Biomedical subjects

Bruce Fischl

Publications and source records attributed to Bruce Fischl.

At least 19 recordsLinked to original sources

PubMed2006

Human cerebral cortex: a system for the integration of volume- and surface-based representations.

We describe an MRI-based system for topological analysis followed by measurements of topographic features for the human cerebral cortex that takes as its starting point volumetric segmentation data. This permits interoperation between volume-based and surface-based topographic analysis and extends the functionality of many existing segmentation schemes. We demonstrate the utility of these operations in individual as well as to group analysis. The methodology integrates analyses of cortical segmentation data generated by manual and semi-automated volumetric morphometry routines (such as the program cardviews) with the procedures of the FreeSurfer program to generate a cortical ribbon of the cerebrum and perform cortical topographic measurements (including thickness, surface area and curvature) in individual subjects as well as in subject populations. This system allows the computation of topographical cortical measurements for segmentation data generated from manual and semi-automated volumetric sources other than FreeSurfer. These measurements can be regionally specific and integrated with systems of cortical parcellation that subdivides the neocortex into gyral-based parcellation units (PUs). This system of topographical analysis of the cerebral cortex is consistent with current views of cortical development and neural systems organization of the human and non-human primate brain.

Adult↗

PubMed2006

Detailed semiautomated MRI based morphometry of the neonatal brain: preliminary results.

In the neonate, regional growth trajectories provide information about the coordinated development of cerebral substructures and help identify regional vulnerability by identifying times of faster growth. Segmentation of magnetic resonance images (MRI) has provided detailed information for the myelinated brain but few reports of regional neonatal brain growth exist. We report the method and preliminary results of detailed semiautomated segmentation of 12 normative neonatal brains (gestational age 31.1-42.6 weeks at time of MRI) using volumetric T1-weighted images. Accuracy was confirmed by expert review of every segmented image. In 5 brains, repeat segmentation resulted in intraclass correlation coefficients >0.9 (except for the right amygdala) and an average percent voxel overlap of 90.0%. Artifacts or image quality limited the number of regions segmented in 9/12 data sets and 1/12 was excluded from volumetric analysis due to ventriculomegaly. Brains were segmented into cerebral exterior (N = 8), cerebral lobes (N = 5), lateral ventricles (N = 8), cerebral cortex (N = 6), white matter (N = 6), corpus callosum (N = 7), deep central gray (N = 8), hippocampi (N = 8), amygdalae (N = 8), cerebellar hemispheres (N = 8), vermis (N = 8), midbrain (N = 8), pons (N = 8) and medulla (N = 8). Linear growth (P < 0.05) was identified in all regions except the cerebral white matter, medulla and ventricles. Striking differences in regional growth rates were noted. These preliminary results are consistent with the heterochronous nature of cerebral development and provide initial estimates of regional brain growth and therefore regional vulnerability in the perinatal time period.

Algorithms↗

PubMed2006

Mapping an intrinsic MR property of gray matter in auditory cortex of living humans: a possible marker for primary cortex and hemispheric differences.

Recently, magnetic resonance properties of cerebral gray matter have been spatially mapped--in vivo--over the cortical surface. In one of the first neuroscientific applications of this approach, this study explores what can be learned about auditory cortex in living humans by mapping longitudinal relaxation rate (R1), a property related to myelin content. Gray matter R1 (and thickness) showed repeatable trends, including the following: (1) Regions of high R1 were always found overlapping posteromedial Heschl's gyrus. They also sometimes occurred in planum temporale and never in other parts of the superior temporal lobe. We hypothesize that the high R1 overlapping Heschl's gyrus (which likely indicates dense gray matter myelination) reflects auditory koniocortex (i.e., primary cortex), a heavily myelinated area that shows comparable overlap with the gyrus. High R1 overlapping Heschl's gyrus was identified in every instance suggesting that R1 may ultimately provide a marker for koniocortex in individuals. Such a marker would be significant for auditory neuroimaging, which has no standard means (anatomic or physiologic) for localizing cortical areas in individual subjects. (2) Inter-hemispheric comparisons revealed greater R1 on the left on Heschl's gyrus, planum temporale, superior temporal gyrus and superior temporal sulcus. This asymmetry suggests greater gray matter myelination in left auditory cortex, which may be a substrate for the left hemisphere's specialized processing of speech, language, and rapid acoustic changes. These results indicate that in vivo R1 mapping can provide new insights into the structure of human cortical gray matter and its relation to function.

