Correlation between Corpus Callosum Sub-Segmental Area and Cognitive Processes in School-Age Children

We assessed the relationship between structural characteristics (area) and microstructure (apparent diffusion coefficient; ADC) of the corpus callosum (CC) in 57 healthy children aged 7.0 to 9.1 years, with diverse cognitive and academic abilities as well as executive functions evaluated with a neuropsychological battery for children. The CC was manually delineated and sub-segmented into six regions, and their ADC and area were measured. There were no significant differences between genders in the callosal region area or in ADC. The CC area and ADC, mainly of anterior regions, correlated with different cognitive abilities for each gender. Our results suggest that the relationship between cognitive abilities and CC characteristics is different between girls and boys and between the anterior and posterior regions of the CC. Furthermore, these findings strenghten the idea that regardless of the different interhemispheric connectivity schemes per gender, the results of cognitive tasks are very similar for girls and boys throughout childhood.     

Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior

Fetal alcohol spectrum disorders constitute a major public health problem. This article presents an overview of important issues that surround these disorders and emphasizes the structural and neurobehavioral consequences associated with prenatal exposure to alcohol. Diagnostic criteria are discussed, and possible moderating factors for the range of outcomes are mentioned. In addition, the prevalence of fetal alcohol spectrum disorders is described, and estimates of the financial impact of these disorders are given. Heavy prenatal alcohol exposure can severely affect the physical and neurobehavioral development of a child. Autopsy and brain imaging studies indicate reductions and abnormalities in overall brain size and shape, specifically in structures such as the cerebellum, basal ganglia, and corpus callosum. A wide range of neuropsychological deficits have been found in children prenatally exposed to alcohol, including deficits in visuospatial functioning, verbal and nonverbal learning, attention, and executive functioning. These children also exhibit a variety of behavioral problems that can further affect their daily functioning. Children exposed to alcohol prenatally, with and without the physical features of fetal alcohol syndrome, display qualitatively similar deficits. Determining the behavioral phenotypes that result from heavy prenatal alcohol exposure is critical, because the identification of these children is crucial for early interventions. In addition, knowing which brain areas are involved might enable the development of better intervention strategies. However, intervention needs to go beyond the affected individual to prevent future cases. As evidenced by the staggering financial impact these disorders have on society, prevention efforts need to be aimed at high-risk groups, and this issue needs to be made a high priority in terms of public health.     

Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis

Tuberous sclerosis is a single-gene disorder caused by heterozygous mutations in the TSC1 (9q34) or TSC2 (16p13.3) gene and is frequently associated with mental retardation, autism and epilepsy. Even individuals with tuberous sclerosis and a normal intelligence quotient (approximately 50%) are commonly affected with specific neuropsychological problems, including long-term and working memory deficits. Here we report that mice with a heterozygous, inactivating mutation in the Tsc2 gene (Tsc2(+/-) mice) show deficits in learning and memory. Cognitive deficits in Tsc2(+/-) mice emerged in the absence of neuropathology and seizures, demonstrating that other disease mechanisms are involved. We show that hyperactive hippocampal mammalian target of rapamycin (mTOR) signaling led to abnormal long-term potentiation in the CA1 region of the hippocampus and consequently to deficits in hippocampal-dependent learning. These deficits included impairments in two spatial learning tasks and in contextual discrimination. Notably, we show that a brief treatment with the mTOR inhibitor rapamycin in adult mice rescues not only the synaptic plasticity, but also the behavioral deficits in this animal model of tuberous sclerosis. The results presented here reveal a biological basis for some of the cognitive deficits associated with tuberous sclerosis, and they show that treatment with mTOR antagonists ameliorates cognitive dysfunction in a mouse model of this disorder.     

Top-down processes in object identification: evidence from experimental psychology,neuropsychology and functional anatomy.

