Katherine Narr | UCLA David Geffen School of Medicine (original) (raw)

Papers by Katherine Narr

Frontiers in Psychiatry

Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in... more Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in abnormal brain development. Here, we quantified the level of individual brain maturation in children with ADHD using structural neuroimaging and a recently developed machine learning algorithm. More specifically, we compared the BrainAGE index between three groups matched for chronological age (mean ± SD: 11.86 ± 3.25 years): 89 children diagnosed with ADHD, 34 asymptomatic siblings of those children with ADHD, and 21 unrelated healthy control children. Brains of children with ADHD were estimated significantly younger (−0.85 years) than brains of healthy controls (Cohen’s d = −0.33; p = 0.028, one-tailed), while there were no significant differences between unaffected siblings and healthy controls. In addition, more severe ADHD symptoms were significantly associated with younger appearing brains. Altogether, these results are in line with the proposed delay of individual brain maturatio...

Cerebral cortex (New York, N.Y. : 1991), Jul 17, 2015

Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neu... more Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neurobehavioral deficits, and reduced brain volume. Studies of cortical thickness in FASD have yielded contradictory findings, with 3 reporting thicker cerebral cortex in frontal and temporal brain regions and 2 showing thinner cortex across multiple regions. All 5 studies included subjects spanning a broad age range, and none have examined continuous measures of prenatal alcohol exposure. We investigated the relation of extent of in utero alcohol exposure to cortical thickness in 78 preadolescent children with FASD and controls within a narrow age range. A whole-brain analysis using FreeSurfer revealed no significant clusters where cortical thickness differed by FASD diagnostic group. However, alcohol dose/occasion during pregnancy was inversely related to cortical thickness in 3 regions-right cuneus/pericalcarine/superior parietal lobe, fusiform/lingual gyrus, and supramarginal/postcentra...

NeuroImage. Clinical, 2014

Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disor... more Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex,...

2010 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2010

We present an intrinsic framework for constructing sulcal shape atlases on the human cortex. We p... more We present an intrinsic framework for constructing sulcal shape atlases on the human cortex. We propose the analysis of sulcal and gyral patterns by representing them by continuous open curves in ℝ 3. The space of such curves, also termed as the shape manifold is equipped with a Riemannian L 2 metric on the tangent space, and shows desirable properties while matching shapes of sulci. On account of the spherical nature of the shape space, geodesics between shapes can be computed analytically. Additionally, we also present an optimization approach that computes geodesics in the quotient space of shapes modulo rigid rotations and reparameterizations. We also integrate the elastic shape model into a surface registration framework for a population of 176 subjects, and show a considerable improvement in the constructed surface atlases.

Introduction: Advanced image analysis tools may be necessary to isolate subtle and regionally-spe... more Introduction: Advanced image analysis tools may be necessary to isolate subtle and regionally-specific cortical gray matter abnormalities in schizophrenia not detectable in volumetric studies. We used novel brain mapping methods to identify and map regional reductions in cortical thickness and gray matter density in first episode schizophrenia. Cortical thickness and gray matter density mapping results were compared.

NeuroReport, 2006

Some empirical data suggest that sexual dimorphisms in callosal morphology exist, but ¢ndings are... more Some empirical data suggest that sexual dimorphisms in callosal morphology exist, but ¢ndings are not consistently replicated across laboratories.We applied novel computational surface-based methods to encode callosal thickness at high spatial resolution. We further examined whether callosal thickness and related gender e¡ects are in£uenced by brain size adjustments achieved through data scaling. Signi¢cant gender di¡erences were absent in scaled data, and women showed no regional thickness increases compared with men (in either scaled or unscaled data). In unscaled data, men exhibited signi¢cantly greater callosal thickness in a number of regions that may be attributable to larger brain dimensions in men. Alternatively, given their regional speci¢city, the observed di¡erences in unscaled callosal thickness may contribute to gender-speci¢c cognition and behavior. NeuroReport 17:1103^1106

