Development Of Corpus Callosum Research Articles

Fetal thick corpus callosum: new insights from neuroimaging and neuropathology in two cases and literature review.

To describe the correlation between fetal imaging (in vivo and ex vivo) and neuropathology in two fetuses at early gestational age (GA) with isolated thick corpus callosum (CC), a rare finding whose pathological significance and neuropathology data are scarce. Two fetuses at 21-week GA underwent fetal MRI (fMRI) for suspected callosal anomalies at ultrasound (US). After fMRI results, termination of pregnancy (TOP) was carried out and post-mortem MRI (pmMRI) was performed. Neuropathology correlation consisted in macro and microscopic evaluation with sections prepared for hematoxylin-eosin and immunohistochemistry staining. Fetal imaging confirmed in both cases the presence of a shorter and thicker CC with respect to the reference standard at the same GA, without a clear distinction between its different parts. Moreover, on pmMRI, an abnormal slightly T2-weighted hyperintense layer along the superior and inferior surface of CC was noted in both cases. At histopathology, these findings corresponded to an increased amount of white matter tracts but also to an abnormal representation of embryological structures that contribute to CC development, naming induseum griseum (IG) and the glioepithelial layer (GL) of the "callosal sling." After reviewing the literature data, we confirmed the recent embryological theory regarding the CC development and provide new insights into the pathophysiology of the abnormal cases. An abnormally thick CC at the early fetal period could be associated to an abnormal representation of the midline glia structures, so to result in potential disturbance of the axon guidance mechanism of callosal formation and eventually in CC dysgenesis.

Roles of A-kinase Anchor Protein 12 in Astrocyte and Oligodendrocyte Precursor Cell in Postnatal Corpus Callosum.

The formation of the corpus callosum in the postnatal period is crucial for normal neurological function, and clinical genetic studies have identified an association of 6q24-25 microdeletion in this process. However, the mechanisms underlying corpus callosum formation and its critical gene(s) are not fully understood or identified. In this study, we examined the roles of AKAP12 in postnatal corpus callosum formation by focusing on the development of glial cells, because AKAP12 is coded on 6q25.1 and has recently been shown to play roles in the regulations of glial function. In mice, the levels of AKAP12 expression was confirmed to be larger in the corpus callosum compared to the cortex, and AKAP12 levels decreased with age both in the corpus callosum and cortex regions. In addition, astrocytes expressed AKAP12 in the corpus callosum after birth, but oligodendrocyte precursor cells (OPCs), another major type of glial cell in the developing corpus callosum, did not. Furthermore, compared to wild types, Akap12 knockout mice showed smaller numbers of both astrocytes and OPCs, along with slower development of corpus callosum after birth. These findings suggest that AKAP12 signaling may be required for postnatal glial formation in the corpus callosum through cell- and non-cell autonomous mechanisms.

Demonstration of Normal Development of Corpus Callosum in Infancy by Magnetic Resonance Imaging

Introduction: Corpus Callosum (CC) is the major anatomical and functional commissure which transmits information across two cerebral hemispheres. It is assessed by looking at its morphology on midsagittal sequence of Magnetic Resonance Imaging (MRI). Physiological variations and diseases alter the structure of CC. It undergoes structural changes throughout the infancy which should be taken into account for better evaluation. Hence, the normal reference biometric data of CC on MRI in infants is needed. There are very limited data of normal reference range of thickness of CC especially in infants. Aim: To establish the normal standards for the CC in first year of life using MRI. Materials and Methods: It was a retrospective observational study conducted in the year 2019-2020 in which the MRI images of 100 patients aged 4 days to 12 months with seizures and trauma were reviewed to evaluate CC. Children with abnormalities on MRI were excluded from the study. The thickness of subregions of the CC (genu, body, splenium) and the length were measured. Age related changes in the size of the subregions of the CC was assessed. Data was entered in Microsoft Excel sheet and statistical analysis was done using SPSS software. Results: In the age group of less than two months, the width of genu, body, isthmus and splenium was 5 mm, 2 mm, 1.52 and 3.45 mm, respectively. The length of CC was 47.24 mm. As the age of children increased, there was increase in width of genu, body, splenium, isthmus and length of CC. At the age group of 11-12 months the width of genu, body, isthmus and splenium was 9.10 mm, 4.90 mm, 2.29 mm and 8.64 mm respectively. The length of CC was 60.57 mm. The study reveals that there is a progressive change in dimension of CC with advancement of age. Conclusion: There is a considerable change in the appearance of CC during infancy, knowledge of which is useful in differentiating between normal and abnormal brain.