Adult↗

PubMed2006

Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer.

In vivo MRI-derived measurements of human cerebral cortex thickness are providing novel insights into normal and abnormal neuroanatomy, but little is known about their reliability. We investigated how the reliability of cortical thickness measurements is affected by MRI instrument-related factors, including scanner field strength, manufacturer, upgrade and pulse sequence. Several data processing factors were also studied. Two test-retest data sets were analyzed: 1) 15 healthy older subjects scanned four times at 2-week intervals on three scanners; 2) 5 subjects scanned before and after a major scanner upgrade. Within-scanner variability of global cortical thickness measurements was <0.03 mm, and the point-wise standard deviation of measurement error was approximately 0.12 mm. Variability was 0.15 mm and 0.17 mm in average, respectively, for cross-scanner (Siemens/GE) and cross-field strength (1.5 T/3 T) comparisons. Scanner upgrade did not increase variability nor introduce bias. Measurements across field strength, however, were slightly biased (thicker at 3 T). The number of (single vs. multiple averaged) acquisitions had a negligible effect on reliability, but the use of a different pulse sequence had a larger impact, as did different parameters employed in data processing. Sample size estimates indicate that regional cortical thickness difference of 0.2 mm between two different groups could be identified with as few as 7 subjects per group, and a difference of 0.1 mm could be detected with 26 subjects per group. These results demonstrate that MRI-derived cortical thickness measures are highly reliable when MRI instrument and data processing factors are controlled but that it is important to consider these factors in the design of multi-site or longitudinal studies, such as clinical drug trials.

Aged↗

PubMed2006

The functional and structural significance of the frontal shift in the old/new ERP effect.

There is a lack of studies mapping electrophysiological event-related potentials (ERPs) to structural neuroanatomical characteristics. The aim of the present study was to integrate electrophysiological memory-related activity with cortical and hippocampal volume, as well as psychometric memory performance, in a life-span sample. More specifically, we wanted to investigate the functional significance of the often-observed frontal shift of ERP amplitude with increasing age and whether neuroanatomical characteristics can explain this shift. Sixty six healthy participants (20-78 years) went through a neuropsychological examination, MRI scans, and a visual recognition ERP task with verbal stimuli. The results showed that ERPs elicited in the recognition memory task (the old/new effect) correlated significantly with cortical volume, but not with hippocampal volume. Large cortex predicted more differentiated ERP activity and not just larger amplitude in general, implying more distinct and efficient retrieval. Furthermore, ERP amplitude, cortical volume, and hippocampal volume all predicted scores on a composite memory scale. All these relationship were dependent upon the common influence of age. Finally, the participants with the most anterior distribution of activity showed the poorest recognition memory performance. Neither cortical nor hippocampal volume were related to this frontal shift. It is concluded that the distribution of activity along the anterior-posterior axis in a memory paradigm may have functional but not neuroanatomical volumetric correlates. The functional correlates need not be restricted to the older age groups.

Adult↗

PubMed2006

Regional cortical thickness matters in recall after months more than minutes.

The aim of this study was to determine the role of regional cortical thickness in recall of verbal material over an extended time period. MRI scans of healthy adults of varying ages were obtained. Two scans were averaged per person to achieve high spatial resolution, and a semi-automated method for continuous measurement of thickness across the entire cortical mantle was employed. Verbal memory tests assessing recall after 5 min, 30 min, and a mean interval of 83 days were administered. A general linear model (GLM) of the effects of thickness at each vertex on the different memory indices was computed, controlling for gender, age, IQ, and intracranial volume. These analyses were repeated with hippocampal volume as an additional variable to be controlled for, to assess to which extent effects of cortical thickness were independent of hippocampal size. Minute effects of cortical thickness were observed with regard to shorter time intervals (5 and 30 min). However, even when controlling for the effects of hippocampal volume, higher recall across months was associated with thicker cortex of distinct areas including parts of the gyrus rectus, the middle frontal gyrus, the parieto-occipital sulcus and the lingual gyrus of both hemispheres. In addition, hemisphere-specific associations were found in parts of the right temporal and parietal lobe as well as parts of the left precuneus. This supports a unique and critical role of the thickness of distinct cortical areas in recall after months, more than after minutes.

Adult↗

PubMed2006

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.

Adult↗

PubMed2006

Comparison of manual and automatic section positioning of brain MR images.