Many models of object identification are bottom-up and serial in nature; processing at a first stage needs to be complete before it is passed on to a subsequent stage, and there is no top-down feedback from the later to the earlier stages. However, data on picture identification in normal observers contradict a strict serial account of processing, since effects of variables on early and late stages of object identification combine in an interactive rather than an additive manner. Recent neuropsychological and functional anatomical data also indicate that object identification involves top-down activation of earlier stages of visual processing. In neuropsychological patients, subtle perceptual deficits can produce naming problems, even when there is good access to associated semantic knowledge; in functional activation studies, there is increased activity in visual processing areas when conditions require object naming relative to object recognition. These studies provide evidence that increased visual processing occurs in identification tasks, suggesting that there is re-current feedback during the identification process.     

Differences in vulnerability between the hemispheres in early childhood and adulthood

There are more left hemisphere damaged than right hemisphere damaged children and adults if one relies on studies of congenital hemiparesis as well as on those done on groups with radiologically demonstrated perinatal and postnatal unilateral stroke, hemispherectomy, or unilateral epilepsy in childhood or adulthood. The main pathogenetic factor seems to be a hemodynamic one, responsible for insufficient blood supply to the left hemisphere. Since adults show a difference in the same direction as children, the blood supply to the left internal carotid artery would seem to be the crucial factor. Around birth, an open ductus arteriosus may play an additional role. The hemodynamic asymmetry does not exclude an intrinsic maturational hemispheric tissue factor, making the left hemisphere more vulnerable than the right to detrimental influences around birth and during the early postnatal period. Immature white matter is especially vulnerable to asphyxia. The text was submitted by the author in English.     

Differences in vulnerability between the hemispheres in early childhood and adulthood

There are more left hemisphere damaged (LHD) than right hemisphere damaged (RHD) children and adults, if one relies on studies of congenital hemiparesis, as well as on those done on groups with radiologically demonstrated perinatal and postnatal unilateral stroke, hemispherectomy or unilateral epilepsy in childhood or adulthood. The main pathogenetic factor seems to be a hemodynamic one, responsible for insufficient blood supply to the left hemisphere (LH). Since adults show a difference in the same direction as children, the blood supply factor to the left internal carotid artery would seem to be the crucial factor. Around birth, an open ductus arteriosus may play an additional role. The hemodynamic asymmetry does not exclude an intrinsic maturational hemispheric tissue factor, making the left hemisphere more vulnerable than the right to detrimental influences around birth and during the early postnatal period. Immature white matter is especially vulnerable to asphyxia.     

Morphometric Changes of the Corpus Callosum in Congenital Blindness

We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12% reduction in the splenium, and a 20% increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness.     

Neurodevelopmental outcome in children with periventricular leukomalacia

The purpose of this study was to question the correlation of different grades of periventricular leukomalacia (PVL) and subsequent neurodevelopmental outcome. In a prospective study we followed 52 preterm infants. Infants were divided into three groups according to their cranial ultrasound findings of PVL (De Vries classification). Seventeen children had PVL 1, 20 children had PVL 2, and 15 children had PVL 3. All 15 (100%) children with PVL 3 developed cerebral palsy with additional visual perceptual dysfunctions and epilepsy. Children with PVL 1 had high frequency of mild neuromotoric delay and visual impairment. PVL 2 and 3 have great predictive value for subsequent severe neurodevelopmental disorder which refers to cerebral palsy, different cognitive deficits, vision impairment and epilepsy. We have determined that due to high frequency of visual impairment and epilepsy we need to include neurophysiologic examinations very early in children with PVL lesions.     

Anatomy of corpus callosum in prenatally malnourished rats

The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particularly in visual connections (splenium).     

伴中央颞区棘波的儿童良性癫痫注意网络功能影响因素的研究进展

摘要：儿童良性癫痫伴中央颞区棘波（BECTS）是目前已知常见和著名的儿童癫痫之一,既往临床中普遍认为其预后良好,但随着神经心理学研究的深入,学者们发现其反复发作可以引起神经、认知、心理、行为、注意网络功能等多重障碍。本文将从注意网络功能的定义、注意网络功能评定方法以及BECTS患儿引起注意网络功能损害的影响因素如发病年龄、睡眠结构改变、大脑结构改变等几方面进行综述。     

Extramotor Damage Is Associated with Cognition in Primary Lateral Sclerosis Patients

Objectives

This is a cross-sectional study aimed at investigating cognitive performances in patients with primary lateral sclerosis (PLS) and using diffusion tensor (DT) magnetic resonance imaging (MRI) to determine the topographical distribution of microstructural white matter (WM) damage in patients with or without cognitive deficits.

