Corpus Medullare Research Articles

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( = .05) and longer epilepsy duration ( = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Altered Cerebellar Volumes and Intrinsic Cerebellar Network in Juvenile Myoclonic Epilepsy

Objectives. This study is aimed at investigating the alterations in cerebellar volumes and intrinsic cerebellar network in patients with juvenile myoclonic epilepsy (JME) in comparison with healthy controls. Methods. Patients newly diagnosed with JME and healthy controls were enrolled. Three-dimensional T1-weighted imaging was conducted, and no structural lesions were found on brain magnetic resonance imaging. Cerebellar volumes were obtained using the ACAPULCO program, while the intrinsic cerebellar network was evaluated by applying graph theory using the BRAPH program. The nodes were defined as individual cerebellar volumes and edges as partial correlations, controlling for the effects of age and sex. Cerebellar volumes and intrinsic cerebellar networks were compared between the two groups. Results. Forty-five patients with JME and 45 healthy controls were enrolled. Compared with the healthy controls, the patients with JME had significantly lower volumes of the right and left cerebellar white matter (3.33 vs. 3.48%, p = 0.009 ; 3.35 vs. 3.49%, p = 0.009 ), corpus medullare (0.99 vs. 1.03%, p = 0.04 ), and left lobule V (0.19 vs. 0.22%, p = 0.002 ). The intrinsic cerebellar networks also showed significant differences between the two groups. The small-worldness index in the patients with JME was significantly lower than that in the healthy controls (0.771 vs. 0.919, p = 0.04 ). Conclusion. The cerebellar volumes and intrinsic cerebellar network demonstrated alterations in the patients with JME when compared with those of the healthy controls. Our study results provide evidence that the cerebellum may play a role in the pathogenesis of JME.

Deep learning identifies morphological determinants of sex differences in the pre-adolescent brain

The application of data-driven deep learning to identify sex differences in developing brain structures of pre-adolescents has heretofore not been accomplished. Here, the approach identifies sex differences by analyzing the minimally processed MRIs of the first 8144 participants (age 9 and 10 years) recruited by the Adolescent Brain Cognitive Development (ABCD) study. The identified pattern accounted for confounding factors (i.e., head size, age, puberty development, socioeconomic status) and comprised cerebellar (corpus medullare, lobules III, IV/V, and VI) and subcortical (pallidum, amygdala, hippocampus, parahippocampus, insula, putamen) structures. While these have been individually linked to expressing sex differences, a novel discovery was that their grouping accurately predicted the sex in individual pre-adolescents. Another novelty was relating differences specific to the cerebellum to pubertal development. Finally, we found that reducing the pattern to a single score not only accurately predicted sex but also correlated with cognitive behavior linked to working memory. The predictive power of this score and the constellation of identified brain structures provide evidence for sex differences in pre-adolescent neurodevelopment and may augment understanding of sex-specific vulnerability or resilience to psychiatric disorders and presage sex-linked learning disabilities.

Accelerated aging and motor control deficits are related to regional deformation of central cerebellar white matter in alcohol use disorder.

The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1-weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248d) and 128 age- and sex-matched control participants; subsets of these participants completed motor testing. We identified an AUD-related volume deficit and accelerated aging in the total corpus medullare. Novel deformation-based surface morphometry revealed regional shrinkage of surfaces adjacent to lobules I-V, lobule IX, and vermian lobule X. In addition, accelerated aging was detected in the regional surface areas adjacent to lobules I-V, lobule VI, lobule VIIB, and lobules VIII, IX, and X. Sex differences were not identified for any measure. For both volume-based and surface-based analyses, poorer performance in gait and balance, manual dexterity, and grip strength were linked to greater regional white matter structural deficits. Our results suggest that local deformation of the corpus medullare has the potential of identifying structurally and functionally segregated networks affected in AUD.

A multicohort, longitudinal study of cerebellar development in attention deficit hyperactivity disorder.