Demonstration of Normal Development of Corpus Callosum in Infancy by Magnetic Resonance Imaging

Demonstration of Normal Development of Corpus Callosum in Infancy by Magnetic Resonance Imaging

Prenatal and postnatal depressive symptoms, infant white matter, and toddler behavioral problems

BackgroundMaternal depression is prevalent during and following pregnancy and is related to adverse outcomes in offspring. Perinatal depression is associated with risk for difficulties in offspring; however, the mechanisms underlying this association are not clear. We examined whether maternal prenatal and postnatal depressive symptoms were associated with infant white matter organization and with behavioral problems in toddlerhood. Methods37 mother–infant dyads (20 male; ages 5.95–7.66 months) participated in this study. We conducted diffusion MRI with infants during natural sleep. Mothers reported on their prenatal and postnatal depressive symptoms at six months postpartum. We calculated fractional anisotropy (FA), radial, axial, and mean diffusivity, and assessed offspring behavioral problems at age 18 months. ResultsPrenatal depressive symptoms were associated with FA of the corpus callosum; postnatal depressive symptoms were not associated with FA of limbic tracts or corpus callosum segmentations. Higher levels of prenatal depressive symptoms were associated with higher FA and lower radial diffusivity of the corpus callosum genu; FA of this region was positively associated with behavioral problems at age 18 months. LimitationsThis study had a small sample size; therefore, findings should be replicated. Further, we used retrospective reports of maternal prenatal depression, but validated them in this study. ConclusionsDepressive symptoms during pregnancy may affect infant corpus callosum development and, in turn, offspring behaviors. These findings suggest that early maternal stress accelerates infant neurodevelopment in a manner that may increase risk for behavioral problems. Thus, efforts to reduce maternal prenatal depression should be a public health priority.

VP27.13: Exposure to toxic and essential metals during pregnancy and corpus callosum development

VP27.13: Exposure to toxic and essential metals during pregnancy and corpus callosum development

Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms.

Brain hemispheres are connected by commissural structures, which consist of white matter fiber tracts that spread excitatory stimuli to various regions of the cortex. This allows an interaction between the two cerebral halves. The largest commissure is the corpus callosum (CC) which is located inferior to the longitudinal fissure, serving as its lower border. Sometimes this structure is not completely developed, which results in the condition known as agenesis of the corpus callosum (ACC). The aim of this paper was to review the latest discoveries related to the genetic and metabolic background of ACC, including the genotype/phenotype correlations as well as the clinical and imaging symptomatology. Due to various factors, including genetic defects and metabolic diseases, the development of CC may be impaired in many ways, which results in complete or partial ACC. This creates several clinical implications, depending on the specificity of the malformation and other defects in patients. Epilepsy, motor impairment and intellectual disability are the most prevalent. However, an asymptomatic course of the disease is even more common. ACC presents with characteristic images on ultrasound and magnetic resonance imaging (MRI).

The early pattern of human corpus callosum development: A transvaginal 3D neurosonographic study.

To provide an in-vivo description of early corpus callosum (CC) development. We reviewed 3D US volumes acquired transvaginally (TVUS) through the anterior fontanelle, between 14 to 17 weeks. The following landmarks were recognized: tela-choroidea (TC), foramina of Moro, early CC and the evolving cavum septi pellucidi. The following measurements were taken: total, anterior and posterior sections, and height of the CC (referenced to the anterior TC border). All measurements were correlated to both the gestational age and the transverse cerebellar diameter (TCD). Eighty nine volumes were included in the study (mean 15.1 weeks ± 0.84, TCD range, 13.1-18.4 mm) with high inter and intra observer correlation of the measurements. We found high correlation between CC length and height, and TCD. The anterior segment of the CC appear earlier than the posterior one, and growth continues bi-directionally. Initially, the posterior elongation is significantly larger than the anterior one. Association of all CC measurements with TCD remained significant when co-varying for maternal age and fetal sex. imaging the fetal CC is feasible from 14 weeks by TVUS, by following the suggested insonation approach. The early CC develops bi-directionally, and the posterior elongation is more significant than the anterior one.

