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Concept: Corpus callosum


OPINION STATEMENT: Background: Optic nerve hypoplasia (ONH) has developed into a leading cause of congenital blindness. The frequently associated features of hypopituitarism and absent septum pellucidum were felt to have embryonic linkage as “septo-optic dysplasia” or “de Morsier’s syndrome.” More recent studies have suggested these associations are independent of one another. This review provides an assessment of the historical and recent evidence linking neuroradiologic, endocrinologic and developmental morbidity in patients with ONH. The prenatal risk factors, heritability, and genetic mutations associated with ONH are described. Results: Recognition of the critical association of ONH with hypopituitarism should be attributed to William Hoyt, not Georges de Morsier. De Morsier never described a case of ONH or recognized its association with hypopituitarism or missing septum pellucidum. Hypopituitarism is caused by hypothalamic dysfunction. This, and other more recently identified associations with ONH, such as developmental delay and autism, are independent of septum pellucidum development. Other common neuroradiographic associations such as corpus callosum hypoplasia, gyrus dysplasia, and cortical heterotopia may have prognostic significance. The predominant prenatal risk factors for ONH are primiparity and young maternal age. Presumed risk factors such as prenatal exposure to drugs and alcohol are not supported by scrutiny of the literature. Heritability and identified gene mutations in cases of ONH are rare. Conclusion: Children with ONH require monitoring for many systemic, developmental, and even life-threatening problems independent of the severity of ONH and presence of brain malformations including abnormalities of the septum pellucidum. “Septo-optic dysplasia” and “de Morsier’s syndrome” are historically inaccurate and clinically misleading terms.

Concepts: Genetics, Mutation, Cerebrum, Corpus callosum, Agenesis of the corpus callosum, Optic nerve hypoplasia, Hypopituitarism, Septo-optic dysplasia


OBJECTIVES: To assess in a large population of patients with clinically isolated syndrome (CIS) the relevance of brain lesion location and frequency in predicting 1-year conversion to multiple sclerosis (MS). METHODS: In this multicenter, retrospective study, clinical and MRI data at onset and clinical follow-up at 1 year were collected for 1,165 patients with CIS. On T2-weighted MRI, we generated lesion probability maps of white matter (WM) lesion location and frequency. Voxelwise analyses were performed with a nonparametric permutation-based approach (p < 0.05, cluster-corrected). RESULTS: In CIS patients with hemispheric, multifocal, and brainstem/cerebellar onset, lesion probability map clusters were seen in clinically eloquent brain regions. Significant lesion clusters were not found in CIS patients with optic nerve and spinal cord onset. At 1 year, clinically definite MS developed in 26% of patients. The converting group, despite a greater baseline lesion load compared with the nonconverting group (7 ± 8.1 cm(3) vs 4.6 ± 6.7 cm(3), p < 0.001), showed less widespread lesion distribution (18% vs 25% of brain voxels occupied by lesions). High lesion frequency was found in the converting group in projection, association, and commissural WM tracts, with larger clusters being in the corpus callosum, corona radiata, and cingulum. CONCLUSIONS: Higher frequency of lesion occurrence in clinically eloquent WM tracts can characterize CIS subjects with different types of onset. The involvement of specific WM tracts, in particular those traversed by fibers involved in motor function and near the corpus callosum, seems to be associated with a higher risk of clinical conversion to MS in the short term.

Concepts: Magnetic resonance imaging, Multiple sclerosis, Cerebrum, Clinically isolated syndrome, White matter, Corpus callosum, Lesion, Optic nerve


People appear to derive intrinsic satisfaction from the perception that they are unique, special, and separable from the masses, which is referred to as a need for uniqueness (NFU). NFU is a universal human trait, along with a tendency to conform to the beliefs and attitudes of others and social norms. We used voxel-based morphometry and a questionnaire to determine individual NFU and its association with brain structures in healthy men (94) and women (91; age, 21.3±1.9years). Individual NFU was associated with smaller gray matter volume of a cluster that included areas in (a) the left middle temporal gyrus, left superior temporal gyrus, and left superior temporal sulcus (STS); (b) the dorsal part of the anterior cingulate gyrus and the anterior part of the middle cingulate gyrus; and © the right inferior frontal gyrus and the ventral part of the precentral gyrus. Individual NFU was also associated with larger white matter concentration of a cluster that mainly included the body of the corpus callosum. These findings demonstrated that variations in NFU reflect the gray and white matter structures of focal regions. These findings suggest a biological basis for individual NFU, distributed across different gray and white matter areas of the brain.

