BACKGROUND: The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions.
METHODS: Typically developing children (TDC; n=38; age 9-15) and healthy adults (HAC; n=31; 18-40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV.
RESULTS: TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ.
CONCLUSIONS: In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The \"inverted U\" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC\'s lower cerebellar vermis volumes.

BACKGROUND: Growth-restricted fetuses may have changes in their neuroanatomical structures that can be detected in prenatal imaging. We aim to compare corpus callosal length (CCL) and cerebellar vermian height (CVH) measurements between fetal growth restriction (FGR) and control fetuses and to correlate them with cerebral Doppler velocimetry in growth-restricted fetuses.
METHODS: This was a prospective cohort of FGR after 20 weeks of gestation with ultrasound measurements of CCL and CVH. Control cohort was assembled from fetuses without FGR who had growth ultrasound after 20 weeks of gestation. We compared differences of CCL or CVH between FGR and controls. We also tested for the correlations of CCL and CVH with middle cerebral artery (MCA) pulsatility index (PI) and vertebral artery (VA) PI in the FGR group. CCL and CVH measurements were adjusted by head circumference (HC).
RESULTS: CCL and CVH were obtained in 68 and 55 fetuses, respectively. CCL/HC was smaller in FGR fetuses when compared to control fetuses (difference = 0.03, 95% CI: [0.02, 0.04], p < 0.001). CVH/HC was larger in FGR fetuses compared to NG fetuses (difference = 0.1, 95% CI: [-0.01, 0.02], p = < 0.001). VA PI multiples of the median were inversely correlated with CVH/HC (rho = -0.53, p = 0.007), while CCL/HC was not correlated with VA PI. Neither CCL/HC nor CVH/HC was correlated with MCA PI.
CONCLUSIONS: CCL/HC and CVH/HC measurements show differences in growth-restricted fetuses compared to a control cohort. We also found an inverse relationship between VA PI and CVH/HC. The potential use of neurosonography assessment in FGR assessment requires continued explorations.

UNASSIGNED: To investigate midbrain growth, including corpus callusum (CC), cerebellar vermis (CV) and cortical development in late fetal growth restriction (FGR) depending on uterine artery (UtA) Pulsatility Index (PI) values.
UNASSIGNED: This was a prospective study including singleton fetuses with late FGR characterized by abnormal cerebral placental ratio (CPR). According to UtA PI values, the FGR fetuses were subdivided into normal ≤95th centile) and abnormal (>95th centile). Neurosonography was performed at 33-44 weeks of gestations to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size.
UNASSIGNED: The study cohort included 60 fetuses with late FGR, 39 with normal UtA PI and 21 with abnormal PI values. The latter group showed significant differences in CC (median (interquartile range) normal 35.9 (28.49-45.53) vs abnormal UtA PI 25.31(19.76-35.13) mm; p < 0.0022), CV (normal 25.78 (18.19-29.35) abnormal UtA PI 17.03 (14.07-24.16)mm; p = 0.0067); SF (normal 10.58 (8.99-11.97)vs abnormal UtA PI 7.44 (6.23-8.46) mm; p < 0.0001), POF (normal 6.85 (6.35-8.14) vs abnormal UtA PI 4.82 (3.46-7.75) mm; p < = 0.0184) and CF (normal 04.157 (2.85-5.41) vs abnormal UtA PI 2.33 (2.49-4.01)); p < 0.0382).
UNASSIGNED: Late onset FGR fetuses with abnormal UtA PI showed shorter CC and CV length and delayed cortical development compared to those with normal uterine PI. These findings support the existence of a link between abnormal brain development and changes in utero placental circulation.

OBJECTIVE: To investigate the effects of mid-pregnancy sleep deprivation (SD) in C57BL/6 J mice on the motor coordination of the offspring and to explore the potential mechanism of microglia activation in the cerebellar vermis of the offspring involved in the induction of impaired motor coordination development.
METHODS: C57BL/6 J pregnant mice were randomly divided into the SD and control groups. SD was implemented by the multi-platform method from first day of the middle pregnancy (gestation day 8, GD8). At postnatal day 21 (PND21), we measured the development of motor behavior and collected cerebellar vermis tissues to observe the activation of microglia by H&E staining, the expression of microglia-specific markers ionized calcium-binding adaptor molecule-1 (Iba-1) and cluster of differentiation 68 (CD68) by immunohistochemical, and interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor -α (TNF-α) by real-time quantitative PCR (RT-qPCR).
RESULTS: In the offspring of SD group, comparing to the control group, the total time of passage and the reverse crawl distance in the balance beam test, and the frequency of falls from the suspension cord was increased; with lower max rotational speed and shorter duration in the rotarod experiment. Further, we found that the microglia of cerebellar vermis tissues emerged an amoeba-like activation. The mean gray value of Iba-1 was lower, the density of positive cells of CD68 and the expression levels of IL-6 and TNF-α were increased.
CONCLUSIONS: The motor coordination of offspring is impaired, accompanying a SD from mid-pregnancy, and the cerebellar vermis showed microglia activation and pro-inflammatory response. It suggested the adverse effects of SD from mid-gestation on the development of motor coordination through the inflammatory response in the cerebellar vermis of the offspring.