Methods

DT MRI scans were obtained from 21 PLS patients and 35 age- and sex-matched healthy controls. All PLS patients underwent a comprehensive neuropsychological battery. Tract-based-spatial-statistics (TBSS) was used to perform a whole-brain voxel-wise analysis of fractional anisotropy (FA), axial, radial (radD) and mean diffusivity (MD).

Results

Ten PLS patients had abnormal scores in at least one neuropsychological test (PLS with cognitive deficits, PLS-cd). Compared with healthy controls and cognitively unimpaired PLS patients (PLS-cu), PLS-cd cases showed decreased FA and increased MD and radD in the corticospinal tract (CST), corpus callosum, brainstem, anterior limb of internal capsule, superior and inferior longitudinal fasciculi, fornix, thalamic radiations, and parietal lobes, bilaterally. Compared with healthy controls, PLS-cd patients showed further decreased FA and increased radD in the cerebellar WM, bilaterally. Compared with controls, PLS-cu patients showed decreased FA in the mid-body of corpus callosum. In PLS, executive and language test scores correlated with WM damage.

Conclusions

This is the first study evaluating the relationship between cognitive performance and WM tract damage in PLS patients. PLS can be associated with a multi-domain cognitive impairment. WM damage to interhemispheric, limbic and major associative WM tracts seem to be the structural correlate of cognitive abnormalities in these patients.     

足月缺氧缺血性脑病患儿磁共振扩散张量成像各向异性分数的动态变化及其诊断价值分析

目的:了解足月缺氧缺血性脑病(HIE)患儿在磁共振扩散张量成像(DTI)下各向异性分数(FA)的动态变化,分析其诊断价值。方法:选取我院从2016年2月~2019年5月收治的足月HIE患儿90例,将其按照病情严重程度的差异分成轻度HIE组45例、中度HIE组27例、重度HIE组18例,另取同期30例正常足月新生儿作为对照组。所有新生儿均进行颅脑常规磁共振成像(MRI)以及DTI扫描,测量并对比内囊前肢、内囊后肢、胼胝体膝部、胼胝体压部以及豆状核的FA值。通过ROC曲线分析各FA值的诊断效能,以Spearman相关性分析各FA值和HIE病情严重程度的相关性。结果:中度HIE组、重度HIE组内囊前肢、内囊后肢、胼胝体膝部、胼胝体压部的FA值均低于对照组,且轻度HIE组、中度HIE组患儿上述FA值高于重度HIE组(均P<0.05)。ROC曲线分析结果显示,内囊后肢FA值对HIE的诊断效能最高,FA值的截断点为0.545,曲线下面积为0.804,其诊断敏感度、特异度以及Youden指数分别为61.4%、85.9%、0.473。Spearman相关性分析显示内囊前肢、内囊后肢、胼胝体膝部、胼胝体压部的FA值与HIE严重程度均呈负相关关系(均P<0.05)。结论:足月HIE患儿中,中、重度HIE患儿的内囊前肢、内囊后肢、胼胝体膝部、胼胝体压部的FA值较正常足月新生儿存在明显的降低,且上述FA值与HIE病情严重程度呈负相关关系,其中内囊后肢FA值对HIE的诊断效能最高,或可作为临床诊断足月新生儿HIE的参考指标。     

Reduced Ventral Cingulum Integrity and Increased Behavioral Problems in Children with Isolated Optic Nerve Hypoplasia and Mild to Moderate or No Visual Impairment

Objectives

To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified.

Patients and Methods

Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed.

Results

Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = −0.52, p<0.02, r = −0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores.

Conclusions

Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.     

