Midsagittal Area Research Articles

Elucidation of developmental patterns of marmoset corpus callosum through a comparative MRI in marmosets, chimpanzees, and humans

The corpus callosum (CC) is present in all primate brains and is the major white matter tract connecting the cerebral hemispheres for integration of sensory, motor and higher-order cognitive information. The midsagittal area of the CC has frequently been used as a sensitive biomarker of brain development. Although the marmoset has been considered as an alternative non-human primate model for neuroscience research, the developmental patterns of the CC have not been explored. The present longitudinal study of magnetic resonance imaging demonstrated that marmosets show a rapid increase of CC during infancy, followed by a slow increase during the juvenile stage, as observed in chimpanzees and humans. Marmosets also show a tendency toward a greater increase in CC during late infancy and the juvenile stage, as observed in humans, but not in chimpanzees. However, several differences between marmosets and humans were identified. There was a tendency toward a greater maturation of the human CC during early infancy. Furthermore, there was a tendency toward a greater increase during late infancy and the juvenile stage in marmosets, compared to that observed in chimpanzees and humans. These differences in the developmental trajectories of the CC may be related to evolutional changes in social behavior.

Structural brain differences in school-age children with and without single-suture craniosynostosis.

OBJECTIVE Single-suture craniosynostosis (SSC), the premature fusion of a cranial suture, is characterized by dysmorphology of the craniofacial skeleton. Evidence to suggest that children with SSC are at an elevated risk of mild to moderate developmental delays and neurocognitive deficits is mounting, but the associations among premature suture fusion, neuroanatomy, and neurocognition are unexplained. The goals of this study were to determine 1) whether differences in the brain are present in young children with the 2 most common forms of SSC (sagittal and metopic) several years following surgical correction, and 2) whether the pattern of differences varies by affected suture (sagittal or metopic). Examination of differences in the brains of children with SSC several years after surgery may illuminate the growth trajectory of the brain after the potential constraint of the dysmorphic cranium has been relieved. METHODS The authors compared quantitative measures of the brain acquired from MR images obtained from children with sagittal or metopic craniosynostosis (n = 36) at 7 years of age to those obtained from a group of unaffected controls (n = 27) at the same age. The authors measured the volumes of the whole brain, cerebral cortex, cerebral white matter, cerebral cortex by lobe, and ventricles. Additionally, they measured the midsagittal area of the corpus callosum and its segments and of the cerebellar vermis and its component lobules. Measurements obtained from children with SSC and controls were compared using linear regression models. RESULTS No volume measures of the cerebrum or of the whole brain differed significantly between patients with SSC and controls (p > 0.05). However, ventricle volume was significantly increased in patients with SSC (p = 0.001), particularly in those with sagittal craniosynostosis (p < 0.001). In contrast, the area of the corpus callosum was significantly reduced in patients with metopic synostosis (p = 0.04), particularly in the posterior segments (p = 0.004). Similarly, the area of lobules VI-VII of the cerebellar vermis was reduced in patients with SSC (p = 0.03), with those with metopic craniosynostosis showing the greatest reduction (p = 0.01). CONCLUSIONS The lack of differences in overall brain size or regional differences in the size of the lobes of the cerebrum in children with metopic and sagittal synostosis suggests that the elevated risk of neurodevelopmental deficits is not likely to be associated with differences in the cerebral cortex. Instead, this study showed localized differences between sagittal and metopic craniosynostosis cases as compared with controls in the ventricles and in the midsagittal structures of the corpus callosum and the cerebellum. It remains to be tested whether these structural differences are associated with the increased risk for developmental delay and neurocognitive deficits in children with SSC.

Partial Agenesis and Hypoplasia of the Corpus Callosum in Idiopathic Autism.

To test the hypothesis that developmental anomalies of the corpus callosum (CC), contribute to the pathogenesis of autism, we characterized the type, topography, and severity of CC pathology corresponding to reduced CC areas that are detected by magnetic resonance imaging in the brains of 11 individuals with autism and 11 controls. In the brains of 3 autistic subjects, partial CC agenesis resulted in complete or partial lack of interhemispheric axonal connections in CC segments III-V. In these cases, a combination of focal agenesis and uniform axonal deficit caused reduction of CC areas by 37%, of axon numbers by 62%, and of the numerical density of axons by 39%. In the CC of 8 autistic subjects without agenesis, there was an 18% deficit of the midsagittal CC area, 48.4% deficit of axon numbers, and 37% reduction of the numerical density of axons. The significantly thinner CC, reduced CC area, and uniform axonal deficit in all autistic subjects were classified as CC hypoplasia. Thus, the byproduct of partial CC agenesis and hypoplasia is reduction of axonal connections between cortical areas known to be involved in behavioral alterations observed in people with autism.

5A: Comparison of midsagittal cross sectional areas above and below the levators in women with and without prolapse

5A: Comparison of midsagittal cross sectional areas above and below the levators in women with and without prolapse

Manual MRI morphometry in Parkinsonian syndromes.

Several morphometric magnetic resonance imaging parameters may serve for differential diagnosis of parkinsonism. The objective of this study was to identify which performs best in clinical routine. We acquired multicentric magnetization-prepared rapid gradient echo sequences in patients with Parkinson's disease (n=204), progressive supranuclear palsy (n=106), multiple system atrophy-cerebellar, (n = 21); multiple system atrophy-parkinsonian (n = 60), and healthy controls (n = 73), performed manual planimetric measurements, and calculated receiver operator characteristics with leave-one-out cross-validation to propose cutoff values. The midsagittal midbrain area was reduced in PSP versus all other groups (P < 0.001). The midsagittal pons area was reduced in MSA-cerebellar, MSA-parkinsonian, and PSP versus PD patients and healthy controls (P < 0.001). The midbrain/pons area ratio was lower in PSP (P < 0.001) and higher in MSA-cerebellar and MSA-parkinsonian versus PD and PSP (P < 0.001). The midsagittal midbrain area most reliably identified PSP, the midsagittal pons area MSA-cerebellar. The midbrain/pons area ratio differentiated MSA-cerebellar and PSP better than the magnetic resonance-Parkinson index. © 2017 International Parkinson and Movement Disorder Society.

Growth changes in the anterior and middle cranial bases assessed with cone-beam computed tomography in adolescents.

Initially, cone-beam computed tomography images from dry skulls were used to 3 dimensionally evaluate intrarater and interrater reliabilities and accuracy of selected 3-dimensional landmarks located in the anterior and middle cranial bases. Thereafter, dimensional changes of the anterior and middle cranial bases with growth were evaluated by using the previously selected landmarks. Cone-beam computed tomography images of 10 dry skulls were used to identify useful landmarks from different areas of the anterior and middle cranial bases based on their reliability and accuracy. These selected landmarks were identified in the images of an already available sample of adolescents (n=60) taken at 2 time points (19months apart) to assess dimensional changes with growth. The majority of the proposed 3-dimensional landmarks with the exception of the lesser wing of the sphenoid showed acceptable intrarater and interrater reliabilities. The distances measured between foramina and canals in the transverse dimension showed evidence of increases in size. However, the mean amounts of increase in these transverse distances were equal to or less than 1.05mm (from 1.1% to 4.1%). No change was observed between the right and left anterior and posterior clinoid processes. The vertical dimensions showed evidence of some changes, but these were within 2% of the original distances. In this adolescent sample, minor growth-related changes were observed in the anterior and middle cranial bases. The midsagittal area of the anterior cranial base (foramen caecum to presphenoid) was stable. The right and left anterior and posterior clinoid processes can be used for transverse superimposition.