The time course of socio-communicative disturbances in children after posterior fossa tumor resection is variable in clinical reports, and its assessment may help to understand the role of the cerebellum in the pathogenesis of socio-communicative disorders and improve rehabilitation plans. We report the 3-year cognitive-behavioral follow-up of a female patient (LZ) who underwent surgical ablation of the vermis due to medulloblastoma at age 9. LZ developed a severe post-operative Cerebellar Cognitive Affective Syndrome (CCAS) with cognitive-executive dysfunctions and behavioral alterations resembling an Autism Spectrum Disorder (ASD)-like syndrome. The lack of empathy and reduced ability to recognize others\' intentions and mental states persisted at follow-up evaluations, as did language alterations. The present case report evidenced that lesions affecting cerebellar and vermal lobules may cause severe CCAS and impairment of social skills overlapping with that observed in ASD. This case is significant in its clinical features, revealing long-term social impairment, while the cognitive, linguistic, and executive functioning improved over time. Prospective case studies should plan the evaluation of symptoms of ASD within the clinical longitudinal assessment.

The central nervous system predictively controls posture against external disturbances; however, the detailed mechanisms remain unclear. We tested the hypothesis that the cerebellar vermis plays a substantial role in acquiring predictive postural control by using a standing task with floor disturbances in rats. The intact, lesioned, and sham groups of rats sequentially underwent 70 conditioned floor-tilting trials, and kinematics were recorded. Six days before these recordings, only the lesion group underwent focal suction surgery targeting vermal lobules IV-VIII. In the naïve stage of the sequential trials, the upright postures and fluctuations due to the disturbance were mostly consistent among the groups. Although the pattern of decrease in postural fluctuation due to learning corresponded among the groups, the learning rate estimated from the lumbar displacement was significantly lower in the lesion group than in the intact and sham groups. These results suggest that the cerebellar vermis contributes to predictive postural controls.

OBJECTIVE: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values.
METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (RESULTS: The study cohort included 60 late FGR, 31 with normal UVBF/AC and 29 with abnormal UVBF/AC values. The latter group showed significant differences in CC (median (interquartile range (IQR) normal 0.96 (0.73-1.16) vs. abnormal UVBF/AC 0.60 (0.47-0.87); p<0.0001)), CV (normal 1.04 (0.75-1.26) vs. abnormal UVBF (AC 0.76 (0.62-1.18)); p=0.0319), SF (normal 0.83 (0.74-0.93) vs. abnormal UVBF/AC 0.56 (0.46-0.68); p<0.0001), POF (normal 0.80 (0.71-0.90) vs. abnormal UVBF/AC l 0.49 (0.39-0.90); p≤0.0072) and CF (normal 0.83 (0.56-1.01) vs. abnormal UVBF/AC 0.72 (0.53-0.80); p<0.029).
CONCLUSIONS: Late onset FGR fetuses with of reduced umbilical vein flow showed shorter CC and CV length and a delayed cortical development when compared to those with normal umbilical vein hemodynamics. These findings support the existence of a link between abnormal brain development and changes in umbilical vein circulation.

The cerebellar projection from the trigeminal nuclear complex is one of the major populations of the cerebellar inputs. Although this projection is essential in cerebellar functional processing and organization, its morphological organization has not been systematically clarified. The present study addressed this issue by lobule-specific retrograde neuronal labeling and single axonal reconstruction with anterograde labeling. The cerebellar projection arose mainly from the interpolaris subdivision of the spinal trigeminal nucleus (Sp5I) and the principal trigeminal sensory nucleus (Pr5). Although crus II, paramedian lobule, lobule IX, and simple lobule were the major targets, paraflocculus, and other lobules received some projections. Reconstructed single trigeminocerebellar axons showed 77.8 mossy fiber terminals on average often in multiple lobules but no nuclear collaterals. More terminals were located in zebrin-negative or lightly-positive compartments than in zebrin-positive compartments. While Pr5 axons predominantly projected to ipsilateral crus II, Sp5I axons projected either predominantly to crus II and paramedian lobule often bilaterally, or predominantly to lobule IX always ipsilaterally. Lobule IX-predominant-type Sp5I neurons specifically expressed Gpr26. Gpr26-tagged neuronal labeling produced a peculiar mossy fiber distribution, which was dense in the dorsolateral lobule IX and extending transversely to the dorsal median apex in lobule IX. The projection to the cerebellar nuclei was observed in collaterals of ascending Sp5I axons that project to the diencephalon. In sum, multiple populations of trigeminocerebellar projections showed divergent projections to cerebellar lobules. The projection was generally complementary with the pontine projection and partly matched with the reported orofacial receptive field arrangement.