The cerebellum supports many cognitive functions disrupted in attention deficit hyperactivity disorder (ADHD). Prior neuroanatomic studies have been often limited by small sample sizes, inconsistent findings, and a reliance on cross-sectional data, limiting inferences about cerebellar development. Here, we conduct a multicohort study using longitudinal data, to characterize cerebellar development. Growth trajectories of the cerebellar vermis, hemispheres and white matter were estimated using piecewise linear regression from 1,656 youth; of whom 63% had longitudinal data, totaling 2,914 scans. Four cohorts participated, all contained childhood data (age 4-12years); two had adolescent data (12-25years). Growth parameters were combined using random-effects meta-analysis. Diagnostic differences in growth were confined to the corpus medullare (cerebellar white matter). Here, the ADHD group showed slower growth in early childhood compared to the typically developing group (left corpus medullare z=2.49, p=.01; right z=2.03, p=.04). This reversed in late childhood, with faster growth in ADHD in the left corpus medullare (z=2.06, p=.04). Findings held when gender, intelligence, comorbidity, and psychostimulant medication were considered. Across four independent cohorts, containing predominately longitudinal data, we found diagnostic differences in the growth of cerebellar white matter. In ADHD, slower white matter growth in early childhood was followed by faster growth in late childhood. The findings are consistent with the concept of ADHD as a disorder of the brain's structural connections, formed partly by developing cortico-cerebellar white matter tracts.

Volumetric Differences in Cerebellar Lobes in Individuals from Multiplex Alcohol Dependence Families and Controls: Their Relationship to Externalizing and Internalizing Disorders and Working Memory.

Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence and related substance use disorders. Greater susceptibility for these disorders may be related to cerebellar morphology. Because posterior regions of the cerebellum are associated with cognitive abilities, we investigated whether high-risk offspring would display regionally specific differences in cerebellar morphology and whether these would be related to working memory performance. The relationship to externalizing and internalizing psychopathology was of interest because cerebellar morphology has previously been associated with a cognitive affective syndrome. A total of 131 participants underwent magnetic resonance imaging (MRI) with volumes of the cerebellar lobes obtained with manual tracing. These individuals were from high-risk (HR) for alcohol dependence families (N = 72) or from low-risk (LR) control families (N = 59). All were enrolled in a longitudinal follow-up that included repeated clinical assessments during childhood and young-adulthood prior to the scan that provided information on Axis I psychopathology. The Working Memory Index of the Wechsler Memory Scale was given at the time of the scan. Larger volumes of the corpus medullare and inferior posterior lobes and poorer working memory performance were found for the HR offspring relative to LR controls. Across all subjects, a significant positive association between working memory and total volume of corpus of the cerebellum was seen, controlling for familial risk. Presence of an internalizing or externalizing disorder interacting with familial risk was also associated with volume of the corpus medullare.

Neurological soft signs in recent-onset schizophrenia: Focus on the cerebellum.

Previous structural neuroimaging studies linked cerebellar deficits to neurological soft signs (NSS) in schizophrenia. However, no studies employed a methodology specifically designed to assess cerebellar morphology. In this study, we evaluated the relationship between NSS levels and abnormalities of the human cerebellum in patients with recent-onset schizophrenia and healthy individuals using an exclusive cerebellar atlas. A group of 26 patients with recent-onset schizophrenia and 26 healthy controls were included. All participants underwent a high-resolution T1-weighted MRI scan on a 3 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with NSS. Compared with healthy controls, patients had significantly smaller cerebellar volumes for both hemispheres. In the patients' group, we identified a significant negative correlation between NSS levels and gray matter volume in the left lobule VI and the right lobule VIIa, corrected for multiple comparisons. Further, NSS performance was significantly associated with white matter volume in the left midbrain and corpus medullare and the right lobule VIIa. In contrast, no significant associations between NSS scores and cerebellar subregions in healthy subjects arose. Our results demonstrate the benefits of SUIT when investigating cerebellar correlates of NSS. These results support the view that distinct parts of sensorimotor and cognitive cerebellum play an important role in the pathogenesis of NSS in schizophrenia.

