Case records of the Massachusetts General Hospital. Case 38-2006. A 5-year-old boy with headache and abdominal pain.
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Abdominal Pain↗
Biomedical subjects
Verne S Caviness
Publications and source records attributed to Verne S Caviness.
Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability.
BACKGROUND: This is a unique hypothalamic magnetic resonance imaging (MRI) study in schizophrenia, an important region in the limbic system. We hypothesized abnormal volumetric increases, with greater severity in multiplex families (more than one ill member) compared with simplex families (one ill). We tested the hypothesis that normal hypothalamic sexual dimorphism is disrupted in schizophrenia. METHODS: Eighty-eight DSM-III-R schizophrenia cases (40 simplex and 48 multiplex), 43 first-degree nonpsychotic relatives, and 48 normal comparisons systematically were compared. A 1.5-Tesla General Electric scanner was used to acquire structural MRI scans, and contiguous 3.1-mm slices were used to segment anterior and posterior hypothalamus. General linear model for correlated data and generalized estimating equations were used to compare cases, relatives, and controls on right and left hypothalamus, controlled for age, sex, and total cerebral volume. Spearman's correlations of hypothalamic volumes with anxiety were calculated to begin to examine arousal correlates with structural abnormalities. RESULTS: Findings demonstrated significantly increased hypothalamic volume in cases and nonpsychotic relatives, particularly in regions of paraventricular and mammillary body nuclei, respectively. This increase was linear from simplex to multiplex cases, was positively correlated with anxiety, and had a greater propensity in women. CONCLUSIONS: Findings suggest important implications for understanding genetic vulnerability of schizophrenia and the high rate of endocrine abnormalities.
Adult↗
Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI study.
Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging, white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus II and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus II and the cingulum bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional FA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey.
Aging↗
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↗
Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitecture in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and EF.
Adolescent↗
Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.
OBJECTIVES: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. METHODS: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. RESULTS: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. CONCLUSIONS: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.
Adult↗
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↗
Decreased volume of left and total anterior insular lobule in schizophrenia.
The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.
Adolescent↗
MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability.
We revisit here a surface assisted parcellation (SAP) system of the human cerebellar cortex originally described in Makris, N., Hodge, S.M., Haselgrove, C., Kennedy, D.N., Dale, A., Fischl, B., Rosen, B.R., Harris, G., Caviness, V.S., Jr., Schmahmann, J.D., 2003. Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging. J Cogn Neurosci 15, 584-599. This system preserves the topographic and morphologic uniqueness of the individual cerebellum and allows for volumetric analysis and representation of multimodal structural and functional data on the cerebellar cortex. This methodology integrates features of automated routines of the program FreeSurfer as well as semi-automated and manual procedures of the program Cardviews to create 64 cerebellar parcellation units based on fissure information and anatomical landmarks of the cerebellar surface. Using this technique, we undertook the parcellation of ten cerebella by two independent raters. The reliability of the resulting parcellation units (64 total) was high, with an average Intraclass Correlation Coefficient (ICC) of 0.724 in the vermis and 0.853 in the hemispheres. Clusters of parcellation units were then created, based on lobar and connectivity data and functional hypotheses. These 36 clusters, when treated as anatomical units, had an average ICC of 0.933. Whereas the individual units provide a high level of detail and anatomical specificity, the clusters add flexibility to the analysis by providing higher reliability.
Algorithms↗
An introduction to MR imaging-based stroke morphometry.
The anatomic description of the stroke lesion is an essential component of clinical diagnosis and treatment and has become an established tool in investigations into underlying stroke pathophysiology. Magnetic resonance (MR) imaging permits quantitative evaluation of the distributed consequences of the pathologic stroke insult. General properties of stroke effects have emerged using these tools. This article surveys the classes of morphometric data that are available from conventional MR images, the methods for extracting quantitative results, and samples of the application of these methods to stroke. These samples highlight anatomic-based considerations regarding the nature of stroke and its repercussions within the brain parenchyma.
Humans↗
Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder.
OBJECTIVE: Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD) have investigated the entire cerebral cortex. Cortical gray matter (GM) volume deficits have been reported in some studies of adults with BPD; this study assessed the presence of such deficits in children with BPD. METHODS: Thirty-two youths with DSM-IV BPD (mean age 11.2 +/- 2.8 years) and 15 healthy controls (HC) (11.2 +/- 3.0 years) had structured and clinical interviews, neurological examinations, neurocognitive testing, and MRI scanning on a 1.5 T GE Scanner. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere, and these units were combined into frontal (FL), temporal (TL), parietal (PL), and occipital (OL) lobe volumes. Volumetric differences were examined using univariate linear regression models with alpha = 0.05. RESULTS: Relative to controls, the BPD youth had significantly smaller bilateral PL, and left TL. Analysis of PL and TL gyri showed significantly smaller volume in bilateral postcentral gyrus, and in left superior temporal and fusiform gyri, while the parahippocampal gyri were bilaterally increased in the BPD group. Although the FL overall did not differ between groups, an exploratory analysis showed that the right middle frontal gyrus was also significantly smaller in the BPD group. CONCLUSIONS: Children with BPD showed deficits in PL and TL cortical GM. Further analyses of the PL and TL found differences in areas involved in attentional control, facial recognition, and verbal and declarative memory. These cortical deficits may reflect early age of illness onset.
