Showing papers on "Corpus callosum published in 2008"

The subgenual anterior cingulate cortex in mood disorders.

Abstract: The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.

Preliminary Evidence for Sensitive Periods in the Effect of Childhood Sexual Abuse on Regional Brain Development

Abstract: Volumetric MRI scans from 26 women with repeated episodes of childhood sexual abuse and 17 healthy female comparison subjects (ages 18-22 years) were analyzed for sensitive period effects on hippocampal and amygdala volume, frontal cortex gray matter volume and corpus callosum area. Hippocampal volume was reduced in association with childhood sexual abuse at ages 3-5 years and ages 11-13 years. Corpus callosum was reduced with childhood sexual abuse at ages 9-10 years, and frontal cortex was attenuated in subjects with childhood sexual abuse at ages 14-16 years. Brain regions have unique windows of vulnerability to the effects of traumatic stress.

Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia.

Abstract: Background Behavioral variant frontotemporal dementia (bvFTD) strikes hardest at the frontal lobes, but the sites of earliest injury remain unclear. Objective To determine atrophy patterns in distinct clinical stages of bvFTD, testing the hypothesis that the mildest stage is restricted to frontal paralimbic cortex. Design A bvFTD cohort study. Setting University hospital dementia clinic. Participants Patients with bvFTD with Clinical Dementia Rating (CDR) scale scores of 0.5 (n = 15), 1 (n = 15), or 2 to 3 (n = 15) age and sex matched to each other and to 45 healthy controls. Main Outcome Measures Magnetic resonance voxel-based morphometry estimated gray matter and white matter atrophy at each disease stage compared with controls. Results Patients with a CDR score of 0.5 had gray matter loss in frontal paralimbic cortices, but atrophy also involved a network of anterior cortical and subcortical regions. A CDR score of 1 showed more extensive frontal gray matter atrophy and white matter losses in corpus callosum and brainstem. A CDR score of 2 to 3 showed additional posterior insula, hippocampus, and parietal involvement, with white matter atrophy in presumed frontal projection fibers. Conclusions Very mild bvFTD targets a specific subset of frontal and insular regions. More advanced disease affects white matter and posterior gray matter structures densely interconnected with the sites of earliest injury.

Loss of resting interhemispheric functional connectivity after complete section of the corpus callosum.

Abstract: Slow (<0.1 Hz), spontaneous fluctuations in the functional magnetic resonance imaging blood oxygen level-dependent (BOLD) signal have been shown to exhibit phase coherence within functionally related areas of the brain. Surprisingly, this phenomenon appears to transcend levels of consciousness. The genesis of coherent BOLD fluctuations remains to be fully explained. We present a resting state functional connectivity study of a 6-year-old child with a radiologically normal brain imaged both before and after complete section of the corpus callosum for the treatment of intractable epilepsy. Postoperatively, there was a striking loss of interhemispheric BOLD correlations with preserved intrahemispheric correlations. These unique data provide important insights into the relationship between connectional anatomy and functional organization of the human brain. Such observations have the potential to increase our understanding of large-scale brain systems in health and disease as well as improve the treatment of neurologic disorders.

Specific Relations between Neurodevelopmental Abilities and White Matter Microstructure in Children Born Preterm.

Abstract: Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR imaging were consistently linearly related to specific local changes in white matter microstructure. We studied 33 children, born at a median (range) gestational age of 28(+5) (24(+4)-32(+1)) weeks. The children were recruited as infants from the Neonatal Intensive Care Unit at Queen Charlotte's and Hammersmith Hospital in the early neonatal period and imaged at a median corrected age of 25.5 (24-27) months. The children underwent diffusion tensor imaging to measure fractional anisotropy (FA) as a measure of tissue microstructure, and neurodevelopmental assessment using the Griffiths Mental Development Scales [giving an overall developmental quotient (DQ) and sub-quotients scores for motor, personal-social, hearing-language, eye-hand coordination and performance scales] at 2 years corrected age. Tract-based spatial statistics with linear regression analysis of voxel-wise cross-subject statistics were used to assess the relationship between FA and DQ/sub-quotient scores and results confirmed by reduced major axis regression of regions with significant correlations. We found that DQ was linearly related to FA values in parts of the corpus callosum; performance sub-scores to FA values in the corpus callosum and right cingulum; and eye-hand coordination sub-scores to FA values in the cingulum, fornix, anterior commissure, corpus callosum and right uncinate fasciculus. This study shows that specific neurodevelopmental impairments in infants born preterm are precisely related to microstructural abnormalities in particular regions of cerebral white matter which are consistent between individuals. FA may aid prognostication and provide a biomarker for therapeutic or mechanistic studies of preterm brain injury.