P059 - Clinical and radiologic correlates of quality of life measures in patients with relapse-onset multiple sclersosis

Objectives Several studies have reported reduced quality of life (QOL) scores in patients with multiple sclerosis (MS) even in absence of physical disability. Thus QOL measures could be served as an adjunct endpoints for clinical trials. In this study we assessed the relationship between QOL scores and brain structures' volume and magnetization transfer ratio (MTR) in patients with MS. Design and methods One hundred and twenty two patients with relapse-onset MS were recruited in the study. They underwent clinical examination and structural magnetic resonance imaging (MRI). QOL was evaluated using SF-36 questionnaire. Brain structure segmentation on lesion-filled T1-weighted images was performed using a multi-atlas algorithm, MAGeT Brain. Correlation between SF-36 physical and mental scores and expanded disability status scale (EDSS), brain structures' volumes (adjusted to intracranial volume) and MTR were assessed using general linear model (GLM) with age and gender as covariate. Results SF-36 physical score (PCS) was negatively correlated with EDSS (P>0.001), cerebellar (P=0.020) and pyramidal (P=0.001) Kurtzke functional system scores and multiple sclerosis functional composite (MSFC) score (P=0.006). Physical and mental Scores of SF-36 showed no significant correlation with total brain volume, volume of right and left thalamus, hippocampus, right and left hemispheres of cerebellum, corpus medullare of cerebellum and lesion load. The correlation between physical and mental subscores of SF-36 and MTR of corona radiate, internal capsule and corpus callosum were also non-significant. Conclusion Clinical measures predicted physical components of QOL. Neither clinical nor radiological measures of MS severity contribute significantly to mental QOL. Several studies have reported reduced quality of life (QOL) scores in patients with multiple sclerosis (MS) even in absence of physical disability. Thus QOL measures could be served as an adjunct endpoints for clinical trials. In this study we assessed the relationship between QOL scores and brain structures' volume and magnetization transfer ratio (MTR) in patients with MS. One hundred and twenty two patients with relapse-onset MS were recruited in the study. They underwent clinical examination and structural magnetic resonance imaging (MRI). QOL was evaluated using SF-36 questionnaire. Brain structure segmentation on lesion-filled T1-weighted images was performed using a multi-atlas algorithm, MAGeT Brain. Correlation between SF-36 physical and mental scores and expanded disability status scale (EDSS), brain structures' volumes (adjusted to intracranial volume) and MTR were assessed using general linear model (GLM) with age and gender as covariate. SF-36 physical score (PCS) was negatively correlated with EDSS (P>0.001), cerebellar (P=0.020) and pyramidal (P=0.001) Kurtzke functional system scores and multiple sclerosis functional composite (MSFC) score (P=0.006). Physical and mental Scores of SF-36 showed no significant correlation with total brain volume, volume of right and left thalamus, hippocampus, right and left hemispheres of cerebellum, corpus medullare of cerebellum and lesion load. The correlation between physical and mental subscores of SF-36 and MTR of corona radiate, internal capsule and corpus callosum were also non-significant. Clinical measures predicted physical components of QOL. Neither clinical nor radiological measures of MS severity contribute significantly to mental QOL.

