)

Advanced magnetic resonance (MR) neuroimaging analysis techniques based on voxel-wise statistics, such as voxel-based morphometry (VBM) and functional MRI, are widely applied to cognitive brain research in both human subjects and in non-human primates. Recent developments in imaging have enabled the evaluation of smaller animal models with sufficient spatial resolution. The common marmoset (Callithrix jacchus), a small New World primate species, has been widely used in neuroscience research, to which voxel-wise statistics could be extended with a species-specific brain template. Here, we report, for the first time, a tissue-segmented, population-averaged standard template of the common marmoset brain. This template was created by using anatomical T(1)-weighted images from 22 adult marmosets with a high-resolution isotropic voxel size of (0.2 mm)(3) at 7-Tesla and DARTEL algorithm in SPM8. Whole brain templates are available at International Neuroinformatics Japan Node website, http://brainatlas.brain.riken.jp/marmoset/.     

Unbiased diffeomorphic atlas construction for computational anatomy

Construction of population atlases is a key issue in medical image analysis, and particularly in brain mapping. Large sets of images are mapped into a common coordinate system to study intra-population variability and inter-population differences, to provide voxel-wise mapping of functional sites, and help tissue and object segmentation via registration of anatomical labels. Common techniques often include the choice of a template image, which inherently introduces a bias. This paper describes a new method for unbiased construction of atlases in the large deformation diffeomorphic setting. A child neuroimaging autism study serves as a driving application. There is lack of normative data that explains average brain shape and variability at this early stage of development. We present work in progress toward constructing an unbiased MRI atlas of 2 years of children and the building of a probabilistic atlas of anatomical structures, here the caudate nucleus. Further, we demonstrate the segmentation of new subjects via atlas mapping. Validation of the methodology is performed by comparing the deformed probabilistic atlas with existing manual segmentations.     

MR-based statistical atlas of the G?ttingen minipig brain.

Thedomestic pig is increasingly being used as an experimental model for brain imaging studies with positron emission tomography (PET). The recording of radiotracer uptake by PET gives functional and physiological information, but with poor spatial resolution. To date, anatomical regions of interest in pig brain have been defined in MR images obtained for each individual animal, because of the lack of a standard stereotaxic coordinate system for the pig brain. In order to define a stereotaxic coordinate system, we coregistered T1-weighted MR images from 22 male G?ttingen minipigs and obtained a statistically defined surface rendering of the average minipig brain in which stereotaxic zero is defined by the position of the pineal gland. The average brain is now used as a target for registration of dynamic PET data, so that time-activity curves can be extracted from standard volumes of interest. In order to define these volumes, MR images from each individual pig were manually segmented into a total of 34 brain structures, including cortical regions, white matter, caudate and putamen, ventricular system, and cerebellum. The mean volumes of these structures had variances in the range of 10-20%. The 34 brain volumes were transformed into the common coordinate system and then used to generate surface renderings with probabilistic threshold greater than 50%. This probabilistic threshold gave nearly quantitative recovery of the mean volumes in native space. The probabilistic volumes in stereotaxic space are now being used to extract time-radioactivity curves from dynamic PET recordings.     

A customizable 3-dimensional digital atlas of the canary brain in multiple modalities

Songbirds are well known for their ability to learn their vocalizations by imitating conspecific adults. This uncommon skill has led to many studies examining the behavioral and neurobiological processes involved in vocal learning. Canaries display a variable, seasonally dependent, vocal behavior throughout their lives. This trait makes this bird species particularly valuable to study the functional relationship between the continued plasticity in the singing behavior and alterations in the anatomy and physiology of the brain. In order to optimally interpret these types of studies, a detailed understanding of the brain anatomy is essential. Because traditional 2-dimensional brain atlases are limited in the information they can provide about the anatomy of the brain, here we present a 3-dimensional MRI-based atlas of the canary brain. Using multiple imaging protocols we were able to maximize the number of detectable brain regions, including most of the areas involved in song perception, learning, and production. The brain atlas can readily be used to determine the stereotactic location of delineated brain areas at any desirable head angle. Alternatively the brain data can be used to determine the ideal orientation of the brain for stereotactic injections, electrophysiological recordings, and brain sectioning. The 3-dimensional canary brain atlas presented here is freely available and is easily adaptable to support many types of neurobiological studies, including anatomical, electrophysiological, histological, explant, and tracer studies.     

