Towards a systems-level view of cerebellar function::the interplay between cerebellum, basal ganglia and cortex

Contains fulltext : 170319.pdf (Publisher’s version ) (Open Access)Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field

Cerebellum: an explanation for dystonia?

Dystonia is a movement disorder that is characterized by involuntary muscle contractions, abnormal movements and postures, as well as by non-motor symptoms, and is due to abnormalities in different brain areas. In this article, we focus on the growing number of experimental studies aimed at explaining the pathophysiological role of the cerebellum in dystonia. Lastly, we highlight gaps in current knowledge and issues that future research studies should focus on as well as some of the potential applications of this research avenue. Clarifying the pathophysiological role of cerebellum in dystonia is an important concern given the increasing availability of invasive and non-invasive stimulation techniques and their potential therapeutic role in this condition

Developmental neurobiology of cerebellar and Basal Ganglia connections

BACKGROUND: The high prevalence of mixed phenotypes of Early Onset Ataxia (EOA) with comorbid dystonia has shifted the pathogenetic concept from the cerebellum towards the interconnected cerebellar motor network. This paper on EOA with comorbid dystonia (EOA-dystonia) explores the conceptual relationship between the motor phenotype and the cortico-basal-ganglia-ponto-cerebellar network. METHODS: In EOA-dystonia, we reviewed anatomic-, genetic- and biochemical-studies on the comorbidity between ataxia and dystonia. RESULTS: In a clinical EOA cohort, the prevalence of dystonia was over 60%. Both human and animal studies converge on the underlying role for the cortico-basal-ganglia-ponto-cerebellar network. Genetic -clinical and -in silico network studies reveal underlying biological pathways for energy production and neural signal transduction. CONCLUSIONS: EOA-dystonia phenotypes are attributable to the cortico-basal-ganglia-ponto-cerebellar network, instead of to the cerebellum, alone. The underlying anatomic and pathogenetic pathways have clinical implications for our understanding of the heterogeneous phenotype, neuro-metabolic and genetic testing and potentially also for new treatment strategies, including neuro-modulation

Examining Cerebellar Modulation of Mesolimbic Dopamine Transmission Using Fixed Potential Amperometry

Examining Cerebellar Modulation of Mesolimbic Dopamine Transmission Using Fixed Potential Amperometr

Longitudinal [18]UCB-H/[18F]FDG imaging depicts complex patterns of structural and functional neuroplasticity following bilateral vestibular loss in the rat

Neuronal lesions trigger mechanisms of structural and functional neuroplasticity, which can support recovery. However, the temporal and spatial appearance of structure–function changes and their interrelation remain unclear. The current study aimed to directly compare serial whole-brain in vivo measurements of functional plasticity (by [ 18 F]FDG-PET) and structural synaptic plasticity (by [ 18 F]UCB-H-PET) before and after bilateral labyrinthectomy in rats and investigate the effect of locomotor training. Complex structure–function changes were found after bilateral labyrinthectomy: in brainstem-cerebellar circuits, regional cerebral glucose metabolism (rCGM) decreased early, followed by reduced synaptic density. In the thalamus, increased [ 18 F]UCB-H binding preceded a higher rCGM uptake. In frontal-basal ganglia loops, an increase in synaptic density was paralleled by a decrease in rCGM. In the group with locomotor training, thalamic rCGM and [ 18 F]UCB-H binding increased following bilateral labyrinthectomy compared to the no training group. Rats with training had considerably fewer body rotations. In conclusion, combined [ 18 F]FDG/[ 18 F]UCB-H dual tracer imaging reveals that adaptive neuroplasticity after bilateral vestibular loss is not a uniform process but is composed of complex spatial and temporal patterns of structure–function coupling in networks for vestibular, multisensory, and motor control, which can be modulated by early physical training

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

Molecular imaging in Parkinson's disease

The present work explores brain functional changes in drug-naïve Parkinson's disease (PD) patients by means of molecular imaging techniques. Thirty-one consecutive drug-naïve PD patients from the Neurological Clinic of the University of Flor-ence underwent clinical assessment, neuropsychological assessment, MRI, [123I]FP-CIT SPECT, [18F]FDG PET. First, [18F]FDG-PET was employed to identify in drug-naïve PD patients brain metabolic alteration uniquely related to disease process and not modulated by anti-parkinsonian therapeutic intervention. Second, [18F]FDG-PET and [123I]FP-CIT SPECT were employed together to explore the early functional changes in brain function related to dopaminergic depletion in the putamen and in the caudate nucleus

Multi-neuroimaging model of identifying neuroplasticity under motor cognitive learning condition: MRI based study.

Motor learning is a fundamental ability and one of the most robust models to study neural plasticity. The majority of human motor learning imaging studies focused on either short-term or long-term learning using one single imaging modality. These studies were thus not able to systematically investigate the dynamic process of motor learning from a multimodal perspective. The current project combined both short-term and long-term motor learning to comprehensively characterize neural plasticity at multiple phenotypic levels of the brain: functional activation, functional connectivity, grey matter volume, and glutamate concentration. To this end, this project involved a cross-sectional and a longitudinal study with multimodal brain imaging techniques (task fMRI, resting-state fMRI, gray matter structural fMRI, pharmacological fMRI, and MRS). Short-term motor learning was significantly correlated with brain network features related to network efficiency. It was also associated with a highly reliable cerebellum-centered network which was significantly modulated by the NMDA antagonist ketamine. Long-term motor learning was associated with increased activation in premotor / SMA and parietal regions and with increased gray matter volume of the SMA and the hippocampus. In addition, long-term motor learning was accompanied by a decrease in the functional connectivity of a network centered on the sensorimotor cortex which was related to handknob glutamate concentration levels and which involved regions that were highlighted by our activation and structural analyses. Taken together, this thesis contributes important evidence to the neurofunctional and neurostructural underpinnings of motor learning and points to the critical roles of the cerebellum, the hippocampus and the relevance of glutamate for motor learning in humans