The study protocol was approved by the institutional review board and was in full compliance with HIPAA guidelines. Informed consent was obtained from all patients. The purpose of this study was to prospectively compare intra- and intersubject variability of manual versus automatic magnetic resonance (MR) imaging section prescription. In two examinations, T2-weighted series were acquired with both methods. All intrasubject and three of six intersubject section prescription variances were significantly higher for manual prescription (P < .01). Root mean square errors confirmed better coregistration of the automated approach (P < .001). Automatic section prescription leads to improved reproducibility of imaging orientations for intra- and intersubject series in clinical practice.

Adult↗

PubMed2006

Quantitative evaluation of automated skull-stripping methods applied to contemporary and legacy images: effects of diagnosis, bias correction, and slice location.

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143-155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060-1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41-54; Shattuck et al. [2001] Neuroimage 13:856-876) to manually stripped images. The methods were applied to uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation-Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1-weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies.

Adult↗

PubMed2006

Location and spatial profile of category-specific regions in human extrastriate cortex.

Subjects were scanned in a single functional MRI (fMRI) experiment that enabled us to localize cortical regions in each subject in the occipital and temporal lobes that responded significantly in a variety of contrasts: faces>objects, body parts>objects, scenes>objects, objects>scrambled objects, and moving>stationary stimuli. The resulting activation maps were co-registered across subjects using spherical surface coordinates [Fischl et al., Hum Brain Mapp 1999;8:272-284] to produce a "percentage overlap map" indicating the percentage of subjects who showed a significant response for each contrast at each point on the surface. Prominent among the overlapping activations in these contrasts were the fusiform face area (FFA), extrastriate body area (EBA), parahippocampal place area (PPA), lateral occipital complex (LOC), and MT+/V5; only a few other areas responded consistently across subjects in these contrasts. Another analysis showed that the spatial profile of the selective response drops off quite sharply outside the standard borders of the FFA and PPA (less so for the EBA and MT+/V5), indicating that these regions are not simply peaks of very broad selectivities spanning centimeters of cortex, but fairly discrete regions of cortex with distinctive functional profiles. The data also yielded a surprise that challenges our understanding of the function of area MT+: a higher response to body parts than to objects. The anatomical consistency of each of our functionally defined regions across subjects and the spatial sharpness of their activation profiles within subjects highlight the fact that these regions constitute replicable and distinctive landmarks in the functional organization of the human brain.

Adult↗

PubMed2005

Meditation experience is associated with increased cortical thickness.

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

Adult↗

PubMed2005

Orbitofrontal thickness, retention of fear extinction, and extraversion.

People differ in their personality traits and in their ability to modulate fear. Does our personality determine how well we extinguish conditioned fear responses? Or is the opposite true? Herein, we examine the relationships between personality traits, memory for fear extinction, and cortical thickness as a measure of brain structure. We found that in healthy humans, extinction retention and thickness of the medial orbitofrontal cortex are positively correlated with extraversion. Path analysis indicates that extinction retention mediates the relationship between the medial orbitofrontal cortex thickness and extraversion, thereby illustrating one path through which brain structure influences personality.

Conditioning, Psychological↗

PubMed2005

Reliability in multi-site structural MRI studies: effects of gradient non-linearity correction on phantom and human data.

Longitudinal and multi-site clinical studies create the imperative to characterize and correct technological sources of variance that limit image reproducibility in high-resolution structural MRI studies, thus facilitating precise, quantitative, platform-independent, multi-site evaluation. In this work, we investigated the effects that imaging gradient non-linearity have on reproducibility of multi-site human MRI. We applied an image distortion correction method based on spherical harmonics description of the gradients and verified the accuracy of the method using phantom data. The correction method was then applied to the brain image data from a group of subjects scanned twice at multiple sites having different 1.5 T platforms. Within-site and across-site variability of the image data was assessed by evaluating voxel-based image intensity reproducibility. The image intensity reproducibility of the human brain data was significantly improved with distortion correction, suggesting that this method may offer improved reproducibility in morphometry studies. We provide the source code for the gradient distortion algorithm together with the phantom data.

Calibration↗

PubMed2005

Selective increase of cortical thickness in high-performing elderly--structural indices of optimal cognitive aging.