Temporal and Spatial Development of Axonal Maturation and Myelination of White Matter in the Developing Brain

Abstract: BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has been widely used to investigate the development of white matter (WM). However, information about this development in healthy children younger than 2 years of age is lacking, and most previous studies have only measured fractional anisotropy (FA). This study used FA and radial and axonal diffusivities in children younger than 2 years of age, aiming to determine the temporal and spatial development of axonal maturation and myelination of WM in healthy children. MATERIALS AND METHODS: A total of 60 healthy pediatric subjects were imaged by using a 3T MR imaging scanner. They were divided into 3 groups: 20 at 3 weeks, 20 at 1 year of age, and 20 at 2 years of age. All subjects were imaged asleep without sedation. FA and axial and radial diffusivities were obtained. Eight regions of interest were defined, including both central and peripheral WM for measuring diffusion parameters. RESULTS: A significant elevation in FA (P CONCLUSIONS: With both FA and directional diffusivities, our results demonstrate the temporal and spatial development of WM in healthy children younger than 2 years of age.

Schizophrenia-Related Neural and Behavioral Phenotypes in Transgenic Mice Expressing Truncated Disc1

Abstract: Disrupted-in-Schizophrenia-1 (DISC1), identified by positional cloning of a balanced translocation (1;11) with the breakpoint in intron 8 of a large Scottish pedigree, is associated with a range of neuropsychiatric disorders including schizophrenia. To model this mutation in mice, we have generated Disc1tr transgenic mice expressing 2 copies of truncated Disc1 encoding the first 8 exons using a bacterial artificial chromosome (BAC). With this partial simulation of the human situation, we have discovered a range of phenotypes including a series of novel features not previously reported. Disc1tr transgenic mice display enlarged lateral ventricles, reduced cerebral cortex, partial agenesis of the corpus callosum, and thinning of layers II/III with reduced neural proliferation at midneurogenesis. Parvalbumin GABAergic neurons are reduced in the hippocampus and medial prefrontal cortex, and displaced in the dorsolateral frontal cortex. In culture, transgenic neurons grow fewer and shorter neurites. Behaviorally, transgenic mice exhibit increased immobility and reduced vocalization in depression-related tests, and impairment in conditioning of latent inhibition. These abnormalities in Disc1tr transgenic mice are consistent with findings in severe schizophrenia.

Prematurely Born Children Demonstrate White Matter Microstructural Differences at 12 Years of Age, Relative to Term Control Subjects: An Investigation of Group and Gender Effects