Deep Brain Stimulation in Cluster Headache: Hypothalamus or Midbrain Tegmentum?

Functional and structural neuroimaging studies have provided pivotal insights into the pathophysiology of trigeminal autonomic cephalalgias (TACs), particularly cluster headache (CH). Functional imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in TACs have reported activation of the posterior hypothalamus. A structural neuroimaging study using voxel-based morphometry in CH reported increased volume of the hypothalamic gray, although another larger study failed to reproduce this finding. These studies in CH prompted the use of stereotactic stimulation of the target point identified by functional and structural neuroimaging. The precise anatomical localization of the deep brain stimulation (DBS) target places it at the midbrain tegmentum rather than the posterior hypothalamus. A comparison of the PET and fMRI studies in TACs reveals that the diencephalic/mesencephalic activation is more posteroinferior in the PET studies, straddling the hypothalamus and midbrain tegmentum, whereas the activation is centered on the hypothalamus in the higher spatial resolution fMRI studies. To optimize the outcomes from DBS, it is likely that patients will need to be studied individually using functional imaging techniques that have high spatial and temporal resolution to enable targeting of the appropriate locus with stereotactic stimulation.     

White matter fiber tracts of the human brain: three-dimensional mapping at microscopic resolution, topography and intersubject variability

The position and extent of individual fiber tracts within the white matter of human brains can be identified in vivo using diffusion tensor imaging (DTI) and fiber tracking methods. Previous to this study, however, the lack of three-dimensional (3-D) probability maps precluded comparing the anatomical precision of MRI studies with microscopically defined fiber tracts in human postmortem brains. The present study provides 3-D registered maps of the topography, course and intersubject variability of major fiber tracts, which were identified at microscopic resolution. The analyzed tracts include the corticospinal tract, optic and acoustic radiations, fornix, cingulum, corpus callosum, superior longitudinal, superior and inferior occipito-frontal and uncinate fascicles; sources and targets of fiber tracts include the lateral and medial geniculate nuclei and mamillary bodies. Tracts and nuclei were identified in serial myelin-stained histological sections of ten postmortem brains. The sections were 3-D reconstructed and registered to a standardized stereotaxic space of an in vivo MR reference brain by means of linear and non-linear, elastic transformations. The individual fiber tracts and nuclei were superimposed in the reference space, and probability maps were generated as a quantitative measure of intersubject variability for each voxel of the stereotaxic space. This study presents the first stereotaxic atlas of the course, location and extent of fiber tracts and related nuclei based on microscopically defined localization and topographic data taken at multiple levels on each of the three orthogonal planes. The maps are useful for evaluating and identifying fiber bundles in DTI, for localizing subcortical lesions visible in anatomical MR images and for studying neuronal connectivity.     

A mean three-dimensional atlas of the human thalamus: Generation from multiple histological data

Functional neurosurgery relies on robust localization of the subcortical target structures, which cannot be visualized directly with current clinically available in-vivo imaging techniques. Therefore, one has still to rely on an indirect approach, by transferring detailed histological maps onto the patient's individual brain images. In contrast to macroscopic MRI atlases, which often represent the average of a population, each stack of sections, which a stereotactic atlas provides, is based on a single specimen. In addition to this bias, the anatomy is displayed with a highly anisotropic resolution, leading to topological ambiguities and limiting the accuracy of geometric reconstruction. In this work we construct an unbiased, high-resolution three-dimensional atlas of the thalamic structures, representing the average of several stereotactically oriented histological maps. We resolve the topological ambiguity by combining the information provided by histological data from different stereotactic directions. Since the stacks differ not only in geometrical detail provided, but also due to inter-individual variability, we adopt an iterative approach for reconstructing the mean model. Starting with a reconstruction from a single stack of sections, we iteratively register the current reference model onto the available data and reconstruct a refined mean three-dimensional model. The results show that integration of multiple stereotactic anatomical data to produce an unbiased, mean model of the thalamic nuclei and their subdivisions is feasible and that the integration reduces problems of atlas reconstruction inherent to histological stacks to a large extent.     