Sex-related difference in human white matter volumes studied: Inspection of the corpus callosum and other white matter by VBM

It has been contended that any observed difference of the corpus callosum (CC) size between men and women is not sex-related but brain-size-related. A recent report, however, showed that the midsagittal CC area was significantly larger in women in 37 brain-size-matched pairs of normal young adults. Since this constituted strong evidence of sexual dimorphism and was obtained from publicly available data in OASIS, we examined volume differences within the CC and in other white matter using voxel-based morphometry (VBM). We created a three-dimensional region of interest of the CC and measured its volume. The VBM statistics were analyzed by permutation test and threshold-free cluster enhancement (TFCE) with the significance levels at FWER < 0.05. The CC volume was significantly larger in women in the same 37 brain-size-matched pairs. We found that the CC genu was the subregion showing the most significant sex-related difference. We also found that white matter in the bilateral anterior frontal regions and the left lateral white matter near to Broca’s area were larger in women, whereas there were no significant larger regions in men. Since we used brain-size-matched subjects, our results gave strong volumetric evidence of localized sexual dimorphism of white matter.

Midsagittal corpus callosum area and conversion to multiple sclerosis after clinically isolated syndrome: A multicentre Australian cohort study.

Patients presenting with clinically isolated syndrome (CIS) may proceed to clinically definite multiple sclerosis (CDMS). Midsagittal corpus callosum area (CCA) is a surrogate marker for callosal atrophy, and can be obtained from a standard MRI study. This study explores the relationship between CCA measured at CIS presentation (baseline) and at 5years post presentation, with conversion from CIS to CDMS. The association between CCA and markers of disability progression is explored. Corpus callosum area was measured on MRI scans at presentation and 5-year review following diagnosis of a first demyelinating event, or evidence of progressive MS, in 143 participants in the Ausimmune/AusLong Study. Relationships between CCA (at baseline and follow-up) and clinical outcomes were assessed. Mean CCA at baseline study was 6.63cm2 (SD 1.01). Patients who converted to MS by 5-year review (n=100) had a significantly smaller mean CCA at follow-up (6.22 vs. 6.74, P=0.007). Greater CCA reduction was associated with higher annualized relapse rate over follow-up. Baseline CCA obtained from standard MRI protocols may be compared with subsequent MRI examinations as a surrogate for neurodegeneration and cerebral atrophy in patients with MS. This study demonstrates an association between CCA and disability in individuals presenting with CIS who convert to MS.

Association between corpus callosum development on magnetic resonance imaging and diffusion tensor imaging, and neurodevelopmental outcome in neonates born very preterm.

To characterize corpus callosum development in neonates born very preterm from early in life to term-equivalent age and its relationship with neurodevelopmental outcome at 18 months corrected age. In a prospective cohort of 193 neonates born preterm, 24 to 32 weeks' gestation, we used magnetic resonance imaging and diffusion tensor imaging acquired early in life (n=193) and at term-equivalent age (n=159) to measure corpus callosum development: mid-sagittal area (including corpus callosum subdivisions) and length, and fractional anisotropy from the genu and splenium. We examined the association of (1) intraventricular haemorrhage (IVH) and white matter injury (WMI) severity, and (2) neurodevelopmental outcome at 18 months corrected age with corpus callosum development. Severe WMI and severe IVH were strongly associated with reduced corpus callosum area (both p<0.001) and WMI with lower fractional anisotropy (p=0.002). Mild WMI predicted smaller corpus callosum area only posteriorly; mild IVH predicted smaller area throughout. Adverse motor outcome was associated with smaller corpus callosum size in the posterior subdivision (p=0.003). Abnormal cognitive outcomes were associated with lower corpus callosum fractional anisotropy (p=0.008). In newborn infants born very preterm, brain injury is associated with changes in simple metrics of corpus callosum development. In this population, the development of the corpus callosum, as reflected by size and microstructure, is associated with neurodevelopmental outcomes at 18 months corrected age.

