Corpus Callosum Volume Research Articles

The genetic architecture of the corpus callosum and its genetic overlap with common neuropsychiatric diseases

BackgroundThe corpus callosum (CC) is the main structure transferring information between the cerebral hemispheres. Although previous large-scale genome-wide association study (GWAS) has illustrated the genetic architecture of white matter integrity of CC, CC volume is less stressed. MethodsUsing MRI data from 33,861 individuals in UK Biobank, we conducted univariate and multivariate GWAS for CC fractional anisotropy (FA) and volume with PLINK 2.0 and MOSTest. All discovered SNPs in the multivariate framework were functionally annotated in FUMA v1.3.8. In the meanwhile, a series of gene property analyses was conducted simultaneously. In addition, we estimated genetic relationship between CC metrics and other neuropsychiatric traits and diseases. ResultsWe identified a total of 36 and 82 significant genomic loci for CC FA and volume (P < 5 × 10−8). And 53 and 27 genes were respectively mapped by four mapping strategies. For CC volume, gene-set analysis revealed pathways mainly relating to cell migration; cell-type analysis found the top enrichment in neuroglia while for CC FA in GABAergic neurons. Furthermore, we found a lot of genetic overlap and shared loci between CC FA and volume and common neuropsychiatric diseases. DiscussionCollectively, this study helps to better understand the genetic architecture of whole CC and CC subregions. However, the way to divide CC FA and volume in our study restricts the interpretations of our results. Future work will be needed to pay attention to the genetic structure of white matter volume, and an appropriate division of CC may help to better understand CC structure.

Clinical Features, Brain-Structure Changes, and Cognitive Impairment in Basal Ganglia Infarcts: A Pilot Study.

Stroke has been considered to raise the risk of dementia in several studies, but the relationship between brain structural changes and poststroke cognitive impairment (PSCI) is unclear. In this study, 23 PSCI patients with basal ganglia infarcts after 2 weeks and 29 age-matched controls underwent magnetic resonance imaging measuring cortical thickness and volume changes, as well as neuropsychological tests. CI was derived from a performance score <1.5 standard deviations for normally distributed scores. We compared Z scores in different cognitive domains and cortical thickness and volumes in two groups. Multiple linear regressions were used to investigate the relationship between cortical thickness and volumes and neuropsychological tests. A majority of PSCI patients were in their 50s (55.19±8.52 years). PSCI patients exhibited significantly decreased Z scores in multiple domains, such as memory, language, visuomotor speed, and attention/executive function. The volumes of the middle posterior corpus callosum, middle anterior corpus callosum, and hippocampus in PSCI patients were markedly lower than controls. The thickness of the right inferior temporal cortex and insula were significantly smaller than controls. It found that the reduced right hippocampus was related to executive dysfunction. Hippocampus dysfunction may be involved in language impairment (p<0.05) in PSCI patients with basal ganglia infarcts. These findings demonstrated that brain structure changed after ischemic stroke, and different gray-matter structural changes could lead to specific cognitive decline in PSCI patients with basal ganglia infarcts. Atrophy of the right hippocampus potentially serves as an imaging marker of early executive function of PSCI.

Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC). Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.

Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume. Healthy controls (n = 49) and SCD participants without overt stroke (n = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions. Reduced hemoglobin was associated with reductions in both GMV (p = 0.032) and WMV (p = 0.005); reduced arterial oxygen content (CaO2) was also associated with reductions in GMV (p = 0.035) and WMV (p = 0.006). Elevated gray matter CBF was associated with reduced WMV (p = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself (p = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei (p = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes (p = 0.002, 0.002, 0.009, 0.002, respectively). We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD.