NeuroImage, 2011

The link between brain structure and intelligence is a well-investigated topic, but existing anal... more The link between brain structure and intelligence is a well-investigated topic, but existing analyses have mainly focused on adult samples. Studies in healthy children and adolescents are rare, and normative data specifically addressing the association between corpus callosum morphology and intellectual abilities is quite limited. To advance this field of research, we mapped the correlations between standardized intelligence measures and callosal thickness based on high-resolution magnetic resonance imaging (MRI) data. Our large and well-matched sample included 200 normally developing subjects (100 males, 100 females) ranging from 6 to 17 years of age. Although the strongest correlations were negative and confined to the splenium, the strength and the direction of intelligence-callosal thickness associations varied considerably with respect to age and sex. While significant correlations in females were mainly positive, significant correlations in males were exclusively negative. However, only the negative correlations in the overall sample (i.e., males and females combined) remained significant when controlling for multiple comparisons. The observed negative correlations between callosal thickness and intelligence in children and adolescents contrast with the positive correlations typically reported in adult samples. However, negative correlations are in line with reports from other pediatric studies relating cognitive measures to other brain attributes such as cortical thickness, gray matter volume, and gray matter density. Altogether, these findings suggest that relationships between callosal morphology and cognition are highly dynamic during brain maturation. Sex effects on links between callosal thickness and intelligence during childhood and adolescence are present but appear rather weak in general.

NeuroImage, 2004

Accurate identification of brain tissue and cerebrospinal fluid (CSF) in a whole-head MRI is a cr... more Accurate identification of brain tissue and cerebrospinal fluid (CSF) in a whole-head MRI is a critical first step in many neuroimaging studies. Automating this procedure can eliminate intra-and interrater variance and greatly increase throughput for a labor-intensive step. Many available procedures perform differently across anatomy and under different acquisition protocols. We developed the Brain Extraction Meta-Algorithm (BEMA) to address these concerns. It executes many extraction algorithms and a registration procedure in parallel to combine the results in an intelligent fashion and obtain improved results over any of the individual algorithms. Using an atlas space, BEMA performs a voxelwise analysis of training data to determine the optimal Boolean combination of extraction algorithms to produce the most accurate result for a given voxel. This allows the provided extractors to be used differentially across anatomy, increasing both the accuracy and robustness of the procedure. We tested BEMA using modified forms of BrainSuite's Brain Surface Extractor (BSE), FSL's Brain Extraction Tool (BET), AFNI's 3dIntracranial, and FreeSurfer's MRI Watershed as well as FSL's FLIRT for the registration procedure. Training was performed on T1-weighted scans of 136 subjects from five separate data sets with different acquisition parameters on separate scanners. Testing was performed on 135 separate subjects from the same data sets. BEMA outperformed the individual algorithms, as well as interrater results from a subset of the scans, when compared for the mean Dice coefficient, a rating of the similarity of output masks to the manually defined gold standards.

NeuroImage, 2005

Using magnetic resonance imaging and well-validated computational cortical pattern matching metho... more Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects, we analyzed the effects of gender on regional gray matter (GM) concentration across the cortex. To clarify discrepancies in previous reports, we also examined sexual dimorphisms for wholebrain tissue volumes with and without controlling for brain size differences. In addition, we generated spatially detailed maps of average GM distributions and variability across the entire cortex given that these descriptors are not well characterized in the normative literature. After brain size correction, we detected numerous cortical regions showing significantly increased GM concentration in females compared to males, but no regionally increased GM concentration in males. Permutation testing confirmed the statistical significance of these findings. Locally increased concentration of cortical GM in females corroborates findings of larger global GM volumes in females after correcting for individual brain sizes. Larger global volumes of GM, white matter and CSF, however, are observed in males when individual brain volumes are not taken into account. Our results show that gender is a major contributor to regional and global GM differences between individuals, although the nature of these effects depend on whether brain size is taken into account.