Action in Perception: Prominent Visuo-Motor Functional Symmetry in Musicians during Music Listening

Musical training leads to sensory and motor neuroplastic changes in the human brain. Motivated by findings on enlarged corpus callosum in musicians and asymmetric somatomotor representation in string players, we investigated the relationship between musical training, callosal anatomy, and interhemispheric functional symmetry during music listening. Functional symmetry was increased in musicians compared to nonmusicians, and in keyboardists compared to string players. This increased functional symmetry was prominent in visual and motor brain networks. Callosal size did not significantly differ between groups except for the posterior callosum in musicians compared to nonmusicians. We conclude that the distinctive postural and kinematic symmetry in instrument playing cross-modally shapes information processing in sensory-motor cortical areas during music listening. This cross-modal plasticity suggests that motor training affects music perception.     

Characterization of Subtle Brain Abnormalities in a Mouse Model of Hedgehog Pathway Antagonist-Induced Cleft Lip and Palate

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly—a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.     

Transient cellular structures in developing corpus callosum of the human brain

The corpus callosum connects two cerebral hemispheres as the most voluminous fiber system in the human brain. The developing callosal fibers originate from immature pyramidal neurons, grow through complex pathways and cross the midline using different substrates in transient fetal structures. We analyzed cellular structures in the human corpus callosum on postmortem brains from the age of 18 weeks post conception to adult, using glial fibrillary acidic protein, neuron-specific nuclear protein, and chondroitin sulphate immunocytochemistry. We found the presence of transient cellular structures, callosal septa, which divide major fiber bundles and ventrally merge with subcallosal zone forming grooves for callosal axons. The callosal septa are composed of glial fibrillary acidic protein reactive meshwork, neurones and the chondroitin sulphate immunoreactive extracellular matrix. The developmental window of prominence of the callosal septa is between 18-34 weeks post conception which corresponds to the period of most intensive growth of callosal axons in human. During the early postnatal period the callosal septa become thinner and shorter, lose their neuronal and chondroitin sulphate content. In conclusion, transient expression of neuronal, glial and extracellular, growing substrate in the callosal septa, as septa itself, indicates their role in guidance during intensive growth of callosal fibers in the human brain. These findings shed some light on the complex morphogenetic events during the growth of the corpus callosum and represent normative parameters necessary for studies of structural plasticity after perinatal lesions.     

Developmental Changes in the Corpus Callosum from Infancy to Early Adulthood: A Structural Magnetic Resonance Imaging Study

Previous research has reported on the development trajectory of the corpus callosum morphology. However, there have been only a few studies that have included data on infants. The goal of the present study was to examine the morphology of the corpus callosum in healthy participants of both sexes, from infancy to early adulthood. We sought to characterize normal development of the corpus callosum and possible sex differences in development. We performed a morphometric magnetic resonance imaging (MRI) study of 114 healthy individuals, aged 1 month to 25 years old, measuring the size of the corpus callosum. The corpus callosum was segmented into seven subareas of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium. Locally weighted regression analysis (LOESS) indicated significant non-linear age-related changes regardless of sex, particularly during the first few years of life. After this increase, curve slopes gradually became flat during adolescence and adulthood in both sexes. Age of local maximum for each subarea of the corpus callosum differed across the sexes. Ratios of total corpus callosum and genu, posterior midbody, as well as splenium to the whole brain were significantly higher in females compared with males. The present results demonstrate that the developmental trajectory of the corpus callosum during early life in healthy individuals is non-linear and dynamic. This pattern resembles that found for the cerebral cortex, further suggesting that this period plays a very important role in neural and functional development. In addition, developmental trajectories and changes in growth do show some sex differences.     

Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses.     

Functional microsurgical partial callosotomy in patients with secondary generalized epilepsies. I. Disruption of bilateral synchrony of spike and wave discharges

Fourteen patients with secondary generalized epilepsy suffering from multiform seizures (MS) not amenable to medication were submitted to partial section of the corpus callosum. In all patients, there was a partial disruption of the previous generalized bilateral synchronous epileptiform discharges (GBSD). The electroencephalographic findings after callosal section are discussed with respect to their implications in furthering our understanding of the mechanisms subserving the organization of GBSD.