MRI Shows a Region-Specific Pattern of Atrophy in Spinocerebellar Ataxia Type 2

In this study, we used manual delineation of high-resolution magnetic resonance imaging (MRI) to determine the spatial and temporal characteristics of the cerebellar atrophy in spinocerebellar ataxia type 2 (SCA2). Ten subjects with SCA2 were compared to ten controls. The volume of the pons, the total cerebellum, and the individual cerebellar lobules were calculated via manual delineation of structural MRI. SCA2 showed substantial global atrophy of the cerebellum. Furthermore, the degeneration was lobule specific, selectively affecting the anterior lobe, VI, Crus I, Crus II, VIII, uvula, corpus medullare, and pons, while sparing VIIB, tonsil/paraflocculus, flocculus, declive, tuber/folium, pyramis, and nodulus. The temporal characteristics differed in each cerebellar subregion: (1) duration of disease: Crus I, VIIB, VIII, uvula, corpus medullare, pons, and the total cerebellar volume correlated with the duration of disease; (2) age: VI, Crus II, and flocculus correlated with age in control subjects; and (3) clinical scores: VI, Crus I, VIIB, VIII, corpus medullare, pons, and the total cerebellar volume correlated with clinical scores in SCA2. No correlations were found with the age of onset. Our extrapolated volumes at the onset of symptoms suggest that neurodegeneration may be present even during the presymptomatic stages of disease. The spatial and temporal characteristics of the cerebellar degeneration in SCA2 are region specific. Furthermore, our findings suggest the presence of presymptomatic atrophy and a possible developmental component to the mechanisms of pathogenesis underlying SCA2. Our findings further suggest that volumetric analysis may aid in the development of a non-invasive, quantitative biomarker.

The nature and extent of cerebellar atrophy in chronic temporal lobe epilepsy

Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques. Study participants were 46 persons with TLE and 31 age- and gender- matched healthy controls. All participants underwent high-resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder). There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p's > 0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy. Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross-sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity-related (superior posterior lobe) features of the disorder.

The cerebellum in children with spina bifida and Chiari II malformation: Quantitative volumetrics by region.

Few volumetric MRI studies of the entire cerebellum have been published; even less quantitative information is available in patients with hindbrain malformations, including the Chiari II malformation which is ubiquitous in patients with spina bifida meningomyelocele (SBM). In the present study, regional volumetric analyses of the cerebellum were conducted in children with SBM/Chiari II and typically developing (TD) children. Total cerebellar volume was significantly reduced in the SBM group relative to the TD group. After correcting for total cerebellum volume, and relative to the TD group, the posterior lobe was significantly reduced in SBM, the corpus medullare was not different, and the anterior lobe was significantly enlarged. Children with thoracic level lesions had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who had smaller volumes compared to TD children. The reduction in cerebellar volume in the group with SBM represents not a change in linear scaling but rather a reconfiguration involving anterior lobe enlargement and posterior lobe reduction.

Cerebellum development during childhood and adolescence: A longitudinal morphometric MRI study

In addition to its well-established role in balance, coordination, and other motor skills, the cerebellum is increasingly recognized as a prominent contributor to a wide array of cognitive and emotional functions. Many of these capacities undergo dramatic changes during childhood and adolescence. However, accurate characterization of co-occurring anatomical changes has been hindered by lack of longitudinal data and methodologic challenges in quantifying subdivisions of the cerebellum. In this study we apply an innovative image analysis technique to quantify total cerebellar volume and 11 subdivisions (i.e. anterior, superior posterior, and inferior posterior lobes, corpus medullare, and three vermal regions) from anatomic brain MRI scans from 25 healthy females and 25 healthy males aged 5–24 years, each of whom was scanned at least three times at approximately 2-year intervals. Total cerebellum volume followed an inverted U shaped developmental trajectory peaking at age 11.8 years in females and 15.6 years in males. Cerebellar volume was 10% to 13% larger in males depending on the age of comparison and the sexual dimorphism remained significant after covarying for total brain volume. Subdivisions of the cerebellum had distinctive developmental trajectories with more phylogenetically recent regions maturing particularly late. The cerebellum's unique protracted developmental trajectories, sexual dimorphism, preferential vulnerability to environmental influences, and frequent implication in childhood onset disorders such as autism and ADHD make it a prime target for pediatric neuroimaging investigations.