Nature Neuroscience, 2004

Cortical complexity, a measure that quantifies the spatial frequency of gyrification and fissurat... more Cortical complexity, a measure that quantifies the spatial frequency of gyrification and fissuration of the brain surface, has not been thoroughly characterized with respect to gender differences in the human brain. Using a new three-dimensional (3D) analytic technique with magnetic resonance imaging, we found greater gyrification in women than men in frontal and parietal regions. Increased complexity implies more cortical surface area, which may offset gender differences in brain volume and account for behavioral gender differences.

Human Brain Mapping, 2012

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus i... more Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high‐resolution structural magnetic resonance imaging data from 30 long‐term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. A...

Human Brain Mapping, 2012

Obesity and overweight are often defined by the body mass index (BMI), which associates with meta... more Obesity and overweight are often defined by the body mass index (BMI), which associates with metabolic and cardiovascular disease, and possibly with dementia as well as variations in brain volume. However, body fat distribution and abdominal obesity (as measured by waist circumference) is more strongly correlated with cardiovascular and metabolic risk than is BMI. While prior studies have revealed negative associations between gray matter tissue volumes and BMI, the relationship with respect to waist circumference remains largely unexplored. We therefore investigated the effects of both BMI and waist circumference on local gray matter volumes in a group of 115 healthy subjects screened to exclude physical or mental disorders that might affect the central nervous system. Results revealed significant negative correlations for both BMI and waist circumference where regional gray matter effects were largest within the hypothalamus and further encompassed prefrontal, anterior temporal an...

Human Brain Mapping, 2012

Surface deformation‐based analysis was used to assess local shape variations in the hippocampi an... more Surface deformation‐based analysis was used to assess local shape variations in the hippocampi and caudate nuclei of children with fetal alcohol spectrum disorders. High‐resolution structural magnetic resonance imaging images were acquired for 31 children (19 controls and 12 children diagnosed with fetal alcohol syndrome/partial FAS). Hippocampi and caudate nuclei were manually segmented, and surface meshes were reconstructed. An iterative closest point algorithm was used to register the template of one control subject to all other shapes in order to capture the true geometry of the shape with a fixed number of landmark points. A point distribution model was used to quantify the shape variations in terms of a change in co‐ordinate positions. Using the localized Hotelling T2 method, regions of significant shape variations between the control and exposed subjects were identified and mapped onto the mean shapes. Binary masks of hippocampi and caudate nuclei were generated from the segm...

Cerebral Cortex, 2005

Significant relationships have been reported between midsagittal areas of the corpus callosum and... more Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fibers.

British Journal of Psychiatry, 2012

SummaryDespite accumulating evidence of structural deficits in individuals with psychopathy, espe... more SummaryDespite accumulating evidence of structural deficits in individuals with psychopathy, especially in frontal regions, our understanding of systems-level disturbances in cortical networks remains limited. We applied novel graph theory-based methods to assess information flow and connectivity based on cortical thickness measures in 55 individuals with psychopathy and 47 normal controls. Compared with controls, the psychopathy group showed significantly altered interregional connectivity patterns. Furthermore, bilateral superior frontal cortices in the frontal network were identified as information flow control hubs in the psychopathy group in contrast to bilateral inferior frontal and medial orbitofrontal cortices as network hubs of the controls. Frontal information flow and connectivity may have a significant role in the neuropathology of psychopathy.

American Journal of Psychiatry, 2008

Objective-Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whe... more Objective-Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early-and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. Method-With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early-(N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups. Results-Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early-and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late-compared to earlyonset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1-CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late-but not early-onset depressed patients or comparison subjects. Conclusions-More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies. Altered hippocampal morphology has an important role in the pathophysiology of elderly depression. Studies using magnetic resonance imaging (MRI) have reported hippocampal volume decreases, sometimes unilateral, in elderly patients with major depression relative to healthy comparison subjects (1-5), although negative reports exist (6-8).