Concepts: Psychology, Neuroanatomy, Cerebrum, Superior temporal gyrus, Corpus callosum, Brodmann area 24, Cingulate gyrus, Gyrus


PURPOSE: Segmentation and diffusion-tensor-imaging of the corpus callosum (CC) have been linked to gait impairment. However, such measurements are impracticable in clinical routine. The purpose of this study was to evaluate the association between simple linear measurements of CC thickness with gait. METHODS: Two hundred and seventy-two community-dwelling subjects underwent neurological assessment and brain MRI. Mid-sagittal reformats of T1-weighted images were used to determine CC thickness. The association of measurements with clinical evaluation of gait was assessed by multivariate regression, controlling for numerous clinical and imaging confounders. Differences in CC thickness were, moreover, compared between subgroups with no, moderate or severe impairment of gait. RESULTS: In univariate analyses, thickness of the genu and body of CC but not the splenium were associated with postural stability (P < 0.01). Multivariate regression revealed thickness of CC genu as the only imaging variable independently associated with gait (P = 0.01). Genu thickness was significantly different between subjects with high and low (P = 0.0003) or high and moderate (P = 0.001) risk of fall. CONCLUSION: Atrophy of the CC genu is an imaging marker of gait impairment in the elderly suggesting higher risk of fall. Simple linear measurements of CC can help in MRI evaluation of patients with gait impairment. KEY POINTS : • Regional atrophy of the corpus callosum reflects disruption of gait regulation • Genu thickness on cranial MRI is an independent marker of gait impairment • Findings help in the MRI evaluation of patients with gait impairment.

Concepts: Brain, Magnetic resonance imaging, Assessment, Corpus callosum, Univariate, Splenium, Agenesis of the corpus callosum, Genu of the corpus callosum


Williams syndrome is a neurodevelopmental genetic disorder caused by a hemizygous deletion on chromosome 7q11.23, resulting in atypical brain structure and function, including abnormal morphology of the corpus callosum. An influence of handedness on the size of the corpus callosum has been observed in studies of typical individuals, but handedness has not been taken into account in studies of callosal morphology in Williams syndrome. We hypothesized that callosal area is smaller and the size of the splenium and isthmus is reduced in individuals with Williams syndrome compared to healthy controls, and examined age, sex, and handedness effects on corpus callosal area. Structural magnetic resonance imaging scans were obtained on 25 individuals with Williams syndrome (18 right-handed, 7 left-handed) and 25 matched controls. We found that callosal thickness was significantly reduced in the splenium of Williams syndrome individuals compared to controls. We also found novel evidence that the callosal area was smaller in left-handed participants with Williams syndrome than their right-handed counterparts, with opposite findings observed in the control group. This novel finding may be associated with LIM-kinase hemizygosity, a characteristic of Williams syndrome. The findings may have significant clinical implications in future explorations of the Williams syndrome cognitive phenotype.

Concepts: Scientific method, Brain, Magnetic resonance imaging, Left-handedness, Corpus callosum, Splenium, Agenesis of the corpus callosum, Handedness


White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery.

Concepts: Nervous system, Receptor, Action potential, White matter, Axon, Myelin, Oligodendrocyte, Corpus callosum


