Callosum Shape Research Articles

Corpus callosum in schizophrenia with deficit and non-deficit syndrome: a statistical shape analysis

BackgroundThe corpus callosum (CC) is the most targeted region in the cerebrum that integrates cognitive data between homologous areas in the right and left hemispheres.AimsOur study used statistical analysis to...

Statistical shape analysis of corpus callosum in restless leg syndrome

ABSTRACT Objectives In this study we aimed to investigate corpus callosum shape differences between restless leg syndrome patients and healthy controls, and to determine whether disease severity and duration are indicators for corpus callosum deformation in RLS patients. Methods This study was conducted using the magnetic resonance imaging scans of 33 restless leg syndrome patients and 33 control subjects. Landmarks were marked on the digital images and callosal landmark coordinate data were used to assess shape difference by performing Generalized Procrustes analysis. The shape deformation from controls to the patients was evaluated performing the Thin Plate Spline approach. Results There was a statistically significant shape difference between the groups. Highest deformation was determined at the posterior midbody of the corpus callosum. Growth curve analyses showed that with the increase in disease duration and severity, the CC size decreased. Discussion The present study demonstrated callosal shape differences in restless leg syndrome using a landmark-based geometric morphometric approach, considering the topographic distribution of corpus callosum for the first time.

The neural code of intelligence: From correlation to causation.

Research into the neural underpinning of intelligence has mainly adopted a construct perspective: trying to find structural and functional brain characteristics that would accommodate the psychological concept of g. Few attempts have been made to explain intelligence exclusively based on brain characteristics - the brain perspective. From a methodological viewpoint the brain intelligence relation has been studied by means of correlational and interventional studies. The later providing a causal elucidation of the brain - intelligence relation. The best neuro-anatomical predictor of intelligence is brain volume showing a modest positive correlation with g, explaining between 9 to 16% of variance. The most likely explanation was that larger brains, containing more neurons, have a greater computational power and in that way allow more complex cognitive processing. Correlations with brain surface, thickness, convolution and callosal shape showed less consistent patterns. The development of diffusion tensor imaging has allowed researchers to look also into the microstructure of brain tissue. Consistently observed was a positively correlation between white matter integrity and intelligence, supporting the idea that efficient information transfer between hemispheres and brain areas is crucial for higher intellectual competence. Based on functional studies of the brain intelligence relationship three theories have been put forward: the neural efficiency, the P-FIT and the multi demand (MD) system theory. On the other hand, The Network Neuroscience Theory of g, based on methods from mathematics, physics, and computer science, is an example for the brain perspective on neurobiological underpinning of intelligence. In this framework network flexibility and dynamics provide the foundation for general intelligence. With respect to intervention studies the most promising results have been achieved with noninvasive brain stimulation and behavioral training providing tentative support for findings put forward by the correlational approach. To date the best consensus based on the diversity of results reported would be that g is predominantly determined by lateral prefrontal attentional control of structured sensory episodes in posterior brain areas. The capacity of flexible transitions between these network states represents the essence of intelligence - g.

Callosal thickness profiles for prognosticating conversion from mild cognitive impairment to Alzheimer's disease: A classification approach.

IntroductionAlzheimer's disease (AD) is the most common form of dementia. Finding biomarkers to prognosticate transition from mild cognitive impairment (MCI) to AD is important to clinical medicine. Promising imaging biomarkers of AD conversion identified so far include atrophy of the cerebral cortex and subcortical gray matter nuclei.MethodsThis study introduces thickness and bending angle of the corpus callosum as a putative white matter marker of MCI to AD conversion. The corpus callosum is computationally less demanding to segment automatically compared to more complicated structures and a subject can be processed in a few minutes. We aimed to demonstrate that callosal shape and thickness measures provide a simple, effective, and accurate prognostication tool in ADNI dataset. Using longitudinal datasets, we classified MCI subjects based on conversion to AD assessed via cognitive testing. We evaluated the classification accuracy of callosal shape features in comparison with the existing “gold standard” cortical thickness and subcortical gray matter volume measures.ResultsThe callosal thickness measures were less accurate in classifying conversion status by cognitive scores compared to gray matter measures for AD.ConclusionsWhile this paper presented a negative result, this method may be more suitable for a disease of the white matter.

Deformation-based Statistical Shape Analysis of the Corpus Callosum in Mild Cognitive Impairment and Alzheimer's Disease.