IEEE Transactions on Medical Imaging, 2012

We present a diffeomorphic approach for constructing intrinsic shape atlases of sulci on the huma... more We present a diffeomorphic approach for constructing intrinsic shape atlases of sulci on the human cortex. Sulci are represented as square-root velocity functions of continuous open curves in ℝ 3 , and their shapes are studied as functional representations of an infinite-dimensional sphere. This spherical manifold has some advantageous properties-it is equipped with a Riemannian metric on the tangent space and facilitates computational analyses and correspondences between sulcal shapes. Sulcal shape mapping is achieved by computing geodesics in the quotient space of shapes modulo scales, translations, rigid rotations and reparameterizations. The resulting sulcal shape atlas preserves important local geometry inherently present in the sample population. The sulcal shape atlas is integrated in a cortical registration framework and exhibits better geometric matching compared to the conventional euclidean method. We demonstrate experimental results

Encyclopedia of Neuroscience, 2009

Commons Attribution (CC BY) license, which allows users to download, copy and build upon publishe... more Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.

Schizophrenia Research, 2015

Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological re... more Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological relatives of patients. However, the neural correlates of successful and unsuccessful encoding, mediated by the medial temporal lobe (MTL) memory system, and the influence of disease-related genetic liability remain under explored. This study employed an event-related functional MRI paradigm to compare activations for successfully and unsuccessfully encoded associative facename stimuli between 26 schizophrenia patients (mean age: 33, 19m/7f), 30 controls (mean age: 29, 24m/6f) and 14 unaffected relatives of patients (mean age: 40, 5m/9f). Compared to controls or unaffected relatives, patients showed hyper-activations in ventral visual stream and temporoparietal cortical association areas when contrasting successfully encoded events to fixation. Follow-up hippocampal regions-of-interest analysis revealed schizophrenia-related hyperactivations in the right anterior hippocampus during successful encoding; contrasting successful versus unsuccessful events produced schizophrenia-related hypo-activations in the left anterior hippocampus. Similar hippocampal hypo-activations were observed in unaffected relatives during successful versus unsuccessful encoding. Post-hoc analyses of hippocampal volume showed reductions in patients, but not in unaffected relatives compared to controls. Findings suggest that

Frontiers in Psychiatry

Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in... more Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in abnormal brain development. Here, we quantified the level of individual brain maturation in children with ADHD using structural neuroimaging and a recently developed machine learning algorithm. More specifically, we compared the BrainAGE index between three groups matched for chronological age (mean ± SD: 11.86 ± 3.25 years): 89 children diagnosed with ADHD, 34 asymptomatic siblings of those children with ADHD, and 21 unrelated healthy control children. Brains of children with ADHD were estimated significantly younger (−0.85 years) than brains of healthy controls (Cohen’s d = −0.33; p = 0.028, one-tailed), while there were no significant differences between unaffected siblings and healthy controls. In addition, more severe ADHD symptoms were significantly associated with younger appearing brains. Altogether, these results are in line with the proposed delay of individual brain maturatio...

Cerebral cortex (New York, N.Y. : 1991), Jul 17, 2015

Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neu... more Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neurobehavioral deficits, and reduced brain volume. Studies of cortical thickness in FASD have yielded contradictory findings, with 3 reporting thicker cerebral cortex in frontal and temporal brain regions and 2 showing thinner cortex across multiple regions. All 5 studies included subjects spanning a broad age range, and none have examined continuous measures of prenatal alcohol exposure. We investigated the relation of extent of in utero alcohol exposure to cortical thickness in 78 preadolescent children with FASD and controls within a narrow age range. A whole-brain analysis using FreeSurfer revealed no significant clusters where cortical thickness differed by FASD diagnostic group. However, alcohol dose/occasion during pregnancy was inversely related to cortical thickness in 3 regions-right cuneus/pericalcarine/superior parietal lobe, fusiform/lingual gyrus, and supramarginal/postcentra...

NeuroImage. Clinical, 2014

Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disor... more Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex,...

