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Biomedical subjects

B Fischl

Publications and source records attributed to B Fischl.

At least 19 recordsLinked to original sources

Neuroimaging H.M.: a 10-year follow-up examination.

In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient H.M.'s surgical resection, based on a comprehensive analysis of magnetic resonance imaging (MRI) scans collected in 1992 and 1993 (Corkin et al. (1997) J Neurosci 17:3964-3979). We subsequently scanned H.M. on several occasions, employing more advanced data acquisition and analysis methods, and now describe additional details about his brain anatomy and pathology. This account combines results from high-resolution T1-weighted scans, which provide measures of cortical and subcortical morphometry, diffusion tensor images, which provide quantitative information about white matter microstructure and the anatomy of major fasciculi, and T2-weighted images, which highlight damage to deep white matter. We applied new MRI analysis techniques to these scans to assess the integrity of areas throughout H.M.'s brain. We documented a number of new changes, including cortical thinning, atrophy of deep gray matter structures, and a large volume of abnormal white matter and deep gray matter signal. Most of these alterations were not apparent in his prior scans, suggesting that they are of recent origin. Advanced age and hypertension likely contributed to these new findings.

Aged↗

Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method.

Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight </=1500 g), 49 term small for gestational age births (SGA, birth weight <10th percentile at term) and 58 control adolescents. A novel method of cortical surface models yielded measurements of cortical thickness and area for each subject's entire brain and computed cross-subject statistics based on cortical anatomy. The cortical surface models demonstrated regional thinning of the parietal, temporal and occipital lobes in the VLBW group, whereas regional thickening was demonstrated in the frontal and occipital lobes. The areas of change were greatest in those with the shortest gestational age at birth and lowest birth weight. Cortical surface area and cortical volume were lower in the VLBW than in the Control group. Within the VLBW group, there was an association between surface area and estimation of the intelligence quotient IQ (IQ(est)) and between cortical volume and IQ(est). Furthermore, cortical grey matter as a proportion of brain volume was significantly lower in the VLBW, but not in the SGA group compared with Controls. This observed reorganization of the developing brain offers a unique opportunity to investigate any relationship between changes in cortical anatomy and cognitive and social impairments, and the increase in psychiatric disorders that have been found in VLBW children and adolescents.

Adolescent↗

Age-related changes in prefrontal white matter measured by diffusion tensor imaging.

Age-related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age-related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures. We used DTI to examine the regional basis of age-related alterations in prefrontal WM. As expected from prior volumetric and DTI studies, prefrontal FA was reduced in older adults (OA) compared to young adults (YA). Although WM volume has been reported to be relatively preserved until late aging, FA was significantly reduced by middle age. Much of prefrontal WM showed reduced FA with increasing age. Ventromedial and deep prefrontal regions showed a somewhat greater reduction compared to other prefrontal areas. Prefrontal WM anisotropy correlated with prefrontal WM volume, but the correlation was significant only when the analysis was limited to participants over age 40. This evidence of widespread and regionally accelerated alterations in prefrontal WM with aging illustrates FA's potential as a microstructural index of volumetric measures.

Adult↗

Age-related alterations in white matter microstructure measured by diffusion tensor imaging.

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.

Adult↗

Size does matter in the long run: hippocampal and cortical volume predict recall across weeks.

OBJECTIVE: To study the morphometric determinants of recall of verbal material for an extended period in an adult lifespan sample. METHODS: Healthy adults of varying ages were studied using automated segmentation of MRI scans with volumes of hippocampus, cortex, and white matter, and verbal memory tests assessing recall after 5 minutes, 30 minutes, and a mean period of 11 weeks. Stepwise regression analyses were performed with 5 minutes, 30 minutes, and 11-week recall as the dependent variables. Hippocampal, cortical, and white matter volumes were included in the initial set of predictor variables in each case, and the analyses were repeated with age as an additional predictor variable. RESULTS: When age was not included, cortical volume was the only variable predicting recall after 5 and 30 minutes, whereas hippocampal and cortical volumes predicted recall after 11 weeks. When age was included in the model, this was the only variable predicting recall after 5 and 30 minutes, whereas age and hippocampus gave contributions in prediction of recall after several weeks. CONCLUSION: This study supports a critical role of cortical and hippocampal size in recall. Hippocampal size seems more important in recall after 11 weeks than after a shorter time interval.

Adult↗

A hybrid approach to the skull stripping problem in MRI.

