BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.
- MeSH
- dospělí MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mladý dospělý MeSH
- modafinil * farmakologie aplikace a dávkování MeSH
- mozeček * účinky léků diagnostické zobrazování metabolismus MeSH
- neokortex účinky léků metabolismus diagnostické zobrazování MeSH
- nervové dráhy účinky léků metabolismus MeSH
- stimulancia farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. OBJECTIVES: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. METHODS: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. RESULTS: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). CONCLUSIONS: This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- alfa-synuklein metabolismus MeSH
- demence s Lewyho tělísky * diagnostické zobrazování patologie MeSH
- kognitivní dysfunkce * diagnostické zobrazování patologie patofyziologie etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- locus coeruleus * diagnostické zobrazování patologie MeSH
- magnetická rezonanční tomografie * MeSH
- neuropsychologické testy MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Esenciální třes (ET) se vyznačuje izolovaným akčním třesem horních končetin, případně i hlavy, hlasu nebo dolních končetin. Nově vymezený syndrom ET plus (ET+) navíc charakterizují přídatné lehké neurologické příznaky, které ale nejsou průkazné pro jiné onemocnění. Cíl: Tato práce zjišťovala výskyt ET+ u našich nemocných s cílem upřesnit patofyziologické podklady obou jednotek, se zvláštním zaměřením na postižení mozečku. Metodika: V souboru 51 pacientů (27 žen, průměrný věk 67,5 ± 13,1 roku) s ET byly ověřeny anamnestické údaje a neurologický nález. Tíže třesu a míra postižení v každodenních činnostech byly hodnoceny pomocí škály The Essential Tremor Rating Assessment Scale (TETRAS) a příznaky postižení mozečku pomocí Scale for the Assessment and Rating of Ataxia (SARA). Výsledky: ET+ jsme konstatovali u 22 pacientů (nejčastěji pro klidový třes rukou), 29 nemocných mělo „čistý“ ET. Obě skupiny se nelišily věkem začátku ani délkou trvání příznaků. Pacienti s ET+ měli ve srovnání s ET vyšší výskyt třesu hlavy (81 vs. 43 %; p < 0,05) a vyšší skóre TETRAS a SARA (vše p < 0,01). Závěr: Pacienti s ET+ vykazují těžší celkové postižení třesem, vyšší výskyt třesu hlavy a těžší známky ataxie než pacienti s „čistým“ ET. Postižení mozečku se významně podílí na projevech charakterizujících syndrom ET+.
Introduction: Essential tremor (ET) is characterized by isolated action tremor of the upper limbs, with or without tremor of the head, voice, or lower limbs. The newly defined ET plus (ET+) syndrome is characterized by the presence of additional mild neurological symptoms that are not indicative of other disease. Aim: This study investigated the incidence of ET+ in our patients to better understand the pathophysiological basis of both entities, with a special focus on cerebellar involvement. Methods: In a cohort of 51 patients with ET (27 women, mean age 67.5 ± 13.1 years), we verified anamnestic data and neurological findings. Tremor severity and the degree of disability in activities of daily living were assessed using The Essential Tremor Rating Assessment Scale (TETRAS), while symptoms of cerebellar involvement used the Scale for the Assessment and Rating of Ataxia (SARA). Results: ET+ was identified in 22 patients (mostly due to resting hand tremor), while 29 patients had “pure” ET. The two groups did not differ in age of onset or symptom duration. Patients with ET+ had a higher incidence of head tremor compared to those with ET (81 vs. 43%; P < 0.05) and higher scores on both the TETRAS and SARA scales (all P < 0.01). Conclusion: ET+ patients exhibited more severe overall tremor disability, a higher incidence of head tremor, and more pronounced signs of ataxia compared to patients with “pure” ET. Cerebellar involvement appears to play a significant role in additional manifestations of disability that characterize ET+ syndrome.