Cognitive event-related potentials in multiple sclerosis: Correlation with MRI and neuropsychological findings

BackgroundCognitive event-related potentials (ERPs) have been previously correlated with T2 lesion load (Τ2LL) in patients with multiple sclerosis (MS). It is currently unknown, however, whether ERPs also correlate with brain atrophy or the presence of T1 hypointense lesions (“black holes”) which reflect tissue destruction and axonal loss. The primary aim of the current study is to explore the effect of neuroradiological parameters such as brain atrophy, T1 and T2 lesion load on auditory ERPs in MS patients. In addition, we correlated cognitive impairment with neurophysiological (ERP) and neuroradiological (MRI) variables and investigated whether a combination of ERP and MRI parameters is capable of distinguishing patients suffering from secondary progressive (SP), primary progressive (PP) and relapsing-remitting (RR) MS. Materials and methodsThe study sample consisted of fifty nine MS patients (mean age±SD: 37.82±1.38 years; average disease duration: 6.76±5.3 years) and twenty six age-matched controls (mean age±SD: 41.42±15.39 years). The patients’ EDSS and NRS scores were 3.77±2.14 (range: 1–7.5) and 75.88±11.99 (range: 42–94) respectively. ERPs were recorded using the auditory “odd-ball” paradigm. T1 and T2 lesions were automatically segmented using an edge-finding tool and total lesion volumes were calculated. MRI measures of brain atrophy included third ventricle width (THIRDVW) and the ratio of mid-sagittal corpus callosum area to the mid-sagittal intracranial skull surface area (CC/MISS). Statistical analysis was performed using multiple regression, principal component (PCA) and discriminant analysis. ResultsT1 lesion load emerged as the most significant predictor of P300 and N200 latency. The rest of the endogenous ERPs parameters (P300 amplitude, N200 amplitude) were not significantly correlated with the MRI variables. PCA of pooled neuroradiological and neurophysiological markers suggested that four components accounted for 64.6% of the total variability. Discriminant analysis based on ERP & MRI markers classified correctly 79.63% of patients in RR, PP and SP subgroups. ConclusionT1 lesion load is the most significant MRI correlate of auditory ERPs in MS patients. Importantly, ERPs in combination with MRI variables can be usefully employed for distinguishing patients with different subtypes of MS.

Relationship between the corpus callosum and neurocognitive disabilities in children with NF-1: diffusion tensor imaging features

PurposeMild neurocognitive disabilities are commonly observed in children with neurofibromatosis type 1 (NF-1). Enlargement of the corpus callosum (CC) is one of the findings in NF-1, but the pathogenesis has not yet been clarified. In this study, we investigated whether diffusion tensor imaging (DTI) features of CC differed between children with NF-1 and healthy control subjects, and we tried to evaluate the association between the microstructural integrity of CC and neurocognitive disabilities, based on apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values. Materials and methodsThe study population consisted of 37 children with NF-1 and 31 healthy controls. Midsagittal CC surface area measurements were obtained from volumetric sagittal T1-weighted turbo spin echo images. FA and ADC values were obtained from the genu and splenium of CC. The results were compared to that of controls. The correlations between neurocognitive test results and measurements of ADC, FA, and surface areas of midsagittal CC in NF-1 patients were investigated. ResultsTotal CC area in children with NF-1 was significantly larger than healthy controls. ADC values obtained from the genu of CC were significantly higher in NF-1 children. A negative correlation was observed between the ADC values of the genu of the CC and the arithmetic and digit span scores and between the FA values of the genu and coding scores in children with NF-1. ConclusionThe DTI changes in the genu of CC in children with NF-1 may indicate subtle structural damage, although conventional MRI is normal. ADC and FA changes in the genu may be due to loss of axonal integrity and vasogenic-like edema in the axons responsible for some intellectual functions. DTI may help clarify the underlying pathophysiology of CC changes in relation to neurocognitive function disorders in children with NF1.

