Neuroanatomy of Down's syndrome: a high-resolution MRI study

OBJECTIVE: Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome. METHOD: Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. RESULTS: Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects. CONCLUSIONS: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome.     

Neuropsychological functioning and MRI signal hyperintensities in geriatric depression

OBJECTIVE: The purpose of this study was to examine the relationship between signal hyperintensities--a probable marker of underlying pathology--on T2-weighted magnetic resonance brain scans and neuropsychological test findings in elderly depressed and normal subjects. METHOD: Elderly subjects with a DSM-III-R diagnosis of major depression (N=41) and normal elderly comparison subjects (N=38) participated in a magnetic resonance imaging study (1.0-T) of signal hyperintensities in periventricular, deep white matter, and subcortical gray matter. Hard copies of scans were rated in random order by research psychiatrists blind to diagnosis; the modified Fazekas hyperintensity rating scale was used. Cognitive performance was independently assessed with a comprehensive neuropsychological battery. Clinical and demographic differences between groups were assessed by t tests and chi-square analysis. Relationships between neuropsychological performance and diagnosis and hyperintensities and their interaction were analyzed by using analysis of covariance, with adjustment for age and education. RESULTS: Elderly depressed subjects manifested poorer cognitive performance on several tests than normal comparison subjects. A significant interaction between hyperintensity location/severity and presence/absence of depression on cognitive performance was found: depressed patients with moderate-to-severe deep white matter hyperintensities demonstrated worse performance on general and delayed recall memory indices, executive functioning and language testing than depressed patients without such lesions and normal elderly subjects with or without deep white matter changes. CONCLUSIONS: Findings validate cognitive performance decrements in geriatric depression and suggest possible neuroanatomic vulnerabilities to developing particular neuropsychological dysfunction in depressed subjects.     

Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors

OBJECTIVE: Segmented brain white matter hyperintensities were compared between subjects with late-life depression and age-matched subjects with similar vascular risk factor scores. Correlations between neuropsychological performance and whole brain-segmented white matter hyperintensities and white and gray matter volumes were also examined. METHOD: Eighty-three subjects with late-life depression and 32 comparison subjects underwent physical examination, psychiatric evaluation, neuropsychological testing, vascular risk factor assessment, and brain magnetic resonance imaging (MRI). Automated segmentation methods were used to compare the total brain and regional white matter hyperintensity burden between depressed patients and comparison subjects. RESULTS: Depressed patients and comparison subjects did not differ in demographic variables, including vascular risk factor, or whole brain-segmented volumes. However, depressed subjects had seven regions of greater white matter hyperintensities located in the following white matter tracts: the superior longitudinal fasciculus, fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, and inferior longitudinal fasciculus. These white matter tracts underlie brain regions associated with cognitive and emotional function. In depressed patients but not comparison subjects, volumes of three of these regions correlated with executive function; whole brain white matter hyperintensities correlated with executive function; whole brain white matter correlated with episodic memory, processing speed, and executive function; and whole brain gray matter correlated with processing speed. CONCLUSIONS: These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.     

Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1

BACKGROUND: Larger gray matter (GM) volume in healthy children is correlated with higher IQ. Children with neurofibromatosis type 1 (NF1) have larger brains, their magnetic resonance images frequently show T2-weighted hyperintensities, and their IQs are lower. OBJECTIVES: To confirm the hypotheses that (1) children with NF1 have larger GM and white matter volumes, (2) the greatest volume differences are in the frontal and parietal regions and in children with NF1 with hyperintensities, and (3) GM volume is inversely related to IQ in children with NF1. DESIGN: Wechsler Intelligence Scale for Children-Third Edition IQ testing and measurement of cerebral volumes and hyperintensities in brain magnetic resonance images were performed on 36 children with NF1 and on 36 matched relatives who served as control subjects. RESULTS: Gray matter and white matter volumes were significantly larger in children with NF1. The greatest difference was observed in cerebral white matter volume, predominantly in the frontal lobes, whereas the greatest difference in GM volume was in the temporal, parietal, and occipital regions. In controls, IQ was significantly related to GM volume, but in children with NF1, IQ was not inversely associated with GM volume, although IQs of children with NF1 were significantly lower. CONCLUSIONS: Children with NF1 do not have the normal relationship between GM volume and IQ. Larger GM volume in the posterior brain regions and larger white matter volumes in the frontal brain regions contribute to the larger brain volume in children with NF1.     