We present a novel skull-stripping algorithm based on a hybrid approach that combines watershed algorithms and deformable surface models. Our method takes advantage of the robustness of the former as well as the surface information available to the latter. The algorithm first localizes a single white matter voxel in a T1-weighted MRI image, and uses it to create a global minimum in the white matter before applying a watershed algorithm with a preflooding height. The watershed algorithm builds an initial estimate of the brain volume based on the three-dimensional connectivity of the white matter. This first step is robust, and performs well in the presence of intensity nonuniformities and noise, but may erode parts of the cortex that abut bright nonbrain structures such as the eye sockets, or may remove parts of the cerebellum. To correct these inaccuracies, a surface deformation process fits a smooth surface to the masked volume, allowing the incorporation of geometric constraints into the skull-stripping procedure. A statistical atlas, generated from a set of accurately segmented brains, is used to validate and potentially correct the segmentation, and the MRI intensity values are locally re-estimated at the boundary of the brain. Finally, a high-resolution surface deformation is performed that accurately matches the outer boundary of the brain, resulting in a robust and automated procedure. Studies by our group and others outperform other publicly available skull-stripping tools.

Algorithms↗

Regional and progressive thinning of the cortical ribbon in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it. METHODS: Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods. RESULTS: Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable. CONCLUSIONS: The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.

Adult↗

Mechanisms of migraine aura revealed by functional MRI in human visual cortex.

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 +/- 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.

Adult↗

Local and global attention are mapped retinotopically in human occipital cortex.

Clinical evidence suggests that control mechanisms for local and global attention are lateralized in the temporal-parietal cortex. However, in the human occipital (visual) cortex, the evidence for lateralized local/global attention is controversial. To clarify this matter, we used functional MRI to map activity in the human occipital cortex, during local and global attention, with sustained visual fixation. Data were analyzed in a flattened cortical format, relative to maps of retinotopy and spatial frequency peak tuning. Neither local nor global attention was lateralized in the occipital cortex. Instead, local attention and global attention appear to be special cases of visual spatial attention, which are mapped consistently with the maps of retinotopy and spatial frequency tuning, in multiple visual cortical areas.

Attention↗

Cortical mechanisms specific to explicit visual object recognition.

The cortical mechanisms associated with conscious object recognition were studied using functional magnetic resonance imaging (fMRI). Participants were required to recognize pictures of masked objects that were presented very briefly, randomly and repeatedly. This design yielded a gradual accomplishment of successful recognition. Cortical activity in a ventrotemporal visual region was linearly correlated with perception of object identity. Therefore, although object recognition is rapid, awareness of an object's identity is not a discrete phenomenon but rather associated with gradually increasing cortical activity. Furthermore, the focus of the activity in the temporal cortex shifted anteriorly as subjects reported an increased knowledge regarding identity. The results presented here provide new insights into the processes underlying explicit object recognition, as well as the analysis that takes place immediately before and after recognition is possible.

Adult↗

Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex.

Highly accurate surface models of the cerebral cortex are becoming increasingly important as tools in the investigation of the functional organization of the human brain. The construction of such models is difficult using current neuroimaging technology due to the high degree of cortical folding. Even single voxel misclassifications can result in erroneous connections being created between adjacent banks of a sulcus, resulting in a topologically inaccurate model. These topological defects cause the cortical model to no longer be homeomorphic to a sheet, preventing the accurate inflation, flattening, or spherical morphing of the reconstructed cortex. Surface deformation techniques can guarantee the topological correctness of a model, but are time-consuming and may result in geometrically inaccurate models. In order to address this need we have developed a technique for taking a model of the cortex, detecting and fixing the topological defects while leaving that majority of the model intact, resulting in a surface that is both geometrically accurate and topologically correct.

Cerebral Cortex↗

Measuring the thickness of the human cerebral cortex from magnetic resonance images.

Accurate and automated methods for measuring the thickness of human cerebral cortex could provide powerful tools for diagnosing and studying a variety of neurodegenerative and psychiatric disorders. Manual methods for estimating cortical thickness from neuroimaging data are labor intensive, requiring several days of effort by a trained anatomist. Furthermore, the highly folded nature of the cortex is problematic for manual techniques, frequently resulting in measurement errors in regions in which the cortical surface is not perpendicular to any of the cardinal axes. As a consequence, it has been impractical to obtain accurate thickness estimates for the entire cortex in individual subjects, or group statistics for patient or control populations. Here, we present an automated method for accurately measuring the thickness of the cerebral cortex across the entire brain and for generating cross-subject statistics in a coordinate system based on cortical anatomy. The intersubject standard deviation of the thickness measures is shown to be less than 0.5 mm, implying the ability to detect focal atrophy in small populations or even individual subjects. The reliability and accuracy of this new method are assessed by within-subject test-retest studies, as well as by comparison of cross-subject regional thickness measures with published values.

Cerebral Cortex↗

Segregation of somatosensory activation in the human rolandic cortex using fMRI.

The segregation of sensory information into distinct cortical areas is an important organizational feature of mammalian sensory systems. Here, we provide functional magnetic resonance imaging (fMRI) evidence for the functional delineation of somatosensory representations in the human central sulcus region. Data were collected with a 3-Tesla scanner during two stimulation protocols, a punctate tactile condition without a kinesthetic/motor component, and a kinesthetic/motor condition without a punctate tactile component. With three-dimensional (3-D) anatomical reconstruction techniques, we analyzed data in individual subjects, using the pattern of activation and the anatomical position of specific cortical areas to guide the analysis. As a complimentary analysis, we used a brain averaging technique that emphasized the similarity of cortical features in the morphing of individual subjects and thereby minimized the distortion of the location of cortical activation sites across individuals. A primary finding of this study was differential activation of the cortex on the fundus of the central sulcus, the position of area 3a, during the two tasks. Punctate tactile stimulation of the palm, administered at 3 Hz with a 5.88(log10.mg) von Frey filament, activated discrete regions within the precentral (PreCG) and postcentral (PoCG) gyri, corresponding to areas 6, 3b, 1, and 2, but did not activate area 3a. Conversely, kinesthetic/motor stimulation, 3-Hz flexion and extension of the digits, activated area 3a, the PreCG (areas 6 and 4), and the PoCG (areas 3b, 1, and 2). These activation patterns were observed in individual subjects and in the averaged data, providing strong evidence for the existence of a distinct representation within area 3a in humans. The percentage signal changes in the PreCG and PoCG regions activated by tactile stimulation, and in the intervening gap region, support this functional dissociation. In addition to this distinction within the fundus of the central sulcus, the combination of high-resolution imaging and 3-D analysis techniques permitted localization of activation within areas 6, 4, 3a, 3b, 1, and 2 in the human. With the exception of area 4, which showed inconsistent activation during punctate tactile stimulation, activation in these areas in the human consistently paralleled the pattern of activity observed in previous studies of monkey cortex.

Adult↗

The representation of illusory and real contours in human cortical visual areas revealed by functional magnetic resonance imaging.

Illusory contours (perceived edges that exist in the absence of local stimulus borders) demonstrate that perception is an active process, creating features not present in the light patterns striking the retina. Illusory contours are thought to be processed using mechanisms that partially overlap with those of "real" contours, but questions about the neural substrate of these percepts remain. Here, we employed functional magnetic resonance imaging to obtain physiological signals from human visual cortex while subjects viewed different types of contours, both real and illusory. We sampled these signals independently from nine visual areas, each defined by retinotopic or other independent criteria. Using both within- and across-subject analysis, we found evidence for overlapping sites of processing; most areas responded to most types of contours. However, there were distinctive differences in the strength of activity across areas and contour types. Two types of illusory contours differed in the strength of activation of the retinotopic areas, but both types activated crudely retinotopic visual areas, including V3A, V4v, V7, and V8, bilaterally. The extent of activation was largely invariant across a range of stimulus sizes that produce illusory contours perceptually, but it was related to the spatial frequency of displaced-grating stimuli. Finally, there was a striking similarity in the pattern of results for the illusory contour-defined shape and a similar shape defined by stereoscopic depth. These and other results suggest a role in surface perception for this lateral occipital region that includes V3A, V4v, V7, and V8.

Brain Mapping↗

High-resolution intersubject averaging and a coordinate system for the cortical surface.

The neurons of the human cerebral cortex are arranged in a highly folded sheet, with the majority of the cortical surface area buried in folds. Cortical maps are typically arranged with a topography oriented parallel to the cortical surface. Despite this unambiguous sheetlike geometry, the most commonly used coordinate systems for localizing cortical features are based on 3-D stereotaxic coordinates rather than on position relative to the 2-D cortical sheet. In order to address the need for a more natural surface-based coordinate system for the cortex, we have developed a means for generating an average folding pattern across a large number of individual subjects as a function on the unit sphere and of nonrigidly aligning each individual with the average. This establishes a spherical surface-based coordinate system that is adapted to the folding pattern of each individual subject, allowing for much higher localization accuracy of structural and functional features of the human brain.

Brain Mapping↗

Cortical surface-based analysis. I. Segmentation and surface reconstruction.

Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging.

Brain Mapping↗

Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system.

The surface of the human cerebral cortex is a highly folded sheet with the majority of its surface area buried within folds. As such, it is a difficult domain for computational as well as visualization purposes. We have therefore designed a set of procedures for modifying the representation of the cortical surface to (i) inflate it so that activity buried inside sulci may be visualized, (ii) cut and flatten an entire hemisphere, and (iii) transform a hemisphere into a simple parameterizable surface such as a sphere for the purpose of establishing a surface-based coordinate system.

Artifacts↗