Cerebellar Structures Research Articles

Functional and structural cerebellar-behavior relationships in aging.

Healthy aging is associated with deficits in cognitive performance and brain changes, including in the cerebellum. Cerebellar communication with the cortex via closed-loop circuits through the thalamus have been established and these circuits are closely related to the functional topography of the cerebellum. In this study, we sought to elucidate relationships between cerebellar structure and function with cognition in healthy aging. We explored this relationship in 138 healthy adults (aged 35-86, 53% female) using resting-state functional connectivity MRI (fcMRI), cerebellar volume, and cognitive and motor assessments. Behavioral tasks assessed attention, processing speed, working memory, episodic memory, and motor abilities. We expected to find negative relationships between lobular volume with age, and positive relationships between specific lobular volumes with motor and cognitive behavior, respectively. We predicted lower cerebello-cortical fcMRI with increased age. Behaviorally, we expected higher cerebello-frontal and cerebello-association area fcMRI cerebellar connectivity to correlate with better behavioral performance. Correlations were conducted between cerebellar lobules I-IV, V, Crus I, Crus II, vermis VI and behavioral measures. We found lower volumes with increased age as well as both higher and lower cerebellar connectivity relationships with increased age, consistent with literature on functional connectivity and network segregation in aging. Further, we revealed unique associations between cerebellar structure and connectivity with comprehensive behavioral measures in a healthy aging population. Our findings further highlight the role of the cerebellum in aging.

Engrailed-2 and inflammation convergently and independently impinge on cerebellar Purkinje cell differentiation

Autism spectrum disorders (ASD) have a complex pathogenesis thought to include both genetic and extrinsic factors. Among the latter, inflammation of the developing brain has recently gained growing attention. However, how genetic predisposition and inflammation might converge to precipitate autistic behavior remains elusive. Cerebellar structure and function are well known to be affected in autism. We therefore used cerebellar slice cultures to probe whether inflammatory stimulation and (over)expression of the autism susceptibility gene Engrailed-2 interact in shaping differentiation of Purkinje cells, key organizers of cerebellar histogenesis and function. We show that lipopolysaccharide treatment reduces Purkinje cell dendritogenesis and that this effect is enhanced by over-expression of Engrailed-2 in these cells. The effects of lipopolysaccharide can be blocked by inhibiting microglia proliferation and also by blocking tumor necrosis factor alpha receptor signaling, suggesting microglia and tumor necrosis factor alpha are major players in this scenario. These findings identify Purkinje cells as a potential integrator of genetic and environmental signals that lead to an autism-associated morphology.

Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control.

Kisspeptin (KP) signaling in the brain is defined by the anatomical distribution of KP-producing neurons, their fibers, receptors, and connectivity. Technological advances have prompted a re-evaluation of these chemoanatomical aspects, originally studied in the early years after the discovery of KP and its receptor Kiss1r. We have previously characterized(1) seven KP neuronal populations in the mouse brain at the mRNA level, including two novel populations, and examined their short-term response to gonadectomy. In this study, we mapped KP fiber distribution in rats and mice using immunohistochemistry under intact and short- and long-term post-gonadectomy conditions. Kiss1r mRNA expression was examined via RNAscope, in relation to vesicular GABA transporter ( Slc32a1 ) in whole mouse brain and to KP and vesicular glutamate transporter 2 ( Kiss1 and Slc17a6 ) in hypothalamic RP3V and arcuate regions. We identified KP fibers in 118 brain regions, primarily in extra-hypothalamic areas associated with sensorial processing and behavioral state control. KP-immunoreactive fiber density and distribution were largely unchanged by gonadectomy. Kiss1r was expressed prominently in sensorial and state control regions such as septal nuclei, the suprachiasmatic nucleus, locus coeruleus, hippocampal layers, thalamic nuclei, and cerebellar structures. Co-expression of Kiss1r and Kiss1 was observed in hypothalamic neurons, suggesting both autocrine and paracrine KP signaling mechanisms. These findings enhance our understanding of KP signaling beyond reproductive functions, particularly in sensorial and behavioral state regulation. This study opens new avenues for investigating KP's role in controlling complex physiological processes, including those not related to reproduction.