Volumetric analysis of regional cerebral development in preterm children

Preterm birth is frequently associated with both neuropathologic and cognitive sequelae. This study examined cortical lobe, subcortical, and lateral ventricle development in association with perinatal variables and cognitive outcome. High-resolution volumetric magnetic resonance imaging scans were acquired and quantified using advanced image processing techniques. Seventy-three preterm and 33 term control children ages 7.3-11.4 years were included in the study. Results indicated disproportionately enlarged parietal and frontal gray matter, occipital horn, and ventricular body, as well as reduced temporal and subcortical gray volumes in preterm children compared with control subjects. Birth weight was negatively correlated with parietal and frontal gray, as well as occipital horn volumes. Intraventricular hemorrhage was associated with reduced subcortical gray matter. Ventricular cerebrospinal fluid was negatively correlated with subcortical gray matter volumes but not with white matter volumes. Maternal education was the strongest predictor of cognitive function in the preterm group. Preterm birth appears to be associated with disorganized cortical development, possibly involving disrupted synaptic pruning and neural migration. Lower birth weight and the presence of intraventricular hemorrhage may increase the risk for neuroanatomic abnormality.     

Thought disorder and frontotemporal volumes in pediatric epilepsy

The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5–16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl’s gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl’s gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.     

Microstructural white matter changes and their relation to neuropsychological deficits in patients with juvenile myoclonic epilepsy

ObjectiveJuvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy syndrome. Neuropsychological, electrophysiological, and neuroimaging studies have led to the hypothesis that JME is related to dysfunction of frontal brain regions and mainly frontal thalamocortical networks.MethodsWe investigated possible microstructural white matter abnormalities of 20 patients with JME as compared with 20 healthy control subjects using diffusion tensor imaging (DTI). We analyzed whole-head DTI scans without an a-priori hypothesis using Tract-Based Spatial Statistics (TBSS). To analyze associated gray matter changes, we applied voxel-based morphometry (VBM) to a 3D T1 magnetization prepared rapid gradient echo (MPRAGE) sequence. Neuropsychological testing and personality trait tests were performed to bridge the gap between structure and function.ResultsIn patients, DTI revealed microstructural white matter changes in anterior parts of the Corpus callosum, anterior parts of the cingulate gyrus, and widespread frontal white matter bilaterally as well as in anterior parts of the right thalamus, which were not accompanied by gray matter changes in VBM. Microstructural changes in the cingulum correlated with personality traits. Neuropsychological test results showed impaired attention and executive functions and reduced short-term memory in the patient group. Also, there was a tendency toward alexithymia and significantly higher scores on depression.SignificanceThe present study results showed neuropsychological deficits including frontal lobe cognitive performance and a tendency toward alexithymia as well as accompanying microstructural neuroimaging changes in patients with JME, which all point to alterations in frontal brain regions and frontal thalamocortical networks in these patients.     

Thought disorder and frontotemporal volumes in pediatric epilepsy

The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5–16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl’s gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl’s gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.     

The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study.

BACKGROUND: Region of interest studies have identified a number of structure-cognition associations in schizophrenia and revealed alterations in structure-cognition relationship in this population. METHODS: We examined the relationship of structural brain alterations, identified using voxel-based morphometry, to cognitive deficits in 45 schizophrenia patients relative to 43 healthy control subjects and tested the hypothesis that structure-cognition relationship is altered in schizophrenia. RESULTS: Patients had smaller total brain, gray matter, and white matter volumes. Regional alterations were left-hemisphere specific, including: gray matter reduction of inferior frontal, lingual, and anterior superior temporal gyri; white matter reduction of posterior and occipital lobes; and gray matter increase of the putamen and the precuneus. Smaller whole brain and gray matter volumes were associated with lower premorbid intelligence quotient (IQ) and poorer performance on IQ-dependent cognitive measures in patients and to a similar extent in control subjects. Larger precuneus was associated with better immediate verbal memory in patients, whereas verbal and nonverbal memory were positively associated with inferior frontal gyrus volume in control subjects. Smaller occipital white matter volume was associated with slower information processing speed in patients but not in control subjects. CONCLUSIONS: Regional volume alterations are associated with specific cognitive deficits in schizophrenia. Some structure-cognition relationships differentiate this population from healthy control subjects.     

