Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination.

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, resulting in the loss of dystrophin, a large cytosolic protein that links the cytoskeleton to extracellular matrix receptors in skeletal muscle. Aside from progressive muscle damage, many patients with DMD also have neurological deficits of unknown etiology. To investigate potential mechanisms for DMD neurological deficits, we assessed postnatal oligodendrogenesis and myelination in the Dmdmdx mouse model. In the ventricular-subventricular zone (V-SVZ) stem cell niche, we found that oligodendrocyte progenitor cell (OPC) production was deficient, with reduced OPC densities and proliferation, despite a normal stem cell niche organization. In the Dmdmdx corpus callosum, a large white matter tract adjacent to the V-SVZ, we also observed reduced OPC proliferation and fewer oligodendrocytes. Transmission electron microscopy further revealed significantly thinner myelin, an increased number of abnormal myelin structures and delayed myelin compaction, with hypomyelination persisting into adulthood. Our findings reveal alterations in oligodendrocyte development and myelination that support the hypothesis that changes in diffusion tensor imaging seen in patients with DMD reflect developmental changes in myelin architecture.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

The Anterior Interhemispheric Transcallosal Approach to the Ventricles: How We Do It.

Intraventricular tumors of the lateral and third ventricles are relatively rare, accounting for 1-2% of all primary brain tumors in most large series [1-4]. They can be uniquely challenging to approach due to their deep location, propensity to become large before they are discovered, and association with hydrocephalus [5, 6]. The surgeon's goal is to develop a route to these deep lesions that will cause the least morbidity, provide adequate working space, and achieve a complete resection. This must be performed with minimal manipulation of the neural structures encircling the ventricles, avoiding functional cortical areas, and acquiring early control of feeding vessels [7, 8].

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer.

BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Diverse and asymmetric patterns of single-neuron projectome in regulating interhemispheric connectivity.

The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric "heterogeneity" to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.

Histological characterization and development of mesial surface sulci in the human brain at 13-15 gestational weeks through high-resolution histology.

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.

5Z-7-Oxozaenol attenuates cuprizone-induced demyelination in mice through microglia polarization regulation.

INTRODUCTION: Demyelination is a key factor in axonal degeneration and neural loss, leading to disability in multiple sclerosis (MS) patients. Transforming growth factor beta activated kinase 1 (TAK1) is a critical molecule involved in immune and inflammatory signaling pathways. Knockout of microglia TAK1 can inhibit autoimmune inflammation of the brain and spinal cord and improve the outcome of MS. However, it is unclear whether inhibiting TAK1 can alleviate demyelination. METHODS: Eight-week-old male c57bl/6j mice were randomly divided into five groups: (a) the control group, (b) the group treated with cuprizone (CPZ) only, (c) the group treated with 5Z-7-Oxozaenol (OZ) only, and (d) the group treated with both cuprizone and 15 µg/30 µg OZ. Demyelination in the mice of this study was induced by administration of CPZ (ig) at a daily dose of 400 mg/kg for consecutive 5 weeks. OZ was intraperitoneally administered at mentioned doses twice a week, starting from week 3 after beginning cuprizone treatment. Histology, rotarod test, grasping test, pole test, Western blot, RT-PCR, and ELISA were used to evaluate corpus callosum demyelination, behavioral impairment, oligodendrocyte differentiation, TAK1 signaling pathway expression, microglia, and related cytokines. RESULTS: Our results demonstrated that OZ protected against myelin loss and behavior impairment caused by CPZ. Additionally, OZ rescued the loss of oligodendrocytes in CPZ-induced mice. OZ inhibited the activation of JNK, p65, and p38 pathways, transformed M1 polarized microglia into M2 phenotype, and increased brain-derived neurotrophic factor (BDNF) expression to attenuate demyelination in CPZ-treated mice. Furthermore, OZ reduced the expression of proinflammatory cytokines and increases anti-inflammatory cytokines in CPZ-treated mice. CONCLUSION: These findings suggest that inhibiting TAK1 may be an effective approach for treating demyelinating diseases.

Mri findings, looking behaviour and affect recognition in very preterm children: A pilot study.

Children born very preterm often exhibit atypical gaze behaviors, affect recognition difficulties and are at risk for cerebral white matter damage. This study explored links between these sequalae. In 24 12-year-old children born very preterm, ventricle size using Evans and posterior ventricle indices, and corpus callosum area were used to measure white matter thickness. The findings revealed a correlation between less attention towards the eyes and larger ventricle size. Ventricle and posterior corpus callosum sizes were correlated to affect-recognition proficiency. Findings suggest a link between white matter damage, gaze behavior, and affect recognition accuracy, emphasizing a relation with social perception.