Reliable prediction and diagnosis of concussion is important for its effective clinical management. Previous model-based studies largely employ peak responses from a single element in a pre-selected anatomical region of interest (ROI) and utilize a single training dataset for injury prediction. A more systematic and rigorous approach is necessary to scrutinize the entire white matter (WM) ROIs as well as ROI-constrained neural tracts. To this end, we evaluated injury prediction performances of the 50 deep WM regions using predictor variables based on strains obtained from simulating the 58 reconstructed American National Football League head impacts. To objectively evaluate performance, repeated random subsampling was employed to split the impacts into independent training and testing datasets (39 and 19 cases, respectively, with 100 trials). Univariate logistic regressions were conducted based on training datasets to compute the area under the receiver operating characteristic curve (AUC), while accuracy, sensitivity, and specificity were reported based on testing datasets. Two tract-wise injury susceptibilities were identified as the best overall via pair-wise permutation test. They had comparable AUC, accuracy, and sensitivity, with the highest values occurring in superior longitudinal fasciculus (SLF; 0.867-0.879, 84.4-85.2, and 84.1-84.6%, respectively). Using metrics based on WM fiber strain, the most vulnerable ROIs included genu of corpus callosum, cerebral peduncle, and uncinate fasciculus, while genu and main body of corpus callosum, and SLF were among the most vulnerable tracts. Even for one un-concussed athlete, injury susceptibility of the cingulum (hippocampus) right was elevated. These findings highlight the unique injury discriminatory potentials of computational models and may provide important insight into how best to incorporate WM structural anisotropy for investigation of brain injury.

Concepts: Cerebrum, White matter, Corpus callosum, Receiver operating characteristic, Binary classification, Predictor, National Football League, Genu of the corpus callosum


Recent research has demonstrated the use of the structural connectome as a powerful tool to characterize the network architecture of the brain and potentially generate biomarkers for neurologic and psychiatric disorders. In particular, the anatomic embedding of the edges of the cerebral graph have been postulated to elucidate the relative importance of white matter tracts to the overall network connectivity, explaining the varying effects of localized white matter pathology on cognition and behavior. Here, we demonstrate the use of a linear diffusion model to quantify the impact of these perturbations on brain connectivity. We show that the eigenmodes governing the dynamics of this model are strongly conserved between healthy subjects regardless of cortical and sub-cortical parcellations, but show significant, interpretable deviations in improperly developed brains. More specifically, we investigated the effect of agenesis of the corpus callosum (AgCC), one of the most common brain malformations to identify differences in the effect of virtual corpus callosotomies and the neurodevelopmental disorder itself. These findings, including the strong correspondence between regions of highest importance from graph eigenmodes of network diffusion and nexus regions of white matter from edge density imaging, show converging evidence toward understanding the relationship between white matter anatomy and the structural connectome.

Concepts: Central nervous system, Psychology, Medicine, Brain, Cerebral cortex, Cerebrum, White matter, Corpus callosum


Purpose To analyze the integrity of white matter (WM) tracts in primary insomnia patients and provide better characterization of abnormal WM integrity and its relationship with disease duration and clinical features of primary insomnia. Materials and Methods This prospective study was approved by the ethics committee of the Guangdong No. 2 Provincial People’s Hospital. Tract-based spatial statistics were used to compare changes in diffusion parameters of WM tracts from 23 primary insomnia patients and 30 healthy control (HC) participants, and the accuracy of these changes in distinguishing insomnia patients from HC participants was evaluated. Voxel-wise statistics across subjects was performed by using a 5000-permutation set with family-wise error correction (family-wise error, P < .05). Multiple regressions were used to analyze the associations between the abnormal fractional anisotropy (FA) in WM with disease duration, Pittsburgh Sleep Quality Index, insomnia severity index, self-rating anxiety scale, and the self-rating depression scale in primary insomnia. Characteristics for abnormal WM were also investigated in tract-level analyses. Results Primary insomnia patients had lower FA values mainly in the right anterior limb of the internal capsule, right posterior limb of the internal capsule, right anterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, body of the corpus callosum, and right thalamus (P < .05, family-wise error correction). The receiver operating characteristic areas for the seven regions were acceptable (range, 0.60-0.74; 60%-74%). Multiple regression models showed abnormal FA values in the thalamus and body corpus callosum were associated with the disease duration, self-rating depression scale, and Pittsburgh Sleep Quality Index scores. Tract-level analysis suggested that the reduced FA values might be related to greater radial diffusivity. Conclusion This study showed that WM tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia. The reduced integrity of these WM tracts may be because of loss of myelination. (©) RSNA, 2016.

Concepts: Regression analysis, Linear regression, Sleep deprivation, Cerebrum, White matter, Corpus callosum, Hypnotic, Agenesis of the corpus callosum


Abnormalities 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.

Concepts: Autism, Pervasive developmental disorder, Corpus callosum, Asperger syndrome, Autism spectrum, PDD-NOS, Agenesis of the corpus callosum