Corpus Callosum Volume Research Articles

The Relevance of Dual Language Experience in Interhemispheric Brain Connectivity in Older Adults

Abstract Objectives to analyze the volumes of sections of the corpus callosum (CC) and the integrity of the interhemispheric fibers that connect homotopic regions of the frontal and temporal lobes in bilinguals and monolinguals and to correlate neuroimaging data with cognitive measures and bilingual variables. Method 107 bilinguals and 89 monolinguals from the 1Florida ADRC were clinically diagnosed as cognitively normal (CN), MCI, or dementia; mean age = 71.28 (10.94). CC volume was calculated from a T1-weighted scan using Freesurfer. Free water (FW) and free water-corrected fractional anisotropy (FAt) maps were calculated from a diffusion MRI scan within frontal and temporal transcallosal tracts (TCATT). Results Bilinguals had a larger proportion of the anterior CC volume compared to monolinguals independent of the diagnostic group. FAt values in the Supplementary Motor Area (SMA) and the inferior temporal lobe tracts (IT TCATTs) were higher in bilinguals compared to monolinguals indicating better white matter integrity. A significant interaction demonstrated that these values were higher in bilinguals for the dementia group. Correlations were significant between the SMA FW values and several cognitive tests particularly executive function tests in both language groups. In bilinguals, the IT TCATTs correlated with language test scores. FAt in the SMA TCATT correlated with the percentage of English exposure and FAt in the IT TCATTs positively correlated with English proficiency. Conclusions Bilingualism interacts with cognitive status in aging and is associated with CC volume and the integrity of white matter in the frontal and temporal lobes supporting its role in the increase of neural reserve.

Subcortical volume in middle-aged adults with fetal alcohol spectrum disorders.

Studies of youth and young adults with prenatal alcohol exposure (PAE) have most consistently reported reduced volumes of the corpus callosum, cerebellum and subcortical structures. However, it is unknown whether this continues into middle adulthood or if individuals with PAE may experience premature volumetric decline with aging. Forty-eight individuals with fetal alcohol spectrum disorders (FASD) and 28 healthy comparison participants aged 30 to 65 participated in a 3T MRI session that resulted in usable T1-weighted and T2-weighted structural images. Primary analyses included volumetric measurements of the caudate, putamen, pallidum, cerebellum and corpus callosum using FreeSurfer software. Analyses were conducted examining both raw volumetric measurements and subcortical volumes adjusted for overall intracranial volume (ICV). Models tested for main effects of age, sex and group, as well as interactions of group with age and group with sex. We found the main effects for group; all regions were significantly smaller in participants with FASD for models using raw volumes (P's < 0.001) as well as for models using volumes adjusted for ICV (P's < 0.046). Although there were no significant interactions of group with age, females with FASD had smaller corpus callosum volumes relative to both healthy comparison females and males with FASD (P's < 0.001). As seen in children and adolescents, adults aged 30 to 65 with FASD showed reduced volumes of subcortical structures relative to healthy comparison adults, suggesting persistent impact of PAE. Moreover, the observed volumetric reduction of the corpus callosum in females with FASD could suggest more rapid degeneration, which may have implications for cognition as these individuals continue to age.

Teriflunomide, cognition and MRI: A longitudinal study

BackgroundAs cognitive impairment in multiple sclerosis (MS) is a frequent and disabling symptom, it is particularly important to identify treatments that have proven efficacy in this aspect of the disease. Several disease-modifying therapies for MS have been evaluated and shown to have a potential effect on cognition and its neurobiological correlates, but to date there is very little data on Teriflunomide (TRF). The aim of this study is to explore the influence of TRF on comprehensive cognitive function and its MRI correlations (global and focal brain volume) in relapsing-remitting multiple sclerosis (RRMS) after two years of therapy. MethodsTwenty-four patients with RRMS were evaluated at baseline and after two years of treatment with BCcogSEP, a French translation of the Brief Repeatable Battery (BRB-N) including 3 additional tests. We explored the performance evolution for each test and correlation with MRI data for all patients. We also differentiated MS patients with and without cognitive impairment. ResultsAfter two years of treatment, an improvement is observed at the Selective Reminding Test for mean number of words (p = 0.044), learning (p = 0.018), and delayed recall (p = 0.002) and at GoNoGo task (p = 0.022). At MRI, the corpus callosum volume variation correlates positively with SRT total recall test (p = 0,047). Intergoup analysis shows that the evolution of group performance differs only for the SRT total recall test. The comparison of patients with or without cognitive impairment showed a clear difference in white matter substance volume (p = 0,003) and in the Percentage Brain Volume Change (p = 0,016). ConclusionResults suggest that TRF treatment in RRMS has a positive effect in cognitive function, and specifically on long term verbal memory and inhibition. Neuroimaging data suggest a link between cognition and global and focal white matter volume, particularly in the corpus callosum which is involved in anatomical disconnection syndrome and therefore brain plasticity capacities.

Volumetric study on sheep brain using stereology technique

AbstractThree‐dimensional morphometric data better show the structural and functional characteristics of the brain. The objective of this study was to estimate the volume of the cerebral structures of the sheep using design‐based stereology. The brains of five sheep were used, fixed in formalin 10% and embedded in agar 6%. An average of 10–12 slab was obtained from each brain. All slabs were stained using Mulligan's method and photographs were recorded. The volume of the brain and its structures were estimated using the Cavalieri's estimator and the point counting system. The total volume was 70604.8 ± 132.45 mm3. The volume fractions of the grey and white matters were calculated as 42.55 ± 0.21% and 24.23 ± 0.51% of the whole brain, respectively. The fractional volume of the caudate nucleus and claustrum were estimated at 2.39 ± 0.08% and at 1.008 ± 0.057% of total brain volume. The volumes of corpus callosum, internal capsule and external capsule were 1.24 ± 0.053%, 3.63 ± 0.22% and 0.698 ± 0.049% of total cerebral volume, respectively. These data could help improve the veterinary comparative neuroanatomy knowledge and development of experimental studies in the field.

Investigating the volume of hippocampus and corpus callosum in Iranian multiple sclerosis patients using magnetic resonance imaging: a retrospective study

Multiple Sclerosis (MS) is one of the most common forms of the acquired autoimmune demyelinating disorder affecting the brain. The neurological symptoms of MS are often presented in a relapsing-remitting manner. This study aims to investigate volume changes in the hippocampus and Corpus Callosum (CC). A cross-sectional study was conducted on 200 MS patients, 100 males and 100 females, aged 20-56 years. According to McDonald’s 2017 criteria,100 patients were in the MS group, and 100 were in the control group. This study assessed volume changes in the hippocampus and CC with ITK-SNAP 4.0 software. Our study revealed that the volumes of the right Hippocampus (P&lt;0.0001), left Hippocampus (P&lt;0.05), and corpus callosum (P&lt;0.001), were significantly decreased in MS group compared to control group, regardless of the sex of the patients. Additionally, our results showed that the volume of these three areas has no significant difference with the age of MS patients. This research shows that some brain regions, including the hippocampus and corpus callosum, can be essential landmarks in determining MS disease.

P.105 Corpus callosum changes in children affected by infantile hydrocephalus

Background: Infantile hydrocephalus is characterized by an atypical accumulation of cerebrospinal fluid in the brain, diagnosed and treated before the age of 2 years. Hydrocephalus development is linked to thinning of the corpus callosum (CC), mainly due to the expansion of lateral ventricles, causing upward elevation and compression of periventricular and subcortical white matter. Methods: This study investigates structural alterations in the CC in children diagnosed with infantile hydrocephalus. We examined both macrostructural and microstructural facets of the CC, providing insights into the nature and extent of alterations associated with this condition. 18 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 utilized to assess CC volume and microstructure, respectively. Results: Our findings reveal reductions in CC volume, particularly in posterior area, and distinct microstructural disparities, notably pronounced in these same segments. Conclusions: Investigating these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on CC integrity, given its role as a neural bridge. This knowledge offers a more nuanced perspective on neurological disorders and underscores the significance of investigating the CC’s health in such contexts.

Ideational Slippage in Middle-Aged and Older Adults: A Preliminary Study.

Ideational slippage-characterized by incorrect word usage and strained logic during dialogue-is common in aging and, at greater frequency, is an indicator of pre-clinical cognitive decline. Performance-based assessment of ideational slippage may be useful in the study of cognitive aging and Alzheimer's-disease-related pathology. In this preliminary study, we examine the association between corpus callosum volume and a performance-based assessment of ideational slippage in middle-aged and older adults (age 61-79 years). Ideational slippage was indexed from cognitive special scores using the Rorschach Inkblot Method (RIM), which are validated indices of deviant verbalization and logical inaccuracy (Sum6, WSum6). Among middle-aged and older adults, smaller splenium volume was associated with greater ideational slippage (ηp2 = 0.48), independent of processing speed and fluid intelligence. The observed negative associations are consistent with visuospatial perception and cognitive functions of the splenium. The effect was strongest with the splenium, and volumes of the genu and total white matter had small effects that were not statistically significant. Conclusions: Results are discussed with future application of RIM special scores for the assessment of pre-clinical cognitive decline and, based on observed effect sizes, power analyses are reported to inform future study planning.

Sex versus gender associations with brain structure

In contrast to sex (a biological distinction), little is known about the associations between gender (a societal construct) and brain structure in the general population. In response to this knowledge gap, we examined the associations of sex vs. gender with FreeSurfer-generated cortical thickness and proportion-adjusted subcortical brain volume regions-of-interest (ROIs) in healthy adults (n = 88) screened for general medical conditions, mental illness, substance abuse, and intracranial pathologies. Gender role endorsement was assessed using the well-established and validated Bem Sex Role Inventory. For our main objectives, we calculated a continuum score as a composite measure of gender. For our secondary objectives, we examined sex-specific associations of the masculine vs. feminine gender role endorsement domains with brain structural outcomes. We found that female sex, independent of continuum scores, was associated with larger proportion-adjusted volumes for the basal ganglia, hippocampus, and ventral diencephalon. Higher continuum scores, independent of sex, were associated with thicker cortical thickness for the left and right superior frontal cortex, caudal and rostral middle frontal cortex, and right pars orbitalis. Female sex and higher continuum scores were independently associated with larger corpus callosum volumes. Post-hoc testing showed sex-specific associations between higher femininity scores and thicker prefrontal cortical thickness for the ROIs in females, but not in males. In conclusion, sex and gender showed semi-independent associations with brain structure in a general population sample. Our research supports the disaggregation of sex and gender to provide a more nuanced perspective on brain structural differences between men and women.

Gender Differences in the Cortical Distribution of Corpus Callosum Fibers.

Introduction Research on gender-based disparities in human brain structure has spanned over a century, yielding conflicting results and ongoing debate. While some studies indicate minimal distinctions, others consistently highlight differences in the corpus callosum (CC), even after accounting for average brain size. Methods Diverging from previous approaches, this study examines the morphology of the entire CC fiber rather than solely focusing on its midsagittal structure. Utilizing advanced neuroimaging techniques and generalized Q-imaging tractography, CC streamlines were constructed to assess gender differences in fractional anisotropy (FA), volume ratio, and cortical distribution. Student's t-test was employed to examine the disparities in FAbetween gender groups, while gender-based distinctions in the normalized volume of the CC and its segments were assessed using analysis of covariance (ANCOVA), with absolute whole white matter volume serving as a covariate. Results No significant gender-based disparities were found in either FA or normalized CC volume. While females exhibited consistently larger normalized volume CC streamlines than males, these differences lost statistical significance after adjusting for absolute total white matter volume as a covariate. Nonetheless, CC streamlines in females displayed a broader spatial distribution, encompassing various cortical regions, including the bilateral prefrontal cortex (medial and lateral surfaces), as well as medial parietal and temporal regions. Conclusion This study elucidates gender-related variations in the morphology of the brain's white matter pathways, indicating a more widespread cortical distribution of CC fibers in females compared to males. However, the study underscores the need for further investigations into connectivity patterns to fully elucidate these gender-based disparities.

Abstract WP323: Late-Stage Degeneration Due to Middle-Cerebral Artery Occlusion Observed in White Matter Tracts and Specific Forebrain Regions in Middle-Aged Female Rats is Attenuated by mir20a-3p Treatment: A Magnetic Resonance-Diffusion Tensor Imaging and Conventional Morphometry Study

Introduction: Our earlier studies show that the small non-coding RNA, mir20a-3p, is neuroprotective after stroke, and reduces sensory-motor impairments in the acute phase and cognitive decline in the long-term in female rats. Cognitive decline due to vascular diseases, such as stroke, is associated with volume loss in the cortex, the limbic structures and white matter tracts. In this study, we examined the volume of forebrain white matter tracts, cortical and limbic structures in animals with characterized cognitive impairment due to stroke, and the efficacy of microRNA treatment. Methodology: Middle-aged females were subjected to ischemic stroke using endothelin 1, injected adjacent to the left middle cerebral artery (MCA). Mir-20a-3p mimic (n=10) or scrambled oligo (n=8) was administered i.v. 4h, 24h and 70d post stroke. Animals were assessed periodically for cognitive performance up to 100d after stroke using both the cued fear conditioning test and the novel object recognition test (NORT). After perfusion fixation, T2 and diffusion tensor imaging (DTI) magnetic resonance imaging of the brain was performed. Thereafter, brains were processed for Weil myelin staining, followed by quantification of the corpus callosum and internal capsule. Results: Stroke resulted in impairment in both the cued fear conditioning test and the NORT, which was attenuated by mir-20a-3p treatment. Compared to sham (no-stroke) animals, volumetric analysis of DTI scans showed a significant reduction in the volume of substantia nigra (p&lt;0.02) and the entorhinal cortex (P=0.0402) in stroke +scrambled group, but not in Stroke+ Mir20 treated group. White matter tracts showed a significant reduction in the corpus callosum and internal capsule volume in the ischemic hemisphere as compared to non-ischemic hemisphere in MCAo animals treated with the scrambled oligo. In contrast, sham and MCAo+Mir-20a-3p animals displayed no hemispheric differences in volume in either tract. Conclusion: Cognitive changes measured with remote fear memory retrieval and NORT were associated with volume reductions in the substantia nigra, the entorhinal cortex, and the major forebrain white matter tracts due to stroke. These stroke-induced deficits were attenuated in Mir-20-3p treated animals.

N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia

Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15–21); and 3) NAC treatment throughout all pregnancy (GD1–21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

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.

Brain ventricle and choroid plexus morphology as predictor of treatment response in major depression: Findings from the EMBARC study

Recent observations suggest a role of the volume of the cerebral ventricle volume, corpus callosum (CC) segment volume, in particular that of the central-anterior part, and choroid plexus (CP) volume for treatment resistance of major depressive disorder (MDD). An increased CP volume has been associated with increased inflammatory activity and changes in the structure of the ventricles and corpus callosum. We attempt to replicate and confirm that these imaging markers are associated with clinical outcome in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study is a placebo controlled randomized study comparing sertraline vs. placebo in patients with MDD to identify biological markers of therapy resistance. Association of baseline volumes of the lateral ventricles (LVV), choroid plexus volume (CPV) and volume of segments of the CC with treatment response after 4 weeks treatment was evaluated. 171 subjects (61 male, 110 female) completed the 4 week assessments; gender and age were taken into account for this analyses. As previously reported, no treatment effect of sertraline vs. placebo was observed, therefore the study characterized prognostic markers of response in the pooled population. Change in depression severity was identified by the ratio of the Hamilton-Depression rating scale 17 (HAMD-17) at week 4 divided by the HAMD-17 at baseline (HAMD-17 ratio). Volumes of the lateral ventricles and choroid plexi were positively correlated with the HAMD-17 ratio, indication worse outcome with larger ventricles and choroid plexus volumes, whereas the volume of the central-anterior corpus callosum was negatively correlated with the HAMD-17 ratio. Responders (n = 54) had significantly smaller volumes of the lateral ventricles and CP compared to non-responders (n = 117), whereas the volume of mid-anterior CC was significantly larger compared to non-responders (n = 117), confirming our previous findings. In an exploratory way associations between enlarged LVV and CPV and signs of lipid dysregulation were observed. In conclusion, we confirmed that volumes of lateral ventricles, choroid plexi and the mid-anterior corpus callosum are associated with clinical improvement of depression and may be indicators of metabolic/inflammatory activity.

The Effects of 3‐month Aerobic‐Strength Training on Cognitive Functions and Adiponectin Levels in Cerebrospinal Fluid and Blood in the Elderly

AbstractBackgroundExercise improves physical fitness, cognitive functions &amp; metabolism in the elderly. Evidence from animal models suggests the role for mediators from muscle or adipose tissue in the exercise‐induced brain plasticity (1). Knowledge on the regulation of these potentially neuroprotective molecules by exercise in humans is limited (2,3). We investigated effects of 3‐month supervised aerobic‐strength training on serum &amp; cerebrospinal fluid/CSF adiponectin in the elderly, in association with cognitive functions &amp; brain volumetry.MethodThe population consisted of sedentary elderly (n = 38, 10M/28F; 66.1±5.9yrs; BMI 26.3±3.7kg/m2). Body composition (MRI), physical fitness (Rockport test), muscle strength (dynamometry), motor tests (walking speed &amp; chair stand tests), resting energy expenditure &amp; substrate preference (REE, RQ, indirect calorimetry), insulin sensitivity &amp; metabolic flexibility (euglycemic hyperinsulinemic clamp/EHC), cognitive functions (cognitive tests), brain volumetry (MRI), serum glucose &amp; insulin were assessed.ResultTraining reduced BMI, blood pressure and insulinemia, while improving insulin sensitivity &amp; metabolic flexibility (EHC), maximal aerobic capacity (VO2max), motor performance, and memory (ACE‐R). Improvements in cognitive functions were more pronounced in patients with MCI (p&lt;0.05). Training led to a small but consistent increase of CSF adiponectin in cognitively healthy seniors (p&lt;0.05), while no change was observed in MCI (p&gt;0.1). CSF adiponectin was positively associated with psychomotor attention score (CogState), and it strongly correlated with the volume of corpus callosum normalized to intracranial volume. Training did not regulate serum adiponectin.ConclusionRelatively short‐term aerobic‐strength training can improve cognitive functions together with a spectrum of anthropometric, metabolic and fitness parameters, which may slow down the ageing‐related cognitive decline. Exercise modulated levels of adiponectin in CSF which correlated with cognitive functions and volume of specific brain areas. This might indirectly indicate the role for adiponectin in the exercise‐related brain plasticity in the elderly. Funding: APVV 20‐0466, VEGA‐2/0076/22, COST DePASS, APVV 15‐0253

RTMS regulates homotopic functional connectivity in the SCD and MCI patients

ObjectiveImpaired interhemispheric connectivity and corpus callosum atrophy have been linked to cognitive impairment in Alzheimer’s disease (AD). Existing evidence indicates that repetitive transcranial magnetic stimulation (rTMS) targeting the bilateral precuneus may enhance cognitive function in AD. This study aims to investigate the effects of precuneus rTMS on cognitive function, as well as alterations in interhemispheric functional connectivity (FC) and its structural basis in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).MethodsA total of 14 patients with SCD and 16 patients with MCI were enrolled in this study and received 10 Hz rTMS intervention on the bilateral precuneus for 2 weeks. Neurocognitive scales, structural and functional magnetic resonance imaging were collected at enrollment and after the rTMS intervention. Interhemispheric FC was assessed using mirror homotopic functional connectivity (VMHC), while the structural equation modeling (SEM) was employed to analyze the relationship between corpus callosum volume, interhemispheric connectivity, and cognitive function after rTMS intervention.ResultsThe precuneus rTMS not only enhanced episodic memory in SCD, but also improved multiple cognitive domains in MCI. Post-rTMS intervention, decreased VMHC values in the lingual cortex, middle occipital gyrus, putamen, and fusiform gyrus were observed in SCD, and an increased VMHC value in the postcentral gyrus along with reduced VMHC value in the cerebellum and putamen in MCI. After intervention, more brain regions show decreased FC in SCD and MCI patients, suggesting that precuneus rTMS may protect cerebral cortical plasticity by reducing excessive functional compensation, and thus improve cognitive function. The SEM indicated that the corpus callosum serves as the structural foundation for rTMS regulation of interhemispheric FC to further improve cognitive function.Conclusion10 Hz rTMS in the bilateral precuneus could be a promising strategy to improve cognitive function in patients with SCD and MCI. Our study implies that improvements in cognition brought about by precuneus rTMS may result from the remodeling of interhemispheric FC, with the corpus callosum possibly acting as the anatomical basis for functional modulation.

Autism Spectrum Disorder Classification Using Machine Learning and Deep Learning- A Survey

Modern, highly developed technology has impacted reputable procedures in the medical and healthcare industries. Smart healthcare prediction to the senior sick patient is not only for quick access to data but also to get dependable treatment in an accurate prediction by healthcare service provider. smart health prediction helps in the identification of numerous diseases. Based on patient experience, Deep learning technology provides a robust application space in the medical sector for health disease prediction problems by applying deep learning techniques to analyze various symptoms. In order to classify things and make precise predictions about diseases, deep learning techniques are utilized. people's health will be more secure, medical care will be of a higher caliber, and personal information will be kept more secret. As deep learning algorithms become more widely used to construct an interactive smart healthcare prediction and evaluation model on the basis of the deep learning model, CNN is upgraded. Advanced deep learning algorithms combined with multi-mode approaches and resting-state functional magnetic resonance represent an innovative approach that researchers have taken. A DL structure for the programmed ID ASD using highlights separated from the corpus callosum and cerebrum volume from the Stand dataset is proposed. Imaging is used to reveal hidden diseased brain connectome patterns to find diagnostic and prognostic indicators.

Larger corpus callosum volume is favorable for theory of mind development in healthy children.

While previous research has demonstrated a link between the corpus callosum (CC) and theory of mind (ToM) abilities in individuals with corpus callosum agenesis (ACC), the relationship between CC volume and ToM remains unclear in healthy children. The present study examined whether CC volume influences children's performance on ToM tasks that assess their understanding of pretense, emotion recognition, and false beliefs. Forty children aged 6-12years underwent structural magnetic resonance imaging (MRI) and a cognitive test battery. We found that larger mid-anterior and central subsections of the CC significantly correlated with better ToM abilities. We could also demonstrate age- and sex-related effects, as the CC-ToM relationship differed between younger (6-8years) and older (9-12years) children, and between female and male participants. Importantly, the older children drove the association between the CC mid-anterior and central subsection volumes and ToM abilities. This study is the first to demonstrate that CC size is associated with ToM abilities in healthy children, underlining the idea that the CC plays a vital role in their socio-cognitive development. CC subsection volumes may thus not only serve as a measure of heterogeneity in neurodevelopmental populations known to exhibit socio-cognitive deficits, but also in typically developing children.

Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits.

The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders. We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits. We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10-6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = -0.09, SE = 0.03; p = 5.9 × 10-3) and drinks consumed per week (rg = -0.09, SE = 0.02; p = 4.8 × 10-4), and volume of the mid-anterior subregion with BD (rg = -0.12, SE = 0.02; p = 2.5 × 10-4), major depressive disorder (MDD) (rg = -0.12, SE = 0.04; p = 3.6 × 10-3), drinks consumed per week (rg = -0.13, SE = 0.04; p = 1.8 × 10-3) and cannabis use (rg = -0.09, SE = 0.03; p = 8.4 × 10-3). Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.

Normative modeling analysis reveals corpus callosum volume changes in early and mid-to-late first episode major depression

BackgroundIt has been widely accepted that major depressive disorder (MDD) impacts brain structures including the Corpus Callosum (CC). However, this assumption is based on scarce literature data involving small sample sizes. Furthermore, it is still unclear whether such CC volume changes may already be present at a first depressive episode. MethodsTo further investigate this question, we compared 369 first-episode MDD patients (mean age = 35 years (sd = 12), 249 females; 283 early onset, 86 mid-to-late onset) from the open-source REST meta-MDD database closely matched for age and gender to 490 never-depressed individuals (mean age = 37 years (sd = 14); 309 females) using Z-scores obtained from normative neuroanatomical modeling to assess individual variability in CC (sub)volumes. ResultsRelative to the norms established by the healthy controls, first-episode MDD patients displayed CC volume (z-score) reductions in the entire CC (including the body), as did mid-to-late-onset first-episode MDD patients (age ≥ 45 y). In early-onset first-episode MDD patients (age ≤ 44 y), depression severity symptoms were related to volume increases in the entire CC, as well as the body and splenium. LimitationsNo data on depressive episode duration. Relatively small sample size for mid-to-late first-episode MDD patients. ConclusionsOur data revealed CC (sub)volume differences in early versus mid-to-late onset first episode MDD. Especially at early onset, depression severity may result in neural white matter activity as potential reaction to stress influences. Our results underline the importance of prompt clinical interventions at early onset MDD.

CRMP2 conditional knockout changes axonal function and ultrastructure of axons in mice corpus callosum

Collapsin response mediator protein 2 (CRMP2) is a member of a protein family, which is highly involved in neurodevelopment, but most of its members become heavily downregulated in adulthood. CRMP2 is an important factor in neuronal polarization, axonal formation and growth cone collapse. The protein remains expressed in adulthood, but is more region specific. CRMP2 is present in adult corpus callosum (CC) and in plastic areas like prefrontal cortex and hippocampus. CRMP2 has been implicated as one of the risk-genes for Schizophrenia (SZ). Here, a CRMP2 conditional knockout (CRMP2-cKO) mouse was used as a model of SZ to investigate how it could affect the white matter and therefore brain connectivity.Multielectrode electrophysiology (MEA) was used to study the function of corpus callosum showing an increase in conduction velocity (CV) measured as Compound Action Potentials (CAPs) in acute brain slices. Light- and electron-microscopy, specifically Serial Block-face Scanning Electron Microscopy (SBF-SEM), methods were used to study the structure of CC in CRMP2-cKO mice. A decrease in CC volume of CRMP2-cKO mice as compared to controls was observed. No differences were found in numbers nor in the size of CC oligodendrocytes (OLs). Similarly, no differences were found in myelin thickness or in node of Ranvier (NR) structure. In contrast, abnormally smaller axons were measured in the CRMP2-cKO mice.Using these state-of-the-art methods it was possible to shed light on specific parts of the dysconnectivity aspect of deletion of CRMP2 related to SZ and add details to previous findings helping further understanding the disease. This paper substantiates the white matter changes in the absence of CRMP2 and ties it to the role it plays in this complex disorder.