Corpus callosum and cerebellum participate in semantic dysfunction of Parkinson's disease: a diffusion tensor imaging-based cross-sectional study.

Language dysfunction is common in Parkinson's disease (PD) patients, among which, the decline of semantic fluency is usually observed. This study aims to explore the relationship between white matter (WM) alterations and semantic fluency changes in PD patients. 127 PD patients from the Parkinson's Progression Markers Initiative cohort who received diffusion tensor imaging scanning, clinical assessment and semantic fluency test (SFT) were included. Tract-based special statistics, automated fiber quantification, graph-theoretical and network-based analyses were performed to analyze the correlation between WM structural changes, brain network features and semantic fluency in PD patients. Fractional anisotropy of corpus callosum, anterior thalamic radiation, inferior front-occipital fasciculus, and uncinate fasciculus, were positively correlated with SFT scores, while a negative correlation was identified between radial diffusion of the corpus callosum, inferior longitudinal fasciculus, and SFT scores. Automatic fiber quantification identified similar alterations with more details in these WM tracts. Brain network analysis positively correlated SFT scores with nodal efficiency of cerebellar lobule VIII, and nodal local efficiency of cerebellar lobule X. WM integrity and myelin integrity in the corpus callosum and several other language-related WM tracts may influence the semantic function in PD patients. Damage to the cerebellum lobule VIII and lobule X may also be involved in semantic dysfunction in PD patients.

Altered white matter functional pathways in Alzheimer's disease.

Alzheimer's disease (AD) is associated with functional disruption in gray matter (GM) and structural damage to white matter (WM), but the relationship to functional signal in WM is unknown. We performed the functional connectivity (FC) and graph theory analysis to investigate abnormalities of WM and GM functional networks and corpus callosum among different stages of AD from a publicly available dataset. Compared to the controls, AD group showed significantly decreased FC between the deep WM functional network (WM-FN) and the splenium of corpus callosum, between the sensorimotor/occipital WM-FN and GM visual network, but increased FC between the deep WM-FN and the GM sensorimotor network. In the clinical groups, the global assortativity, modular interaction between occipital WM-FN and visual network, nodal betweenness centrality, degree centrality, and nodal clustering coefficient in WM- and GM-FNs were reduced. However, modular interaction between deep WM-FN and sensorimotor network, and participation coefficients of deep WM-FN and splenium of corpus callosum were increased. These findings revealed the abnormal integration of functional networks in different stages of AD from a novel WM-FNs perspective. The abnormalities of WM functional pathways connect downward to the corpus callosum and upward to the GM are correlated with AD.

Atypical dermoid cyst of the corpus callosum: a case report.

BACKGROUND: Intracranial dermoid cysts (DCs) represent an infrequent subset of congenital ectodermal inclusion cysts predominantly observed near the midline structures. In spite of their benign nature, they can cause clinical manifestations, necessitating surgical removal as the main therapeutic measure. CASE REPORT: We present here an extremely rare case characterized by a radiologically atypical dermoid cyst located within the corpus callosum, an extremely rare location for such tumors. Successful surgical excision resulted in good clinical outcomes. CONCLUSIONS: This paper underscores the importance of a timely, proper radiological diagnostic process, which sees magnetic resonance imaging (MRI) as the main step, as well as the fact that interpretation of MRI data can sometimes be challenging, as it was in the patient of this report.

Subcallosal cingulate deep brain stimulation evokes two distinct cortical responses via differential white matter activation.

Subcallosal cingulate (SCC) deep brain stimulation (DBS) is an emerging therapy for refractory depression. Good clinical outcomes are associated with the activation of white matter adjacent to the SCC. This activation produces a signature cortical evoked potential (EP), but it is unclear which of the many pathways in the vicinity of SCC is responsible for driving this response. Individualized biophysical models were built to achieve selective engagement of two target bundles: either the forceps minor (FM) or cingulum bundle (CB). Unilateral 2 Hz stimulation was performed in seven patients with treatment-resistant depression who responded to SCC DBS, and EPs were recorded using 256-sensor scalp electroencephalography. Two distinct EPs were observed: a 120 ms symmetric response spanning both hemispheres and a 60 ms asymmetrical EP. Activation of FM correlated with the symmetrical EPs, while activation of CB was correlated with the asymmetrical EPs. These results support prior model predictions that these two pathways are predominantly activated by clinical SCC DBS and provide first evidence of a link between cortical EPs and selective fiber bundle activation.