The Association between Positive Maternal Parenting and Corpus Callosum Development in Young Children

In this prospective study, we aimed to determine the impact of maternal parenting and attachment on brain development in early childhood. This study...

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study

The corpus callosum (CC) is the largest connective pathway in the human brain, linking cerebral hemispheres. There is longstanding debate in the scientific literature whether sex differences are evident in this structure, with many studies indicating the structure is larger in females. However, there are few data pertaining to this issue in infancy, during which time the most rapid developmental changes to the CC occur. In this study, we examined longitudinal brain imaging data collected from 104 infants at ages 6, 12, and 24 months. We identified sex differences in brain-size adjusted CC area and thickness characterized by a steeper rate of growth in males versus females from ages 6–24 months. In contrast to studies of older children and adults, CC size was larger for male compared to female infants. Based on diffusion tensor imaging data, we found that CC thickness is significantly associated with underlying microstructural organization. However, we observed no sex differences in the association between microstructure and thickness, suggesting that the role of factors such as axon density and/or myelination in determining CC size is generally equivalent between sexes. Finally, we found that CC length was negatively associated with nonverbal ability among females.

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study

OC14.06: Differential effect in corpus callosum development in fetuses with congenital heart defect

OC14.06: Differential effect in corpus callosum development in fetuses with congenital heart defect

EP08.20: Early corpus callosum development and midline fluid collection during early second trimester

EP08.20: Early corpus callosum development and midline fluid collection during early second trimester

PlexinA1 is crucial for the midline crossing of callosal axons during corpus callosum development in BALB/cAJ mice.

The corpus callosum (CC) is the biggest commissure that links cerebral hemispheres. Guidepost structures develop in the cortical midline during CC development and express axon guidance molecules that instruct neurons regarding the proper direction of axonal elongation toward and across the cortical midline. Neuropilin-1 (Npn1), a high affinity receptor for class 3 semaphorins (Sema3s) localized on cingulate pioneering axons, plays a crucial role in axon guidance to the midline through interactions with Sema3s. However, it remains unclear which type of Plexin is a component of Sema3 holoreceptors with Npn1 during the guidance of cingulate pioneering axons. To address the role of PlexinA1 in CC development, we examined with immunohistochemistry the localization of PlexinA1, Npn1, and Sema3s using embryonic brains from wild-type (WT) and PlexinA1-deficient (PlexinA1 knock-out (KO)) mice with a BALB/cAJ background. The immunohistochemistry confirmed the expression of PlexinA1 in callosal axons derived from the cingulate and neocortex of the WT mice on embryonic day 17.5 (E17.5) but not in the PlexinA1 KO mice. To examine the role of PlexinA1 in the navigation of callosal axons, the extension of callosal axons toward and across the midline was traced in brains of WT and PlexinA1 KO mice at E17.5. As a result, callosal axons in the PlexinA1 KO brains had a significantly lower incidence of midline crossing at E17.5 compared with the WT brains. To further examine the role of PlexinA1 in CC development, the CC phenotype was examined in PlexinA1 KO mice at postnatal day 0.5 (P0.5). Most of the PlexinA1 KO mice at P0.5 showed agenesis of the CC. These results indicate the crucial involvement of PlexinA1 in the midline crossing of callosal axons during CC development in BALB/cAJ mice.

Callosal septa express guidance cues and are paramedian guideposts for human corpus callosum development.

The early development and growth of the corpus callosum are supported by several midline transient structures in mammals that include callosal septa (CS), which are present only in the second half of gestation in humans. Here we provide new data that support the guidance role of CS in corpus callosum development, derived from the analysis of 46 postmortem fetal brains, ranging in age from 16 to 40 post conception weeks (PCW). Using immunohistochemical methods, we show the expression pattern of guidance cues ephrinA4 and neogenin, extracellular protein fibronectin, as well as non-activated microglia in the CS. We found that the dynamic changes in expression of guidance cues, cellular and extracellular matrix constituents in the CS correlate well with the growth course of the corpus callosum at midsagittal level. The CS reach and maintain their developmental maximum between 20 and 26 PCW and can be visualized as hypointense structures in the ventral callosal portion with exvivo (invitro) T2-weighted 3T magnetic resonance imaging (MRI). The maximum of septal development overlaps with an increase in the callosal midsagittal area, whereas the slow, gradual resolution of CS coincides with a plateau of midsagittal callosal growth. The recognition of CS existence in human fetal brain and the ability to visualize them by exvivoMRI attributes a potential diagnostic value to these transient structures, as advancement in imaging technologies will likely also enable invivoMRI visualization of the CS in the near future.