In this study, we investigated the influence that the pathology of Alzheimer's disease (AD) exerts upon the corpus callosum (CC) using a total of 325 mild cognitive impairment (MCI) subjects, 155 AD subjects, and 185 healthy control (HC) subjects. Regionally-specific morphological CC abnormalities, as induced by AD, were quantified using a large deformation diffeomorphic metric curve mapping based statistical shape analysis pipeline. We also quantified the association between the CC shape phenotype and two cognitive measures; the Mini Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Behavior Section (ADAS-cog). To identify AD-relevant areas, CC was sub-divided into three subregions; the genu, body, and splenium (gCC, bCC, and sCC). We observed significant shape compressions in AD relative to that in HC, mainly concentrated on the superior part of CC, across all three sub-regions. The HC-vs-MCI shape abnormalities were also concentrated on the superior part, but mainly occurred on bCC and sCC. The significant MCI-vs-AD shape differences, however, were only detected in part of sCC. In the shape-cognition association, significant negative correlations to ADAS-cog were detected for shape deformations at regions belonging to gCC and sCC and significant positive correlations to MMSE at regions mainly belonging to sCC. Our results suggest that the callosal shape deformation patterns, especially those of sCC, linked tightly to the cognitive decline in AD, and are potentially a powerful biomarker for monitoring the progression of AD.

Automatic Extraction of the Centerline of Corpus Callosum from Segmented Mid-Sagittal MR Images.

The centerline, as a simple and compact representation of object shape, has been used to analyze variations of the human callosal shape. However, automatic extraction of the callosal centerline remains a sophisticated problem. In this paper, we propose a method of automatic extraction of the callosal centerline from segmented mid-sagittal magnetic resonance (MR) images. A model-based point matching method is introduced to localize the anterior and posterior endpoints of the centerline. The model of the endpoint is constructed with a statistical descriptor of the shape context. Active contour modeling is adopted to drive the curve with the fixed endpoints to approximate the centerline using the gradient of the distance map of the segmented corpus callosum. Experiments with 80 segmented mid-sagittal MR images were performed. The proposed method is compared with a skeletonization method and an interactive method in terms of recovery error and reproducibility. Results indicate that the proposed method outperforms skeletonization and is comparable with and sometimes better than the interactive method.

Geometric morphometrics reveal altered corpus callosum shape in pyridoxine-dependent epilepsy.

To evaluate the features and maturational changes in overall callosal shape in patients with pyridoxine-dependent epilepsy (PDE). Measurements were conducted through landmark-based geometric morphometrics applied on cerebral MRIs of patients with PDE and age-matched control subjects. The outline of the corpus callosum was manually traced in the midsagittal plane. Three hundred semi-landmarks along the outline were collected and underwent statistical generalized Procrustes analysis. An allometric regression was applied to evaluate the callosal shape due to growth over time. Thirty-eight patients with PDE and 38 age- and sex-matched control subjects were included. Mean age at the time of the MRI in the patient group was 9.3 years (median 6.3 years, range 0.01-48 years). Significant differences (p < 0.01) in the mean callosal shape between patients and controls were found. The allometric regression model revealed significant shape variations (p < 0.01) between the 2 study groups across the developmental course after controlling for the effect of callosal size on shape. This latter effect turned out to be significant as well (p < 0.001). Patients with PDE show an altered callosal shape and variations in callosal ontogeny, which are likely secondary to the underlying genetic defect with abnormal function of antiquitin, the product of the ALDH7A1 gene.

Statistical shape analysis of the corpus callosum in Schizophrenia

We present a statistical shape-analysis framework for characterizing and comparing morphological variation of the corpus callosum. The midsagittal boundary of the corpus callosum is represented by a closed curve and analyzed using an invariant shape representation. The shape space of callosal curves is endowed with a Riemannian metric. Shape distances are given by the length of shortest paths (geodesics) that are invariant to shape-confounding transformations. The statistical framework enables computation of shape averages and covariances on the shape space in an intrinsic manner (unique to the shape space). The statistical framework makes use of the tangent principal component approach to achieve dimension reduction on the space of corpus callosum shapes. The advantages of this approach are - it is fully automatic, invariant, and avoids the use of landmarks to define shapes. We applied our method to determine the effects of sex, age, schizophrenia and schizophrenia-related genetic liability on callosal shape in a large sample of patients and controls and their first-degree relatives (N=218). Results showed significant age, sex, and schizophrenia effects on both global and local callosal shape structure.