2010 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2010

We present an intrinsic framework for constructing sulcal shape atlases on the human cortex. We p... more We present an intrinsic framework for constructing sulcal shape atlases on the human cortex. We propose the analysis of sulcal and gyral patterns by representing them by continuous open curves in ℝ 3. The space of such curves, also termed as the shape manifold is equipped with a Riemannian L 2 metric on the tangent space, and shows desirable properties while matching shapes of sulci. On account of the spherical nature of the shape space, geodesics between shapes can be computed analytically. Additionally, we also present an optimization approach that computes geodesics in the quotient space of shapes modulo rigid rotations and reparameterizations. We also integrate the elastic shape model into a surface registration framework for a population of 176 subjects, and show a considerable improvement in the constructed surface atlases.

Introduction: Advanced image analysis tools may be necessary to isolate subtle and regionally-spe... more Introduction: Advanced image analysis tools may be necessary to isolate subtle and regionally-specific cortical gray matter abnormalities in schizophrenia not detectable in volumetric studies. We used novel brain mapping methods to identify and map regional reductions in cortical thickness and gray matter density in first episode schizophrenia. Cortical thickness and gray matter density mapping results were compared.

NeuroReport, 2006

Some empirical data suggest that sexual dimorphisms in callosal morphology exist, but ¢ndings are... more Some empirical data suggest that sexual dimorphisms in callosal morphology exist, but ¢ndings are not consistently replicated across laboratories.We applied novel computational surface-based methods to encode callosal thickness at high spatial resolution. We further examined whether callosal thickness and related gender e¡ects are in£uenced by brain size adjustments achieved through data scaling. Signi¢cant gender di¡erences were absent in scaled data, and women showed no regional thickness increases compared with men (in either scaled or unscaled data). In unscaled data, men exhibited signi¢cantly greater callosal thickness in a number of regions that may be attributable to larger brain dimensions in men. Alternatively, given their regional speci¢city, the observed di¡erences in unscaled callosal thickness may contribute to gender-speci¢c cognition and behavior. NeuroReport 17:1103^1106

NeuroImage, 2011

The link between brain structure and intelligence is a well-investigated topic, but existing anal... more The link between brain structure and intelligence is a well-investigated topic, but existing analyses have mainly focused on adult samples. Studies in healthy children and adolescents are rare, and normative data specifically addressing the association between corpus callosum morphology and intellectual abilities is quite limited. To advance this field of research, we mapped the correlations between standardized intelligence measures and callosal thickness based on high-resolution magnetic resonance imaging (MRI) data. Our large and well-matched sample included 200 normally developing subjects (100 males, 100 females) ranging from 6 to 17 years of age. Although the strongest correlations were negative and confined to the splenium, the strength and the direction of intelligence-callosal thickness associations varied considerably with respect to age and sex. While significant correlations in females were mainly positive, significant correlations in males were exclusively negative. However, only the negative correlations in the overall sample (i.e., males and females combined) remained significant when controlling for multiple comparisons. The observed negative correlations between callosal thickness and intelligence in children and adolescents contrast with the positive correlations typically reported in adult samples. However, negative correlations are in line with reports from other pediatric studies relating cognitive measures to other brain attributes such as cortical thickness, gray matter volume, and gray matter density. Altogether, these findings suggest that relationships between callosal morphology and cognition are highly dynamic during brain maturation. Sex effects on links between callosal thickness and intelligence during childhood and adolescence are present but appear rather weak in general.