Abstract: OBJECTIVE. The goal was to use diffusion tensor imaging to test the hypothesis that prematurely born children demonstrate long-term, white matter, microstructural differences, relative to term control subjects. METHODS. Twenty-nine preterm subjects (birth weight: 600–1250 g) without neonatal brain injury and 22 matched, term, control subjects were evaluated at 12 years of age with MRI studies, including diffusion tensor imaging and volumetric imaging; voxel-based morphometric strategies were used to corroborate regional diffusion tensor imaging results. Subjects also underwent neurodevelopmental assessments. RESULTS. Neurodevelopmental assessments showed significant differences in full-scale, verbal, and performance IQ and Developmental Test of Visual Motor Integration scores between the preterm and term control subjects. Diffusion tensor imaging studies demonstrated widespread decreases in fractional anisotropy (a measure of fiber tract organization) in the preterm children, compared with the control subjects. Regions included both intrahemispheric association fibers subserving language skills, namely, the right inferior frontooccipital fasciculus and anterior portions of the uncinate fasciculi bilaterally, and the deep white matter regions to which they project, as well as the splenium of the corpus callosum. These changes in fractional anisotropy occurred in subjects with significant differences in frontal, temporal, parietal, and deep white matter volumes. Fractional anisotropy values in the left anterior uncinate correlated with verbal IQ, full-scale IQ, and Peabody Picture Vocabulary Test-Revised scores for preterm male subjects. In addition, preterm male subjects were found to have the lowest values for fractional anisotropy in the right anterior uncinate fasciculus, and fractional anisotropy values in that region correlated with both verbal IQ and Peabody Picture Vocabulary Test-Revised scores for the preterm groups; these findings were supported by changes identified with voxel-based morphometric analyses. CONCLUSIONS. Compared with term control subjects, prematurely born children with no neonatal ultrasound evidence of white matter injury manifest changes in neural connectivity at 12 years of age.

White matter abnormalities in mild traumatic brain injury: a diffusion tensor imaging study.

Abstract: BACKGROUND AND PURPOSE: Traumatic axonal injury is a primary brain abnormality in head trauma and is characterized by reduction of fractional anisotropy (FA) on diffusion tensor imaging (DTI). Our hypothesis was that patients with mild traumatic brain injury (TBI) have widespread brain white matter regions of reduced FA involving a variety of fiber bundles and show fiber disruption on fiber tracking in a minority of these regions. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Twenty-one patients with mild TBI were investigated (men:women, 12:9; mean age ± SD, 32 ± 9 years). In a voxel-based comparison with 11 control subjects (men:women, 8:3; mean age, 37 ± 9 years) using z score analysis, patient regions with abnormally reduced FA were defined in brain white matter. MR imaging, DTI, and fiber tracking characteristics of these regions were described and analyzed using Pearson correlation, linear regression analysis, or the χ2 test when appropriate. RESULTS: Patients had on average 9.1 regions with reduced FA, with a mean region volume of 525 mm3, predominantly found in cerebral lobar white matter, cingulum, and corpus callosum. These regions mainly involved supratentorial projection fiber bundles, callosal fibers, and fronto-temporo-occipital association fiber bundles. Internal capsules and infratentorial white matter were relatively infrequently affected. Of all of the involved fiber bundles, 19.3% showed discontinuity on fiber tracking. CONCLUSION: Patients with mild TBI have multiple regions with reduced FA in various white matter locations and involving various fiber bundles. A minority of these fiber bundles show discontinuity on fiber tracking.

Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability: a voxel-wise analysis of diffusion tensor imaging.

Abstract: The purpose of the present study is to identify otherwise occult white matter abnormalities in patients suffering persistent cognitive impairment due to mild traumatic brain injury (TBI). The study had Institutional Review Board (IRB) approval, included informed consent and complied with the U.S. Health Insurance Portability and Accountability Act (HIPAA) of 1996. We retrospectively analyzed diffusion tensor MRI (DTI) of 17 patients (nine women, eight men; age range 26-70 years) who had cognitive impairment due to mild TBI that occurred 8 months to 3 years prior to imaging. Comparison was made to 10 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) images derived from DTI (1.5 T; 25 directions; b = 1000) were compared using whole brain histogram and voxel-wise analyses. Histograms of white matter FA show an overall shift toward lower FA in patients. Areas of significantly decreased FA (p < 0.005) were found in the subject group in corpus callosum, subcortical white matter, and internal capsules bilaterally. Co-located elevation of mean diffusivity (MD) was found in the patients within each region. Similar, though less extensive, findings were demonstrated in each individual patient. Multiple foci of low white matter FA and high MD are present in cognitively impaired mild TBI patients, with a distribution that conforms to that of diffuse axonal injury. Evaluation of single subjects also reveals foci of low FA, suggesting that DTI may ultimately be useful for clinical evaluation of individual patients.