Infant Perioperative Risk Factors and Adverse Brain Findings Following Long-Gap Esophageal Atresia Repair

Recent findings implicate brain vulnerability following long-gap esophageal atresia (LGEA) repair. We explored the relationship between easily quantifiable clinical measures and previously reported brain findings in a pilot cohort of infants following LGEA repair. MRI measures (number of qualitative brain findings; normalized brain and corpus callosum volumes) were previously reported in term-born and early-to-late premature infants (n = 13/group) <1 year following LGEA repair with the Foker process. The severity of underlying disease was classified by an (1) American Society of Anesthesiologist (ASA) physical status and (2) Pediatric Risk Assessment (PRAm) scores. Additional clinical end-point measures included: anesthesia exposure (number of events; cumulative minimal alveolar concentration (MAC) exposure in hours), length (in days) of postoperative intubated sedation, paralysis, antibiotic, steroid, and total parenteral nutrition (TPN) treatment. Associations between clinical end-point measures and brain MRI data were tested using Spearman rho and multivariable linear regression. Premature infants were more critically ill per ASA scores, which showed a positive association with the number of cranial MRI findings. Clinical end-point measures together significantly predicted the number of cranial MRI findings for both term-born and premature infant groups, but none of the individual clinical measures did on their own. Listed easily quantifiable clinical end-point measures could be used together as indirect markers in assessing the risk of brain abnormalities following LGEA repair.

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P≤0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

Counting on random number generation: Uncovering mild executive dysfunction in congenital heart disease

Congenital heart disease (CHD) is associated with various neurocognitive deficits, particularly targeting executive functions (EFs), of which random number generation (RNG) is one indicator. RNG has, however, never been investigated in CHD. We administered the Mental Dice Task (MDT) to 67 young adults with CHD and 55 healthy controls. This 1-minute-task requires the generation of numbers 1 to 6 in a random sequence. RNG performance was correlated with a global EF score. Participants underwent MRI to examine structural-volumetric correlates of RNG. Compared to controls, CHD patients showed increased backward counting, reflecting deficient inhibition of automatized behavior. They also lacked a small-number bias (higher frequency of small relative to large numbers). RNG performance was associated with global EF scores in both groups. In CHD patients, MRI revealed an inverse association of counting bias with most of the volumetric measurements and the amount of small numbers was positively associated with corpus callosum volume, suggesting callosal involvement in the “pseudoneglect in number space”.In conclusion, we found an impaired RNG performance in CHD patients, which is associated with brain volumetric measures. RNG, reportedly resistant to learning effects, may be an ideal task for the longitudinal assessment of EFs in patients with CHD.

Three dimensional development and asymmetry of the corpus callosum in the 0-18 age group: A retrospective magnetic resonance imaging study.

Most of the corpus callosum (CC) developmental studies are concerned with its two-dimensional structure. Linear and area measurements do not directly assess the CC size but estimate the overall structure from the cross-sectional image. This study investigated age- and sex-related changes in volumetric development and asymmetry of CC from birth to 18. For this retrospective study, we selected 696 patients (329 [47.27%] females) with both 3D-T1-weighted sequence and normal radiological anatomy from patients 0-18 years of age who had brain magnetic resonance imaging (MRI) between 2012 and 2020. The genu, body, splenium, and total volume of CC were calculated using MRICloud. The measurement results of 23 age groups were analyzed with SPSS (ver.28). Total CC volume was 18740.76 ± 4314.06 mm3 between 0 and 18 years of age, and its ratio to total brain volume (TBV) was 1.70% ± 0.23%. We observed that the total CC volume has six developmental periods 0 years, 1, 2-4, 5-9, 10-16, and 17-18 years. Genu and body grew in five developmental periods, while splenium in seven. There was intermittent sexual dimorphism in the CC volume in the first 4 years of life (p < 0.05). However, sex factor was insignificant in CC ratio to TBV. Total CC was right lateralized on average 1.81% (ranging -0.59% to 4.52%). Genu was 8.70% lateralized to the right, the body was 2.99% to the left, and the splenium was 1.41% to the right. The three-dimensional development of CC agreed with the two-dimensional developmental data of CC except for some differences.