Cerebellar Structural and N-Acetylaspartate, Choline, and Creatine Metabolic Profiles in Parkinson's Disease and Essential Tremor.

The role of the cerebellum in Parkinson's disease (PD), particularly in tremor-dominant subtypes, is increasingly recognized. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) provide anatomical and metabolic insights, suggesting compensatory hyperactivity or degenerative changes in the cerebellum in PD. Volumetric analysis of cerebellar structures in MRI images, combined with metabolic profiles from MRS, offers possibilities for differentiating PD from essential tremor (ET). The cerebellum may be a potential therapeutic target due to its role in neurocircuitry of PD and ET. Brain structural data were obtained using MRI, and cerebellar metabolic profiles, focusing on the quantification of N-acetylaspartate (NAA), choline, and creatine peaks were obtained using MRS. This study enrolled patients with ET and PD, both with and without tremor, as well as disease controls with cerebellar atrophy (including spinocerebellar ataxia and multiple system atrophy). Volumetric analysis of cerebellar structures was performed. Differences in MRI and MRS parameters were analyzed using one-way analysis of covariance with a significance threshold of p < 0.05. From November 2018 to March 2023, 111 patients were enrolled, including 29 ET, 29 cerebellar atrophy, 12 PD without tremor, and 41 PD with tremor. No significant differences in cerebellar volume and N-acetylaspartate/creatine and choline/creatine ratios were found between ET and PD with tremor. This preliminary retrospective study suggests similarities in cerebellar structures and metabolic profiles between ET and PD, highlighting the need for advanced imaging techniques to better differentiate between these conditions. Future research should integrate clinical data, such as tremor severity and cognitive assessments, to explore the relationships with cerebellar MRI parameters.

Increased understanding of complex neuronal circuits in the cerebellar cortex.

The prevailing belief has been that the fundamental structures of cerebellar neuronal circuits, consisting of a few major neuron types, are simple and well understood. Given that the cerebellum has long been known to be crucial for motor behaviors, these simple yet organized circuit structures seemed beneficial for theoretical studies proposing neural mechanisms underlying cerebellar motor functions and learning. On the other hand, experimental studies using advanced techniques have revealed numerous structural properties that were not traditionally defined. These include subdivided neuronal types and their circuit structures, feedback pathways from output Purkinje cells, and the multidimensional organization of neuronal interactions. With the recent recognition of the cerebellar involvement in non-motor functions, it is possible that these newly identified structural properties, which are potentially capable of generating greater complexity than previously recognized, are associated with increased information capacity. This, in turn, could contribute to the wide range of cerebellar functions. However, it remains largely unknown how such structural properties contribute to cerebellar neural computations through the regulation of neuronal activity or synaptic transmissions. To promote further research into cerebellar circuit structures and their functional significance, we aim to summarize the newly identified structural properties of the cerebellar cortex and discuss future research directions concerning cerebellar circuit structures and their potential functions.

Brain metabolic response to repetitive transcranial magnetic stimulation to lesion network in cervical dystonia

BackgroundA previous study identified a brain network underlying cervical dystonia (CD) based on causal brain lesions. This network was shown to be abnormal in idiopathic CD and aligned with connections mediating treatment response to deep brain stimulation, suggesting generalizability across etiologies and relevance for treatment. The main nodes of this network were located in the deep cerebellar structures and somatosensory cortex (S1), the latter of which can be easily reached via non-invasive brain stimulation. To date, there are no studies testing brain stimulation to networks identified using lesion network mapping. ObjectivesTo assess target engagement by stimulating the S1 and testing the brain's acute metabolic response to repetitive transcranial magnetic stimulation in CD patients and healthy controls. MethodsThirteen CD patients and 14 controls received a single session of continuous theta burst (cTBS) and sham to the right S1. Changes in regional brain glucose metabolism were measured using [18F]FDG-PET. ResultscTBS increased metabolism at the stimulation site in CD (P = 0.03) but not in controls (P = 0.15; group difference P = 0.01). In subcortical regions, cTBS increased metabolism in the brainstem in CD only (PFDR = 0.04). The remote activation was positively associated with dystonia severity and efficacy of sensory trick phenomenon in CD patients. ConclusionsOur results provide further evidence of abnormal sensory system function in CD and show that a single session of S1 cTBS is sufficient to induce measurable changes in brain glucose metabolism. These findings support target engagement, motivating therapeutic trials of cTBS to the S1 in CD.

Multimodal evidence for cerebellar influence on cortical development in autism: structural growth amidst functional disruption.

Despite perinatal damage to the cerebellum being one of the highest risk factors for later being diagnosed with autism spectrum disorder (ASD), it is not yet clear how the cerebellum might influence the development of cerebral cortex and whether this co-developmental process is distinct between neurotypical and ASD children. Leveraging a large structural brain MRI dataset of neurotypical children and those diagnosed with ASD, we examined whether structural variation in cerebellar tissue across individuals was correlated with neocortical variation during development, including the thalamus as a coupling factor. We found that the thalamus plays a distinct role in moderating cerebro-cerebellar structural coordination in ASD. Notably, structural coupling between cerebellum, thalamus, and neocortex was strongest in younger childhood and waned by early adolescence, mirroring a previously undescribed trajectory of behavioral development between ASD and neurotypical children. Complementary functional connectivity analyses likewise revealed atypical connectivity between cerebellum and neocortex in ASD. This relationship was particularly prominent in a model of cerebellar structure predicting functional connectivity, where ASD and neurotypical children showed divergent patterns. Interestingly, these functional-structural relationships became more prominent with age, while structural effects were most prominent earlier in childhood, and showed significant lateralization. This pattern may suggest a developmental sequence where early uncoordinated structural growth amongst regions is followed by increasingly atypical functional synchronization. These findings provide multimodal evidence in the living brain for a cerebellar diaschisis model of autism, where both increased cerebellar-cerebral structural coupling and altered functional connectivity in cerebro-cerebellar pathways contribute to the ontogeny of this neurodevelopmental disorder.

Effect of Core Stability Exercise and Treadmill Training on Balance in a patient with Cerebellar Ataxic Cerebral palsy- A Case Report

Cerebral palsy (CP) is defined as a set of developmental illnesses that affect posture and mobility, causing activity restriction owing to abnormalities that are not progressive in the developing brain of the fetus or neonate. Children with cerebellar ataxic CP often exhibit undeveloped or malformed cerebellar structures, resulting in challenges for the cerebellum to integrate the neural input required to control movement and balance smoothly. Patients with cerebellar ataxic cerebral palsy have difficulty in maintaining balance and trunk control which leads to difficulty in performing their activities of daily living and result in dependency. Thus, reporting cases like these is crucial to evaluate the impact of core stabilization intervention and treadmill walking on balance in a child having cerebellar ataxic cerebral palsy. A 7-year-old female child born at full term delivered via normal vaginal delivery with a birth weight of 2700 gm had no difficulties during antenatal, natal or postnatal phases. At the age of 6 years, mother noticed that the child had difficulty in standing and walking independently, she had difficulty in performing her activities of daily living independently. The patient underwent an 8-week intervention consisting of core stabilization exercise protocol and treadmill walking along with traditional physiotherapy intervention. The outcome measures included Pediatric Balance Scale for static balance and MFT for dynamic balance. The patient showed significant improvement in both static as well as dynamic balance following the intervention. Thus, combined impact of core stabilization exercise protocol and treadmill walking can bring early effective changes on balance in a patient with cerebellar ataxic cerebral palsy.

Early Adversity Affects Cerebellar Structure and Function-A Systematic Review of Human and Animal Studies.