Cytotoxic Lesions of the Corpus Callosum Associated with Aneurysmal Subarachnoid Hemorrhage May Influence Shunt-Dependent Chronic Hydrocephalus.

BACKGROUND: Cytotoxic lesions of the corpus callosum (CLOCCs) are occasionally associated with aneurysmal subarachnoid hemorrhage (aSAH). The effects of aSAH on clinical outcomes in such cases are unclear. The present study aimed to investigate the frequency and characteristics of CLOCCs associated with aSAH to ascertain the predictors of shunt-dependent chronic hydrocephalus (SDCH) after aSAH. METHODS: We retrospectively investigated cases of aSAH treated by coil embolization. Patients were divided into those with and without CLOCCs. Between-group differences were evaluated, including clinical outcomes and the characteristics of both the patients and the aneurysms. Patients were divided into those with and without SDCH to identify predictive factors of SDCH after aSAH focusing on CLOCCs. RESULTS: This single-center study included 196 patients with aSAH. All patients received coil embolization between April 2013 and March 2020. CLOCCs were detected in 38 (19.4%) patients. In the group with CLOCCs, male sex, poor severity grade at onset, acute hydrocephalus, SDCH (all P < 0.01), and Fisher group 3 or 4 (P = 0.04) were significantly more common than in the group without CLOCCs. Diabetes and CLOCCs were significant predictors of SDCH after aSAH in multivariate analysis (diabetes: P < 0.01, odds ratio: 6.73, 95% confidence interval: 1.61-28.09; CLOCCs: P < 0.01, odds ratio: 6.86, 95% confidence interval: 2.87-16.38). CONCLUSIONS: CLOCCs and SDCH were common in patients with poor-grade aSAH, and CLOCCs were independent predictors of SDCH after aSAH. Meticulous follow-up is necessary to detect SDCH after aSAH, especially in patients with poor-grade aSAH and CLOCCs.

Structural Alterations of the Corpus Callosum in Children With Infantile Hydrocephalus.

This study investigates structural alterations of the corpus callosum in children diagnosed with infantile hydrocephalus. We aim to assess both macrostructural (volume) and microstructural (diffusion tensor imaging metrics) facets of the corpus callosum, providing insights into the nature and extent of alterations associated with this condition. Eighteen patients with infantile hydrocephalus (mean age = 9 years) and 18 age- and sex-matched typically developing healthy children participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were used to assess corpus callosum volume and microstructure, respectively. Our findings reveal significant alterations in corpus callosum volume, particularly in the posterior area, as well as distinct microstructural disparities, notably pronounced in these same segments. These results highlight the intricate interplay between macrostructural and microstructural aspects in understanding the impact of infantile hydrocephalus. Examining these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on corpus callosum integrity, given its pivotal role in interhemispheric communication. This knowledge offers a more nuanced perspective on neurologic disorders and underscores the significance of investigating the corpus callosum's health in such contexts.

Obesity is associated with alterations in anatomical connectivity of frontal-corpus callosum.

Obesity has been linked to abnormal frontal function, including the white matter fibers of anterior portion of the corpus callosum, which is crucial for information exchange within frontal cortex. However, alterations in white matter anatomical connectivity between corpus callosum and cortical regions in patients with obesity have not yet been investigated. Thus, we enrolled 72 obese and 60 age-/gender-matched normal weight participants who underwent clinical measurements and diffusion tensor imaging. Probabilistic tractography with connectivity-based classification was performed to segment the corpus callosum and quantify white matter anatomical connectivity between subregions of corpus callosum and cortical regions, and associations between corpus callosum-cortex white matter anatomical connectivity and clinical behaviors were also assessed. Relative to normal weight individuals, individuals with obesity exhibited significantly greater white matter anatomical connectivity of corpus callosum-orbitofrontal cortex, which was positively correlated with body mass index and self-reported disinhibition of eating behavior, and lower white matter anatomical connectivity of corpus callosum-prefrontal cortex, which was significantly negatively correlated with craving for high-calorie food cues. The findings show that alterations in white matter anatomical connectivity between corpus callosum and frontal regions involved in reward and executive control are associated with abnormal eating behaviors.

Role of corpus callosum in unconscious vision.

