Subregions Of Corpus Callosum Research Articles

Corpus callosum deficits in antipsychotic-naïve schizophrenia: Evidence for neurodevelopmental pathogenesis

The corpus callosum (CC), the largest inter-hemispheric tract connecting the association cortices, has been shown to be affected in disorders with aberrant neurodevelopment. Previous studies that investigated CC abnormalities in schizophrenia have reported mixed findings potentially due to various confounding factors. In this study, we used magnetic resonance imaging to examine a large sample of antipsychotic-naïve schizophrenia patients ( n = 66) in comparison with age-, sex-, and handedness-matched (as a group) healthy comparison subjects ( n = 46). Mid-sagittal areas of CC sub-regions – namely, the genu, body, isthmus and splenium – were measured based on Witelson's method with good inter- and intra-rater reliability. The genu and body of the CC were significantly smaller in schizophrenia patients in comparison to healthy subjects after controlling for the potential confounding effects of age, sex and intracranial area. In male schizophrenia patients, there was a significant positive correlation between the age at onset of psychosis and the area of the genu. Together, these findings suggest neurodevelopmentally mediated hypoconnectivity in schizophrenia.

When, where, and how the corpus callosum changes in MCI and AD

The corpus callosum (CC) has been shown to be susceptible to atrophy in Alzheimer disease (AD) as a correlate of wallerian degeneration or retrogenesis. However, when and where these 2 mechanisms intervene is still unclear. In 3 memory clinics, we recruited 38 patients with amnestic mild cognitive impairment (MCI), 38 patients with mild AD, and 40 healthy controls (HC). Combining voxel-based morphometry and diffusion tensor imaging, we investigated CC white matter (WM) density and fractional anisotropy (FA), radial diffusivity (DR), and axial diffusivity (DA). Compared with HC, patients with amnestic MCI showed reduced WM density in the anterior CC subregion; however, FA, DR, and DA did not differ between the 2 groups. Significant changes were found in patients with mild AD compared with HC in the anterior and posterior CC regions. These differences were evident in both voxel-based morphometry and diffusion tensor imaging analyses. Specifically, we found reduced callosal WM density in the genu, posterior body, and splenium; decreased FA and increased DR in the anterior CC subregion; and increased DA, with no difference in the FA, in the posterior CC subregion. Callosal changes are already present in patients with amnestic mild cognitive impairment (MCI) and mild Alzheimer disease (AD). The precocious involvement of the anterior callosal subregion in amnestic MCI extends to posterior regions in mild AD. Two different mechanisms might contribute to the white matter changes in mild AD: wallerian degeneration in posterior subregions of the corpus callosum (suggested by increased axial diffusivity without fractional anisotropy modifications) and a retrogenesis process in the anterior callosal subregions (suggested by increased radial diffusivity without axial diffusivity modifications).

Asymmetrical interhemispheric fiber tracts in patients with hemimegalencephaly on diffusion tensor magnetic resonance imaging

The internal structures of cerebral white matter in patients with hemimegalencephaly have not yet been investigated except for one, which evaluated aberrant fibers. We examined interhemispheric fiber tracts (FT) passing through the corpus callosum using magnetic resonance (MR) diffusion tensor imaging (DTI). MR studies, including DTI, were performed in nine consecutive patients with hemimegalencephaly and in 11 patients with West syndrome as disease controls. The interhemispheric FT passing through the corpus callosum were evaluated in six regional geometric subdivisions in every hemimegalencephaly and West syndrome patient (54 and 66 subregions, respectively), and the distribution and volume differences between affected and unaffected hemispheres were all compared. In patients with hemimegalencephaly, interhemispheric FT were symmetrically distributed in 27 (50%) of the 54 corpus callosum subregions. However, the FT were distributed to different areas in the same lobes in 22 (40%) subregions, and to different lobes in five (9%) subregions. FT volumes were symmetrical in 35 (65%) subregions, while FT volumes on the affected side were greater, but less than those on the unaffected side, in 14 (26%) and five (9%) subregions, respectively. In contrast, in the West syndrome patients, interhemispheric FT showed symmetrical distributions and volumes in all regions. Asymmetrical interhemispheric FT are often observed in patients with hemimegalencephaly, and DTI was a useful means of elucidating the internal structures of white matter.