Recent research has highlighted cerebellar involvement in cognition and several psychiatric conditions such as mood and anxiety disorders and schizophrenia. Attention-deficit/hyperactivity disorder and autism spectrum disorder have been linked to reduced cerebellar volume as well. Cerebellar alterations are frequently present after early adversity in humans and animals, but a systematic integration of results is lacking. To this end, a systematic literature search was conducted in PubMed, Web of Science, and EBSCO databases using the keywords "early adversity OR early life stress" AND "cerebellum OR cerebellar." A total of 45 publications met the inclusion criteria: 25 studies investigated human subjects and 20 reported results from animal models. Findings in healthy subjects show bilateral volume reduction and decreased functional connectivity within the cerebellum and between the cerebellum and frontal regions after adversity throughout life, especially when adversity was assessed with the Childhood Trauma Questionnaire. In clinical populations, adults demonstrate increased cerebellar volume and functional connectivity after adversity, whereas pediatric patients show reduced cerebellar volume. Animal findings reveal cerebellar alterations without necessarily co-occurring pathological behavior, highlighting alterations in stress hormone receptor levels, cell density, and neuroinflammation markers. Cerebellar alterations after early adversity are robust findings across human and animal studies and occur independent of clinical symptoms.

Cerebellar involvement in Parkinson's disease: Pathophysiology and neuroimaging.

Parkinson's disease (PD) is a neurodegenerative disease characterized by various motor and non-motor symptoms. The complexity of its symptoms suggests that PD is a heterogeneous neurological disorder. Its pathological changes are not limited to the substantia nigra-striatal system, but gradually extending to other regions including the cerebellum. The cerebellum is connected to a wide range of central nervous system regions that form essential neural circuits affected by PD. In addition, altered dopaminergic activity and α-synuclein pathology are found in the cerebellum, further suggesting its role in the PD progression. Furthermore, an increasing evidence obtained from imaging studies has demonstrated that cerebellar structure, functional connectivity, and neural metabolism are altered in PD when compared to healthy controls, as well as among different PD subtypes. This review provides a comprehensive summary of the cerebellar pathophysiology and results from neuroimaging studies related to both motor and non-motor symptoms of PD, highlighting the potential significance of cerebellar assessment in PD diagnosis, differential diagnosis, and disease monitoring.

Cerebellar Functions Beyond Movement and Learning.

The cerebellum has a well-established role in controlling motor functions, including coordination, posture, and the learning of skilled movements. The mechanisms for how it carries out motor behavior remain under intense investigation. Interestingly though, in recent years the mechanisms of cerebellar function have faced additional scrutiny since nonmotor behaviors may also be controlled by the cerebellum. With such complexity arising, there is now a pressing need to better understand how cerebellar structure, function, and behavior intersect to influence behaviors that are dynamically called upon as an animal experiences its environment. Here, we discuss recent experimental work that frames possible neural mechanisms for how the cerebellum shapes disparate behaviors and why its dysfunction is catastrophic in hereditary and acquired conditions-both motor and nonmotor. For these reasons, the cerebellum might be the ideal therapeutic target.

Infectious Cerebellitis Rare Entity About Two Cases

Introduction: Cerebellitis is an inflammatory pathology of cerebellar structures more common in children, frequently of post-infectious origin or following vaccination, seldom during a viral or bacterial infection. Ataxia is most frequently caused by dysfunction of the complex circuitry connecting the cerebellum, basal ganglia and cerebral cortex. Results: We report the case of 2 patients aged 3 and 10 years presenting acute cerebellitis of infectious origin: Ataxic syndrome associated with balance disorders and speech disorders and fever. The evolution was quickly favorable with corticosteroid therapy and proprioceptive physiotherapy. The absence of fatalities in our case report suggests early diagnosis, and steroid treatment can increase the chance of recovery. Discussion: Clinical presentations are deceptive and variable with cerebellar symptoms of acute kinetic and static ataxia with inflammatory signs. The treatment is based on steroids when symptoms are moderate to severe. Antimicrobial therapy should always be considered, because ataxia can be a presenting sign of both viral encephalitis and bacterial meningitis. The prognosis for acute cerebellitis is generally favorable. The courses vary from what is commonly a benign and self-limiting disease to what occasionally is fulminant disease resulting in several cerebellar damage or even sudden death. Conclusion: Recognizing ataxia in children can be difficult, which is why a lumbar punction should be considered if infectious cerebellitis is suspected. Most people fully recover, however there is a risk of lasting disability.