Altered structural and functional homotopic connectivity associated with the progression from mild cognitive impairment to Alzheimer's disease

The progressive mild cognitive impairment (pMCI) is associated with an increased risk of Alzheimer's disease (AD). Many studies have reported the disrupted brain alteration during the imminent conversion from pMCI to AD. However, the subtle difference of structural and functional of inter-hemispheric between pMCI and stable mild cognitive impairment (sMCI) remains unknown. In the present study, we scanned the multimodal magnetic resonance imaging of 38 sMCI, 26 pMCI, and 50 healthy controls (HC) and assessed the cognitive function. The voxel-mirrored homotopic connectivity (VMHC) and volume of corpus callosum were calculated. A structural equation modeling (SEM) was established to determine the relationships between the corpus callosum, the inter-hemispheric connectivity, and cognitive assessment. Compared to sMCI, pMCI exhibited decreased VMHC in insular and thalamus, and reduced volume of corpus callosum. SEM results showed that decreased inter-hemispheric connectivity was directly associated with cognitive impairment and corpus callosum atrophy, and corpus callosum atrophy indirectly caused cognitive impairment by mediating inter-hemispheric connectivity in pMCI. In conclusion, the destruction of homotopic connectivity is related to cognitive impairment, and the corpus callosum atrophy partially mediates the association between the homotopic connectivity and cognitive impairment in pMCI.

White-matter correlates of anxiety: The contribution of the corpus-callosum to the study of anxiety and stress-related disorders.

Traumatic stress has been associated with increased risk for brain alterations and development of anxiety disorders. Studies conducted in posttraumatic patients have shown white-mater volume and diffusion alterations in the corpus-callosum. Decreased cognitive performance has been demonstrated in acute stress disorder and posttraumatic patients. However, whether cognitive alterations result from stress related neuropathology or reflect a predisposition is not known. In the current study, we examined in healthy controls, whether individual differences in anxiety are associated with those cognitive and brain alterations reported in stress related pathologies. Twenty healthy volunteers were evaluated for anxiety using the state-trait inventory (STAI), and were tested for memory performance. Brain imaging was employed to extract volumetric and diffusion characteristics of the corpus-callosum. Significant correlations were found between trait anxiety and all three diffusion parameters (fractional-anisotropy, mean and radial-diffusivity). Associative-memory performance and corpus-callosum volume were also significantly correlated. We suggest that cognitive and brain alterations, as tested in the current work and reported in stress related pathologies, are present early and possibly persist throughout life. Our findings support the hypothesis that individual differences in trait anxiety predispose individuals towards negative cognitive outcomes and brain alterations, and potentially to stress related disorders.

Microstructural organization of the corpus callosum in young endurance athletes: A global tractography study.

Aerobic exercise training has been shown to improve microstructural organization of the corpus callosum (CC); however, evidence of this topographic effect is limited. To compare the CC microstructural organization between endurance athletes and sedentary adults using a white-matter fiber tractography approach. Diffusion tensor imaging (DTI) and T1-weighted structural data were collected from 15 male young endurance athletes and 16 age- and sex-matched sedentary adults. DTI data were analyzed with a global probabilistic tractography method based on neighborhood anatomical information. Fractional anisotropy (FA) and mean, radial (RD), and axial diffusivities were measured in the eight CC tracts: rostrum, genu, splenium, and body's prefrontal, premotor, central, parietal, and temporal tracts. Cortical thickness of the CC tract endpoints and the CC tract length and volume were also measured. Physical activity level was assessed by metabolic equivalents (METs). The athlete group had an average VO2max of 69.5 ± 3.1 ml/kg/min, which is above 90%ile according to the American College of Sports Medicine guideline. Compared with the sedentary group, the athlete group had higher FA in the CC body's premotor and parietal tracts and the CC splenium. These tracts showed lower RD in the athlete compared with sedentary group. The voxelwise analysis confirmed that the athlete group had higher FA in the CC and other white matter regions than the sedentary group, including the corona radiata, internal capsule, and superior longitudinal fasciculus. Cortical thickness of the CC tract endpoints and the CC tract lengths and volumes were similar between the two groups. Physical activity levels were positively correlated with FA in the CC body's parietal (r = 0.486, p = 0.006) and temporal (r = 0.425, p = 0.017) tracts and the CC splenium (r = 0.408, p = 0.023). Young endurance athletes have higher microstructural organization of the CC tracts connected the sensorimotor and visual cortices than the age- and sex-matched sedentary adults.