- Klíčová slova
- esenciální třes plus, klidový třes rukou, třes hlavy,
- MeSH
- esenciální tremor * patofyziologie MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozeček patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tremor patofyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
The cerebellum, a lateralised organ, plays a crucial role in motor control. Still, its involvement in hand and foot dominance remains inadequately understood, primarily in the right and left-side dominant population. A potential manifestation of this lateralisation is the neocerebellar extinction syndrome, previously linked to mild muscle hypotonia and moderate passivity in the non-preferred hand. A more precise understanding of the cerebellum's role in limb dominance patterns could provide valuable insights into motor learning, rehabilitation therapies, and neuroplasticity. This study explored the relationship between physiological neocerebellar extinction syndrome and hand/ft dominance in left and right-side dominant individuals. Data were collected from 80 university participants (40 left-side dominant, 40 right-side dominant, mean age = 24.7 ± 0.92 years) during controlled limb falls using 3D kinematic analysis. In these falls, theoretically suggested hypotonia in non-dominant limbs was analysed through attenuation coefficients and frequency differences. Using a linear mixed model, we found significantly lower hand attenuation in the non-dominant hand-(β = 0.10, p < 0.001), showing hypotonia compared to the dominant hand regardless of upper limb side dominance. Foot preference and dominance had minimal influence on leg attenuation or frequency, although right-footed, right-dominant individuals demonstrated significantly higher leg oscillation frequency, likely due to increased proximal muscle mass. Our findings suggest that distinct differences in cortical representation, lateralised control, and pathway specialisation exist due to the unique demands of each limb's motor functions, which are pronounced more neocerebellar extinction syndrome in the upper extremities. Therefore, the results showed potentially new perspectives on the cerebellum's nuanced role in motor control and laterality. The differential effects observed between the upper and lower limbs point to distinct cerebellar pathways and hypotonia. This work could significantly enhance the precision of therapeutic approaches and broaden our knowledge of laterality in motor function.
- MeSH
- biomechanika MeSH
- dospělí MeSH
- funkční lateralita * fyziologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- mozeček * patofyziologie MeSH
- noha (od hlezna dolů) fyziologie MeSH
- ruka MeSH
- svalová hypotonie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cerebellar extinction lesions can manifest themselves with cerebellar motor and cerebellar cognitive affective syndromes. For investigation of the functions of the cerebellum and the pathogenesis of cerebellar diseases, particularly hereditary neurodegenerative cerebellar ataxias, various cerebellar mutant mice are used. The Lurcher mouse is a model of selective olivocerebellar degeneration with early onset and rapid progress. These mice show both motor deficits as well as cognitive and behavioral changes i.e., pathological phenotype in the functional domains affected in cerebellar patients. Therefore, Lurcher mice might be considered as a tool to investigate the mechanisms of functional impairments caused by cerebellar degenerative diseases. There are, however, limitations due to the particular features of the neurodegenerative process and a lack of possibilities to examine some processes in mice. The main advantage of Lurcher mice would be the expected absence of significant neuropathologies outside the olivocerebellar system that modify the complex behavioral phenotype in less selective models. However, detailed examinations and further thorough validation of the model are needed to verify this assumption.
- MeSH
- cerebelární ataxie genetika patofyziologie patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- mozeček patologie patofyziologie MeSH
- myši - mutanty neurologické MeSH
- myši MeSH
- nemoci mozečku * patologie patofyziologie genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: The cerebellum is one of the major central nervous structures consistently altered in obesity. Its role in higher cognitive function, parts of which are affected by obesity, is mediated through projections to and from the cerebral cortex. We therefore investigated the relationship between body mass index (BMI) and cerebellocerebral connectivity. METHODS: We utilized the Human Connectome Project's Young Adults dataset, including functional magnetic resonance imaging (fMRI) and behavioral data, to perform connectome-based predictive modeling (CPM) restricted to cerebellocerebral connectivity of resting-state fMRI and task-based fMRI. We developed a Python-based open-source framework to perform CPM, a data-driven technique with built-in cross-validation to establish brain-behavior relationships. Significance was assessed with permutation analysis. RESULTS: We found that (i) cerebellocerebral connectivity predicted BMI, (ii) task-general cerebellocerebral connectivity predicted BMI more reliably than resting-state fMRI and individual task-based fMRI separately, (iii) predictive networks derived this way overlapped with established functional brain networks (namely, frontoparietal networks, the somatomotor network, the salience network, and the default mode network), and (iv) we found there was an inverse overlap between networks predictive of BMI and networks predictive of cognitive measures adversely affected by overweight/obesity. CONCLUSIONS: Our results suggest obesity-specific alterations in cerebellocerebral connectivity, specifically with regard to task execution. With brain areas and brain networks relevant to task performance implicated, these alterations seem to reflect a neurobiological substrate for task performance adversely affected by obesity.