Sex-steroid hormones relate to cerebellar structure and functional connectivity across adulthood.

Aging involves complex biological changes that affect disease susceptibility and aging trajectories. Although females typically live longer than males, they have a higher susceptibility to diseases like Alzheimer's, speculated to be influenced by menopause, and reduced ovarian hormone production. Understanding sex-specific differences is crucial for personalized medical interventions and gender equality in health. Our study aims to elucidate sex differences in regional cerebellar structure and connectivity during normal aging by investigating both structural and functional connectivity variations, with a focus on investigating these differences in the context of sex-steroid hormones. The study included 138 participants (mean age = 57(13.3) years, age range = 35-86 years, 54% women). The cohort was divided into three groups: 38 early middle-aged individuals (EMA) (mean age = 41(4.7) years), 48 late middle-aged individuals (LMA) (mean age = 58(4) years), and 42 older adults (OA) (mean age = 72(6.3) years). All participants underwent MRI scans, and saliva samples were collected for sex-steroid hormone quantification (17β-estradiol (E), progesterone (P), and testosterone (T)). We found less connectivity in females between Lobule I-IV and the cuneus, and greater connectivity in females between Crus I, Crus II, and the precuneus with increased age. Higher 17β-estradiol levels were linked to greater connectivity in Crus I and Crus II cerebellar subregions. Analyzing all participants together, testosterone was associated with both higher and lower connectivity in Lobule I-IV and Crus I, respectively, while higher progesterone levels were linked to lower connectivity in females. Structural differences were observed, with EMA males having larger volumes compared to LMA and OA groups, particularly in the right I-IV, right Crus I, right V, and right VI. EMA females showed higher volumes in the right lobules V and VI. These results highlight the significant role of sex hormones in modulating cerebellar connectivity and structure across adulthood, emphasizing the need to consider sex and hormonal status in neuroimaging studies to better understand age-related cognitive decline and neurological disorders.

Functional and Structural Cerebellar-Behavior Relationships in Aging.

Healthy aging is associated with deficits in cognitive performance and brain changes, including in the cerebellum. Yet, the precise link between cerebellar function/structure and cognition in aging remains poorly understood. We explored this relationship in 138 healthy adults (aged 35-86, 53% female) using resting-state functional connectivity MRI (fcMRI), cerebellar volume, and cognitive and motor assessments in an aging sample. We expected to find negative relationships between lobular volume for with age, and positive relationships between specific lobular volumes with motor and cognition respectively. We predicted lower cerebellar fcMRI to cortical networks and circuits with increased age. Behaviorally, we expected higher cerebello-frontal fcMRI cerebellar connectivity with association areas to correlate with better behavioral performance. Behavioral tasks broadly assessed attention, processing speed, working memory, episodic memory, and motor abilities. Correlations were conducted between cerebellar lobules I-IV, V, Crus I, Crus II, vermis VI and behavioral measures. We found lower volumes with increased age as well as bidirectional cerebellar connectivity relationships with increased age, consistent with literature on functional connectivity and network segregation in aging. Further, we revealed unique associations for both cerebellar structure and connectivity with comprehensive behavioral measures in a healthy aging population. Our findings underscore cerebellar involvement in behavior during aging.

QOL-16. IMPACT OF LESION LOCATION ON MOTOR AND COGNITIVE OUTCOMES IN PEDIATRIC CEREBELLAR TUMORS

Abstract BACKGROUND Children with cerebellar damage are at increased risk for various adverse outcomes, including higher rates of autism and long term neurocognitive challenges. Traditionally considered a motor structure, extensive evidence links the cerebellum to a range of behaviors and atypical cerebellar structure and function have been reported in multiple neurodevelopmental and psychiatric conditions. A key feature of cerebellar neuroanatomy are the functional subregions that support sensorimotor and non-motor functions, leading to the hypothesis that motor, cognitive and behavioral outcomes should be predicted by the cerebellar lesion location.We aimed to determine how lesion location relates to outcomes in pediatric cerebellar patients. We predicted that lesions of the anterior lobe would disrupt motor performance, posterolateral lesions would impact cognitive functions, and behavioral dysregulation would be associated with posterior midline damage. METHODS We conducted lesion-symptom mapping in 30 children with a history of cerebellar tumor resection (sex: 19 male, 11 female; age at diagnosis, mean 6.8 years [SD 4.2]). Clinical MRI scans and neuropsychological data were used to evaluate the impact of lesion location on motor (pegboard), cognitive (verbal comprehension, verbal fluency, working memory, processing speed) and behavioral control measures (BRIEF). We mapped individual lesions using T1-weighted MRIs and normalized the lesion maps into standard template space for group analyses. RESULTS Behavioral scores ranged from impaired to above average. Lesion overlap maps were used to assess the lesion patterns associated with performance. As predicted, anterior and medial lesions disrupted motor performance and processing speed; posterolateral lesions were associated with impaired cognitive scores. CONCLUSIONS These preliminary analyses indicate that long-term outcomes are associated with disruption of specific cerebellar subregions. This could aid in prognosis and management of pediatric cerebellar tumor patients. Future work will address age of surgery, longitudinal changes in performance, and the developmental impact of early cerebellar disruption on supratentorial structures.

HISTOSTRUCTURAL ALTERATIONS IN THE CEREBRAL ARCHITECTURE ASSOCIATED WITH THE PROGRESSION OF ALCOHOL INTOXICATION: AN EXPERIMENTAL ANALYSIS

The aim of this study is to evaluate the histological changes in the cerebellum of rat brains following chronic alcohol intoxication. Materials and Methods. We employed a classical approach for modeling chronic alcohol intoxication by administering 40% ethanol to rats (n=55) in a dosage of 2 ml per 100 g of body weight daily for three months. The cerebellar structure was then analyzed. Results. This study investigates the impact of chronic alcohol intoxication on the histological structures of the cerebellar cortex. The cerebellum, like the nervous system overall, possesses a significant cellular and functional reserve. However, teratogenic factors, including ethanol, notably influence the activity of cerebellar neurons, increasing it. Ethanol exposure during early pregnancy can lead to prenatal growth retardation, stillbirth, cleft palate, hydrocephaly, and reductions in fetal body size. There is evidence suggesting a correlation between blood ethanol levels and a reduction in the number of Purkinje cells. Chronic alcohol consumption results in cerebellar ataxia, alterations in upper limb movements, decreased reaction speeds, reduced attention concentration, impaired coordination accuracy, and disturbances in postural stability and balance. Conclusion. The cerebellum, especially during development, is particularly vulnerable to the toxic effects of alcohol. Recent research suggests that changes in the neurotransmission of gamma-aminobutyric acid (GABA)-dependent receptors may contribute to cerebellar dysfunction induced by ethanol. Ethanol exposure increases the release of GABA not only in Purkinje cells but also in the interneurons of the molecular layer and granule cells.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Diffusion-tensor-imaging 1-year-old and 2-year-old infant brain atlases with comprehensive gray and white matter labels.

Human infancy is marked by fastest postnatal brain structural changes. It also coincides with the onset of many neurodevelopmental disorders. Atlas-based automated structure labeling has been widely used for analyzing various neuroimaging data. However, the relatively large and nonlinear neuroanatomical differences between infant and adult brains can lead to significant offsets of the labeled structures in infant brains when adult brain atlas is used. Age-specific 1- and 2-year-old brain atlases covering all major gray and white matter (GM and WM) structures with diffusion tensor imaging (DTI) and structural MRI are critical for precision medicine for infant population yet have not been established. In this study, high-quality DTI and structural MRI data were obtained from 50 healthy children to build up three-dimensional age-specific 1- and 2-year-old brain templates and atlases. Age-specific templates include a single-subject template as well as two population-averaged templates from linear and nonlinear transformation, respectively. Each age-specific atlas consists of 124 comprehensively labeled major GM and WM structures, including 52 cerebral cortical, 10 deep GM, 40 WM, and 22 brainstem and cerebellar structures. When combined with appropriate registration methods, the established atlases can be used for highly accurate automatic labeling of any given infant brain MRI. We demonstrated that one can automatically and effectively delineate deep WM microstructural development from 3 to 38 months by using these age-specific atlases. These established 1- and 2-year-old infant brain DTI atlases can advance our understanding of typical brain development and serve as clinical anatomical references for brain disorders during infancy.