Selective increase in posterior corpus callosum thickness between the age of 4 and 11 years

Establishing an efficient functional and structural connectivity between the two cerebral hemispheres is an important developmental task during childhood, and alterations in this development have accordingly been linked to a series of neurodevelopmental and pediatric disorders. The corpus callosum, the major white-matter structure connecting the hemispheres, has been shown to increase in size throughout the three first decades of life. However, behavioral studies indicate that adult-like performance levels of functional hemispheric interaction are already reached during middle and late childhood. Thus, here we specifically examine the structural development of the corpus callosum during the functionally relevant time period by for the first time (a) selectively addressing prospective childhood development and (b) analyzing a sample in which also younger children are well represented. Corpus callosum anatomy was assessed from 732 T1-weighted MRI datasets acquired from 428 children (213 boys, 215 girls) aged of 4.1 and 10.9years, of which 304 were scanned at two time points. Regional callosal thickness was determined from an outline-based segmentation of the mid-sagittal cross-sectional surface area. Linear-mixed model analyses revealed a significant increase in thickness with age (effect size: up to 15% explained variance) equivalent to a growth in callosal thickness of up to 0.19mm per year in the posterior corpus callosum. The age effect was found to be stronger in posterior segments (i.e., splenium) than in other callosal subregions. Also, the age effect was found to be comparable between boys and girls, and was detected irrespective of whether developmental or individual differences in overall brain size where accounted for or not. Our results demonstrate a selective increase in posterior corpus-callosum thickness during middle and late childhood. Since axons crossing the midline in the splenium mainly connect occipital and parietal cortices, the accentuated posterior growth might reflect the onset of a posterior-to-anterior moving maturation wave in cortical development known to take place in the same time period.

Articulatory idiosyncrasy inferred from relative size and mobility of the tongue

Origins of individual characteristics of speech sounds have been a mystery. Individual patterns of higher spectra could be attributed to quasi-static hypopharyngeal-cavity resonance, while those of lower spectra are puzzling because both spectra and vocal-tract shapes radically change during speech. A possible clue to look into articulatory idiosyncrasy may be the relation between relative size and mobility of the tongue in the oropharyngeal cavity. To this end, combined cine- and tagged-MRI collected from four Chinese speakers producing two-syllable words were processed. The relative tongue size was indexed by midsagittal tongue area divided by tongue plus airway area both measured above the level of the superior genial tubercle in static MRI during /i/. The mobility of the tongue was measured by average velocity of tag points located along the oral and pharyngeal surface of the tongue. In the result, the velocity monotonically decreased with the relative tongue size, suggesting that the smaller the tongue the faster the movement according to a speaker-specific anatomical constraint derived from the space available for tongue articulation in vowel production. [Work supported by National NSF Programs (No. 61573254 and 61304250), and National One-Thousand Program (WQ20111200010) in China.]

Sex differences of human corpus callosum revealed by polar coordinate system: magnetic resonance imaging study.

Evaluation of morphological and size changes related to various pathological conditions of the corpus callosum (CC) requires the data about sex dimorphism of the CC. The purpose of our study is to define potential morphological sex differences of the CC by the use of polar coordinate system as a system of measurements. After division of the CC into three equal segments by the use of polar coordinate system, we investigated the length of the hemisphere (A-A'), the CC size as its midsagittal section area (CCA), the size of its segments (C1, C2, C3), thickness of the thinnest part of the CC (TCC) and the angular coordinate (a angle) of dorsal point of the TCC in a sample of 30 human brains magnetic resonance images (15 males and 15 females, age 20-50 years). We found significantly larger CCA, C3 segment and the TCC in males. Statistically significant correlation in both, males and females, was found between parameters of the CCA and of all of its segments (C1, C2, C3), the C1 and C2, the C2 and C3 segments, as well as like as between the C2 and TCC. Sex differences were also in findings of significant correlation between the C1 and C3 segments, between CCA and TCC, and of significant negative correlation between the a angle and A-A' only in females. We concluded that the use of polar coordinate system appropriately reflects the anatomical and encephalometric characteristics of human CC.