Expanding the Spectrum of Early Neuroradiologic Findings in β Propeller Protein-Associated Neurodegeneration.

β propeller protein-associated neurodegeneration (BPAN) is the most common neurodegeneration with brain iron accumulation disorder. Typical radiologic findings are T2 hypointensity in the substantia nigra and globus pallidus, as well as a T1 halolike substantia nigra hyperintense signal surrounding a hypointense central area. However, these findings are often subtle or absent on initial scans, risking diagnostic delay. In this study, we sought to investigate radiologic findings that could aid in the early diagnosis of BPAN. A retrospective cohort study was performed in a national referral center, including all pediatric patients with confirmed pathogenic WDR45 mutations and consistent clinical semiology. MR imaging findings were independently reported by 2 pediatric neuroradiologists. Fifteen patients were included in the study, and 27 scans were available for review. The initial neuroimaging study was undertaken at a mean age of 3.2 years. Iron deposition was uncommon in patients younger than 4 years of age. Neuroradiologic features from very early on included dentate, globus pallidus, and substantia nigra swelling, as well as a thin corpus callosum and small pontine volume. Optic nerve thinning was also present in all patients. Our study highlights the key early MR imaging features of BPAN. Iron deposition in the globus pallidus and substantia nigra is not common in children younger than 4 years of age; clinicians should not be deterred from suspecting BPAN in the presence of the findings described in this study and the appropriate clinical context.

Outdoor residential air pollution exposure and the development of brain morphology across childhood: a longitudinal study

Background and aim: Emerging evidence suggests a relationship between exposure to air pollution and brain morphology in children, but little is known about how air pollution exposure influences the development of brain structures throughout childhood. We aim to study the association of air pollution exposure during pregnancy and childhood with the development of brain morphology from age 6-16 years. Methods: We used data from 4,243 children of the Generation R study, a birth cohort in Rotterdam, the Netherlands. We estimated the concentrations of fourteen air pollutants at participant´s home addresses during pregnancy and childhood, using land use regression models. We included structural brain images at three time points, namely at age 6-10 years, 9-12 years, and 13-16 years. We assessed the association between the air pollutants and brain volumes with linear mixed models, fitting an interaction term for age and each pollutant. Models were adjusted for socioeconomic status and lifestyle characteristics. Results: Higher air pollution exposure during pregnancy was associated with a slower decrease of cortical grey matter volume starting at around age 10 and a slower increase of corpus callosum volume (e.g. -12.7 mm3 increase in corpus callosum volume [95%CI -22.0; -3.3] with each year of age per 10 &amp;#x3bc;g/m3 increase in nitrogen dioxide exposure). Childhood exposure was associated with a faster decrease of putamen and caudate nucleus volume, and a slower increase of hippocampus volume. Higher exposure to air pollution during pregnancy and childhood was associated with a slower increase of thalamus volume. Air pollution exposure was not associated with cerebellum, amygdala, nucleus accumbens or globus pallidus volume. Conclusions: Air pollution exposure was associated with region-specific differences in age-related growth trajectories. Air pollution exposure during childhood might affect different brain regions than exposure during pregnancy. Keywords: air pollution, neurodevelopment, children, traffic