Caffeine for apnea of prematurity and brain development at 11years of age.

ObjectiveCaffeine therapy for apnea of prematurity has been reported to improve brain white matter microstructure at term‐equivalent age, but its long‐term effects are unknown. This study aimed to investigate whether caffeine affects (1) brain structure at 11 years of age, and (2) brain development from term‐equivalent age to 11 years of age, compared with placebo.MethodsPreterm infants born ≤1250 g were randomly allocated to caffeine or placebo. Magnetic resonance imaging (MRI) was performed on 70 participants (33 caffeine, 37 placebo) at term‐equivalent age and 117 participants (63 caffeine, 54 placebo) at 11 years of age. Global and regional brain volumes and white matter microstructure were measured at both time points.ResultsIn general, there was little evidence for differences between treatment groups in brain volumes or white matter microstructure at age 11 years. There was, however, evidence that the caffeine group had a smaller corpus callosum than the placebo group. Volumetric brain development from term‐equivalent to 11 years of age was generally similar between treatment groups. However, there was evidence that caffeine was associated with slower growth of the corpus callosum, and slower decreases in axial, radial, and mean diffusivities in the white matter, particularly at the level of the centrum semiovale, over time than placebo.InterpretationThis study suggests any benefits of neonatal caffeine therapy on brain structure in preterm infants weaken over time and are not clearly detectable by MRI at age 11 years, although caffeine may have long‐term effects on corpus callosum development.

Application of super-resolution track-density technique: Earlier detection of aging-related subtle alterations than morphological changes in corpus callosum from normal population?

There are rare quantitative fiber density measurement techniques based on voxel measure changes of each corpus callosum (CC) subsegment with age. To observe the regularity of corpus callosum development in normal aging from subvoxel to macroscopic volume. Retrospective. In all, 131 healthy volunteers divided into six age groups. 3T MR with 32-channel head coil T1 -3D and diffusion-weighted imaging with six b-values in a 30 directions sequence. Track-density imaging (TDI) was used to visualize the complexity and the differences occurring in corpus callosum (CC) with age. TDI were reconstructed with a higher spatial voxel resolution of 0.1 mm subvoxel; TDI values are recognized as a subvoxel metric of real tract density. We reconstructed track density maps by using probabilistic streamline tractography combined with constrained spherical deconvolution. The CC was segmented into five subregions, and TDI, volume, and fractional anisotropy (FA) of each subregion in all the groups were measured using T1 W-3D images and compared. Polynomial regression was done to between age and (CC1, CC2, CC3, CC4, CC5) of TDI/volume/FA. Multiple comparisons test two-way analysis of variance (ANOVA) were used to compare the differences between different age groups and sex groups in each subregion. Fisher's least significant difference test was used for the correction of the multiple comparisons. From the 20-70 age groups, TDI values of CC2, CC3, and CC4 increased until 40 years, when they were highest, and then decreased. CC2 (7.35556, 7.56587, 8.06036, 7.53841, 6.6956, 6.56494), CC3 (7.75372, 8.41447, 9.13178, 8.72605, 7.50106, 5.69513), CC4 (8.63414, 9.1518, 9.22451, 9.03154, 8.11556, 7.1967). There was a significant difference in the CC3 TDI between the 50/60 years groups and the 60/70 years groups (P = 0.03853 and 0.00285, respectively). The volumes of CC2, CC3, and CC4 increased between 30 and 50 years and decreased between 50 and 60 years, CC2 (0.06557, 0.07244, 0.08062, 0.07353, 0.08576, 0.06294), CC3 (0.03421, 0.03867, 0.03891, 0.03916, 0.03058, 0.03658), CC4 (0.0242, 0.01948, 0.02445, 0.02887, 0.01938, 0.01956). FA of CC2, CC3, and CC4 decreased between years 40 and 60.CC2 (0.45981, 0.47392, 0.45654, 0.45702, 0.39982, 0.35767), CC3 (0.4628, 0.49056, 0.49701, 0.46667, 0.44795, 0.36799), CC4 (0.46599, 0.52887, 0.4971, 0.53257, 0.42861, 0.43158). TDI had high sensitivity for the detection of age-related CC differences. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:164-175.