Corpus callosal area differences and gender dimorphism in neuroleptic-naïve, recent-onset schizophrenia and healthy control subjects

The study of corpus callosal morphometry is important to unravel the underlying connectivity disturbance in schizophrenia. We studied the corpus callosal area in schizophrenia subjects compared to healthy subjects, while controlling for several confounders that could affect morphometric measures of the corpus callosum (CC). Areas of the whole CC and its sub-regions obtained by two geometric partitioning schemes were studied in 23 right-handed neuroleptic-naïve, recent-onset, schizophrenia patients and compared with 23 right-handed age-, sex- and education-matched healthy subjects. The patients did not differ from controls in whole CC area. On tripartite division of the CC, the area of the anterior sub-region was significantly higher in patients compared to controls. On radial division into 5 sub-regions, the anterior truncus area was significantly higher in patients compared to controls. There was a significant effect of gender (F>M) on the area measures; however there was no significant diagnosis⁎gender effect. Age, age of onset, duration of illness and psychopathology ratings did not show any significant correlations with whole CC area and area of CC sub-regions. The finding of increased area of the anterior truncus that possibly comprises white fibres connecting the temporal association cortices could be indicative of an “abnormal functional hyperconnection” involving these regions in positive symptom schizophrenia. Additionally, the finding of females having larger areas of the whole CC and of the anterior and middle sub-regions could reflect a “normal hyperconnection” underlying increased ambilaterality in females.

White Matter Changes Contribute to Corpus Callosum Atrophy in the Elderly: The LADIS Study

The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects. In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions. Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy. Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.

Gestational Age at Preterm Birth in Relation to Corpus Callosum and General Cognitive Outcome in Adolescents

Prematurity is associated with corpus callosum abnormalities and low general cognitive functioning. The present study explores the specific relationship between gestational age, corpus callosum, and intelligence quotient (IQ) in a sample of preterm-born adolescents. Sixty-four adolescents born at a gestational age of 36 weeks or less were divided into 4 groups attending to their gestational age (GA) (group 1, < or = 27; group 2, 28-30; group 3, 31-33; group 4, 34-36). These individuals were compared with 53 adolescents born at term and of similar age, gender, and sociocultural status. Individuals born at a gestational age of 27 or less (group 1) presented a generalized corpus callosum reduction in the posterior part (posterior midbody, isthmus, and splenium) as well as in the anterior part (anterior midbody and genu), a reduced total white-matter volume, and a low Full-Scale IQ. Group 2 (GA between 28 and 30) also showed a low IQ, but corpus callosum reduction was only found in the splenium, without total white-matter volume reductions. Group 3 (GA between 31 and 33) did not present differences in corpus callosum size or a reduced total white- matter volume, but they showed a low Full-Scale IQ. Group 4 (GA between 34 and 36) did not show a smaller corpus callosum or a lower general cognitive performance. Specific significant correlations were found between corpus callosum subregions and gestational age. These results suggest the importance of gestational age in prematurity in relation to brain structural and functional outcome. Premature babies born at a gestational age of 27 weeks or less are the target group for long-term corpus callosum and white-matter anomalies and for a low IQ.

Interhemispheric transfer time and structural properties of the corpus callosum

The present study examined how interhemispheric transfer time (IHTT) is affected by interindividual differences in corpus callosum (CC) architecture. For this purpose the CC of 42 healthy male subjects was assessed by applying a combination of morphological and diffusion-tensor magnetic resonance imaging to characterize the CC on macro- (midsagittal area) and microstructural level (mean diffusion, fractional anisotropy). Following the so-called Poffenberger paradigm, IHTT was determined with both reaction time measures and event-related potentials recorded in response to stimuli briefly presented to either left or right visual hemifield. Statistical analysis revealed significant negative correlations between mean diffusion and IHTT estimates derived from the P100 component (at O1/O2 electrode pair), particularly in the posterior CC subregion. Interpreting mean diffusion as an index of microstructural tissue properties, IHTT appears to be directly related to the structural integrity of the posterior CC.