Another Step Forward in Relating Facial and Brain Dysmorphologies Associated with Prenatal Alcohol Exposure

Another Step Forward in Relating Facial and Brain Dysmorphologies Associated with Prenatal Alcohol Exposure

Characterization of the corpus callosum in very preterm and full-term infants utilizing MRI

The corpus callosum is the largest white matter tract, important for interhemispheric communication. The aim of this study was to investigate and compare corpus callosum size, shape and diffusion characteristics in 106 very preterm infants and 22 full-term infants. Structural and diffusion magnetic resonance images were obtained at term equivalent. The corpus callosum was segmented, cross-sectional areas were calculated, and shape was analyzed. Fractional anisotropy, mean, axial and radial diffusivity measures were obtained from within the corpus callosum, with additional probabilistic tractography analysis. Very preterm infants had significantly reduced callosal cross-sectional area compared with term infants (p=0.004), particularly for the mid-body and posterior sub-regions. Very preterm callosi were more circular (p=0.01). Fractional anisotropy was lower (p=0.007) and mean (p=0.006) and radial (p=0.001) diffusivity values were higher in very preterm infants’ callosi, particularly at the anterior and posterior ends. The volume of tracts originating from the corpus callosum was reduced in very preterm infants (p=0.001), particularly for anterior mid-body (p=0.01) and isthmus tracts (p=0.04). This study characterizes callosal size, shape and diffusion in typically developing infants at term equivalent age, and reports macrostructural and microstructural abnormalities as a result of prematurity.

Callosal microstructural abnormalities in Alzheimer's disease and alcoholism: same phenotype, different mechanisms

Magnetic resonance (MRI) and diffusion tensor imaging (DTI) data were acquired in 13 Alzheimer's disease (AD) patients, 15 elderly alcoholics, and 32 elderly controls. Midsagittal area, length, dorsoventral height, fractional anisotropy (FA), and mean diffusivity (MD) of the total corpus callosum and volume of the lateral ventricles were measured; area, FA, and MD were also determined for the callosal genu, body, and splenium. On DTI, both patient groups had lower FA and higher MD than controls in all callosal regions. On MRI, both patient groups had smaller genu than controls; additional size deficits were present in the alcoholism group's callosal body and the AD group's splenium. The callosal arch was higher in the AD but not the alcoholic group compared with controls. The two patient groups had larger ventricles than controls, and the AD group had larger ventricles than the alcoholic group. Callosal area correlated with its height, and callosal FA and MD correlated with ventricular volume in AD, whereas callosal area correlated only with FA in alcoholics. In AD, the disruption of the callosal integrity, which was associated with distorted callosal shape, was related to ventricular dilation, which has been shown in twin studies to be under a multitude of genetic, polygenetic, and environmental influences. Conversely, in alcoholism, disruption of callosal microstructural integrity was related to shrinkage of the corpus callosum itself.

Corpus callosum morphology and relationship to orbitofrontal and lateral ventricular volume in teenagers with first-presentation borderline personality disorder

Previous studies have demonstrated alterations to fronto-limbic circuitry and callosal structure in borderline personality disorder (BPD). We predicted that a first-presentation BPD cohort who demonstrated orbitofrontal cortex (OFC) reductions would show regional reductions in the anterior corpus callosum. Method Twenty teenage first-presentation BPD patients and twenty matched healthy controls underwent Magnetic resonance imaging (MRI) was performed in 20 teenaged first-presentation BPD patients and 20 matched healthy controls. Corpus callosum size and shape and ventricular volume were estimated using established methods and compared between the two groups. The relationship between illness variables and callosal morphology was also examined. OFC volume was correlated with callosal and ventricular variables. Results BPD participants and controls did not differ on measures of callosal size or shape, or ventricular size. BPD participants showed an alteration to the pattern of age-related expansions seen in the callosum. BPD participants with a history of trauma did not demonstrate significant neuroanatomical differences from those without. OFC volumes did not correlate with the thickness of the anterior corpus callosum. Conclusion Gross neuroanatomical changes are not present at the level of the callosum in teenagers with first-presentation BPD. Changes seen in other studies might reflect factors associated with the duration of BPD, such as recurrent comorbidity with axis I disorders, or treatment.