- MeSH
- dospělí MeSH
- index tělesné hmotnosti * MeSH
- konektom * metody MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mladý dospělý MeSH
- mozeček * diagnostické zobrazování fyziologie MeSH
- nervová síť diagnostické zobrazování fyziologie MeSH
- obezita diagnostické zobrazování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Functional and molecular alterations in the cerebellum are among the most widely recognised associates of autism spectrum disorders (ASD). As a critical computational hub of the brain, the cerebellum controls and coordinates a range of motor, affective and cognitive processes. Despite well-described circuits and integrative mechanisms, specific changes that underlie cerebellar impairments in ASD remain elusive. Studies in experimental animals have been critical in uncovering molecular pathology and neuro-behavioural correlates, providing a model for investigating complex disease conditions. Herein, we review commonalities and differences of the most extensively characterised genetic lines of ASD with reference to the cerebellum. We revisit structural, functional, and molecular alterations which may contribute to neurobehavioral phenotypes. The cross-model analysis of this study provides an integrated outlook on the role of cerebellar alterations in pathobiology of ASD that may benefit future translational research and development of therapies.
OBJECTIVE: To date, very few studies have focused on structural changes and their association with cognitive performance in isolated REM sleep behaviour disorder (iRBD). Moreover, the results of these studies are inconclusive. This study aims to evaluate differences in the associations between brain morphology and cognitive tests in iRBD and healthy controls. METHODS: Sixty-three patients with iRBD and thirty-six controls underwent MRI with a 3 T scanner. The cognitive performance was assessed by a comprehensive neuropsychological battery. Based on performance, the iRBD group was divided into two subgroups with (iRBD-MCI) and without mild cognitive impairment (iRBD-NC). The high-resolution T1-weighted images were analysed using an automated atlas segmentation tool, voxel-based (VBM) and deformation-based (DBM) morphometry to identify between-group differences and correlations with cognitive performance. RESULTS: VBM, DBM and the comparison of ROI volumes yielded no significant differences between iRBD and controls. In the iRBD group, significant correlations in VBM were found between several cortical and subcortical structures primarily located in the temporal, parietal, occipital lobe, cerebellum, and basal ganglia and three cognitive tests assessing psychomotor speed and one memory test. Between-group analysis of cognition revealed a significant difference between iRBD-MCI and iRBD-NC in tests including a processing speed component. CONCLUSIONS: iRBD shows deficits in several cognitive tests that correlate with morphological changes, the most prominent of which is in psychomotor speed and visual attention as measured by the TMT-A and associated with the volume of striatum, insula, cerebellum, temporal lobe, pallidum and amygdala.
Recent fMRI resting-state findings show aberrant functional connectivity within somatomotor network (SMN) in schizophrenia. Moreover, functional connectivity aberrations of the motor system are often reported to be related to the severity of psychotic symptoms. Thus, it is important to validate those findings and confirm their relationship with psychopathology. Therefore, we decided to take an entirely data-driven approach in our fMRI resting-state study of 30 chronic schizophrenia outpatients and 30 matched control subjects. We used independent component analysis (ICA), dual regression, and seed-based connectivity analysis. We found reduced functional connectivity within SMN in schizophrenia patients compared to controls and SMN hypoconnectivity with the cerebellum in schizophrenia patients. The latter was strongly correlated with the severity of alogia, one of the main psychotic symptoms, i.e. poverty of speech and reduction in spontaneous speech,. Our results are consistent with the recent knowledge about the role of the cerebellum in cognitive functioning and its abnormalities in psychiatric disorders, e.g. schizophrenia. In conclusion, the presented results, for the first time clearly showed the involvement of the cerebellum hypoconnectivity with SMN in the persistence and severity of alogia symptoms in schizophrenia.
- MeSH
- afázie patofyziologie diagnostické zobrazování etiologie patologie MeSH
- chronická nemoc MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mozeček * diagnostické zobrazování patofyziologie MeSH
- nervová síť diagnostické zobrazování patofyziologie MeSH
- nervové dráhy patofyziologie diagnostické zobrazování MeSH
- schizofrenie * diagnostické zobrazování patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Parallel fibers (PFs) in the cerebellar cortex are involved in a series of coordinated responses in the fear conditioning paradigm induced by footshock. However, whether footshock can activate cerebellar climbing fibers (CFs) remains unclear. In this study, we recorded calcium (Ca2+) activity in CFs by optical fiber photometry in the cerebellar vermis lobule IV/V of freely moving mice with footshock stimulation. We found that the activation of CFs in the lobule IV/V was highly correlated with footshock stimulation but not with the sound stimulation used as a control. This result suggests that afferent information from CFs might be associated with the motor initiation of fear-related behaviors or fear emotion itself. Thus, our results suggest that a characteristic CF signal in the cerebellar cortex might be related to fear processing or footshock-related behaviors (such as startle responses or pain sensation).
- MeSH
- elektrický šok MeSH
- kůra mozečku fyziologie MeSH
- mozeček fyziologie MeSH
- myši inbrední C57BL * MeSH
- myši MeSH
- strach * fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