Corpus callosal connection mapping using cortical gray matter parcellation and DT-MRI

Abstract: Population maps of the corpus callosum (CC) and cortical lobe connections were generated by combining cortical gray matter parcellation with the diffusion tensor fiber tractography of individual subjects. This method is based on the fact that the cortical lobes of both hemispheres are interconnected by the corpus callosal fibers. T1-weighted structural MRIs and diffusion tensor MRIs (DT-MRI) of 22 right-handed, healthy subjects were used. Forty-seven cortical parcellations in the dorsal prefrontal cortex, ventral prefrontal cortex, sensory-motor cortex, parietal cortex, temporal cortex, and occipital cortex were semi-automatically derived from structural MRIs, registered to DT-MRI, and used to identify callosal fibers. The probabilistic connections to each cortex were mapped on entire mid-sagittal CC voxels that had anatomical homology between subjects as determined by spatial registration. According to the population maps of the callosal connections, the ventral prefrontal cortex and parts of the dorsal prefrontal cortex both project fibers through the genu and rostrum. The CC regions through which the superior frontal cortex passes extend into the posterior body. Fibers arising from the parietal lobe and occipital lobe run mainly through the splenium, while fibers arising from the sensory-motor cortex pass through the isthmus. In general, dorsal or medial cortical lobes project fibers through the dorsal region of the CC, while lateral cortical lobes project fibers through the ventral region of the CC. The probabilistic subdivision of the CC by connecting cortical gray matter provides a more precise understanding of the CC. Hum Brain Mapp 2008. © 2006 Wiley-Liss, Inc.

Developmental Differences in White Matter Architecture Between Boys and Girls

Abstract: Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5-18 in a cross-sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito-parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex-age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence.

Short-term DTI predictors of cognitive dysfunction in mild traumatic brain injury

Abstract: Primary objective: To explore whether baseline diffusion tensor imaging (DTI) metrics are predictive of cognitive functioning 6 months post-injury in patients with mild traumatic brain injury (MTBI).Research design: Seventeen patients with MTBI and 29 sex- and age-matched healthy controls were studied.Methods and procedures: Participants underwent an MRI protocol including DTI, at an average of 4.0 (range: 1–10) days post-injury. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the following white matter (WM) regions: centra semiovale, the genu and the splenium of the corpus callosum and the posterior limb of the internal capsule. Participants underwent neuropsychological (NP) testing at baseline and at 6-month follow-up. Least squares regression analysis was used to evaluate the association of MD and FA with each NP test score at baseline and follow-up.Main outcomes and results: Compared to controls, average MD was significantly higher (p= 0.02) and average FA significantly lower (p=...

Diffusion Tensor Imaging Characteristics of the Corpus Callosum in Mild, Moderate, and Severe Traumatic Brain Injury

Abstract: BACKGROUND AND PURPOSE: The corpus callosum is an important predilection site for traumatic axonal injury but may be unevenly affected in head trauma. We hypothesized that there were local differences in axonal injury within the corpus callosum as investigated with diffusion tensor imaging (DTI), varying among patients with differing severity of traumatic brain injury (TBI). MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Ten control subjects (7 men, 3 women; mean age, 37 ± 9 years) and 39 patients with TBI (27 men, 12 women; 34 ± 12 years) were investigated, of whom 24 had mild; 9, moderate; and 6, severe TBI. Regions of interest were selected in the callosal genu, body, and splenium to calculate fractional anisotropy (FA), apparent diffusion coefficient (ADC), and the number of fibers passing through. Statistical comparison was made through analysis of variance with the Scheffe post hoc analysis. RESULTS: Compared with controls, patients with mild TBI investigated CONCLUSION: Mild TBI is associated with DTI abnormalities in the genu

Alterations of the visual pathways in congenital blindness.