Cerebellar substructures and neurological soft signs in first-episode schizophrenia

A subtle impairment of motor coordination and sensory integration functions is frequently found in schizophrenia. Clinically these deficits present as neurological soft signs (NSS). Because of its crucial role in motor function, control of muscle tone and equilibrium, the cerebellum is likely to be involved in the appearance of NSS. Magnetic resonance imaging (MRI) was performed in 30 patients with first-episode schizophrenia – all treated with atypical neuroleptics – and 21 healthy controls. NSS were rated on the Heidelberg Scale. By manual tracing, the cerebellum was divided into the following subregions bilaterally: anterior lobe, superior posterior lobe, inferior posterior lobe, and corpus medullare, respectively. Volumetric measures were compared between the two groups and related to NSS scores. NSS scores were significantly higher in patients than in controls. Cerebella of patients were significantly smaller with atrophy pronounced in the corpus medullare bilaterally. In the patients' group, higher NSS scores were found to be related to reduced volumes of the posterior lobes of the cerebellum. In contrast, no significant associations between NSS scores and cerebellar subregions in healthy subjects arose. Our findings support the hypothesis of cerebellar involvement in schizophrenia and indicate that alterations in distinct cerebellar regions are related to NSS.

The cerebellum in mild cognitive impairment and Alzheimer’s disease – A structural MRI study

Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimer’s disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in four substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Our findings lend further support for cerebellar involvement in AD.

The unique neuroradiology of complex I deficiency due to NDUFA12L defect

In two patients who presented at late infancy with hypotonia, nystagmus and ataxia, interspersed with acute episodes of encephalopathy, we identified a mutation in a complex I assembly factor, NDUFA12L, which resulted in a marked reduction of the NDUFA12L protein and of complex I activity. The involvement of the mamillothalamic tracts, substantia nigra/medial lemniscus, medial longitudinal fasciculus, the corpus medullare and the cerebellum, with relative sparing of the cortex and subcortical white matter was distinctive and resembled the findings in the first and only known patient with mutation in the NDUFA12L gene.

Spatial, temporal, and cellular distribution of the activated extracellular signal regulated kinases 1 and 2 in the developing and mature rat cerebellum

The extracellular signal regulated kinases 1 and 2 (ERK1/2) are important members of an intracellular signaling cascade that is involved in many aspects of the cellular physiology and development of neurons and glia. ERK1/2 are expressed in many brain regions including the cerebellum; however, their role during cerebellar development is poorly understood. Immunohistochemical approaches using phosphorylation-state specific antiserum that recognizes only the activated-ERK1/2 (pERK) were used to characterize the spatial and temporal patterns of activated-ERK in the developing and adult rat cerebellum. The distribution and cell type-specificity of pERK-immunoreactivity (IR) followed an age-related pattern, with the density of pERK-IR Purkinje cells decreasing between P6 and P15 and increasing at later times. Immunopositive granule cell neurons increased from P6 to P12, became decreased during much of late postnatal cerebellar development, and absent in adults. Co-localization of pERK with glial fibrillary acidic protein or the neuronal marker β-tubulin revealed that activated ERK is present in maturing Purkinje and granule cells, and the soma of Bergmann glia on P4, P10 and P15; pERK was detected in astrocytes on P10 and P15. Associated with weaning, there was a general increase in activated-ERK in all cell types on P22. In adults, pERK-IR was confined to the Purkinje cell layer and scattered cells in the corpus medullare. In summary, a high degree of developmental plasticity was observed in the spatiotemporal distribution of cerebellar pERK-IR suggesting that the ERK-pathway plays a dynamic role in regulating neuronal and glial migration, proliferation and differentiation in the developing cerebellum. In the mature cerebellum, ERK signaling may also mediate postsynaptic information processing.