Cerebellum Purkinje cell vulnerability in aged rats with memory impairment.

The cerebellum is involved in higher order cognitive function and is susceptible to age-related atrophy. However, limited evidence has directly examined the cerebellum's role in cognitive aging. To interrogate potential substrates of the relationship between cerebellar structure and memory in aging, here we target the Purkinje cells (PCs). The sole output neurons of the cerebellum, PC loss and/or degeneration underlie a variety of behavioral abnormalities. Using a rat model of normal cognitive aging, we immunostained sections through the cerebellum for the PC-specific protein, calbindin-D28k. Although morphometric quantification revealed no significant difference in total PC number as a function of age or cognitive status, regional cell number was a more robust correlate of memory performance in the young cerebellum than in aged animals. Parallel biochemical analysis of PC-specific protein levels in whole cerebellum additionally revealed that calbindin-D28k and Purkinje cell protein-2 (pcp-2) levels were lower selectively in aged rats with spatial memory impairment compared to both young animals and aged rats with intact memory. These results suggest that cognitive aging is associated with cerebellum vulnerability, potentially reflecting disruption of the cerebellum-medial temporal lobe network.

ОСОБЕННОСТИ КЛИНИЧЕСКИХ ПРОЯВЛЕНИЙ ПРИ МАЛЬФОРМАЦИИ КИАРИ 0, 1 И «ПОГРАНИЧНОГО» ТИПОВ

Introduction. Introduction of advanced neuroimaging methods has made it possible to identify subtle structural features of the posterior cranial fossa and craniovertebral junction, as well as the dislocation of cerebellar tonsils into the foramen magnum, which have clinically overt and subclinical forms. Aim: To study the clinical manifestation features of Chiari type 0, 1, and “borderline” malformations. Materials and Methods. For literature analysis, the sources were used from international databases, such as Web of Science, Scopus, and PubMed, and the Russian library system, eLibrary. Results and Discussion. The most common pathology of the posterior cranial fossa is Chiari type 1 malformation associated with a mesodermal defect and with discrepancies between the sizes of the posterior cranial fossa and the neural structures that fill it. To assess the Chiari malformation grade, it is advisable to specify the dislocation grades of cerebellar tonsils. There is a common classification of cerebellar tonsil dislocations, in which the dislocation grade 1 of cerebellar tonsils is characterized by the descent of cerebellar tonsils below the foramen magnum level; grade 2 is inherent in dislocation of the cerebellar tonsils down to the C2 vertebra level in combination with displacing the pons and medulla oblongata below the Twining line. Grade 3 dislocation of the cerebellar tonsils is where the cerebellum tonsil displacement is combined with intracranial hypertension. In case of the degree 4 dislocation of the cerebellar tonsils, cerebellar hypoplasia is observed, accompanied by a displacement of the medulla oblongata. The occurrence of syringomyelia in Chiari type 0 malformation is associated with liquor dynamic disorders in the craniovertebral junction region; the similar liquor circulation disorders are detected in Chiari type 1 malformation. Chiari type 1 and “borderline”- type malformations manifest as persistent cranialgia, pain in the cervical spine, otoneurologic and visual disorders, respiratory, psychological, and cognitive disorders, damage to the cerebellar and stem structures of the brain, damage to the spinal cord, and other, more rare signs of damage to the central nervous system. Conclusions. Thus, it is necessary to further study the features of developing clinical symptoms in Chiari type 1, 0, and “borderline” malformations to assess the changes in the course of the disease and select an adequate treatment strategy.