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.     

多发性硬化患者智能改变与头颅磁共振成像测量及弥散张量成像研究

目的　研究多发性硬化 (MS)患者认知功能障碍的发生情况及认知改变的病理解剖基础。方法　对 70例MS患者进行韦氏智力量表测查及头颅MRI检查 ,对其中 5 0例患者的头颅MRI成像进行了定量测量 ;7例患者进行了弥散张量成像 (DTI)扫描。结果　智能测试发现MS组全量表智商低于正常 (<90分 )者为 4 0 % (2 8/ 70 ) ,与正常组比较差异有非常显著意义 (P <0 0 1)。智能测试与MRI测量中的两侧尾状核比率相关性最显著 ,其次为胼胝体指数。DTI显示病灶周围看似正常组织、看似正常白质及灰质较对照组相应部位脑组织的表观扩散系数增高 ,各向异性值减低。结论　MS患者中存在认知障碍。病灶的范围及其严重程度 ,包括看似正常白质中的微小病灶的数量和严重程度决定认知障碍的程度。灰质功能障碍也与认知改变有关。     

Quantitative morphology of the corpus callosum in children with neurofibromatosis and attention-deficit hyperactivity disorder

Neurofibromatosis-1 is a common autosomal-dominant genetic disorder associated with numerous physical anomalies and an increased incidence of attention-deficit hyperactivity disorder (ADHD). Studies of children with idiopathic ADHD have suggested a link between corpus callosum size and symptom severity. This study examines the contribution of corpus callosum morphology to symptoms of ADHD in children with neurofibromatosis. Eighteen control subjects and 36 children with neurofibromatosis underwent magnetic resonance imaging of the brain. Twelve subjects with neurofibromatosis had evidence of ADHD and 24 did not. Subjects with neurofibromatosis had significantly larger total corpus callosum area and significantly larger regional measurements in three of seven areas. However, there were no differences between the neurofibromatosis alone and neurofibromatosis plus ADHD groups. Increased severity of attention problems was associated with smaller total callosal areas. These results suggest that some features of ADHD in children with neurofibromatosis could be linked to quantifiable differences in brain morphology, but the nature of the genetic mutation in neurofibromatosis suggests that neurochemical effects also could be important.     

Cognitive profiles of neurofibromatosis type 1 patients with minor brain malformations

Neurofibromatosis type 1 is a genetic condition associated with increased risk of abnormal brain development. The relationship between a specific type of brain malformation and a distinct cognitive sign/deficiency remains unknown. This study investigated the frequency of brain malformations in children with neurofibromatosis type 1, and the impact of those brain malformations on cognitive performance. A retrospective examination was performed of cranial magnetic resonance imaging and clinical records in 604 neurofibromatosis type 1 patients. Eighteen patients with brain malformations and intellectual evaluations were available and compared to a subset of neurofibromatosis type 1 patients (n = 20) without brain malformations. The most common brain malformations included hypothalamic hamartomas and Chiari I malformation. More complex migration disorders were also observed. Comparisons of cognitive profiles between groups revealed differences in patients with hamartomas compared with those manifesting Chiari I malformations or control subjects. As a group, those with hamartomas demonstrated below-average global intellect, whereas patients with Chiari I or no malformations performed in the average range. Disorders in cell organization, expressed as brain malformations (hamartomas or more complex defects), may comprise part of the expression of organizational and developmental defects in patients with neurofibromatosis type 1 and possibly other rat sarcoma gene-mitogen activated protein kinase pathway disorders.     

Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II

Purpose:   Cortical dysplasia (FCD) is a frequent cause of epilepsy in childhood. Two major pathological variants are distinguished, FCD type I and II. The aim of the study was to characterize differences between FCD type I and II with respect to imaging and EEG findings, clinical and neuropsychological presentations, and surgical outcome.
Methods:   Forty children with refractory epilepsy and histopathologically confirmed FCD were retrospectively analyzed. FCD type I was identified in 24 and FCD type II in 16 patients.
Results:   Characteristic MRI abnormalities in FCD type I included subtle white matter signal changes and regional reduction of the white matter volume. Typical MRI findings in FCD type II were increased cortical thickness, transmantle sign, gray-white matter junction blurring, fluid-attenuated inversion recovery (FLAIR) and proton density (PD) gray matter signal changes as well as T1w, and PD white matter signal changes. Continuous EEG slowing was significantly more common in patients with FCD type I. Children with FCD type I presented with lower levels of intelligence and were suffering more often from maladaptive behavior and behavioral disorders. Surgical outcome was significantly worse in the FCD type I group (seizure freedom was achieved in 21% FCD type I patients and in 75% FCD type II subjects, p < 0.001).
Conclusions:   Clinically important differences were found in children with distinct histopathological subtypes of FCD. Due to prominent neuropsychological deficits and worse seizure outcome, treatment strategies in FCD type I are more challenging than previously reported and these children should be recognized and specifically addressed within the incoherent group of patients with malformative brain disorders.     

The structure of the corpus callosum in obsessive compulsive disorder

Abnormal brain connectivity has recently been reported in obsessive compulsive disorder (OCD). However, structural differences in the corpus callosum (CC), the primary structure connecting the two hemispheres, have not been extensively studied. In this case-control study, we recruited 30 patients with OCD and 30 healthy control subjects carefully matched for age, sex and handedness. Combining surface-based mesh-modeling and voxel-based morphometry (VBM), we compared callosal thickness and white matter (WM) density in patients and controls. We investigated associations between callosal structure and cortical gray matter (GM) density, and we related CC measures to neuropsychological performance in OCD. OCD patients showed small anterior and posterior callosal regions compared to healthy control subjects. In the OCD group, anterior callosal thickness was positively correlated with GM density of the right mid-dorso-lateral prefrontal (BA 9/46) area, while posterior callosal thickness was positively correlated with GM density in the left supramarginal gyrus (BA 40). Moreover, posterior callosal WM density was positively correlated with verbal memory, visuo-spatial memory, verbal fluency, and visuo-spatial reasoning performances. Callosal attributes were related to GM density in cortical areas innervated by the CC, and were also related to performance in cognitive domains impaired in the disorder. The CC may therefore be integrally involved in OCD.     

Cognitive correlates of 1H MRS measures in the healthy elderly brain

Ageing is associated with cognitive decline, with some studies indicating that this decline can be mostly accounted for by slowing of information processing speed. Whilst it is likely that this is associated with age-related changes in fronto-subcortical neuronal circuits, such changes are not visible on routine neuroimaging. We examined the integrity of this brain region using proton magnetic resonance spectroscopy (1H MRS) and hypothesised that functional changes measured by 1H MRS would be associated with cognitive performance. Fifty-nine healthy elderly subjects (age 58-85 years) underwent single-voxel 1H MRS in frontal white matter and occipito-parietal gray matter, and a comprehensive neuropsychological battery. The results showed a significant correlation between frontal white matter NAA/H2O and a composite measure of neuropsychological performance representing speed of information processing, attentional function and visual memory, controlling for age and sex. This research highlights the importance of the relationship between regional brain changes and cognitive function in the ageing brain, and suggests that MRS may be a sensitive marker of subclinical change in cognition.     

Cognitive correlates of H MRS measures in the healthy elderly brain

Ageing is associated with cognitive decline, with some studies indicating that this decline can be mostly accounted for by slowing of information processing speed. Whilst it is likely that this is associated with age-related changes in fronto-subcortical neuronal circuits, such changes are not visible on routine neuroimaging. We examined the integrity of this brain region using proton magnetic resonance spectroscopy (1H MRS) and hypothesised that functional changes measured by 1H MRS would be associated with cognitive performance. Fifty-nine healthy elderly subjects (age 58-85 years) underwent single-voxel 1H MRS in frontal white matter and occipito-parietal gray matter, and a comprehensive neuropsychological battery. The results showed a significant correlation between frontal white matter NAA/H2O and a composite measure of neuropsychological performance representing speed of information processing, attentional function and visual memory, controlling for age and sex. This research highlights the importance of the relationship between regional brain changes and cognitive function in the ageing brain, and suggests that MRS may be a sensitive marker of subclinical change in cognition.     