Brain mapping in stereotactic surgery: a brief overview from the probabilistic targeting to the patient-based anatomic mapping

In this article, we briefly review the concept of brain mapping in stereotactic surgery taking into account recent advances in stereotactic imaging. The gold standard continues to rely on probabilistic and indirect targeting, relative to a stereotactic reference, i.e., mostly the anterior (AC) and the posterior (PC) commissures. The theoretical position of a target defined on an atlas is transposed into the stereotactic space of a patient's brain; final positioning depends on electrophysiological analysis. The method is also used to analyze final electrode or lesion position for a patient or group of patients, by projection on an atlas. Limitations are precision of definition of the AC-PC line, probabilistic location and reliability of the electrophysiological guidance. Advances in MR imaging, as from 1.5-T machines, make stereotactic references no longer mandatory and allow an anatomic mapping based on an individual patient's brain. Direct targeting is enabled by high-quality images, an advanced anatomic knowledge and dedicated surgical software. Labeling associated with manual segmentation can help for the position analysis along non-conventional, interpolated planes. Analysis of final electrode or lesion position, for a patient or group of patients, could benefit from the concept of membership, the attribution of a weighted membership degree to a contact or a structure according to its level of involvement. In the future, more powerful MRI machines, diffusion tensor imaging, tractography and computational modeling will further the understanding of anatomy and deep brain stimulation effects.     

Prefrontal activation due to Stroop interference increases during development--an event-related fNIRS study

Although it is well known that executive processes supported by the frontal lobe develop during childhood and adolescence, only one functional imaging study has used the Stroop task to investigate the relationship between frontal lobe function and cognition from a developmental point of view. Hence, we measured brain activation in the lateral prefrontal cortex of children with functional near-infrared imaging during an event-related, color-word matching Stroop task and compared results with a previous study, conducted with the same paradigm in adults. In children, the Stroop task elicited significant brain activation in the left lateral prefrontal cortex comparable to adults. However, the hemodynamic response occurred later in children than adults. Individual brain activation due to Stroop interference varied much more in children than adults, which was paralleled by a higher behavioral variance in children. Data suggest that children differed in their individual cognitive development independent of their chronological age more than adults. Brain activation due to Stroop interference increased with age in the dorsolateral prefrontal cortex in correlation with an improvement of behavioral performance. In conclusion, our results indicate that neuromaturational processes regarding resolution of Stroop interference may depend on increased ability to recruit frontal neural resources.     

Migraine pain location: how do children differ from adults?

The present report provides a detailed head to head comparative study of migraine pain location at onset and during established headache between children and adults belonging to the same ethnic group. Migraine pain location in 200 children and adolescents had already been reported (Chakravarty et al. in Cephalalgia 27:1109-1114, 2007). The present report includes data collected simultaneously and in a similar fashion from 800 adult migraineurs. Significant differences have been noted in migraine pain location. Unilateral onset pain is common in adults, side locked and vertex onset pain unusual in children, holocranial onset pain much common in children and cervico-occipital onset pain much less common in children. There have been differences in evolution of migraine pain as well. During established headache unilateral pain was recorded in only a small proportion of children (10.5%) whereas it was noted in many adults' subjects (40.5%). Such a detailed comparative study had not been made earlier.     

Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10-20 system oriented for transcranial functional brain mapping

The recent advent of multichannel near-infrared spectroscopy (NIRS) has expanded its technical potential for human brain mapping. However, NIRS measurement has a technical drawback in that it measures cortical activities from the head surface without anatomical information of the object to be measured. This problem is also found in transcranial magnetic stimulation (TMS) that transcranially activates or inactivates the cortical surface. To overcome this drawback, we examined cranio-cerebral correlation using magnetic resonance imaging (MRI) via the guidance of the international 10-20 system for electrode placement, which had originally been developed for electroencephalography. We projected the 10-20 standard cranial positions over the cerebral cortical surface. After examining the cranio-cerebral correspondence for 17 healthy adults, we normalized the 10-20 cortical projection points of the subjects to the standard Montreal Neurological Institute (MNI) and Talairach stereotactic coordinates and obtained their probabilistic distributions. We also expressed the anatomical structures for the 10-20 cortical projection points probabilistically. Next, we examined the distance between the cortical surface and the head surface along the scalp and created a cortical surface depth map. We found that the locations of 10-20 cortical projection points in the standard MNI or Talairach space could be estimated with an average standard deviation of 8 mm. This study provided an initial step toward establishing a three-dimensional probabilistic anatomical platform that enables intra- and intermodal comparisons of NIRS and TMS brain imaging data.     