NeuroImage, 2004

Accurate identification of brain tissue and cerebrospinal fluid (CSF) in a whole-head MRI is a cr... more Accurate identification of brain tissue and cerebrospinal fluid (CSF) in a whole-head MRI is a critical first step in many neuroimaging studies. Automating this procedure can eliminate intra-and interrater variance and greatly increase throughput for a labor-intensive step. Many available procedures perform differently across anatomy and under different acquisition protocols. We developed the Brain Extraction Meta-Algorithm (BEMA) to address these concerns. It executes many extraction algorithms and a registration procedure in parallel to combine the results in an intelligent fashion and obtain improved results over any of the individual algorithms. Using an atlas space, BEMA performs a voxelwise analysis of training data to determine the optimal Boolean combination of extraction algorithms to produce the most accurate result for a given voxel. This allows the provided extractors to be used differentially across anatomy, increasing both the accuracy and robustness of the procedure. We tested BEMA using modified forms of BrainSuite's Brain Surface Extractor (BSE), FSL's Brain Extraction Tool (BET), AFNI's 3dIntracranial, and FreeSurfer's MRI Watershed as well as FSL's FLIRT for the registration procedure. Training was performed on T1-weighted scans of 136 subjects from five separate data sets with different acquisition parameters on separate scanners. Testing was performed on 135 separate subjects from the same data sets. BEMA outperformed the individual algorithms, as well as interrater results from a subset of the scans, when compared for the mean Dice coefficient, a rating of the similarity of output masks to the manually defined gold standards.

NeuroImage, 2005

Using magnetic resonance imaging and well-validated computational cortical pattern matching metho... more Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects, we analyzed the effects of gender on regional gray matter (GM) concentration across the cortex. To clarify discrepancies in previous reports, we also examined sexual dimorphisms for wholebrain tissue volumes with and without controlling for brain size differences. In addition, we generated spatially detailed maps of average GM distributions and variability across the entire cortex given that these descriptors are not well characterized in the normative literature. After brain size correction, we detected numerous cortical regions showing significantly increased GM concentration in females compared to males, but no regionally increased GM concentration in males. Permutation testing confirmed the statistical significance of these findings. Locally increased concentration of cortical GM in females corroborates findings of larger global GM volumes in females after correcting for individual brain sizes. Larger global volumes of GM, white matter and CSF, however, are observed in males when individual brain volumes are not taken into account. Our results show that gender is a major contributor to regional and global GM differences between individuals, although the nature of these effects depend on whether brain size is taken into account.

Nature Neuroscience, 2004

Cortical complexity, a measure that quantifies the spatial frequency of gyrification and fissurat... more Cortical complexity, a measure that quantifies the spatial frequency of gyrification and fissuration of the brain surface, has not been thoroughly characterized with respect to gender differences in the human brain. Using a new three-dimensional (3D) analytic technique with magnetic resonance imaging, we found greater gyrification in women than men in frontal and parietal regions. Increased complexity implies more cortical surface area, which may offset gender differences in brain volume and account for behavioral gender differences.

Human Brain Mapping, 2012

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus i... more Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high‐resolution structural magnetic resonance imaging data from 30 long‐term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. A...

Human Brain Mapping, 2012

Obesity and overweight are often defined by the body mass index (BMI), which associates with meta... more Obesity and overweight are often defined by the body mass index (BMI), which associates with metabolic and cardiovascular disease, and possibly with dementia as well as variations in brain volume. However, body fat distribution and abdominal obesity (as measured by waist circumference) is more strongly correlated with cardiovascular and metabolic risk than is BMI. While prior studies have revealed negative associations between gray matter tissue volumes and BMI, the relationship with respect to waist circumference remains largely unexplored. We therefore investigated the effects of both BMI and waist circumference on local gray matter volumes in a group of 115 healthy subjects screened to exclude physical or mental disorders that might affect the central nervous system. Results revealed significant negative correlations for both BMI and waist circumference where regional gray matter effects were largest within the hypothalamus and further encompassed prefrontal, anterior temporal an...

Human Brain Mapping, 2012

Surface deformation‐based analysis was used to assess local shape variations in the hippocampi an... more Surface deformation‐based analysis was used to assess local shape variations in the hippocampi and caudate nuclei of children with fetal alcohol spectrum disorders. High‐resolution structural magnetic resonance imaging images were acquired for 31 children (19 controls and 12 children diagnosed with fetal alcohol syndrome/partial FAS). Hippocampi and caudate nuclei were manually segmented, and surface meshes were reconstructed. An iterative closest point algorithm was used to register the template of one control subject to all other shapes in order to capture the true geometry of the shape with a fixed number of landmark points. A point distribution model was used to quantify the shape variations in terms of a change in co‐ordinate positions. Using the localized Hotelling T2 method, regions of significant shape variations between the control and exposed subjects were identified and mapped onto the mean shapes. Binary masks of hippocampi and caudate nuclei were generated from the segm...