Adolescent↗
Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder.
BACKGROUND: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. RESULTS: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. CONCLUSIONS: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.
Adolescent↗
Segmentation of subcomponents within the superior longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study.
Previous research in non-human primates has shown that the superior longitudinal fascicle (SLF), a major intrahemispheric fiber tract, is actually composed of four separate components. In humans, only post-mortem investigations have been available to examine the trajectory of this tract. This study evaluates the hypothesis that the four subcomponents observed in non-human primates can also be found in the human brain using in vivo diffusion tensor magnetic resonance imaging (DT-MRI). The results of our study demonstrated that the four subdivisions could indeed be identified and segmented in humans. SLF I is located in the white matter of the superior parietal and superior frontal lobes and extends to the dorsal premotor and dorsolateral prefrontal regions. SLF II occupies the central core of the white matter above the insula. It extends from the angular gyrus to the caudal-lateral prefrontal regions. SLF III is situated in the white matter of the parietal and frontal opercula and extends from the supramarginal gyrus to the ventral premotor and prefrontal regions. The fourth subdivision of the SLF, the arcuate fascicle, stems from the caudal part of the superior temporal gyrus arches around the caudal end of the Sylvian fissure and extends to the lateral prefrontal cortex along with the SLF II fibers. Since DT-MRI allows the precise definition of only the stem portion of each fiber pathway, the origin and termination of the subdivisions of SLF are extrapolated from the available data in experimental material from non-human primates.
Adult↗
Decreased absolute amygdala volume in cocaine addicts.
The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.
Adult↗
Localization of white matter volume increase in autism and developmental language disorder.
Increased brain volume in autism appears to be driven mainly by an unexplained white matter enlargement, and we have reported a similar phenomenon in developmental language disorder (DLD). Localization of this enlargement would strongly guide research into its cause, tissue basis, and functional implications. We utilized a white matter parcellation technique that divides cerebral white matter into an outer zone containing the radiate compartment and an inner zone containing sagittal and bridging system compartments. In both high-functioning autism and DLD, enlargement localized to the radiate white matter (all lobes in autism, all but parietal in DLD), whereas inner zone white matter compartments showed no volume differences from controls. Furthermore, in both autism and DLD, later or longer-myelinating regions showed greater volume increases over controls. Neither group showed cerebral cortex, corpus callosum, or internal capsule volume differences from control. Radiate white matter myelinates later than deep white matter; this pattern of enlargement thus is consistent with striking postnatal head circumference percentile increases reported in autism. These findings suggest an ongoing postnatal process in both autism and DLD that is probably intrinsic to white matter, that primarily affects intrahemispheric and corticocortical connections, and that places these two disorders on the same spectrum.
Autistic Disorder↗
Language-association cortex asymmetry in autism and specific language impairment.
Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca's area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca's area asymmetry reversal is related more to language impairment than specifically to autism diagnosis.
Adolescent↗
Selective rotation of egocentric spatial representation following right putaminal hemorrhage.
Although the role of frontoparietal cortex in spatial egocentric processing is well established, recent animal-lesion and human functional imaging studies have suggested that the neostriatum may also be a critical modulator in the processing of body-centred spatial orientation. We describe here a patient with right putamen-centred hemorrhage who exhibited a consistent counterclockwise rotation of approximately 90 degrees when drawing and writing from memory. A more detailed assessment with a series of representational clock tests demonstrated that the rotation was present only in tasks requiring the use of egocentric cues. In the absence of external cues the patient would adopt and maintain a stable but incorrectly-oriented egocentric representation of the imagined or recollected object. By contrast, performance could be rectified by presentation of correctly-oriented stimuli. These findings suggest that the putamen is part of a circuit underlying egocentric, as opposed to allocentric, representation of space in humans.
Adult↗
Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging.
We describe a system of surface-assisted parcellation (SAP) of the human cerebellar cortex derived from neural systems functional and behavioral anatomy. This system is based on MRI and preserves the unique morphologic and topographic features of the individual cerebellum. All major fissures of the cerebellum were identified and traced in the flattened representation of the cerebellar cortex using the program "FreeSurfer." Parcellation of the cerebellar cortex followed using the fissure information in conjunction with landmarks using the program "Cardviews" to create 64 gyral-based cerebellar parcellation units. Computer-assisted algorithms enable the execution of the cerebellar parcellation procedure as well as volumetric measurements and topographic localization. The SAP technique makes it possible to represent multimodal structural and functional imaging data on the flattened surface of the cerebellar cortex as illustrated in one functional MRI experiment.
Adult↗