Mapping of histologically identified long fiber tracts in human cerebral hemispheres to the MRI volume of a reference brain: position and spatial variability of the optic radiation.

The interpretation of the anatomical basis of functional deficits after subcortical infarcts could be considerably improved, if the precise topography and interindividual variability in size and course of long fiber tracts in adult human cerebral hemispheres were available in a spatial reference system. We therefore developed a method enabling the mapping of long fiber tracts to the volume of a standard reference brain. The examined fiber tracts were identified in myelin-stained histological serial sections of 10 human brains. The reference brain is a 3-D reconstruction of in vivo obtained magnetic resonance images (MRIs). The warping of histological volumes with the labeled fiber tracts to the reference brain by means of linear and nonlinear transformation procedures results in population maps that demonstrate the interindividual variability in position, size, and course of fiber tracts. In this paper, we present population maps of the optic radiation and the lateral geniculate body as a first example of this mapping strategy. Both structures present a considerable interindividual variability. Furthermore, voxel-based morphometry shows significant side differences with larger volumes of both structures in the left hemisphere than in the right hemisphere. A more than twofold variability of size in the interhemispheric extension of the optic radiation and the lateral geniculate body is found even after normalization of absolute brain size. Our observations demonstrate that the present approach based on population maps of fiber tracts and nuclei can improve the anatomical localization and interpretation of brain lesions visible in MRIs at the level of microstructurally identified architectonical units.     

Development of attentional networks: an fMRI study with children and adults

Data on the development of the attentional systems remain scarce. We used structural and event-related functional magnetic resonance imaging to investigate differences in the neural mechanisms associated with alerting, reorienting, and executive control of attention between children (ages 8 to 12 years) and adults, while controlling for effects of performance and brain morphology. Behaviorally, children exhibited a numerically smaller alerting effect and significantly larger invalidity (reorienting) and interference (executive control of attention) effects. Neurally, children showed significantly reduced brain activation in a priori defined regions-of-interest in right-sided frontal-midbrain regions during alerting, in the right-sided temporo-parietal junction during reorienting of attention, and in the dorsolateral prefrontal cortex during executive control of attention. In addition, children activated significantly more brain regions outside the a priori defined regions-of-interest, such as the superior frontal gyrus during reorienting and the superior temporal gyrus during executive control of attention. Functional group differences overlapped with structural group differences in gray matter volume in particular within the frontopolar areas. The data suggest that there is a transition from functional yet immature systems supporting attentional functions in children to the more definitive adult networks and that the differences observed may reflect both developmental changes in cognitive strategies and morphology.     

Properties of MEG tomographic maps obtained with spatial filtering

Magnetoencephalography (MEG) has, in comparison with other functional imaging modalities, unique properties which makes it the prime candidate for the noninvasive investigation of long-range oscillatory interactions in the human brain. Recent methodological developments based on spatial filtering introduced the computation of functional tomographic maps covering the entire brain and representing the distribution of coherence to a given reference signal or the distribution of power. Because of the spatially inhomogeneous sensitivity profile of the MEG sensors, the spatial resolution of the resulting functional maps is not isotropic across the brain. Here, we introduce a convenient analytic expression for the computation of the spatial resolution at any given point in the brain. We derive the dependence of the resolution on the signal-to-noise ratio and on the changes of the leadfields. The resolution map can be displayed on anatomical MRI in the same way as the functional maps. In addition, we establish a procedure for computing a confidence volume of local maxima which is based on a bootstrap method. The confidence volume is a measure for the uncertainty of the localization. It is important for assigning local maxima of activation to specific anatomical structures and may be used to test for differences in localization between different experimental conditions.