BACKGROUND: Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations is a rare neurological disorder that is associated with typical clinical and imaging features. The syndrome is caused by pathogenic variants in the MAST1 gene, which encodes a microtubule-associated protein that is predominantly expressed in postmitotic neurons in the developing nervous system.
METHODS: Fetal DNA from umbilical cord blood samples and genomic DNA from peripheral blood lymphocytes were subjected to whole-exome sequencing. The potential causative variants were verified by Sanger sequencing.
RESULTS: A 26-year-old primigravid woman was referred to our prenatal center at 25 weeks of gestation due to abnormal ultrasound findings in the brain of the fetus. The brain abnormalities included wide cavum septum pellucidum, shallow and incomplete bilateral lateral fissure cistern, bilateral dilated lateral ventricles, hyperplastic corpus callosum, lissencephaly, and cortical dysplasia. No obvious abnormalities were observed in the brainstem or cerebellum hemispheres, but the cerebellum vermis was small. Whole-exome sequencing identified a de novo, heterozygous missense variant, c.695T>C(p.Leu232Pro), in the MAST1 gene and a genetic diagnosis of mega-corpus-callosum syndrome was considered.
CONCLUSIONS: This study is the first prenatal case of MAST1-related disorder reported in the Chinese population and has expanded the mutation spectrum of the MAST1 gene.

OBJECTIVE: Fetuses with late growth restriction (FGR) have a higher risk of sub-optimal 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 structures and cortical development in fetuses with late growth restriction 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.
METHODS: Prospective cross-sectional study including fetuses with late FGR undergoing neurosonography between 32 and 34 weeks of gestation. Midline structures (corpus callosum (CC) and cerebellar vermis (CV) length) and cortical development, including the depth of Sylvian (SF), parieto-occipital (POF) and calcarine (CF) were compared between FGR, small (SGA) and appropriate for gestational age (AGA) fetuses, defined upon the Delphi criteria. Sub-group analysis according to the severity of FGR (normal vs abnormal fetal Dopplers) was also performed. Univariate analysis was used to analyze the data.
RESULTS: 52 FGR with normal, 60 with abnormal Dopplers, 64 SGA and 100 AGA fetuses were included in the analysis. SGA and FGR fetuses showed significant differences in absolute values of CC (median (interquartile range) control 43.47 (28.9-56.05), vs SGA 41.85 (27.82-51.79), vs FGR ND 38.54 (29.12-50.53), vs FGR AD 31.72 (23.8-40.19) K= 26.68; p<0.0001), CV (control 24.85 (17.55-29.21), SGA K=16.71; p=0.0008), SF (control 14.52 (10.65-16.76) vs SGA 12.71 (9.8-15.10) vs FGR ND 11.93 (9.12-13.43) VS FGR A 8.30 (6.72-10.33) K=75.82; p<0.0001), POF (control 8.56 (6.31-11.09) vs SGA 8.11 (5.58-10.43) vs FGR ND 7.81 (6.14-9.29) vs FGR AD 6.56 (4.22-7.99), K=45.06; p<0.0001) and CF ( control 9.27 (6.70-11.45) vs SGA 8.23 (5.67-10.65) vs FGR ND 7.68 (5.22-9.41) vs FGR AD 6.26 (4.48-7.19) K=46.14; p<0.0001) when compared to AGA controls with a progressive reduction across groups. When neurosonographic variables were corrected for fetal HC values, significant difference in the length of CC, SF, POF and CF but CV were observed only in FGR fetuses with abnormal Doppler when compared to AGA controls.
CONCLUSIONS: Late onset small fetuses showed shorter CC length and a delayed cortical development when compared to control. After controlling for HC size these differences remain significant only in FGR fetuses with abnormal Dopplers. These findings support the existence of a link between brain development and impaired placental function. This article is protected by copyright. All rights reserved.