The existence of unconscious visually triggered behavior in patients with cortical blindness (e.g., homonymous hemianopia) has been amply demonstrated and the neural bases of this phenomenon have been thoroughly studied. However, a crosstalk between the two hemispheres as a possible mechanism of unconscious or partially conscious vision has not been so far considered. Thus, the aim of this study was to assess the relationship between structural and functional properties of the corpus callosum (CC), as shown by probabilistic tractography (PT), behavioral detection/discrimination performance and level of perceptual awareness in the blind field of patients with hemianopia. Twelve patients were tested in two tasks with black-and-white visual square-wave gratings, one task of movement and the other of orientation. The stimuli were lateralized to one hemifield either intact or blind. A PT analysis was carried out on MRI data to extract fiber properties along the CC (genu, body, and splenium). Compared with a control group of participants without brain damage, patients showed lower FA values in all three CC sections studied. For the intact hemifield we found a significant correlation between PT values and visual detection/discrimination accuracy. For the blind hemifield the level of perceptual awareness correlated with PT values for all three CC sections in the movement task. Importantly, significant differences in all three CC sections were found also between patients with above-vs. chance detection/discrimination performance while differences in the genu were found between patients with and without perceptual awareness. Overall, our study provides evidence that the properties of CC fibers are related to the presence of unconscious stimulus detection/discrimination and to hints of perceptual awareness for stimulus presentation to the blind hemifield. These results underline the importance of information exchange between the damaged and the healthy hemisphere for possible partial or full recovery from hemianopia.

A de novo pathogenic variant in DHX30 gene in a fetus with isolated dysgenesis of the corpus callosum.

A 36 years old woman in her first pregnancy was referred at 24w3d for a dedicated neurosonographic examination due to a suspected short corpus callosum (CC). The examination depicted a dysgenetic CC with asymmetric thickness at the level of the body in coronal views, very thin in the midline and thicker in both sides, suggesting bilateral formation of Probst bundles. The BPD, HC, and transverse cerebellar diameters were in the normal low range without associated growth restriction. Associated anomalies were not detected in the brain or other organs. Following genetic consultation and a normal CMA, trio exome sequencing was performed and a de novo missense pathogenic mutation c.2353 C > T in the DHX30 gene was detected. This variant has been previously reported in children and adults, mostly with a severe phenotype including neurodevelopmental disorder with variable motor and language impairment, but also mild phenotypes have been reported. MRI describes delayed myelination, ventriculomegaly, and cortical and cerebellar atrophy as imaging features in affected patients. This is the first prenatal report of a DHX30-associated neurodevelopmental disorder in which the fetus presents with isolated callosal dysgenesis, stressing the importance of exome sequencing in fetuses with this condition, as far as it is phenotypic presentation of numerous syndromes with different outcomes.

Neuroanatomical comparison of treatment-resistant and treatment-responsive schizophrenia patients using the cloud-based brain magnetic resonance image segmentation and parcellation system: An MRIcloud study.

Recent developments in neuroimaging have improved our understanding of the biological mechanisms underlying schizophrenia. However, neuroimaging findings in treatment-resistant schizophrenia (TRS) remain unclear. In the present study, we aimed to explore potential neuroanatomical regions that may be associated with treatment resistance in schizophrenia patients by comparing neuroanatomical regions of TRS and non-TRS patients using the MRICloud method. A total of 33 schizophrenia patients (meeting DSM 5 diagnostic criteria for schizophrenia) were included in the study. Patients were dichotomized into TRS (n = 18) and non-TRS (n = 15) groups, and all patients underwent MRI. Neuroanatomical regions of TRS and non-TRS patients were compared using the MRICloud method. Disease severity was measured using the Positive and Negative Syndrome Scale (PANSS). Interestingly, a statistically significant greater left Corpus Collosum (CC) thickness was found in TRS patients compared to non-TRS patients. It is clear that further studies comparing TRS patients with non-TRS patients are needed, and these studies should focus on the circuits in the corpus callosum that are thought to play a role in treatment resistance. Further longitudinal studies are also needed to complement the cross-sectional studies, using a multimodal imaging approach in the patients with clearly defined TRS criteria.

MR insights into fetal brain development: what is normal and what is not.

Fetal brain development is a complex, rapid, and multi-dimensional process that can be documented with MRI. In the second and third trimesters, there are predictable developmental changes that must be recognized and differentiated from disease. This review delves into the key biological processes that drive fetal brain development, highlights normal developmental anatomy, and provides a framework to identify pathology. We will summarize the development of the cerebral hemispheres, sulci and gyri, extra-axial and ventricular cerebrospinal fluid, and corpus callosum and illustrate the most common abnormal findings in the clinical setting.