Corpus Callosum Segment Circumference Is Associated With Response Control in Children With Attention-Deficit Hyperactivity Disorder (ADHD)

Response control is impaired in attention-deficit hyperactivity disorder (ADHD). Given the corpus callosum's role in response control, we compared callosal morphology in 64 children with ADHD and 64 typically developing children, aged 7 to 13 years, and investigated the relationships between callosal morphology and response control. Area and circumference of 5 callosal segments (genu, rostral body, midbody, isthmus, and splenium) were normalized for cerebral volume and examined for correlation with mean reaction time, intrasubject variability, and/or commission error rate from a go/no-go task. There were no between-group differences in segment areas or circumferences. Reaction time correlated with midbody circumference for boys with ADHD and isthmus circumference for girls with ADHD. For the entire cohort, rostral body circumference correlated with intrasubject variability. Impaired response control in ADHD is associated with anomalies in frontal interhemispheric connections. Future studies examining callosal shape will illuminate the anatomic basis of correlations between callosal segment circumference and response control.

Corpus callosum size and shape alterations in individuals with bipolar disorder and their first-degree relatives

Reductions in the size of the corpus callosum (CC) have been described in patients with bipolar disorder (BD), although the contribution of genetic factors to these changes is unclear. We previously showed a global thinning of the CC in BD patients, and found those with a family history of affective disorders had a larger CC than those without. In this study, we compared callosal size and shape in 180 individuals: 70 with BD, 45 of their first-degree relatives, and 75 healthy controls. The callosum was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images, and its total area, length and curvature were compared across groups. A non-parametric permutation method was used to examine for alterations in width of the callosum along 39 points. Validating our previous findings, a significant global reduction in callosal thickness was seen in BD patients, with a disproportionate thinning in the anterior body. First-degree relatives did not differ in callosal size or shape from controls. In BD patients, duration of illness and age were associated with thinning in the anterior body; BD patients on lithium treatment showed a thicker anterior mid-body than those on other psychotropics. Global and regional thinning of the callosum is seen in BD but not in their first-degree relatives. This suggests that CC abnormalities are linked to disease expression in BD and may not represent a marker of familial predisposition.

Corpus Callosum Size and Shape in Established Bipolar Affective Disorder

Callosal structural and functional alterations have been demonstrated in a range of neuropsychiatric illnesses, including bipolar disorder, but no study has examined regional callosal thickness in this phenotype. The aim of the present study was therefore to examine callosal size and shape in a well-defined group of bipolar affective disorder patients and controls. The participants included 24 patients with DSM-IV bipolar I disorder and 24 matched healthy controls. The corpus callosum was extracted from mid-callosal images from T1-weighted magnetic resonance imaging scans on all participants, and callosal area, length, bending angle and regional callosal thickness measures were computed from these images. The callosum was thinner in the bipolar group overall, with a disproportionately reduced thickness in the splenium. Psychotic and non-psychotic patients did not differ, although patients without a family history of mood disorders had a thinner callosum. Callosal reductions are present in established bipolar disorder, and affect posterior regions more than anterior regions. This may reflect a primary disturbance to myelination, or a secondary effect of grey matter changes.

Callosal morphology in Williams syndrome: a new evaluation of shape and thickness

We applied novel mesh-based geometrical modeling methods to calculate and compare the thickness of the corpus callosum at high spatial resolution and to create profiles of average callosal shape in a well-matched sample (n=24) of individuals with Williams syndrome and controls. In close agreement with previous observations, superimposed surface maps indicate that the corpus callosum in Williams syndrome individuals is shorter and less curved. Moreover, we observed significantly thinner callosal regions in Williams syndrome individuals across the posterior surface, where group effects were less pronounced and spatially restricted in brain-size-adjusted data compared with native data. Circumscribed structural alterations in callosal morphology might be candidate anatomic substrates for the unique cognitive and behavioral profile associated with Williams syndrome.

Gross Anatomy of the Corpus Callosum in Alzheimer’s Disease: Regions of Degeneration and Their Neuropsychological Correlates

Background/Aims: Differences in the gross shape of the corpus callosum (CC) and its subregional areas were investigated on brain MRI of patients with probable Alzheimer’s disease (AD) and age- and gender-matched healthy normal control subjects. The AD patients differed from the normal control subjects in terms of a more convex shape and a reduced area of the CC. Methods: As for the comparisons of the subregional areas of the CC, we adapted a splitting method which takes into account the modification of the global shape of the CC, and we implemented it by normalizing the CC, to avoid the bias introduced by the observed callosal shape variability. Results: The application of this method unveiled that the regional CC reductions were located in the anterior and posterior third of the CC, i.e. where small myelinated fibers are more frequent. None of the neuropsychological scores collected at the time of the MRI investigation of AD could predict a regional and/or overall callosal area reduction. The only measure that correlated with area of the isthmus of the CC was the MMSE that was administered to all participants. Conclusions: This latter result may be used as an in vivo indicator of the progress of neocortical disintegration in AD.

Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage.

Prenatal exposure to high levels of alcohol often induces birth defects that combine morphological stigmata with neurological or neuropsychological deficits. But it has proved problematic to diagnose these syndromes in adolescents and adults, in whom the morphological signs are absent or attenuated, the behavioral deficits nonspecific, and the exposure history often difficult to reconstruct. Localizing the associated brain abnormalities might circumvent most of these difficulties. To this end, three-dimensional (3D) locations were recorded for 67 homologous points on or near the corpus callosum in magnetic resonance (MR) brain images from 60 adolescents and adults who were normal, 60 diagnosed with fetal alcohol syndrome, and 60 diagnosed with fetal alcohol effects. We combined the standard statistical approach to this type of geometric data, Procrustes analysis, with a multivariate strategy focusing on differences in variability. In this data set, the shape of the corpus callosum and its vicinity proves systematically much more variable in the alcohol-affected brains than in those of the normal subjects. From this excess variability follows a promising classification rule, having both high sensitivity (100 out of 117) and high specificity (49 out of 60) in this sample. The discrimination uses four landmark points and two summary scores of callosal outline shape. The information from the corpus callosum and vicinity, as viewed in MR brain images of full-grown subjects, may serve as a permanent record of the prenatal effects of alcohol, even in patients who are first suspected of these syndromes relatively late in life or who lack the facial signs of prenatal alcohol damage. The statistical pattern underlying the callosal diagnosis also leads to speculations on mechanisms of the prenatal damage.

Corpus Callosum Shape and Neuropsychological Deficits in Adult Males with Heavy Fetal Alcohol Exposure

Persons with brain damage consequent to prenatal alcohol exposure have typically been diagnosed with either fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE), depending on facial features. There is great variability of behavioral deficits within these groups. We sought to combine neuroanatomical measures with neurocognitive and neuromotor measures in criteria of greater sensitivity over the variety of consequences of alcohol exposure. To this end, midline curves of the corpus callosum were carefully digitized in three dimensions from T1-weighted MR scans of 15 adult males diagnosed with FAS, 15 with FAE, and 15 who were unexposed and clinically normal. From 5 h of neuropsychological testing we extracted 260 scores and ratings pertaining to attention, memory, executive function, fine and gross motor performance, and intelligence. Callosal midline shape was analyzed by new morphometric methods, and the relation of shape to behavior by partial least squares. The FAS and FAE subgroups have strikingly more variability of callosal shape than our normal subjects. With the excess shape variation are associated two different profiles of behavioral deficit unrelated to full-scale IQ or to the FAS/FAE distinction within the exposed subgroup. A relatively thick callosum is associated with a pattern of deficit in executive function; one that is relatively thin, with a deficit in motor function. The two combine in a very promising bipolar discrimination of the exposed from the unexposed in this sample. Thus there is considerable information in callosal form for prognosis of neuropsychological deficits in this frequently encountered birth defect.

Geometric morphometrics of corpus callosum and subcortical structures in the fetal-alcohol-affected brain.

Although experienced clinicians have been diagnosing fetal alcohol syndrome (FAS) for nearly 30 years, the rest of the spectrum of fetal alcohol damage is not being classified effectively. This article describes a quantification of neuroanatomical structure that may supply a useful discriminator of prenatal brain damage from alcohol. It is demonstrated in a data set of adults of both sexes. Ninety adults (45 males) were examined by magnetic resonance imaging (MRI). These subjects were group-matched for age and ethnicity across three diagnoses: FAS, fetal alcohol effects (FAE), and normals. All FAS and FAE were heavily alcohol-exposed in utero; normals were not. From T(1)-weighted MR brain images, we extracted 3D morphometric representations of shape for 33-landmark point configurations and 40-point outlines of the corpus callosum along its midline (a slightly nonplanar structure). There are striking differences between exposed and unexposed in the statistical distributions of these two shapes. The differences are better characterized by excess variance in the exposed group than by any change in average landmark or outline shape. For each sex, combining the callosal outline data with the landmark data leads to a powerful quadratic discriminator of exposed from unexposed. The discriminating features include the relationship of brain stem to diencephalon, and localized variabilities of callosal outline shape, but not diagnosis (FAS vs. FAE). Statistical analysis of brain shape is a powerful new source of information relevant to fetal alcohol spectrum nosology and etiology. Patients with FAS and FAE do not differ in these brain shape features, but both differ from the unexposed. The aspects of brain shape that are especially variable may be entailed in the underlying neuroteratogenetic mechanisms.