Relationship Between the Thickness of Cortical Bone at Maxillary Mid-palatal Area and Facial Height Using CBCT.

Introduction : Orthodontic mini-implants have been incorporated into orthodontic treatment modalities. Adequate bone at mini-implant placement site can influence the success or failure of anchorage. The present study was to determine the thickness of cortical bone in the maxillary mid-palatal area at predetermined points for the placement of orthodontic mini-implants using Cone Beam CT technique in order to evaluate the relationship of these values with the facial height. Materials and Methods : A total of 161 patients, consisting of 63 males (39.13%) and 98 females (60.87%), were evaluated in the present study; 38% of the subjects had normal facial height, 29% had short face and 33% had long face. In order to determine which patient belongs to which facial height category, i.e. normal, long or short, two angular and linear evaluations were used: the angle between S-N and Go-Me lines and the S-Go/N-Me ratio. Twenty points were evaluated in all the samples. First the incisive foramen was located. The paracoronal cross-sections were prepared at distances of 4, 8, 16 and 24 mm from the distal wall of the incisive foramen and on each cross-section the mid-sagittal and para-sagittal areas were determined bilaterally at 3- and 6-mm distances (a total of 5 points). The thicknesses of the cortical plate of bone were determined at the predetermined points. Results : There was a significant relationship between the mean cortical bone thickness and facial height (p<0.01), with significantly less thickness in long faces compared to short faces. However, the thickness of cortical bone in normal faces was similar to that in long and short faces. Separate evaluation of the points showed that at point a16 subjects with short faces had thicker cortical bone compared to subjects with long and normal faces. At point b8 in long faces, the thickness of the cortical bone was significantly less than that in short and normal faces. At point d8, the thickness of the cortical bone in subjects with short faces was significantly higher than that in subjects with long faces. Conclusion : At the point a16 the cortical bone thickness in short faces was significantly higher than normal and long faces. The lower thickness of the cortical bone in the palatal area at points b8 and d8 in subjects with long faces might indicate a lower anchorage value of these points in these subjects.

Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder.

BackgroundAbnormalities in the corpus callosum have been reported in individuals with autism spectrum disorder (ASD), but few studies have evaluated young children. Sex differences in callosal organization and diffusion characteristics have also not been evaluated fully in ASD.MethodsStructural and diffusion-weighted images were acquired in 139 preschool-aged children with ASD (112 males/27 females) and 82 typically developing (TD) controls (53 males/29 females). Longitudinal scanning at two additional annual time points was carried out in a subset of these participants. Callosal organization was evaluated using two approaches: 1) diffusion tensor imaging (DTI) tractography to define subregions based on cortical projection zones and 2) as a comparison to previous studies, midsagittal area analysis using Witelson subdivisions. Diffusion measures of callosal fibers were also evaluated.ResultsAnalyses of cortical projection zone subregions revealed sex differences in the patterns of altered callosal organization. Relative to their sex-specific TD counterparts, both males and females with ASD had smaller regions dedicated to fibers projecting to superior frontal cortex, but patterns differed in callosal subregions projecting to other parts of frontal cortex. While males with ASD had a smaller callosal region dedicated to the orbitofrontal cortex, females with ASD had a smaller callosal region dedicated to the anterior frontal cortex. There were also sex differences in diffusion properties of callosal fibers. While no alterations were observed in males with ASD relative to TD males, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were all increased in females with ASD relative to TD females. Analyses of Witelson subdivisions revealed a decrease in midsagittal area of the corpus callosum in both males and females with ASD but no regional differences in specific subdivisions. Longitudinal analyses revealed no diagnostic or sex differences in the growth rate or change in diffusion measures of the corpus callosum from 3 to 5 years of age.ConclusionsThere are sex differences in the pattern of altered corpus callosum neuroanatomy in preschool-aged children with ASD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0005-4) contains supplementary material, which is available to authorized users.

