Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

• Klíčová slova
• Affective, Aging, Alzheimer’s Disease, Cerebellum, Cognitive, Motor,
• MeSH
• depresivní porucha unipolární * MeSH
• dospělí MeSH
• konsensus MeSH
• kvalita života MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozeček patologie   MeSH
• průřezové studie MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The possibilities of substantial long-term improvement of predictive timing might be sometimes seen as limited, with scanty information of neural substrates underlying the potential learning process. To address this issue, we have investigated the performance of 21 baseball professionals and 21 matched controls in a predictive motor timing task previously shown to engage the cerebellum. Baseball players, hypothesized as a model of overtraining of the prediction of future state of the surroundings, showed significantly higher quantitative performance than nonathletic controls, with a substantial part of the baseball players reaching levels far beyond the range observed in common population. Furthermore, the qualitative performance profile of baseball players under various conditions as target speed and acceleration modes did not differ from the profile of healthy controls. Our results suggest that regular exigent training has the potential to vastly improve predictive motor timing. Moreover, the quantitative but not qualitative difference in the performance profile allows us to hypothesize that the selective honing of the same cerebellar processes and networks as in non-trained individuals is the substrate for the quantitative performance improvement, without substantial engagement of further neural nodes.

• Klíčová slova
• Cerebellar learning, Cerebellum, Overtraining, Predictive motor timing,
• MeSH
• baseball MeSH
• cvičení fyziologie   MeSH
• dospělí MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• psychomotorický výkon fyziologie   MeSH
• sportovci * MeSH
• učení fyziologie   MeSH
• vnímání času fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: An evolving pathophysiological concept of essential tremor (ET) points to diffuse brain network involvement, which emphasizes the need to investigate white matter (WM) changes associated with motor symptoms of ET. OBJECTIVES: To investigate ET-related WM changes and WM correlates of tremor severity using tremor clinical rating scales and accelerometry. METHODS: Tract-based spatial statistics (TBSS) approach was utilized to compare 3 Tesla diffusion tensor imaging (DTI) data from 12 ET patients and 10 age- and gender-matched healthy individuals. Clinical scales, tremor frequency and amplitude as measured by accelerometry were correlated with DTI data. RESULTS: ET patients demonstrated mean (MD) and radial diffusivity (RD) abnormalities in tracts involved in primary and associative motor functions such as bilateral corticospinal tracts, the superior longitudinal fascicles, and the corpus callosum but also in nonmotor regions including the inferior fronto-occipital and longitudinal fascicles, cingulum bundles, anterior thalamic radiations, and uncinate fascicles. A combined tremor frequency and amplitude score correlated with RD and MD in extensive WM areas, which partially overlapped the regions that were associated with tremor frequency. No significant relationship was found between DTI measures and clinical rating scales scores. CONCLUSIONS: The results show that ET-related diffusion WM changes and their correlates with tremor severity are preferentially located in the primary and associative motor areas. In contrast, a relationship between WM was not detected with clinical rating scales. Accelerometry parameters may, therefore, serve as a potentially useful clinical measures that relate to WM deficits in ET.

• Klíčová slova
• Guillain-Mollaret triangle, TremScore, diffusion tensor imaging, essential tremor, radial diffusivity, tremor network,
• MeSH
• akcelerometrie MeSH
• bílá hmota diagnostické zobrazování   fyziologie   MeSH
• dospělí MeSH
• esenciální tremor diagnostické zobrazování   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mapování mozku metody   MeSH
• mladý dospělý MeSH
• pilotní projekty MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• zobrazování difuzních tenzorů metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The cerebellum has a striking homogeneous cytoarchitecture and participates in both motor and non-motor domains. Indeed, a wealth of evidence from neuroanatomical, electrophysiological, neuroimaging and clinical studies has substantially modified our traditional view on the cerebellum as a sole calibrator of sensorimotor functions. Despite the major advances of the last four decades of cerebellar research, outstanding questions remain regarding the mechanisms and functions of the cerebellar circuitry. We discuss major clues from both experimental and clinical studies, with a focus on rodent models in fear behaviour, on the role of the cerebellum in motor control, on cerebellar contributions to timing and our appraisal of the pathogenesis of cerebellar tremor. The cerebellum occupies a central position to optimize behaviour, motor control, timing procedures and to prevent body oscillations. More than ever, the cerebellum is now considered as a major actor on the scene of disorders affecting the CNS, extending from motor disorders to cognitive and affective disorders. However, the respective roles of the mossy fibres, the climbing fibres, cerebellar cortex and cerebellar nuclei remains unknown or partially known at best in most cases. Research is now moving towards a better definition of the roles of cerebellar modules and microzones. This will impact on the management of cerebellar disorders.

• Klíčová slova
• Anatomy, Cerebellum, Cognition, Fear, History, Motor, Timing, Tremor,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Essential tremor (ET), clinically characterized by postural and kinetic tremors, predominantly in the upper extremities, originates from pathological activity in the dynamic oscillatory network comprising the majority of nodes in the central motor network. Evidence indicates dysfunction in the thalamus, the olivocerebellar loops, and intermittent cortical engagement. Pathology of the cerebellum, a structure with architecture intrinsically predisposed to oscillatory activity, has also been implicated in ET as shown by clinical, neuroimaging, and pathological studies. Despite electrophysiological studies assessing cerebellar impairment in ET being scarce, their impact is tangible, as summarized in this review. The electromyography-magnetoencephalography combination provided the first direct evidence of pathological alteration in cortico-subcortical communication, with a significant emphasis on the cerebellum. Furthermore, complex electromyography studies showed disruptions in the timing of agonist and antagonist muscle activation, a process generally attributed to the cerebellum. Evidence pointing to cerebellar engagement in ET has also been found in electrooculography measurements, cerebellar repetitive transcranial magnetic stimulation studies, and, indirectly, in complex analyses of the activity of the ventral intermediate thalamic nucleus (an area primarily receiving inputs from the cerebellum), which is also used in the advanced treatment of ET. In summary, further progress in therapy will require comprehensive electrophysiological and physiological analyses to elucidate the precise mechanisms leading to disease symptoms. The cerebellum, as a major node of this dynamic oscillatory network, requires further study to aid this endeavor.

• Klíčová slova
• Cerebellum, Dynamic oscillatory network, Electrophysiology, Essential tremor,
• MeSH
• esenciální tremor patofyziologie   MeSH
• lidé MeSH
• mozeček patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH