Corpus Callosum Research Articles

Reduced interhemispheric transfer in older adults: Evidence from a divided visual field one-back task.

One of the pivotal structural changes observed in the ageing brain pertains to the corpus callosum, the largest neural pathway interconnecting the two cerebral hemispheres. Studies have highlighted the degeneration of the corpus callosum, particularly in its anterior segments, as individuals age. This prompts an essential question regarding the potential functional repercussions of these structural changes on interhemispheric communication among older adults. Two experiments were conducted to explore potential compromises in the interhemispheric transfer of visual working memory (VWM) in older adults. Both young individuals (aged 18-28 years) and healthy older adults (aged 65-85 years) engaged in modified versions of the one-back paradigm. In this task, stimuli were sequentially presented in either the left or right hemifield, and participants indicated whether each stimulus matched the preceding one. Notably, when two stimuli are matched, they could appear either in the same hemifield or in opposite hemifields. The results revealed that, in comparison to young adults, older adults demonstrated a significant increase in matching errors when the two stimuli were presented in opposite hemifields rather than the same hemifield. This new finding strongly suggests a reduced interhemispheric transfer of VWM in older adults, potentially attributed to age-related atrophy in the anterior part of the corpus callosum. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Injury Progression in Acute Blast-Induced Mild Traumatic Brain Injury in Rats Reflected by Diffusion Tensor Imaging and Immunohistochemical Examination.

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. In this study, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube, to investigate whole-brain DTI changes at 1, 3, and 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy, and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days post-injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days post-injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD, and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.

Diffusion indices alteration in major white matter tracts of children with tic disorder using TRACULA

BackgroundTic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis.MethodsWe analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts.ResultsOur findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation.ConclusionThese results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis.

A preliminary study of white matter disconnections underlying deficits in praxis in left hemisphere stroke patients.

Limb apraxia is a higher-order motor disorder often occurring post-stroke, which affects skilled actions. It is assessed through tasks involving gesture production or pantomime, recognition, meaningless gesture imitation, complex figure drawing, single and multi-object use. A two-system model for the organisation of actions hypothesizes distinct pathways mediating praxis deficits via conceptual, 'indirect', and perceptual 'direct' routes to action. Traditional lesion- symptom mapping techniques have failed to identify these distinct routes. We assessed 29 left hemisphere stroke patients to investigate white matter disconnections on deficits of praxis tasks from the Birmingham Cognitive Screening. White matter disconnection maps derived from patients' structural T1 lesions were created using a diffusion-weighted healthy participant dataset acquired from the human connectome project (HCP). Initial group-level regression analyses revealed significant disconnection between occipital lobes via the splenium of the corpus callosum and involvement of the inferior longitudinal fasciculus in meaningless gesture imitation deficits. There was a trend of left fornix disconnection in gesture production deficits. Further, voxel-wise Bayesian Crawford single-case analyses performed on two patients with the most severe meaningless gesture imitation and meaningful gesture production deficits, respectively, confirmed distinct posterior interhemispheric disconnection, for the former, and disconnections between temporal and frontal areas via the fornix, rostrum of the corpus callosum and anterior cingulum, for the latter. Our results suggest distinct pathways associated with perceptual and conceptual deficits akin to 'direct' and 'indirect' action routes, with some patients displaying both. Larger studies are needed to validate and elaborate on these findings, advancing our understanding of limb apraxia.

Sex-related variability of white matter tracts in the whole HCP cohort.

Behavioral differences between men and women have been studied extensively, as have differences in brain anatomy. However, most studies have focused on differences in gray matter, while white matter has been much less studied. We conducted a comprehensive study of 77 deep white matter tracts to analyze their volumetric and microstructural variability between men and women in the full Human Connectome Project (HCP) cohort of 1065 healthy individuals aged 22-35years. We found a significant difference in total brain volume between men and women (+ 12.6% in men), consistent with the literature. 16 tracts showed significant volumetric differences between men and women, one of which stood out due to a larger effect size: the corpus callosum genu, which was larger in women (+ 7.3% in women, p = 5.76 × 10-19). In addition, we found several differences in microstructural parameters between men and women, both using standard Diffusion Tensor Imaging (DTI) parameters and more complex microstructural parameters from the Neurite Orientation Dispersion and Density Imaging (NODDI) model, with the tracts showing the greatest differences belonging to motor (cortico-spinal tracts, cortico-cerebellar tracts) or limbic (cingulum, fornix, thalamo-temporal radiations) systems. These microstructural differences may be related to known behavioral differences between the sexes in timed motor performance, aggressiveness/impulsivity, and social cognition.

Diffusion spectrum imaging in patients with idiopathic normal pressure hydrocephalus: correlation with ventricular enlargement

BackgroundTo investigate the association between white matter changes and ventricular expansion in idiopathic normal pressure hydrocephalus (iNPH) based on diffusion spectrum imaging (DSI).MethodsWe included 32 patients with iNPH who underwent DSI using a 3T MRI scanner. The lateral ventricles were manually segmented, and ventricular volumes were measured. Two methods were utilised in the study: manual region-of-interest (ROI) delineation and tract diffusion profile analysis. General fractional anisotropy (GFA) and fractional anisotropy (FA) were extracted in different white matter regions, including the bilateral internal capsule (anterior and posterior limbs) and corpus callosum (body, genu, and splenium) with manual ROI delineation. The 18 main tracts in the brain of each patient were extracted; the diffusion metrics of 100 equidistant nodes on each fibre were calculated, and Spearman’s correlation coefficient was used to determine the correlation between diffusion measures and ventricular volume of iNPH patients.ResultsThe GFA and FA of all ROI showed no significant correlation with lateral ventricular volume. However, in the tract diffusion profile analysis, lateral ventricular volume was positively correlated with part of the cingulum bundle, left corticospinal tract, and bilateral thalamic radiation posterior, whereas it was negatively correlated with the bilateral cingulum parahippocampal (all p < 0.05).ConclusionsThe effect of ventricular enlargement in iNPH on some white matter fibre tracts around the ventricles was limited and polarizing, and most white matter fibre tract integrity changes were not associated with ventricular enlargement; this reflects that multiple pathological mechanisms may have been combined to cause white matter alterations in iNPH.

Prediction of adolescent idiopathic scoliosis with machine learning algorithms using brain volumetric measurements.

It is known that neuroanatomical and neurofunctional changes observed in the brain, brainstem and cerebellum play a role in the etiology of adolescent idiopathic scoliosis (AIS). This study aimed to investigate whether volumetric measurements of brain regions can be used as predictive indicators for AIS through machine learning techniques. Patients with a severe degree of curvature in AIS (n = 32) and healthy individuals (n = 31) were enrolled in the study. Volumetric data from 169 brain regions, acquired from magnetic resonance imaging (MRI) of these individuals, were utilized as predictive factors. A comprehensive analysis was conducted using the twelve most prevalent machine learning algorithms, encompassing thorough parameter adjustments and cross-validation processes. Furthermore, the findings related to variable significance are presented. Among all the algorithms evaluated, the random forest algorithm produced the most favorable results in terms of various classification metrics, including accuracy (0.9083), AUC (0.993), f1-score (0.970), and Brier score (0.1256). Additionally, the most critical variables were identified as the volumetric measurements of the right corticospinal tract, right corpus callosum body, right corpus callosum splenium, right cerebellum, and right pons, respectively. The outcomes of this study indicate that volumetric measurements of specific brain regions can serve as reliable indicators of AIS. In conclusion, the developed model and the significant variables discovered hold promise for predicting scoliosis development, particularly in high-risk individuals.

Decreased Cerebral Creatine and N-Acetyl Aspartate Concentrations after Severe COVID-19 Infection: A Magnetic Resonance Spectroscopy Study

Background/Objectives: The aim of this study was to evaluate brain metabolism using MR spectroscopy (MRS) after recovery from Coronavirus disease (COVID-19) and to test the impact of disease severity on brain metabolites. Methods: We performed MRS on 81 individuals (45 males, 36 females, aged 40–60), who had normal MRI findings and had recovered from COVID-19, classifying them into mild (17), moderate (36), and severe (28) groups based on disease severity during the acute phase. The study employed two-dimensional spectroscopic imaging above the corpus callosum, focusing on choline (Cho), creatine (Cr), and N-acetylaspartate (NAA). We analyzed Cho/Cr and NAA/Cr ratios as well as absolute concentrations using water as an internal reference. Results: Results indicated that the Cho/Cr ratio was higher with increasing disease severity, while absolute Cho and NAA/Cr ratios showed no significant differences across the groups. Notably, absolute Cr and NAA levels were significantly lower in patients with severe disease. Conclusions: These findings suggest that the severity of COVID-19 during the acute phase is associated with significant changes in brain metabolism, marked by an increase in Cho/Cr ratios and a reduction in Cr and NAA levels, reflecting substantial metabolic alterations post-recovery.

Feature attention graph neural network for estimating brain age and identifying important neural connections in mouse models of genetic risk for Alzheimer’s disease

Abstract Alzheimer's disease (AD), a widely studied neurodegenerative disorder, poses significant research challenges due to its high prevalence and complex etiology. Age, a critical risk factor for AD, is typically assessed by comparing physiological and estimated brain ages. This study utilizes mouse models expressing human alleles of APOE and human nitric oxide synthase 2 (hNOS2), replicating genetic risks for AD alongside a human-like immune response. We developed a multivariate model that incorporates brain structural connectomes, APOE genotypes, demographic traits (age and sex), environmental factors such as diet, and behavioral data to estimate brain age. Our methodology employs a Feature Attention Graph Neural Network (FAGNN) to integrate these diverse datasets. Behavioral data are processed using a 2D convolutional neural network (CNN), demographic traits via a 1D CNN, and brain connectomes through a graph neural network equipped with a quadrant attention module that accentuates critical neural connections. The FAGNN model demonstrated a mean absolute error in age prediction of 31.85 days and a root mean squared error of 41.84 days, significantly outperforming simpler models. Our analysis further focused on the brain age delta, which assesses accelerated or delayed aging by comparing brain age, predicted by FAGNN, to the chronological age. A high-fat diet and the presence of the human NOS2 gene were identified as significant accelerators of brain aging in the old age group. Key neural connections identified by FAGNN, such as those between the cingulum, corpus callosum, striatum, hippocampus, thalamus, hypothalamus, cerebellum, and piriform cortex, were found to be significant in the aging process. Validation using diffusion MRI-based metrics, including fractional anisotropy and return-to-origin probability measures across these connections, revealed significant age-related differences. These findings suggest that white matter degradation in the connections highlighted by FAGNN plays a key role in aging. Our findings suggest that the complex interplay of APOE genotype with sex, immunity, and environmental factors modulates brain aging and enhances our understanding of AD risk in mouse models of aging.

Corpus Callosum Abnormality in a Free-Ranging Coyote (Canis latrans).

A juvenile coyote (Canis latrans) was presented to a wildlife rehabilitation center with intermittent circling, hypernatremia, and elevated blood urea nitrogen. Diagnostic testing supported a diagnosis of hypodipsic hypernatremia. Postmortem magnetic resonance imaging (MRI) and necropsy revealed marked hypoplasia of the corpus callosum, a finding not previously reported in a free-ranging animal.

NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, we explore these pathogenic mechanisms utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice. We observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus) after r-mTBI. This elevation was accompanied by astrogliosis, microgliosis, and the accumulation of amyloid precursor protein (APP). Mice subjected to r-mTBI displayed impaired motor learning and spatial memory. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as pathological signatures of gliosis, oxidative stress, axonal damage, and white matter damage. These findings indicate NHE1 upregulation plays a role in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 may be a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Male-Biased Vulnerability of Mouse Brain Tryptophan/Kynurenine and Glutamate Systems to Adolescent Exposures to Concentrated Ambient Ultrafine Particle Air Pollution

Air pollution (AP) exposures have been associated with numerous neurodevelopmental and psychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia, all male-biased disorders with onsets from early life to late adolescence/early adulthood. While prior experimental studies have focused on effects of AP exposures during early brain development, brain development actually extends well into early adulthood. The current study in mice sought to extend the understanding of developmental brain vulnerability during adolescence, a later but significant period of brain development and maturation to the ultrafine particulate (UFPs) component of AP, considered its most reactive component. Additionally, it examined adolescent response to UFPs when preceded by earlier developmental exposures, to ascertain the trajectory of effects and potential enhancement or mitigation of adverse consequences. Outcomes focused on shared features associated with multiple neurodevelopmental disorders. For this purpose, C57Bl/6J mice of both sexes were exposed to ambient concentrated UFPs or filtered air from PND (postnatal day) 4-7 and PND10-13, and again at PND39-42 and 45-49, resulting in 3 exposure postnatal/adolescent treatment groups per sex: Air/Air, Air/UFP, and UFP/UFP. Features common to neurodevelopmental disorders were examined at PND50. Mass exposure concentration from postnatal exposure averaged 44.34 μg/m3 and the adolescent exposure averaged 49.18 μg/m3. Male brain showed particular vulnerability to UFP exposures in adolescence, with alterations in frontal cortical and striatal glutamatergic and tryptophan/serotonergic neurotransmitters and concurrent reductions in levels of astrocytes in corpus callosum and in serum cytokine levels, with combined exposures resulting in significant reductions in corpus callosum myelination and serum corticosterone. Reductions in serum corticosterone in males correlated with reductions in neurotransmitter levels, and reductions in striatal glutamatergic function specifically correlated with reductions in corpus callosum astrocytes. UFP-induced changes in neurotransmitter levels in males were mitigated by prior postnatal exposure, suggesting potential adaptation, whereas reductions in corticosterone and in corpus callosum neuropathological effects were further strengthened by combined postnatal and adolescent exposures. UFP-induced changes in females occurred primarily in striatal dopamine systems and as reductions in serum cytokines only in response to combined postnatal and adolescent exposures. Findings in males underscore the importance of more integrated physiological assessments of mechanisms of neurotoxicity. Further, these findings provide biological plausibility for an accumulating epidemiologic literature linking air pollution to neurodevelopmental and psychiatric disorders. As such, they support a need for consideration of the regulation of the UFP component of air pollution.

An Improved Postprocessing Method to Mitigate the Macroscopic Cross-Slice B0 Field Effect on R2* Measurements in the Mouse Brain at 7T

The MR transverse relaxation rate, R2*, has been widely used to detect iron and myelin content in tissue. However, it is also sensitive to macroscopic B0 inhomogeneities. One approach to correct for the B0 effect is to fit gradient-echo signals with the three-parameter model, a sinc function-weighted monoexponential decay. However, such three-parameter models are subject to increased noise sensitivity. To address this issue, this study presents a two-stage fitting procedure based on the three-parameter model to mitigate the B0 effect and reduce the noise sensitivity of R2* measurement in the mouse brain at 7T. MRI scans were performed on eight healthy mice. The gradient-echo signals were fitted with the two-stage fitting procedure to generate R2corr_t*. The signals were also fitted with the monoexponential and three-parameter models to generate R2nocorr* and R2corr*, respectively. Regions of interest (ROIs), including the corpus callosum, internal capsule, somatosensory cortex, caudo-putamen, thalamus, and lateral ventricle, were selected to evaluate the within-ROI mean and standard deviation (SD) of the R2* measurements. The results showed that the Akaike information criterion of the monoexponential model was significantly reduced by using the three-parameter model in the selected ROIs (p = 0.0039–0.0078). However, the within-ROI SD of R2corr* using the three-parameter model was significantly higher than that of the R2nocorr* in the internal capsule, caudo-putamen, and thalamus regions (p = 0.0039), a consequence partially due to the increased noise sensitivity of the three-parameter model. With the two-stage fitting procedure, the within-ROI SD of R2corr* was significantly reduced by 7.7–30.2% in all ROIs, except for the somatosensory cortex region with a fast in-plane variation of the B0 gradient field (p = 0.0039–0.0078). These results support the utilization of the two-stage fitting procedure to mitigate the B0 effect and reduce noise sensitivity for R2* measurement in the mouse brain.

Treatment of vascular dementia in female rats with AV-001, an Angiopoietin-1 mimetic peptide, improves cognitive function

BackgroundVascular dementia (VaD) is a complex neurodegenerative disorder. We previously found that treatment of VaD in middle-aged male rats subjected to multiple microinfarction (MMI) with AV-001, a Tie2 receptor agonist, significantly improves cognitive function. Age and sex affect the development and response of VaD to therapeutic intervention. Thus, the present study investigated the therapeutic effect of AV-001 on VaD in aged female rats subjected to MMI.MethodsFemale 18-month-old Wistar rats were subjected to MMI by injecting either 1,000 (low dose, LD-MMI) or 6,000 (high dose, HD-MMI) cholesterol crystals of size 70–100 μm into the right internal carotid artery. AV-001 (1 μg/Kg, i.p.) was administered once daily after MMI for 1 month, with treatment initiated 1 day after MMI. A battery of behavioral tests to examine sensorimotor and cognitive functions was performed at 21–28 days after MMI. All rats were sacrificed at 1 month after MMI.ResultsAged female rats subjected to LD-MMI exhibit severe neurological deficits, memory impairment, and significant white matter (WM) and oligodendrogenesis injury in the corpus callosum compared with control rats. HD-MMI in aged female rats induces significant anxiety- and depression-like behaviors, which were not detected in LD-MMI aged female rats. Also, HD-MMI induces significantly increased WM injury compared to LD-MMI. AV-001 treatment of LD-MMI and HD-MMI increases oligodendrogenesis, myelin and axon density in the corpus callosum and striatal WM bundles, promotes WM integrity and attenuates neurological and cognitive deficits. Additionally, both LD-MMI and HD-MMI rats exhibit a significant increase, while AV-001 significantly decreases the levels of inflammatory factors in the cerebrospinal fluid (CSF).ConclusionMMI reduces oligodendrogenesis, and induces demyelination, axonal injury and WM injury, and causes memory impairment, while HD-MMI induces increased WM injury and further depression-like behaviors compared to LD-MMI rats. AV-001 has a therapeutic effect on aged female rats with MMI by reducing WM damage and improving neuro-cognitive outcomes.

Abnormal hypothalamic functional connectivity associated with cognitive impairment in craniopharyngiomas

ObjectiveThis study sought to characterize resting-state functional connectivity (rsFC) patterns of the hypothalamic and extrahypothalamic nuclei in craniopharyngioma (CP) patients, and to investigate potential correlations between hypothalamic and extrahypothalamic rsFC maps and neurocognitive performance. MethodsNinety-two CP patients and 40 demographically-matched healthy controls were included. Whole-brain seed-to-voxel analyses were used to test for between-group rsFC differences, and regression analyses were used to correlate neurocognitive performance with voxel-wise hypothalamic and extrahypothalamic rsFC maps for CP patients. Finally, spectral DCM analysis was used to explore the hypothalamus circuit associated with neurocognitive performance. ResultsThe seed-to-voxel analyses demonstrated that the hypothalamic nuclei showed mainly significant rsFC reduction in brain areas overlayed with the cortical regions of default mode network (DMN), notably in the bilateral anterior cingulate cortices and posterior cingulate cortices. The extrahypothalamic nuclei showed significant rsFC reduction in the limbic system of bilateral caudate nuclei, corpus callosum, fornix, and thalamus. Regression analyses revealed that worse cognitive performance was correlated with abnormal hypothalamic rsFC with brain areas in DMN, and DCM analysis revealed a hypothalamus-DMN circuit responsible for functional modulation of cognitive impairment in CP patients. ConclusionsOur study demonstrated that CPs invading into hypothalamus impacted hypothalamic and extrahypothalamic rsFC with brain areas of DMN and limbic system, the severity of which was parallel with the grading system of hypothalamus involvement. In addition to the CP-induced structural damage to the hypothalamus alone, abnormal functional connectivity within the hypothalamus-DMN circuit might be a functional mechanism leading to the cognitive impairment in CP patients.

Childhood obesity's impact on cognition and brain connectivity worsens with low family income.

Childhood obesity and its adverse health consequences have risen worldwide, with low socioeconomic status increasing the risk in high-income countries like the US. Understanding the interplay between childhood obesity, cognition, socioeconomic factors, and the brain is crucial for prevention and treatment. Using data from the ABCD study, we investigated how body mass index (BMI) relates to brain structural and functional connectivity metrics. Obese/overweight children (n = 2,356) were more likely to live in poverty and exhibited lower cognitive performance compared to normal weight children (n = 4,754). Higher BMI was associated with multiple brain measures that were strongest for lower longitudinal diffusivity in corpus callosum, increased activity in cerebellum, insula, and somatomotor cortex, and decreased functional connectivity in multimodal brain areas, with effects more pronounced among children from low-income families. Notably, nearly 80% of the association of low income and 70% of the association of impaired cognition on BMI were mediated by higher brain activity in somatomotor areas. Increased resting activity in somatomotor areas and decreased structural and functional connectivity likely contribute to the higher risk of overweight/obesity among children from low-income families. Supporting low-income families and implementing educational interventions to improve cognition may promote healthy brain function and reduce the risk of obesity.

Childhood obesity's impact on cognition and brain connectivity worsens with low family income.

Childhood obesity and its adverse health consequences have risen worldwide, with low socioeconomic status increasing the risk in high-income countries like the US. Understanding the interplay between childhood obesity, cognition, socioeconomic factors, and the brain is crucial for prevention and treatment. Using data from the ABCD study, we investigated how body mass index (BMI) relates to brain structural and functional connectivity metrics. Obese/overweight children (n = 2,356) were more likely to live in poverty and exhibited lower cognitive performance compared to normal weight children (n = 4,754). Higher BMI was associated with multiple brain measures that were strongest for lower longitudinal diffusivity in corpus callosum, increased activity in cerebellum, insula, and somatomotor cortex, and decreased functional connectivity in multimodal brain areas, with effects more pronounced among children from low-income families. Notably, nearly 80% of the association of low income and 70% of the association of impaired cognition on BMI were mediated by higher brain activity in somatomotor areas. Increased resting activity in somatomotor areas and decreased structural and functional connectivity likely contribute to the higher risk of overweight/obesity among children from low-income families. Supporting low-income families and implementing educational interventions to improve cognition may promote healthy brain function and reduce the risk of obesity.

Advancing understanding of the role of IL-22 in myelination: insights from the Cuprizone mouse model

Despite significant advancements in the field, the pathophysiology of multiple sclerosis (MS) remains partially understood, with limited therapeutic options available for this debilitating condition. The precise impact of Interleukin-22 (IL-22) in the context of MS is still incompletely elucidated with some evidence suggesting its protective role. To provide a more comprehensive understanding of the role of IL-22, we investigated its effect on remyelination in a mouse model of demyelination induced by Cuprizone. Mice underwent a 6 week regimen of Cuprizone or vehicle, followed or not by intraperitoneal administration of IL-22. Behavioral assessments including tail suspension and inverted screen tests were conducted, alongside histological, histochemical, and quantitative PCR analyses. In Cuprizone-treated mice, IL-22 significantly improved motor and behavioral performance and robustly promoted remyelination in the corpus callosum. Additionally, IL-22 administration led to a significant elevation in MBP transcription in brain biopsies of treated mice. These findings collectively suggest a crucial role for IL-22 in the pathophysiology of MS, particularly in supporting the process of remyelination. These results offer potential avenues for expanding therapeutic strategies for MS treatment. Ongoing experiments aim to further unravel the underlying mechanisms of IL-22 action.

Midline structures and cortical development in late-onset fetal growth restriction according to Doppler status: prospective study.

Fetuses with late-onset growth restriction (FGR) have a higher risk of suboptimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structure growth and cortical development in fetuses with late-onset FGR according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. This was a prospective observational study that included fetuses with late-onset FGR (defined according to the Delphi FGR criteria) undergoing neurosonography between 32 and 34 weeks' gestation. Midline structure (corpus callosum (CC) and cerebellar vermis (CV)) length and cortical development, including the depth of the Sylvian (SF), parieto-occipital (POF) and calcarine (CF) fissures, were compared between late-onset FGR, small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) fetuses. Subgroup analysis according to the severity of FGR (normal vs abnormal fetal Doppler) was also performed. Univariate analysis was used to analyze the data. A total of 52 late-onset FGR fetuses with normal Doppler findings, 60 late-onset FGR fetuses with abnormal Doppler findings, 64 SGA fetuses and 100 AGA fetuses were included in the analysis. When comparing AGA controls with SGA fetuses, late-onset FGR fetuses with normal Doppler findings and late-onset FGR fetuses with abnormal Doppler findings, there was a progressive and significant reduction in the absolute values of the following parameters: CC length (median (interquartile range (IQR)), 43.5 (28.9-56.1) mm vs 41.9 (27.8-51.8) mm vs 38.5 (29.1-50.5) mm vs 31.7 (23.8-40.2) mm; K = 26.68; P < 0.0001), SF depth (median (IQR), 14.5 (10.7-16.8) mm vs 12.7 (9.8-15.1) mm vs 11.9 (9.1-13.4) mm vs 8.3 (6.7-10.3) mm; K = 75.82; P < 0.0001), POF depth (median (IQR), 8.6 (6.3-11.1) mm vs 8.1 (5.6-10.4) mm vs 7.8 (6.1-9.3) mm vs 6.6 (4.2-8.0) mm; K = 45.06; P < 0.0001) and CF depth (median (IQR), 9.3 (6.7-11.5) mm vs 8.2 (5.7-10.7) mm vs 7.7 (5.2-9.4) mm vs 6.3 (4.5-7.2) mm; K = 46.14; P < 0.0001). Absolute CV length was significantly higher in AGA fetuses compared with all other groups, although the same progressive pattern was not noted (median (IQR), 24.9 (17.6-29.2) mm vs 21.6 (15.2-26.1) mm vs 19.1 (13.8-25.9) mm vs 21.0 (13.5-25.8) mm; K = 16.72; P = 0.0008). When the neurosonographic variables were corrected for fetal head circumference, a significant difference in the CC length and SF, POF and CF depths, but not CV length, was observed only in late-onset FGR fetuses with abnormal Doppler findings when compared with AGA and SGA fetuses. Fetuses with late-onset FGR had shorter CC length and delayed cortical development when compared with AGA fetuses. After controlling for fetal head circumference, these differences remained significant only in late-onset FGR fetuses with abnormal Doppler. These findings support the existence of a link between brain development and impaired placental function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Diffusion Basis Spectrum Imaging of White Matter in Schizophrenia and Bipolar Disorder.

Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been few in vivo tools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies. We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =27), schizophrenia (SCZ, n =21), and bipolar disorder (BPD, n =21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants. In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups. Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.