Corpus callosum atrophy rate in mild cognitive impairment and prodromal Alzheimer's disease.

Corpus callosum (CC) size and shape have been previously studied in Alzheimer's disease (AD) with the majority of studies having been cross-sectional. Due to the large variance in normal CC morphology, cross-sectional studies are limited in statistical power. Determining individual rates of change requires longitudinal data. Physiological changes are particularly relevant in mild cognitive impairment (MCI), in which CC morphology has not been previously studied longitudinally. To study temporal rates of change in CC morphology in MCI patients over a one-year period, and to determine whether these rates differ between MCI subjects who converted to AD (MCI-C) and those who did not (MCI-NC) over an average (±SD) observation period of 5.4 (±1.6) years. We used a novel multi-atlas based algorithm to segment the mid-sagittal cross-sectional area of the CC in longitudinal MRI scans. Rates of change of CC circularity, total area, and five sub-areas were compared between 57 MCI-NC and 81 MCI-C subjects. The CC became less circular (-0.89% per year in MCI-NC, -1.85% per year in MCI-C) with time, with faster decline in MCI-C (p = 0.0002). In females, atrophy rates were higher in MCI-C relative to MCI-NC in total CC area (p = 0.0006), genu/rostrum (p = 0.005), and splenium (0.002). In males, these rates did not differ between groups. A greater than normal decline in CC circularity was shown to be an indicator of prodromal AD in MCI subjects. This measure is potentially useful as an imaging biomarker of disease and a therapeutic target in clinical trials.

Corpus callosum atrophy associated with the degree of cognitive decline in patients with Alzheimer's dementia or mild cognitive impairment: A meta-analysis of the region of interest structural imaging studies

Individual structural neuroimaging studies of the corpus callosum (CC) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) with the region of interest (ROI) analysis have yielded inconsistent findings. The aim of this study was to conduct a meta-analysis of structural imaging studies using ROI technique to measure the CC midsagittal area changes in patients with AD or MCI. Databases of PubMed, the Cochrane Library, the ISI Web of Science, and Science Direct from inception to June 2014 were searched with key words “corpus callosum” or “callosal”, plus “Alzheimer's disease” or “mild cognitive impairment”. Twenty-three studies with 603 patients with AD, 146 with MCI, and 638 healthy controls were included in this meta-analysis. Effect size was used to measure the difference between patients with AD or MCI and healthy controls. Significant callosal atrophy was found in MCI patients with an effect size of −0.36 (95% CI, -0.57 to −0.14; P = 0.001). The degree of the CC atrophy in mild AD was less severe than that in moderate AD with a mean effect size −0.69 (95% CI, -0.89 to −0.49) versus −0.92 (95% CI, -1.16 to −0.69), respectively. Comparing with healthy controls, patients with MCI had atrophy in the anterior portion of the CC (i.e., rostrum and genu). In contrast, patients with AD had atrophy in both anterior and posterior portions (i.e., splenium). These results suggest that callosal atrophy may be related to the degree of cognitive decline in patients with MCI and AD, and it may be used as a biomarker for patients with cognitive deficit even before meeting the criteria for AD.

Maternal insulin-like growth factor 1 and 2 differentially affect the renin–angiotensin system during pregnancy in the guinea pig