Cerebral Cortex, 2005

Significant relationships have been reported between midsagittal areas of the corpus callosum and... more Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fibers.

British Journal of Psychiatry, 2012

SummaryDespite accumulating evidence of structural deficits in individuals with psychopathy, espe... more SummaryDespite accumulating evidence of structural deficits in individuals with psychopathy, especially in frontal regions, our understanding of systems-level disturbances in cortical networks remains limited. We applied novel graph theory-based methods to assess information flow and connectivity based on cortical thickness measures in 55 individuals with psychopathy and 47 normal controls. Compared with controls, the psychopathy group showed significantly altered interregional connectivity patterns. Furthermore, bilateral superior frontal cortices in the frontal network were identified as information flow control hubs in the psychopathy group in contrast to bilateral inferior frontal and medial orbitofrontal cortices as network hubs of the controls. Frontal information flow and connectivity may have a significant role in the neuropathology of psychopathy.

American Journal of Psychiatry, 2008

Objective-Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whe... more Objective-Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early-and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. Method-With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early-(N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups. Results-Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early-and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late-compared to earlyonset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1-CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late-but not early-onset depressed patients or comparison subjects. Conclusions-More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies. Altered hippocampal morphology has an important role in the pathophysiology of elderly depression. Studies using magnetic resonance imaging (MRI) have reported hippocampal volume decreases, sometimes unilateral, in elderly patients with major depression relative to healthy comparison subjects (1-5), although negative reports exist (6-8).

IEEE Transactions on Medical Imaging, 2012

We present a diffeomorphic approach for constructing intrinsic shape atlases of sulci on the huma... more We present a diffeomorphic approach for constructing intrinsic shape atlases of sulci on the human cortex. Sulci are represented as square-root velocity functions of continuous open curves in ℝ 3 , and their shapes are studied as functional representations of an infinite-dimensional sphere. This spherical manifold has some advantageous properties-it is equipped with a Riemannian metric on the tangent space and facilitates computational analyses and correspondences between sulcal shapes. Sulcal shape mapping is achieved by computing geodesics in the quotient space of shapes modulo scales, translations, rigid rotations and reparameterizations. The resulting sulcal shape atlas preserves important local geometry inherently present in the sample population. The sulcal shape atlas is integrated in a cortical registration framework and exhibits better geometric matching compared to the conventional euclidean method. We demonstrate experimental results

Encyclopedia of Neuroscience, 2009

Commons Attribution (CC BY) license, which allows users to download, copy and build upon publishe... more Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.

Schizophrenia Research, 2015

Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological re... more Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological relatives of patients. However, the neural correlates of successful and unsuccessful encoding, mediated by the medial temporal lobe (MTL) memory system, and the influence of disease-related genetic liability remain under explored. This study employed an event-related functional MRI paradigm to compare activations for successfully and unsuccessfully encoded associative facename stimuli between 26 schizophrenia patients (mean age: 33, 19m/7f), 30 controls (mean age: 29, 24m/6f) and 14 unaffected relatives of patients (mean age: 40, 5m/9f). Compared to controls or unaffected relatives, patients showed hyper-activations in ventral visual stream and temporoparietal cortical association areas when contrasting successfully encoded events to fixation. Follow-up hippocampal regions-of-interest analysis revealed schizophrenia-related hyperactivations in the right anterior hippocampus during successful encoding; contrasting successful versus unsuccessful events produced schizophrenia-related hypo-activations in the left anterior hippocampus. Similar hippocampal hypo-activations were observed in unaffected relatives during successful versus unsuccessful encoding. Post-hoc analyses of hippocampal volume showed reductions in patients, but not in unaffected relatives compared to controls. Findings suggest that