The relation between forebrain volume and midsagittal size of the corpus callosum in children.

Applying in vivo magnetic resonance (MR) morphometry in healthy adults we have recently discovered that the relationship between forebrain volume (FBV) and the midsagittal size of the corpus callosum (CC) follows a geometrical rule according to which larger brains have a relatively smaller midsagittal CC. This allometric relation was taken as support for the hypotheses of Ringo and co-workers suggesting that brain size may be an important factor influencing interhemispheric connectivity and lateralization. In this paper we examined whether the aforementioned relation between FBV and CC size also holds for healthy children between 3 and 14 years of age. We confirmed this relationship as previously found for adults. Thus, the geometrical rule and the implications associated with it apply for a wide age range. In addition we found significant correlations with age for posterior and mid-parts of the CC even when FBV was controlled for, suggesting an anterior to posterior maturation gradient of CC development.     

Size of the corpus callosum in normal subjects and patients with Alzheimer's disease--magnetic resonance imaging study

The area of the corpus callosum (CC) on midsagittal spin-echo sequence magnetic resonance (MR) scans was measured in 64 normal subjects and 12 patients with Alzheimer's disease (AD). The normal subjects consisted of 32 males and 32 females, aged 25 to 83 years old. There was no significant age difference between males and females. Fifty-five out of 64 subjects were right-handed (RH) and 9 were left-handed or ambidextrous (NRH). Among patients with AD, 5 were males and 7 were females, aged 53 to 79 years old. Diagnosis of AD was performed mainly based on clinical history, magnetic resonance image (MRI) and positron emission tomographic findings. The outline of the CC on midsagittal MR film was traced and the total callosal sectional area (CCT) as well as the anterior half (CCA), posterior half (CCP) and posterior 5th or splenium (CCS) area measurements were performed using a planimeter. In either normal males or females, the CCA showed a significant negative correlation with age, but the CCP and the CCS did not correlate with age. Total CC (CCT) area was 691.2 +/- 91.0 sq. mm for the whole group and no difference was found between males and females. When the CC area was normalized with respect to the midsagittal area of the supratentorial portion of the brain (MSB), females were found to have a larger CC than males. No portion of the CC area was significantly different between RH and NRH subjects in absolute or normalized measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional cerebral perfusion abnormalities in developmental language disorder

Objective A voxel based investigation of cerebral blood flow was conducted to identify brain functional differences during resting state between children with developmental language disorder (DLD) and normal controls. Method Using DSM–IV criteria, we selected 21 children with DLD.All children were examined by technetium–99m–HMPAO Brain SPECT. Using SPM analyses, we compared the SPECT images of children with DLD and those of 17 control subjects on a voxel by voxel basis using ANCOVA covarying for age. Results Reduced cerebral blood flow in the right putamen,the right inferior parietal cortex, and the left globus pallidus were found in children with DLD versus the controls. However, no area of increased cerebral blood flow was observed in children with DLD compared to the controls. Conclusion Though results should be interpreted cautiously, this study confirms the presence of functional defects in the basal ganglia and the inferior parietal lobe during the resting state of the brains of children with DLD. It also gives further evidence for functional deficits in basal ganglia as an important factor in the etiology of DLD.     

Corpus callosum volume in children with autism

The corpus callosum (CC) is the main commissure connecting the cerebral hemispheres. Previous evidence suggests the involvement of the CC in the pathophysiology of autism. However, most studies examined the mid-sagittal area and investigations applying novel methods are warranted. The goal of this investigation is to apply a volumetric method to examine the size of the CC in autism and to identify any association with clinical features. An MRI-based morphometric study of the total CC volume and its seven subdivisions was conducted and involved 22 children with autism (age range 8.1–12.7 years) and 23 healthy, age-matched controls. Reductions in the total volume of the CC and several of its subdivisions were found in the autism sample. Associations were observed between CC structures and clinical features including social deficits, repetitive behaviors, and sensory abnormalities. Volumetric alterations of the CC observed in this investigation are consistent with midsagittal area tracings of decreased CC size in autism. These findings support the aberrant connectivity hypothesis with possible decrease in interhemispheric communications.     

Quantitative magnetic resonance analysis in vascular dementia

The potential role of magnetic resonance imaging (MRI) in differentiating between specific causes of cognitive decline in patients with vascular dementia (VD) has not yet been fully established. We therefore decided to assess the supratentorial cerebral contents in 24 patients with a diagnosis of probable VD and in 24 normal subjects, matched for age and education level, using MRI volumetric parameters obtained by means of a quantitative method. The volumes of subarachnoid and ventricular spaces, cerebral tissue, and hyperintense areas on T2-weighted images were calculated. In order to reduce interindividual variability caused by differences in intracranial size, each absolute measurement was normalized to the relative size of the intracranial volume. In addition, we calculated the ratio between the areas of the corpus callosum (CC) and supratentorial brain at the same level on the T1-weighted image midsagittal plane. The MRI data were correlated with the deterioration of cognitive functions. Patients with VD showed significantly lower cerebral tissue volume and CC area, and higher ventricular space volume than normal subjects. Furthermore, the total volume of the T2 signal alterations was higher in VD patients than in normal subjects. In VD patients, this volume was found to be proportional to the increase in the volume of the ventricular space. On the other hand, no correlation was found between the volume of the T2 signal alterations and the area of the CC. The degree of global cognitive dysfunction and the score of each neuropsychological test did not show any correlation with the MRI data. Our results suggest that ventricular enlargement in VD patients is correlated with the increase in volume of the T2 signal abnormalities, but that the degree of global cognitive dysfunction is not influenced by the volume of these T2 signal abnormalities. Furthermore, the CC atrophy does not influence the score of any neuropsychological test or the degree of global cognitive dysfunction. Received: 22 Februar 1996 Received in revised form: 14 October 1996 Accepted: 30 December 1996     

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. Received: 16 August 1999 / Accepted: 5 October 1999     

Reduction of corpus callosum growth after severe traumatic brain injury in children

OBJECTIVE: To study effects of closed head injury (CHI) severity on development of corpus callosum (CC) in children, using MRI. BACKGROUND: Vulnerability of CC to diffuse axonal injury has been shown in adults and children by neuropathologic and MRI studies. Given continued development of CC through the second decade, serial MRI could characterize effects of CHI on CC growth in children. METHOD: MRI performed at 3 and 36 months after severe (mean age = 10.3 years, n = 25) and mild to moderate (mean age = 9.7 years, n = 28) CHI. Mild to moderate and severe CHI groups did not differ in demographic features. Morphometry of T1-weighted midsagittal CC by two operators with satisfactory interrater reliability yielded uncorrected and corrected CC volume. RESULTS: An interaction of occasion with CHI severity was present as CC area decreased from 3 to 36 months in severely injured children and increased in the mild to moderate CHI group. Uncorrected CC area was correlated with acute CHI severity and functional outcome at 36 months postinjury. CONCLUSIONS: Morphometric measurement of CC area provides a useful index of diffuse injury, which is related to functional outcome of CHI in children.     

Morphology of the corpus callosum in treatment‐resistant schizophrenia and major depression

Objective: To identify possible differences in the mean midsagittal corpus callosum (CC) total and subdivision areas in treatment‐resistant schizophrenia and depression (TRS and TRD) patients. Method: Areas of the total CC and its five equidistant subregions (from CC1 to CC5) obtained by parallel grid partitioning schemes were manually segmented from brain MRI of 42 TRS, 45 TRD patients and 30 healthy controls. The intracranial volume (ICV) normalized areas were calculated and compared between groups. Results: When compared with controls, patients with TRS had reduced ICV and a larger CC5, and TRD patients had a smaller CC4 while no significant difference in CC total area in patients with TRS or TRD was found. Multiple individual segments and total CC areas were significantly larger in TRS than TRD patients after normalization. Conclusion: Patients with TRS and TRD have different CC morphological characteristics, and therefore there may be aberrant interhemispheric connectivity in schizophrenia and major depressive disorder patients.     

Social communication in young children with traumatic brain injury: Relations with corpus callosum morphometry

The purpose of the present investigation was to characterize the relations of specific social communication behaviors, including joint attention, gestures, and verbalization, with surface area of midsagittal corpus callosum (CC) subregions in children who sustained traumatic brain injury (TBI) before 7 years of age. Participants sustained mild (n = 10) or moderate–severe (n = 26) noninflicted TBI. The mean age at injury was 33.6 months; mean age at MRI was 44.4 months. The CC was divided into seven subregions. Relative to young children with mild TBI, those with moderate–severe TBI had smaller surface area of the isthmus. A semi-structured sequence of social interactions between the child and an examiner was videotaped and coded for specific social initiation and response behaviors. Social responses were similar across severity groups. Even though the complexity of their language was similar, children with moderate–severe TBI used more gestures than those with mild TBI to initiate social overtures; this may indicate a developmental lag or deficit as the use of gestural communication typically diminishes after age 2. After controlling for age at scan and for total brain volume, the correlation of social interaction response and initiation scores with the midsagittal surface area of the CC regions was examined. For the total group, responding to a social overture using joint attention was significantly and positively correlated with surface area of all regions, except the rostrum. Initiating joint attention was specifically and negatively correlated with surface area of the anterior midbody. Use of gestures to initiate a social interaction correlated significantly and positively with surface area of the anterior and posterior midbody. Social response and initiation behaviors were selectively related to regional callosal surface areas in young children with TBI. Specific brainbehavior relations indicate early regional specialization of anterior and posterior CC for social communication.     

Midsagittal Corpus Callosum Area,Intelligence and Language In Epilepsy

Alterations in midsagittal corpus callosum (CC) area and morphology have been suggested in several disease processes of the nervous system. In addition, some studies found a relation of CC area to handedness, language dominance, and gender. The relation of CC area to measures of intelligence and memory and the effect of epilepsy on CC area have received less attention. In this study CC area was measured on midsagittal magnetic resonance images in 48 patients undergoing presurgical evaluation of epilepsy and in 20 control subjects. All patients had the Wada test and formal neuropsychological testing. The mean CC area of the epilepsy group was significantly smaller than that of control subjects (p < 0.00001). CC area showed a positive correlation with presurgical performance IQ (p = 0.008) and full-scale IQ (p = 0.048), but not with memory scores or language dominance. There was no relation of CC area to location of epileptic focus, seizure types, age at onset, epilepsy duration, or etiology. The presence of an atrophic lesion was associated with a smaller CC area. The correlation of total CC area with performance and full-scale IQs may reflect axonal loss in patients with a low IQ, resulting from the etiology of epilepsy or the epilepsy itself.     

Decreased corpus callosum size in sickle cell disease: relationship with cerebral infarcts and cognitive functioning.

We assessed midsagittal corpus callosum size in sickle cell disease (SCD) and its relationship to lesion volume, lesion location, and cognitive functioning. Twenty-eight children with SCD and 16 demographic controls completed magnetic resonance imaging (MRI) and neuropsychological testing. Corpus callosum (CC) size was smaller for children with silent infarcts (n = 8) or overt stroke (n = 8) than for those without visible infarcts (n = 12) or control participants. Lesion volume was a robust predictor of IQ and other cognitive scores; total CC size did not typically add explanatory power for these measures. The size of the rostral body of the CC, however, independently predicted measures of distractibility, speeded production, and working memory. Posterior CC size was also decreased among many of the children with SCD, even in the absence of visible infarcts in this region. Brain morphology appears to provide additional information about SCD-related effects on the brain above and beyond visible infarcts.     

Growth of the mouse corpus callosum

Brains of BALB/cCF inbred mice were examined at 15 ages ranging from 16.5 to 50.5 days from conception and cross-sectional areas of major forebrain fibre tracts at the midsagittal plane were measured. The anterior commissure appeared prior to the corpus callosum (CC), which was first seen at midplane at 17.0 days, and both tracts underwent a very rapid increase in size in the prenatal and early postnatal period, reaching the adult range of size at about 1 week after birth or several days prior to the onset of myelination. The growth spurt of these fibre tracts was much more pronounced than that of whole brain. By comparing BALB/c mice with hybrid mice that always have normal CC, it was found that some BALB/c mice at 18.5 days of age which have very small or absent CC do so because the growth of the whole brain is retarded whereas others have CC that is small for the brain size. Evidence also suggested that many mice with no CC but normal brain size at 18.5 days prenatally do eventually acquire at least a small CC. Observations at 3 postnatal ages of BALB/c mice weighed and marked at birth revealed that the 'runts' with low birth weight, which were presumably retarded prenatally, either die or catch up with mice of normal birth weight and do not have unusually small adult CC.     

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.     

The effects of early experience on callosal development and functional lateralization in pigmental BALB/c mice

A proportion of animals of the BALB/c inbred mouse strain have an unusually small (sometimes absent) midsagittal area of the corpus callosum (CC). In this study, we used a large sample of both males and females (total n = 198) from a pigmented congenic BALB/c line to investigate the relations among preweaning handling, area of CC, and direction and degree of lateralization as measured by Collins' paw preference task. Twenty litters were handled daily from the day after birth until day 25 (weaning) according to Denenberg's procedure and 18 litters were left undisturbed until weaning. All animals were tested for degree and direction of paw preference in a modification of Collins' apparatus at about 60 days and measures taken on CNS structures at 100 days of age. There were no handling or sex effects on degree or direction of paw preference or on the extent of CC defects, but for animals in the normal range (CC > or = 0.7 mm2), those which had been handled had significantly smaller callosa. No significant differences were detected between right and left hemisphere weights, and these measures did not appear to be related to the behavioural measures. There was no significant correlation between CC area and degree of paw preference nor was there any relationship between total agenesis and degree of handedness. This last result is particularly interesting in light of recent evidence that ILn/J mice, all acallosal, are exclusively ambilateral.     

Increased Axon Number in the Anterior Commissure of Mice Lacking a Corpus Callosum

Relatively few behavioral deficits are apparent in subjects with hereditary absence of the corpus callosum (CC). The anterior commissure (AC) has been suggested to provide an extracallosal route for the transfer of interhemispheric information in subjects with this congenital defect. Anterior commissure size, axon number, axon diameter, and neuronal distribution were compared between normal mice and those with complete CC absence. No difference in midsagittal AC area was found between normals and acallosals, nor were differences found in the numbers or diameters of myelinated axons. However, axon counts indicated an 17% increase or about 70,000 more unmyelinated axons in the AC of acallosal mice, and the mean diameter of unmyelinated axons was slightly less than in normal mice (0.24 vs 0.26 μm). This decrease in axon diameter enabled more axons to pass through the AC without increasing its midsagittal area. The topographical distribution of neurons sending axons through the AC, assessed with lipophilic dyes, was qualitatively similar for almost all the known regions of origin of the anterior commissure in normal and acallosal mice. There was a pronounced deficit of AC cells in the anterior piriform cortex of BALB/c mice, but this occurred whether or not the mouse suffered absent CC. Although the increase in AC axon number is far smaller than the number of CC axons that fail to reach the opposite hemisphere, the higher number of axons present in the AC of acallosal mice may contribute to the functional compensation for the loss of the CC.     

Corpus callosum: musician and gender effects

Previously we found that musicians have significantly larger anterior corpus callosum (CC). In the current study, we intended to replicate and extend our previous results using a new and larger sample of gender-matched subjects (56 right-handed professional musicians and 56 age- and handedness-matched controls). We found a significant gender x musicianship interaction for anterior and posterior CC size; male musicians had a larger anterior CC than non-musicians, while females did not show a significant effect of musicianship. The lack of a significant effect in females may be due to a tendency for a more symmetric brain organization and a disproportionately high representation of absolute pitch (AP) musicians among females. Although a direct causal effect between musicianship and alterations in the midsagittal CC size cannot be established, it is likely that the early commencement and continuous practice of bimanual motor training serves as an external trigger that can influence midsagittal CC size through changes in the actual callosal fiber composition and in the degree of myelinization, which will have implications for interhemispheric connectivity.     

Corpus callosum morphology from magnetic resonance images in Tourette's syndrome

We measured the midline cross-sectional area and other morphologic features of the corpus callosum (CC) from magnetic resonance (MR) images in 14 unmedicated patients with Tourette's syndrome (TS) and 14 normal control subjects matched for age, sex, handedness, and socioeconomic status. Each CC was manually circumscribed on midline images from a T1-weighted sagittal series, and the area of the entire CC and five anatomic subdivisions were measured. CC circumference, regional width, and mean callosal curvature were also measured. CC cross-sectional area correlated positively with brain size and basal ganglia volumes. The magnitude of reduction (17.7%) in total CC area in TS patients compared with control subjects was similar to the reductions seen in all CC subdivision areas. Analyses of covariance with total midsagittal cross-sectional head area as a covariate revealed the reductions to be statistically significant for the overall CC area and all subregion areas. CC width tended to be nonsignificantly thinner in all subdivisions (from 5% to 11%), and the overall length of the center line measured from rostrum to splenium was significantly reduced in the TS group (by 5.3%). Measures of mean callosal curvature suggested that CCs in TS patients are less rounded than those of normal control subjects. Worst-ever motor tic symptoms showed the strongest significant correlation with the length of the CC center line in TS patients (r = 0.88). These findings suggest that structural interhemispheric connectivity may be aberrant in the central nervous systems of TS patients, and they provide indirect supportive evidence for the presence of altered cerebral lateralization in the disorder.     

Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia

Corpus callosum size has been found to be abnormal in adult schizophrenia, and other studies have implicated abnormal interhemispheric communication in this disorder. To assess continuity with brain abnormalities in the later onset disorder and to further localize brain maldevelopment, this structure was examined in a unique sample of childhood onset schizophrenics. Anatomic brain magnetic resonance imaging scans were acquired for 25 patients (mean age 13.9 ± 2.1) who had onset of schizophrenia by age 12 (mean age at onset 9.9 ± 1.9) and 55 normal children. The midsagittal area of the corpus callosum was divided into seven sections. With no adjustment for brain volume, no diagnostic differences were observed. After adjustment for the smaller cerebral volume of the schizophrenics, larger total, anterior and posterior corpus callosum areas emerged for the schizophrenics. These findings provide further evidence for continuity between childhood onset and later onset schizophrenia and support other studies showing white matter sparing in the context of decreased cortical volume.     

Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis.

Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function.     

Brainstem involvement in high functioning autistic children

To determine involvements of the brainstem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. A positive correlation between age and area of the cerebellar vermis was observed in autistic children but not in control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children and that growth of the cerebellar vermis in autistic children was different from normal children.