ObjectiveInsulin-like growth factors (IGFs) are known to interact with the renin–angiotensin system (RAS). We previously demonstrated that administration of IGF1 to guinea pigs in early to mid pregnancy promotes placental function and fetal growth in mid to late gestation. Early administration of IGF2 had sustained, but not acute, effects on these parameters and also on placental structural differentiation. Here, we aimed to determine whether the IGFs interact with the placental RAS in early to mid gestation to modulate placental development and increase fetal growth and survival, and if IGF2 binding the IGF2R is implicated in the sustained effects of IGF2 treatment. DesignAt day 20 of pregnancy, guinea pigs were infused with 1mg/kg/day of IGF1, IGF2, Leu27IGF2 or vehicle for 18days and sacrificed on either day 62 (late pregnancy) or during the infusion period on day 35 (early–mid pregnancy). Placental structure at day 35 was analyzed using morphometric technique and expression of RAS genes in the placenta and placental and plasma renin activity were measured at both time points. ResultsCompared with vehicle at day 35 of gestation, IGF1 infusion reduced the total midsagittal cross-sectional area of the placenta (−17%, p=0.02) and the labyrinth area (−22%, p=0.014) but did not alter the labyrinth volume nor labyrinth:interlobium ratios. IGF2 treatment did not affect placental structure.IGF1 did not alter placental mRNA for any of the RAS genes quantified at day 35 (AGTR1, ACE, AGT, TGFB1) but increased TGFB1 expression by more than 16-fold (p=0.005) at day 62. IGF2 increased placental expression of AGTR1 (+88%, p=0.03) and decreased AGT (−73%, p=0.01) compared with the vehicle-treated group at day 35, and both IGF2 and Leu27IGF2 increased expression of TGFB1 at day 62 by 9-fold (p=0.016) and 6-fold (p=0.019) respectively.Both IGFs increased the ratio of active:total placental renin protein (+22% p=0.026 p=0.038) compared to vehicle compared to vehicle at day 35 but not 62. At day 62, IGF2-treated mothers showed a marked increase in total plasma renin (+495%) and active renin (+359%) compared to vehicle but decreased the ratio of active to total renin by 41% (p=0.042). Leu27IGF2-treated animals had higher levels of placental active renin (+73%, p=0.001) and total renin (+71%, p=0.001) compared with the vehicle control. ConclusionsThe data obtained in the current study suggest the potential for alternate roles for the induction of the RAS after IGF treatment. IGF1 and 2 treatments increase the activation of prorenin to renin in the placenta, possibly due to increased protease activity. In addition, IGF2 treatment in early pregnancy may enhance the maternal adaptation to pregnancy through stimulation of renin in the kidney. The sustained effects on placental differentiation and function after IGF2 treatment suggest therapeutic potential for exogenous administration of IGFs in improving pregnancy outcomes.

The corpus callosum and recovery of working memory after epilepsy surgery.

For patients with medically intractable focal epilepsy, the benefit of epilepsy surgery must be weighed against the risk of cognitive decline. Clinical factors such as age and presurgical cognitive level partially predict cognitive outcome; yet, little is known about the role of cross-hemispheric white matter pathways in supporting postsurgical recovery of cognitive function. The purpose of this study is to determine whether the presurgical corpus callosum (CC) midsagittal area is associated with pre- to postsurgical change following epilepsy surgery. In this observational study, we retrospectively identified 24 adult patients from an epilepsy resection series who completed preoperative high-resolution T1 -weighted magnetic resonance imaging (MRI) scans, as well as pre- and postsurgical neuropsychological testing. The total area and seven subregional areas of the CC were measured on the midsagittal MRI slice using an automated method. Standardized indices of auditory-verbal working memory and delayed memory were used to probe cognitive change from pre- to postsurgery. CC total and subregional areas were regressed on memory-change scores, after controlling for overall brain volume, age, presurgical memory scores, and duration of epilepsy. Patients had significantly reduced CC area relative to healthy controls. We found a positive relationship between CC area and change in working memory, but not delayed memory; specifically, the larger the CC, the greater the postsurgical improvement in working memory (β = 0.523; p = 0.009). Effects were strongest in posterior CC subregions. There was no relationship between CC area and presurgical memory scores. Findings indicate that larger CC area, measured presurgically, is related to improvement in working memory abilities following epilepsy surgery. This suggests that transcallosal pathways may play an important, yet little understood, role in postsurgical recovery of cognitive functions.