Relationship between diffusion tensor imaging and brain morphology in patients with myotonic dystrophy

Myotonic dystrophy type 1 (MyD) is a common inherited neuromuscular disorder. In addition to neuromuscular symptoms, many MyD patients show central nervous system neuropathology. This study evaluated whether MyD patients display diffusion tensor (DT) abnormalities associated with regional cortical atrophy and clinical features. Three-dimensional T1-weighted and DT magnetic resonance images of the brain were obtained in 11 MyD patients and 13 age- and sex-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in corpus callosum subregions with DT imaging (DTI) along with volumetric changes, and correlations with clinical features were examined. Differences between MyD patients and healthy subjects were analyzed statistically. Significantly lower FA and higher MD values were found in the genu, rostral body, anterior midbody, posterior midbody and splenium in MyD patients than in control subjects ( p < 0.05, corrected; lower FA in the splenium was at a trend level). These corpus callosum subregions were the areas connected to cortical areas where significantly lower volumes were found in MyD patients. No significant decrease in volumes was noted in the parietal cortex, where connecting fibers pass through the isthmus in which DTI abnormalities were not detected in MyD patients. Significant negative correlations to volumes of frontal areas were noted, particularly bilateral motor areas, with cytosine thymine guanidine (CTG) triplet expansion. DTI results in corpus callosum may reflect morphological changes in the connecting cortical areas of MyD patients.

Age-related degeneration of corpus callosum measured with diffusion tensor imaging

The corpus callosum is the major commissure connecting the cerebral hemispheres, and there is evidence of its change with aging. The sub-regions of the corpus callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus, splenium) respectively comprise fibers connecting heteromodal- and unimodal-associated cortical regions, and it is known that abnormalities of the corpus callosum are correlated with abnormalities in cognition and behavior. Yet, little is known about changes in the tissue characteristics of its sub-regions. We assessed age-related changes in fractional anisotropy and mean diffusivity in the sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42 healthy right-handed individuals aged 21–73 years. There were no significant interactions of sex × region. Age has significant negative correlation with fractional anisotropy in the genu ( P < 0.001), rostral body ( P < 0.001), and isthmus ( P = 0.005). Fractional anisotropy of the anterior midbody was correlated negatively with age at a trend level ( P = 0.022). Age was significantly positively correlated with mean diffusivity in the genu ( P = 0.001), rostral body ( P = 0.002), anterior midbody ( P = 0.001), and isthmus ( P = 0.001). Age-related changes were detected in the sub-regions where their projection areas are thought to be vulnerable to normal aging. This suggested that fractional anisotropy and mean diffusivity values of the corpus callosum sub-regions could serve as markers of disturbance across the respective projection areas.

Fractional anisotropy-based divisions of midsagittal corpus callosum

The authors first divided the midsagittal corpus callosum of 22 healthy volunteers using three different subdivision methods: Witelson's geometric subdivision, boundary model-based subdivision, and medial model-based subdivision. Next, subdivisions of the corpus callosum were clustered on the basis of homogeneity of the fractional anisotropy values as produced from diffusion tensor images. Nine subregions of corpus callosum, similar in location and size, were successfully clustered when medial model-based or boundary model-based subdivisions were applied. These nine subregions of the corpus callosum were different from the seven subregions defined by Witelson's geometric subdivision, especially at the anterior and posterior tips of the corpus callosum. Our method of corpus callosum division can be potentially utilized to assess structural changes in the midsagittal corpus callosum.

Reduced area of the corpus callosum in posttraumatic stress disorder

Magnetic resonance imaging (MRI) studies have revealed decreases in the mid-sagittal area of the corpus callosum (CC) in pediatric posttraumatic stress disorder (PTSD), but at present no data are available in adult PTSD patients. We have previously reported decreased whole-brain white matter (WM) volume in adults with PTSD and now report corpus callosum area from the same sample. MRI was used to obtain whole-brain images in 12 adult patients with PTSD and 10 matched controls. Total parenchyma (white matter plus gray matter [GM]) volume, mid-sagittal area of the CC and seven sub-regions of this structure were calculated. In PTSD patients, the total CC area, absolute and normalized to total brain parenchyma, was smaller compared with control values. Several absolute and normalized CC sub-regions were also smaller in PTSD patients: genu (region 2), mid-body (region 5) and isthmus (region 6). There was also a trend for the anterior mid-body (area 4) to be smaller in PTSD patients. No differences were found in the rostrum (region 1), rostral body (region 3) or splenium (region 7). Adult patients with PTSD had decreased CC area after correcting for total brain tissue, indicating that these differences are not attributable to generalized white matter atrophy. These findings are similar to previous results in children with PTSD and suggest specific changes in the CC.