Novel de novo ZBTB20 mutations in three cases with Primrose syndrome and constant corpus callosum anomalies.

Corpus callosum (CC) is the major brain commissure connecting homologous areas of cerebral hemispheres. CC anomalies (CCAs) are the most frequent brain anomalies leading to variable neurodevelopmental outcomes making genetic counseling difficult in the absence of a known etiology that might inform the prognosis. Here, we used whole exome sequencing, and a targeted capture panel of syndromic CCA known causal and candidate genes to screen a cohort of 64 fetuses with CCA observed upon autopsy, and 34 children with CCA and intellectual disability. In one fetus and two patients, we identified three novel de novo mutations in ZBTB20, which was previously shown to be causal in Primrose syndrome. In addition to CCA, all cases presented with additional features of Primrose syndrome including facial dysmorphism and macrocephaly or megalencephaly. All three variations occurred within two out of the five zinc finger domains of the transcriptional repressor ZBTB20. Through homology modeling, these variants are predicted to result in local destabilization of each zinc finger domain suggesting subsequent abnormal repression of ZBTB20 target genes. Neurohistopathological analysis of the fetal case showed abnormal regionalization of the hippocampal formation as well as a reduced density of cortical upper layers where originate most callosal projections. Here, we report novel de novo ZBTB20 mutations in three independent cases with characteristic features of Primrose syndrome including constant CCA. Neurohistopathological findings in fetal case corroborate the observed key role of ZBTB20 during hippocampal and neocortical development. Finally, this study highlights the crucial role of ZBTB20 in CC development in human.

Normal Development of the Corpus Callosum and Evolution of Corpus Callosum Sexual Dimorphism in Infancy.

The aim of this study was to establish reference ranges for the corpus callosum in infancy and to clarify how sexual dimorphism evolves between the fetal stage and infancy. Normal sonograms from cerebral ultrasonographic examinations of 1- to 6-month-old healthy full-term infants were selected. The length and thickness of the corpus callosum were determined, and the effect of sex on these values was analyzed. Studies on corpus callosum sexual dimorphism were reviewed. In total, sonograms from 236 1- to 6-month-old infants (120 male and 116 female) were collected, and the typical values (5th-95th percentiles) of the corpus callosum were determined for each group. During the first 2 months, with and without brain size adjustment, the corpus callosum in female infants was significantly thicker than that in male infants (mean thickness ± SD: 1 month, male infant, 1.8 ± 0.3 mm; female infant, 2.1 ± 0.3 mm; P = .005; 2 months, male infant, 1.8 ± 0.2 mm; female infant, 2.0 ± 0.3 mm; P = .002). The corpus callosum thickness of male and female infants had no significant differences after 2 months of age. Sexual dimorphism was not detected in corpus callosum length. Our study provides reference data on typical corpus callosum development in infants. In the fetal period and early infancy, the corpus callosum in female infants is thicker than that in male infants. From 3 months onward, the corpus callosum sexual dimorphism becomes insignificant throughout childhood. The evolvement of corpus callosum sexual dimorphism suggests that maternal factors may influence brain development.

Proteome dynamics during postnatal mouse corpus callosum development

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled amino acids in mammals (SILAM). The analyzed corpus callosi had distinct proteomic profiles depending on age, indicating rapid progression of specific molecular events during this period. The proteomic profiles were then segregated into five separate clusters, each with distinct trajectories relevant to their intended developmental functions. Our analysis both confirms many previously-identified proteins in aspects of corpus callosum development, and identifies new candidates in understudied areas of development including callosal axon refinement. We present a valuable resource for identifying new proteins integral to corpus callosum development that will provide new insights into the development and diseases afflicting this structure.