Corpus Callosum Volume in Patients with First-Episode Psychosis

Objective In first-episode psychosis, a relationship may exist between disruption communication between two brain hemispheres and psychosis symptomatology. We aimed to investigate the relationship between corpus callosum (CC) volume and psychosis symptomatology in patients with first-episode psychosis. Methods This is a retrospective case-control study wherein first-episode psychosis cases and healthy controls were included from inpatient unit archives of the Department of Psychiatry and Department of Radiology, Dokuz Eylül University School of Medicine. Psychosis symptoms were assessed using the positive and negative syndrome scale (PANSS). The CC, the chief connection between two brain hemispheres, was examined using magnetic resonance imaging (MRI); 27 patients with first-episode psychosis and 29 healthy volunteers were evaluated via 1.5-T MR. MRI findings of CC volumes of the two groups were compared. Correlations between PANSS scores and CC volume were also evaluated. Results The CC volume was lower in patients with first-episode psychosis than in healthy controls. Moreover, we observed a significant negative correlation between the CC volume and emotional withdrawal scores, and a significant positive correlation between the CC volume and hallucinations. Conclusions The CC is a vital structure that connects two frontal lobes of the brain. There may be CC abnormalities in first-episode psychosis. Emotional withdrawal is associated with decreased CC volume, whereas hallucinations are associated with increased CC volume. The development of these symptoms may be associated with changes in CC connections.

Investigating the use of plasma pTau181 in retired contact sports athletes.

Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration. Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging. Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08pg/mL vs. 6.00 ± 2.53pg/mL, respectively; 95% BCa CI 1.38-4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (β = - 0.002; 95% BCa CI - 0.003 to - 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10-3 mm2/s vs. 0.90 ± 0.03 × 10-3 mm2/s, p = 0.003; CC axial diffusivity: 1.49 ± 0.04 × 10-3 mm2/s vs. 1.41 ± 0.02 × 10-3 mm2/s, p < 0.001, respectively). Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.

Reduced and delayed myelination and volume of corpus callosum in an animal model of Fetal Alcohol Spectrum Disorders partially benefit from voluntary exercise

1 in 20 live births in the United States is affected by prenatal alcohol exposure annually, creating a major public health crisis. The teratogenic impact of alcohol on physical growth, neurodevelopment, and behavior is extensive, together resulting in clinical disorders which fall under the umbrella term of Fetal Alcohol Spectrum Disorders (FASD). FASD-related impairments to executive function and perceptual learning are prevalent among affected youth and are linked to disruptions to corpus callosum growth and myelination in adolescence. Targeted interventions that support neurodevelopment in FASD-affected youth are nonexistent. We evaluated the capacity of an adolescent exercise intervention, a stimulator of myelinogenesis, to upregulate corpus callosum myelination in a rat model of FASD (third trimester-equivalent alcohol exposure). This study employs in vivo diffusion tensor imaging (DTI) scanning to investigate the effects of: (1) neonatal alcohol exposure and (2) an adolescent exercise intervention on corpus callosum myelination in a rodent model of FASD. DTI scans were acquired twice longitudinally (pre- and post-intervention) in male and female rats using a 9.4 Tesla Bruker Biospec scanner to assess alterations to corpus callosum myelination noninvasively. Fractional anisotropy values as well as radial/axial diffusivity values were compared within-animal in a longitudinal study design. Analyses using mixed repeated measures ANOVA’s confirm that neonatal alcohol exposure in a rodent model of FASD delays the trajectory of corpus callosum growth and myelination across adolescence, with a heightened vulnerability in the male brain. Alterations to corpus callosum volume are correlated with reductions to forebrain volume which mediates an indirect relationship between body weight gain and corpus callosum growth. While we did not observe any significant effects of voluntary aerobic exercise on corpus callosum myelination immediately after completion of the 12-day intervention, we did observe a beneficial effect of exercise intervention on corpus callosum volume growth in all rats. In line with clinical findings, we have shown that prenatal alcohol exposure leads to hypomyelination of the corpus callosum in adolescence and that the severity of damage is sexually dimorphic. Further, exercise intervention improves corpus callosum growth in alcohol-exposed and control rats in adolescence.