Fractal analysis of magnetic resonance images(MRI): A comparative study of schizophrenia and obsessive-compulsive disorder

The corpus callosum (CC), the largest inter-hemispheric tract connecting the association cortices, has been shown to be affected in disorders with aberrant neurodevelopment. Previous studies that investigated CC abnormalities in schizophrenia have reported mixed findings potentially due to various confounding factors. In this study, we used magnetic resonance imaging to examine a large sample of antipsychotic-naïve schizophrenia patients (n = 66) in comparison with age-, sex-, and handedness-matched (as a group) healthy comparison subjects (n = 46). Mid-sagittal areas of CC sub-regions – namely, the genu, body, isthmus and splenium – were measured based on Witelson's method with good inter- and intra-rater reliability. The genu and body of the CC were significantly smaller in schizophrenia patients in comparison to healthy subjects after controlling for the potential confounding effects of age, sex and intracranial area. In male schizophrenia patients, there was a significant positive correlation between the age at onset of psychosis and the area of the genu. Together, these findings suggest neurodevelopmentally mediated hypoconnectivity in schizophrenia.

Sex differences in brain maturation in maltreatment-related pediatric posttraumatic stress disorder

Background. Recent investigations suggested that pediatric posttraumatic stress disorder (PTSD) is associated with adverse brain development. However, sex differences are poorly understood. Methods. In this study, 61 medically healthy children and adolescents (31 males and 30 females) with chronic PTSD secondary to abuse, who had similar trauma and mental health histories, and 122 healthy controls (62 males and 60 females) underwent comprehensive psychiatric assessments and an anatomical MRI brain scan. Results. When gender groups were analyzed separately, findings of larger prefrontal lobe CSF volumes and smaller midsagittal area of the corpus callosum subregion 7 (splenium) were seen in both boys and girls with maltreatment-related PTSD compared to their gender-matched comparison subjects. Subjects with PTSD did not show the normal age related increases in the area of the total corpus callosum and its region 7 (splenium) compared to non-maltreated subjects; however, this finding was more prominent in males with PTSD. Significant sex by group effects demonstrated smaller cerebral volumes and corpus callosum regions 1 (rostrum) and 6 (isthmus) in PTSD males and greater lateral ventricular volume increases in maltreated males with PTSD than maltreated females with PTSD. Conclusions. These data suggest that there are sex differences in the brain maturation of boys and girls with maltreatment-related PTSD. Longitudinal MRI brain investigations of childhood PTSD and the relationship of gender to psychosocial outcomes are warranted.

Handedness and corpus callosum morphology

Investigations of a relationship between callosal size and functional behavioral lateralization lead to the hypothesis that, as the size of the corpus callosum (CC) increases, interhemispheric information transfer is facilitated and behavioral laterality effects become smaller. The aim of our in vivo study was to investigate the relationship between functional asymmetry of handedness and CC size in healthy subjects. Magnetic resonance images of the CC and five CC subregions were obtained with a 1.5-T Magnetom using a three-dimensional T1 sequence in 46 healthy men. Handedness was determined using the ‘handedness dominance test’ (HDT). According to the HDT values, 32 consistent and 14 non-consistent right-handers were identified. No significant difference between handedness subgroups in CC regions and no significant correlations between HDT values and CC areas were detected.

In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET.

Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, (18)FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with (18)FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.

Development of the corpus callosum in childhood, adolescence and early adulthood

The corpus callosum (CC) is the major commissure connecting the cerebral hemispheres and there is evidence of its continuing development into young adulthood [Ann. Neurol. 34 (1993) 71]. Yet, little is known about changes in the size and tissue characteristics of its sub-regions. The sub-regions of the CC (genu, body, isthmus and splenium) are topographically organized to carry inter-hemispheric fibres representing heteromodal and unimodal cortical brain regions. Studies of the development of each of these sub-regions can therefore provide insights into the time course of brain development. We assessed age-related changes in the size and the signal intensities (SI) of the sub-regions of the corpus callosum in the Magnetic Resonance Imaging (MRI) scans of a cross-sectional sample of 109 healthy young individuals aged 7–32 years. Age was significantly positively correlated with the size of the callosal sub-regions (with the exception of the isthmus). On the other hand, there was an age-related decrease in SI across all the CC sub-regions. The rates of CC regional size increases appeared to be most pronounced in childhood. By contrast, SI decreases occurred during childhood and adolescence but reached an asymptote during young adulthood. Finally, the observed size and SI changes were similar across CC sub-regions. The observed increases in CC size in conjunction with the decreases in signal intensity reflect continued maturation of the structure from childhood through young adulthood. An increase in axonal size may underlie growth in the size of the CC during childhood. The continued decrease in the CC signal intensity during adolescence may in addition be related to ongoing maturation of the axonal cytoskeleton. CC maturational changes appeared synchronous across sub-regions suggesting parallel maturation of diverse brain regions during childhood and adolescence.

Less developed corpus callosum in dyslexic subjects—a structural MRI study

Background: Based on previous studies and due to the characteristics of dyslexia as an auditory phonological decoding disorder, we predicted that the shape of the posterior corpus callosum (CC) would differ between dyslexic and control subjects. Method: Twenty right-handed boys with developmental dyslexia were selected from a carefully screened general population sample (mean age 11 years) and compared to a matched control group. The CC contour was manually traced on the aligned midsagittal MR slice and total callosal area and its subregions were compared between the groups. A statistical shape analysis and subsequent CC classification was performed using a recently developed shape model method. Results: The shape analysis revealed shorter CC shape in the dyslexic group, localised in the posterior midbody/isthmus region. This region contains interhemispheric fibers from primary and secondary auditory cortices. A shape length difference larger than a fixed threshold in the posterior midbody region could correctly discriminate between control and dyslexic subject in 78% of the cases, where a dyslexic CC was shorter in this region than a control CC. However, there were no significant group differences with respect to overall CC area or subregions. Conclusion: A clear shape difference in the posterior midbody of the CC was found between dyslexic and control subjects. This fits with recent other studies that have reported a strong growth factor in this CC region during the late childhood years, coinciding with literacy acquisition. Our results show that the dyslexic group has not undergone the same growth pattern as the normal reading group.

Corpus callosum size in schizophrenia--a magnetic resonance imaging analysis.

Previous MRI studies have shown differences in corpus callosum size between schizophrenic patients and controls. The corpus callosum (CC), as the main interhemispheric fiber tract, plays an important role in interhemispheric integration and communication. Though MRI studies suggest smaller CC in schizophrenia, there are still conflicting findings. Using in vivo magnetic resonance imaging, it was investigated whether the midsagittal area of CC differs between twenty-three right-handed male schizophrenic patients and twenty-three matched controls. Total CC area, five subregions of CC, total brain volume, gray and white matter were measured. No differences between schizophrenic patients and controls were found regarding all CC measurements, total brain volume, and gray matter tissue. However, a significant reduction of white matter tissue in the patient group emerged. There was no correlation between CC morphology and clinical variables such as age of onset, length of illness or symptom severity. Interestingly, five schizophrenic patients with a positive family history of schizophrenia showed significant reduction of the subregion C3, associated with a reduced total brain and gray and white matter volume. Significant reduction in the CC and its subregions was not confirmed in this group of patients with schizophrenia. In the subgroup of schizophrenic patients with a positive family history of schizophrenia, a significant reduction of the subregion corresponding to a part of the trunk of the CC was found.

Testosterone is correlated with regional morphology of the human corpus callosum

Theoretical speculation in humans (S.F. Witelson, Psychoneuroendocrinology 16 (1991) 131–153) and empirical findings in animals (R.H. Fitch, P.E. Cowell, L.M. Schrott, V.H. Denenberg, Int. J. Dev. Neurosci. 9 (1991) 35–38) suggest that testosterone (T) may play a significant role in the development of the corpus callosum (CC). However, there are currently no empirical studies directly relating T concentrations to callosal morphology in humans. The purpose of the present study was to investigate the relationship between free T concentrations as determined by radioimmunoassay, and the mid-sagittal area of the corpus callosum, as determined by magnetic resonance imaging (MRI). Subjects were 68 young adult (20–35 years), neurologically normal, right-handed males. All subjects underwent MRI and provided two samples of saliva for radioimmunoassay of T and cortisol. Anatomical regions of interest included total brain volume, left and right hemisphere volume and regional areas of the CC. CC regions were defined using two different measurement techniques, each dividing the CC into six sub-sections. Anatomical measurements were performed blind with respect to the hormone levels of subjects. A significant positive correlation between T concentration and cross-sectional area of the posterior body of the CC was found. This finding was consistent across the two measurement techniques and was not attributable to individual differences in total brain volume. All correlations between cortisol and CC sub-regions were non-significant. The results of this study are consistent with the notion that T, at an earlier stage in development, may play a significant role in modulating cortical/callosal architecture in humans.