Spatial, temporal, and cellular distribution of the activated extracellular signal regulated kinases 1 and 2 in the developing and mature rat cerebellum

The extracellular signal regulated kinases 1 and 2 (ERK1/2) are important members of an intracellular signaling cascade that is involved in many aspects of the cellular physiology and development of neurons and glia. ERK1/2 are expressed in many brain regions including the cerebellum; however, their role during cerebellar development is poorly understood. Immunohistochemical approaches using phosphorylation-state specific antiserum that recognizes only the activated-ERK1/2 (pERK) were used to characterize the spatial and temporal patterns of activated-ERK in the developing and adult rat cerebellum. The distribution and cell type-specificity of pERK-immunoreactivity (IR) followed an age-related pattern, with the density of pERK-IR Purkinje cells decreasing between P6 and P15 and increasing at later times. Immunopositive granule cell neurons increased from P6 to P12, became decreased during much of late postnatal cerebellar development, and absent in adults. Co-localization of pERK with glial fibrillary acidic protein or the neuronal marker β-tubulin revealed that activated ERK is present in maturing Purkinje and granule cells, and the soma of Bergmann glia on P4, P10 and P15; pERK was detected in astrocytes on P10 and P15. Associated with weaning, there was a general increase in activated-ERK in all cell types on P22. In adults, pERK-IR was confined to the Purkinje cell layer and scattered cells in the corpus medullare. In summary, a high degree of developmental plasticity was observed in the spatiotemporal distribution of cerebellar pERK-IR suggesting that the ERK-pathway plays a dynamic role in regulating neuronal and glial migration, proliferation and differentiation in the developing cerebellum. In the mature cerebellum, ERK signaling may also mediate postsynaptic information processing.

Neuropathological observation of rabbits (Oryctolagus cuniculus) affected with raccoon roundworm (Baylisascaris procyonis) larva migrans in Japan.

Larvae of the raccoon roundworm, Baylisascaris procyonis (B. procyonis) are a known cause of cerebrospinal larva migrans in animals and humans. The present paper described details of the central nervous lesion in the rabbits (Oryctolagus cuniculus) affected with B. procyonis larva migrans in Japan. Clinically affected animals showed neurological signs including circling, torticollis, tremor of head, or ataxic gait. The most characteristic pathological alterations were large malacic lesions associated with an activated astroglial proliferation which was seen at the corpus medullare in the cerebellum including the cerebellar peduncle. Moreover, focal malacic lesions with perivascular cuffing and infiltration by lymphocytes and heterophiles were scattered everywhere throughout the brain. In these lesions or normal-appearing areas away from obvious lesions, ascarid larvae, about a maximum 65-75 micro m in diameter, were recognized. Other prominent features were minute lesions (we call them migration tract-like lesions) composed of lymphocytes, hemosiderin-laden macrophages and reactive astrocytes scattering throughout the cerebrum. In this study, we demonstrated ascarid larvae in only eight out of 23 animals diagnosed as B. procyonis larva migrans. Since it is not always possible to detect the larvae, the possibility of B. procyonis larva migrans must be given serious consideration to the characteristic lesions described above.

Manual and Semiautomated Measurement of Cerebellar Subregions on MR Images

Previous structural and functional imaging studies suggest that the corticocerebellar–thalamic–cortical circuit is dysfunctional in schizophrenia. Accurate identification and volumetric measurement of cerebellar subregions are essential to the assessment of the cerebellum's role in healthy and disease states. Manual parcellation of the cerebellum on MR images was performed with the use of guide traces. Guide traces identified relevant fissures and borders in several planes, and their intersections with the primary tracing plane were used to maintain consistency and accuracy during the parcellation. The cerebellum was parcellated into right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. A systematic review of the final traces ensured their accuracy. An artificial neural network was trained using a novel landmark-warped method to help account for wide variability in structure size and location. Overlaps of the manually traced lobes (intersection/union) ranged from 0.78 to 0.85 and intraclass correlations ( r 2) ranged from 0.82 to 0.94. In a comparison of the semiautomated method with the manual method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.92 to 0.97. For two raters using the semiautomated method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.97 to 0.99. The semiautomated method was built on the groundwork of the manual method to produce more reliable results in a fraction of the time, making valid measurements possible on a large number of subjects.