Reduced Volume of Anterior Corpus Callosum in Alzheimer’s Disease With Psychotic Symptoms: Cross-Sectional Magnetic Resonance Imaging Study

Objective: Although previous studies have shown association between anterior corpus callosum (ACC) and various psychotic disorder, the effect of ACC on development on psychotic symptoms in Alzheimer’s disease (AD) is still unclear. The purpose of this study is to investigate the association of ACC with the development of psychosis in patients with AD. Methods: This is a hospital based cross-sectional study of 241 AD patients. The main outcome measure is the volume of ACC that were measured as regions of interest with magnetic resonance imaging and the FreeSurfer analysis at baseline. Analysis of covariance and Logistic regression analysis conducted to assess the association between the volume of ACC and the presence of psychosis in AD, adjusting for age, education, Clinical Dementia Rating-Sum of Boxes, and total intracranial volume. Results: We found that the volume of ACC is significantly reduced in AD with psychosis (AD+P) compared to AD without psychosis (AD-P) (774.27±142.96 vs. 833.09±142.04, p=0.005). The volume of ACC associated with the presence of psychosis in AD (odds ratio=0.995; 95% confidence interval=0.993-0.997; p=0.006). Conclusion: We have found that reduced volume of ACC in AD+P, suggesting that ACC might play an important role in the underlying pathogenesis of development of psychotic symptoms in AD.

Impact of Infant Thoracic Non-cardiac Perioperative Critical Care on Homotopic-Like Corpus Callosum and Forebrain Sub-regional Volumes.

Previously, we reported quantitatively smaller total corpus callosum (CC) and total forebrain size in critically ill term-born and premature patients following complex perioperative critical care for long-gap esophageal atresia (LGEA) that included Foker process repair. We extended our cross-sectional pilot study to determine sub-regional volumes of CC and forebrain using structural brain MRI. Our objective was to evaluate region-specific CC as an in-vivo marker for decreased myelination and/or cortical neural loss of homotopic-like sub-regions of the forebrain. Term-born (n = 13) and premature (n = 13) patients, and healthy naïve controls (n = 21) <1-year corrected age underwent non-sedated MRI using a 3T Siemens scanner, as per IRB approval at Boston Children's Hospital following completion of clinical treatment for Foker process. We used ITK-SNAP (v.3.6) to manually segment six sub-regions of CC and eight sub-regions of forebrain as per previously reported methodology. Group differences were assessed using a general linear model univariate analysis with corrected age at scan as a covariate. Our analysis implicates globally smaller CC and forebrain with sub-region II (viz. rostral body of CC known to connect to pre-motor cortex) to be least affected in comparison to other CC sub-regions in LGEA patients. Our report of smaller subgenual forebrain implicates (mal)adaptation in limbic circuits development in selected group of infant patients following LGEA repair. Future studies should include diffusion tractography studies of CC in further evaluation of what appears to represent global decrease in homotopic-like CC/forebrain size following complex perioperative critical care of infants born with LGEA.

Functional and Structural Brain Connectivity in Children With Bilateral Cerebral Palsy Compared to Age-Related Controls and in Response to Intensive Rapid-Reciprocal Leg Training.

BackgroundCompared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes.MethodsObjective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (<34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate.ResultsImages were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found.ConclusionsResults reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level.

Corpus Callosum Volumes in Children with Autism Spectrum Disorders: Sex-Associated Differences.

This study aimed to analyze the relationship between sex and corpus callosum (CC) volume in children with autism spectrum disorders (ASD) aged 2-4years. This prospective study included 50 children with ASD and 50 typically developing (TD) children aged 2-4years. Midsagittal slices of the CCs of the participants were divided into five subregions using FreeSurfer software. The PMCC, AMCC and TCC volumes were significantly higher in ASD participants than in TD participants, and results were significant in females with ASD rather than in males with ASD (all P < 0.05). In toddlers with ASD, the CC volumes were increased and more pronounced in females than in males. This could be due to overgrowth of axons or/and axonal pruning disorders.