The aim of this study was to identify cortical areas important for optimal cognitive aging. 74 participants (20-88 years) went through neuropsychological tests and two MR sessions. The sample was split into two age groups. In each, every participant was classified as "high" or "average" on fluid ability tests and on neuropsychological tests related to executive function. The groups were compared with regard to thickness on a point-by-point basis across the entire cortical mantle. The old high fluid performers had thicker cortex than the average performers in large areas of cortex, while there was minimal difference between the groups of high vs. average executive function. Furthermore, the old group with high fluid function had thicker cortex than the young participants in the posterior cingulate and adjacent areas. Further analyses showed that the latter was a result of a complex aging pattern, differing between the two performance groups, with decades of cortical thickening and subsequent thinning.

Adult↗

PubMed2005

On-line automatic slice positioning for brain MR imaging.

In clinical brain MR imaging protocols, the technician collects a quick localizer and manually positions the subsequent scans using the localizer as a guide. We present a method for automatic slice positioning using a rapidly acquired 3D localizer. The localizer is automatically aligned to a statistical atlas representing 40 healthy subjects. The atlas contains the probability of a given tissue type occurring at a given location in atlas space and the conditional probability distribution of the multi-spectral MRI intensity values for a given tissue class. Accurate rigid alignment of each subject to an atlas ensures that all patients' scans are acquired in a consistent manner. A further benefit is that slices are positioned consistently over time, so that scans of patients returning for follow-up imaging can be compared side-by-side to accurately monitor the progression of illness. The procedure also helps ensure that left/right asymmetries reflect true anatomy rather than being the result of oblique slice positioning relative to the underlying anatomy. The use of an atlas-based procedure eliminates the need to refer to a database of previously scanned images of the same patient and ensures corresponding alignment across scanners and sites, without requiring fiducial markers. Since the registration method is probabilistic, the registration error tends to increase smoothly in the presence of increasing noise and unusual anatomy or pathology rather than failing catastrophically. Translations and rotations relative to the atlas can be set so that planning can be done in anatomical space, rather than scanner coordinates, and stored as part of the protocol allowing standardization of slice orientations.

Algorithms↗

PubMed2005

Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory.

The ventromedial prefrontal cortex (vmPFC) has been implicated in fear extinction [Phelps, E. A., Delgado, M. R., Nearing, K. I. & Ledoux, J. E. (2004) Neuron 43, 897-905; Herry, C. & Garcia, R. (2003) Behav. Brain Res. 146, 89-96]. Here, we test the hypothesis that the cortical thickness of vmPFC regions is associated with how well healthy humans retain their extinction memory a day after having been conditioned and then extinguished. Fourteen participants underwent a 2-day fear conditioning and extinction protocol. The conditioned stimuli (CSs) were pictures of virtual lights, and the unconditioned stimulus (US) was an electric shock. On day 1, participants received 5 CS+US pairings (conditioning), followed by 10 CS trials with no US (extinction). On day 2, the CS was presented alone to test for extinction memory. Skin conductance response (SCR) was the behavioral index of conditioning and extinction. Participants underwent MRI scans to obtain structural images, from which cortical thickness was measured. We performed a vertex-based analysis across the entire cortical surface and a region-of-interest analysis of a priori hypothesized territories to measure cortical thickness and map correlations between this measure and SCR. We found significant, direct correlation between thickness of the vmPFC, specifically medial orbitofrontal cortex, and extinction retention. That is, thicker medial orbitofrontal cortex was associated with lower SCR to the conditioned stimulus during extinction recall (i.e., greater extinction memory). These results suggest that the size of the vmPFC might explain individual differences in the ability to modulate fear among humans.

Adult↗

PubMed2005

Effects of age on volumes of cortex, white matter and subcortical structures.

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.

Adult↗

PubMed2005

Cortical volume and speed-of-processing are complementary in prediction of performance intelligence.

The rationale for the present study was to investigate the relationship between cortical volume, the latency of the ERP component P3a (as a measure of speed-of-processing), and performance intelligence (not adjusted for age differences). Seventy-one participants aged 20-88 years underwent a visual 3-stimuli oddball ERP task, an MRI-scan, and intelligence testing. P3a latency and cortical volume shared 9% variance (p<.05) and both were significantly related to performance intelligence (R2=.26 and .40, respectively). The amount of explained variance increased significantly (to R2=.51) when both measures were used as simultaneous predictors. When a path diagram was constructed including age as an exogenous variable, P3a latency and cortical volume both significantly predicted performance intelligence, but were no longer related to one another. The main conclusion from the study is that speed and size are complementary in prediction of performance intelligence, and the theoretical implications are discussed.

Adult↗