Abstract: We used whole brain MRI voxel-based morphometry (VBM) to study the anatomical organization of the visual system in congenitally blind (CB) adults. Eleven CB without a history of visual perception were compared with 21 age- and sex-matched normal-sighted controls (NS). CB showed significant atrophy of the geniculo-striate system, encompassing the optic nerves, the optic chiasm, the optic radiations and the primary visual cortex (BA17). The volume decrease in BA17 reached 25% in both hemispheres. The pulvinar and its projections to the associative visual areas were also dramatically altered, BA18/19 and the middle temporal cortex (MT) showing volume reductions of up to 20%. Additional significant white matter alterations were observed in the inferior longitudinal tract and in the posterior part of the corpus callosum, which links the visual areas of both hemispheres. Our data indicate that the afferent projections to the visual cortex in CB are largely atrophied. Despite the massive volume reductions in the occipital lobes, there is compelling evidence from the literature (reviewed in Noppeney 2007; Ptito and Kupers 2005) that blind subjects activate their visual cortex when performing tasks that involve somatosensory or auditory inputs, suggesting a reorganization of the neural pathways that transmit sensory information to the visual cortex.

Brain diffusion abnormalities in children with fetal alcohol spectrum disorder.

Abstract: Background: Children with fetal alcohol spectrum disorder (FASD) have a variety of cognitive, behavioral, and neurological impairments, including structural brain damage. Despite the importance of white matter connections for proper brain function, little is known about how these connections, and the deep gray matter structures that act as relay stations, are affected in children with FASD. The purpose of this study was to use diffusion tensor imaging, an advanced magnetic resonance imaging technique, to examine microstructural differences of white and deep gray matter in children with FASD. Methods: Subjects were 24 children aged 5–13 years previously diagnosed with FASD and 95 healthy children over the same age range. Diffusion tractography was used to delineate 10 major white matter tracts in each individual, and region-of-interest analysis was used to assess 4 deep gray matter structures. Fractional anisotropy, an indicator of white matter integrity, and mean diffusivity, a measure of the average water diffusion, were assessed in all 14 brain structures. Results: Diffusion tensor imaging revealed significant differences of diffusion parameters in several areas of the brain, including the genu and splenium of the corpus callosum, cingulum, corticospinal tracts, inferior fronto-occipital fasciculus, inferior and superior longitudinal fasciculi, globus pallidus, putamen, and thalamus. Reduced white and gray matter volumes, as well as total brain volume, were observed in the FASD group. Conclusions: These results demonstrate diffusion abnormalities in FASD beyond the corpus callosum and suggest that several specific white matter regions, particularly commissural and temporal connections, and deep gray matter areas of the brain are sensitive to prenatal alcohol exposure.

A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia.

Abstract: Background. Diffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia. Method. Subjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n = 25) and healthy controls (n = 26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership. Results. In patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls. Conclusions. Widespread structural dysconnectivity, including the subcortical region, is already present in neuro-leptic-naive patients in their first episode of illness.

Corpus callosum in maltreated children with posttraumatic stress disorder: A diffusion tensor imaging study

Abstract: Contrary to expectations derived from preclinical studies of the effects of stress, and imaging studies of adults with posttraumatic stress disorder (PTSD), there is no evidence of hippocampus atrophy in children with PTSD. Multiple pediatric studies have reported reductions in the corpus callosum--the primary white matter tract in the brain. Consequently, in the present study, diffusion tensor imaging was used to assess white matter integrity in the corpus callosum in 17 maltreated children with PTSD and 15 demographically matched normal controls. Children with PTSD had reduced fractional anisotropy in the medial and posterior corpus, a region which contains interhemispheric projections from brain structures involved in circuits that mediate the processing of emotional stimuli and various memory functions--core disturbances associated with a history of trauma. Further exploration of the effects of stress on the corpus callosum and white matter development appears a promising strategy to better understand the pathophysiology of PTSD in children.