Human immunodeficiency virus‐related decreases in corpus callosal integrity and corresponding increases in functional connectivity

People living with human immunodeficiency virus (PLWH) often have neurocognitive impairment. However, findings on HIV‐related differences in brain network function underlying these impairments are inconsistent. One principle frequently absent from these reports is that brain function is largely emergent from brain structure. PLWH commonly have degraded white matter; we hypothesized that functional communities connected by degraded white matter tracts would show abnormal functional connectivity. We measured white matter integrity in 69 PLWH and 67 controls using fractional anisotropy (FA) in 24 intracerebral white matter tracts. Then, among tracts with degraded FA, we identified gray matter regions connected to these tracts and measured their functional connectivity during rest. Finally, we identified cognitive impairment related to these structural and functional connectivity systems. We found HIV‐related decreased FA in the corpus callosum body (CCb), which coordinates activity between the left and right hemispheres, and corresponding increases in functional connectivity. Finally, we found that individuals with impaired cognitive functioning have lower CCb FA and higher CCb functional connectivity. This result clarifies the functional relevance of the corpus callosum in HIV and provides a framework in which abnormal brain function can be understood in the context of abnormal brain structure, which may both contribute to cognitive impairment.     

Regional cortical white matter reductions in velocardiofacial syndrome: a volumetric MRI analysis.

BACKGROUND: Velocardiofacial syndrome, caused by a microdeletion on chromosome 22q.11, is associated with craniofacial anomalies, cardiac defects, learning disabilities, and psychiatric disorders. To understand how the 22q.11 deletion affects brain development, this study examined gray and white matter volumes in major lobar brain regions of children with velocardiofacial syndrome relative to control subjects. METHODS: Subjects were ten children with velocardiofacial syndrome and ten age- and gender-matched unaffected children. Coronal images were acquired with a 3-D spoiled gradient echo series and partitioned into 124, 1.5-mm contiguous slices. A stereotaxic grid was used to subdivide brain tissue into cerebral lobes, which were segmented into gray, white, and CSF compartments using an algorithm based on intensity values and tissue boundaries. Nonparametric statistics were used to compare lobar volumes of gray and white matter. RESULTS: Analyses indicated that children with velocardiofacial syndrome had significantly smaller volumes in nonfrontal, but not frontal, lobar brain regions. Volume reductions affected nonfrontal white matter to a greater extent than nonfrontal gray matter. CONCLUSIONS: The presence of white matter reductions may be related to disturbances in myelination or axonal integrity in velocardiofacial syndrome. Further work is required to delineate the nature and extent of white matter anomalies, and to link them to variation in the neurocognitive and neuropsychiatric phenotype of velocardiofacial syndrome.     

Reduced relationship to cortical white matter volume revealed by tractography-based segmentation of the corpus callosum in young children with developmental delay

OBJECTIVE: The corpus callosum is the primary anatomical substrate for interhemispheric communication, which is important for a range of adaptive and cognitive behaviors in early development. Previous studies that have measured the corpus callosum in developmental populations have been limited by the use of rather arbitrary methods of subdividing the corpus callosum. The purpose of this study was to measure the corpus callosum in a clinical group of developmentally delayed children using a subdivision that more accurately reflected the anatomical properties of the corpus callosum. METHOD: The authors applied tractography to subdivide the corpus callosum into regions corresponding to the cortical regions to and from which its fibers travel in a clinical group of very young children with developmental delay, a precursor to general mental retardation, in comparison with typically developing children. RESULTS: The data demonstrate that the midsagittal area of the entire corpus callosum is reduced in children presenting with developmental delay, reflected in the smaller area of each of the fiber-based callosal subdivisions. In addition, while the area of each subdivision was strongly and significantly correlated with the corresponding cortical white matter volume in comparison subjects, this correlation was prominently absent in the developmentally delayed group. CONCLUSIONS: A fiber-based subdivision successfully separates lobar regions of the corpus callosum, and the areas of these regions distinguish a developmentally delayed clinical group from the comparison group. This distinction was evident both in the area measurements themselves and in their correlation to the white matter volumes of the corresponding cortical lobes.