Clinical impact of the callosal angle in the diagnosis of idiopathic normal pressure hydrocephalus

Abstract: The utility of measuring the corpus callosal angle (CA) for the diagnosis of idiopathic normal pressure hydrocephalus (INPH) was investigated. Three-dimensional magnetic resonance imaging (MRI) was performed in 34 INPH patients, 34 Alzheimer’s disease (AD) patients, and 34 normal control (NC) subjects. Measurement of the CA on the coronal MR images of the posterior commissure perpendicular to the anteroposterior commissure plane was performed for all subjects. The CA of the INPH group (mean ± SD, 66 ± 14°) was significantly smaller than those of the AD (104 ± 15°) and NC (112 ± 11°) groups. When using the threshold of the mean − 2SD value of the NC group (= 90°), an accuracy of 93%, sensitivity of 97%, and specificity of 88% were observed for discrimination of INPH from AD patients. Measuring the CA helps in differentiating INPH patients from AD and normally aged subjects.

Agenesis of the corpus callosum in California 1983-2003: a population-based study.

Abstract: The objective of this study was to characterize the prevalence, demographic risk factors, and malformations associated with agenesis and hypoplasia of the corpus callosum diagnosed in infancy. Using a large population-based registry of birth defects, we ascertained 630 cases of agenesis (ACC) and hypoplasia (HCC) of the corpus callosum diagnosed in the first year of life among 3.4 million live births from 1983 to 2003. Infants with destructive lesions or specific complex central nervous system (CNS) malformations (neural tube defects, lissencephaly, and holoprosencephaly) were excluded. Multivariable Poisson regression analysis was used to examine demographic risk factors. The combined prevalence of ACC and HCC was 1.8 per 10,000 live births. Fifty-two percent of cases were male. Infants with ACC had an almost fourfold higher prevalence among infants born prematurely when compared with children born > or =37 weeks gestation (RR 3.7, 95% CI 2.5-5.3). After adjusting for paternal age, advanced maternal age >/=40 years was associated with ACC in infants with a chromosomal disorder (ACC RR 5.9; 95% CI 1.8-19.3, HCC RR 3.5; 95% CI 0.9-14.1). Paternal age was not significantly associated with ACC after adjusting for maternal age. Callosal anomalies were often seen in the context of a chromosomal abnormality (17.3%) and with accompanying somatic (musculoskeletal 33.5% and cardiac 27.6%) and CNS malformations (49.5%). Callosal anomalies form a clinically significant and relatively frequent group of malformations of the CNS that are associated with increased risk of premature birth, are more common with advanced maternal age and are frequently part of a complex, multisystem disorder.

Mapping white matter integrity and neurobehavioral correlates in children with fetal alcohol spectrum disorders.

Abstract: Brain structural abnormalities and neurocognitive dysfunction have been observed in individuals with fetal alcohol spectrum disorders (FASDs). Little is known about how white matter integrity is related to these functional and morphological deficits. We used a combination of diffusion tensor and T1-weighted magnetic resonance imaging to evaluate white matter integrity in individuals with FASDs and related these findings to neurocognitive deficits. Seventeen children and adolescents with FASDs were compared with 19 typically developing age-and gender-matched controls. Lower fractional anisotropy (FA) was observed in individuals with FASDs relative to controls in the right lateral temporal lobe and bilaterally in the lateral aspects of the splenium of the corpus callosum. White matter density was also lower in some, but not all regions in which FA was lower. FA abnormalities were confirmed to be in areas of white matter in post hoc region of interest analyses, further supporting that less myelin or disorganized fiber tracts are associated with heavy prenatal alcohol exposure. Significant correlations between performance on a test of visuomotor integration and FA in bilateral splenium, but not temporal regions were observed within the FASD group. Correlations between the visuomotor task and FA within the splenium were not significant within the control group, and were not significant for measures of reading ability. This suggests that this region of white matter is particularly susceptible to damage from prenatal alcohol exposure and that disruption of splenial fibers in this group is associated with poorer visuomotor integration.

Diffusion Tensor Tractography of Traumatic Diffuse Axonal Injury

Abstract: Background Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem. Objective To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome. Design Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. Setting Inpatient traumatic brain injury unit. Patients From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age- and sex-matched controls. Main Outcome Measures Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale–Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients. Results At least 1 fiber variable of each region showed diffuse axonal injury–associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale–Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. Conclusion Diffusion tensor tractography–based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome.