[Role of the cerebellum in the control of distal motor activities in patients with akinetic-rigid Parkinson disease].
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Abstract:
Using f-MRI, we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of nine akinetic PD patients and compared to that of healthy volunteers. Compared with normal subjects, PD patients showed a reduction of activation of motor and SMA areas, an increase of activation of parietal areas and a bilateral activation of cerebellar hemispheres, which are likely to participate in the attempt to recruit parallel motor circuits in order to overcome the striatocortical defective loop.Keywords:
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Objective: The cerebellum, basal ganglia (BG), and other cortical regions have emerged as important structures for timing, yet the modulation of functional connectivity between them remains unexplored. Background Patients with Parkinson9s disease (PD) have marked deficits in motor and perceptual timing. We investigated the effective connectivity between the SMA, striatum, and cerebellum and its modulation during the motor timing task in healthy individuals and in early PD patients. Design/Methods: We used dynamic causal modeling on fMRI data obtained during a dynamic motor timing prediction task in 16 patients with PD and 17 healthy controls. Two types of behavioral events (hits and errors) constituted the driving input connected to the cerebellum, and the modulation was assessed relative to the hit condition. Results: The structure of intrinsic connectivity in both groups showed that the cerebellum has unidirectional connections with both sides of the BG, the BG with the SMA, and the SMA with the cerebellum. In the control group, the modulatory input decreased the relation of the cerebellum with the SMA and left BG with a more pronounced symmetry of these connections. PD subjects showed an increased EC between the cerebellum and both BG sides with more pronounced asymmetry (stronger connection with left BG). The modulatory input decreased the relation of the SMA with the cerebellum more in the PD subjects than in the controls. Conclusions: Although PD subjects and controls use similar functional circuits to maintain a successful outcome in predictive motor timing behavior, the strength of EC and its modulation differ. These functional changes represent the first step of cortical reorganization aimed at maintaining a normal performance in the brain affected by PD and implications for the neuro-rehabilitation field. Supported by: CEITEC - Central European Institute of Technology project (CZ.1.05/1.1.00/02.0068) from the European Regional Development Fund and by the Czech Ministry of Education Research Program MSM 0021622404. Disclosure: Dr. Bares has received personal compensation for activities with Novartis, Ipsen, Medtronic, Inc., UCB Pharma, GlaxoSmithKline, Inc., Neomed, Abbott Labratories as a consultant and a speaker. Dr. Husarova has received personal compensation for activities with Bayer Pharmaceutical Corporation and Neomed as a consultant. Dr. Mikl has nothing to disclose. Dr. Lungu has nothing to disclose. Dr. Marecek has nothing to disclose. Dr. Vanicek has nothing to disclose.
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We used retrograde transneuronal transport of neurotropic viruses in Cebus monkeys to examine the organization of basal ganglia and cerebellar projections to two cortical areas on the medial wall of the hemisphere, the supplementary motor area (SMA) and the pre-SMA. We found that both of these cortical areas are the targets of disynaptic projections from the dentate nucleus of the cerebellum and from the internal segment of the globus pallidus (GPi). On average, the number of pallidal neurons that project to the SMA and pre-SMA is approximately three to four times greater than the number of dentate neurons that project to these cortical areas. GPi neurons that project to the pre-SMA are located in a rostral, “associative” territory of the nucleus, whereas GPi neurons that project to the SMA are located in a more caudal and ventral “sensorimotor” territory. Similarly, dentate neurons that project to the pre-SMA are located in a ventral, “nonmotor” domain of the nucleus, whereas dentate neurons that project to the SMA are located in a more dorsal, “motor” domain. The differential origin of subcortical projections to the SMA and pre-SMA suggests that these cortical areas are nodes in distinct neural systems. Although both systems are the target of outputs from the basal ganglia and the cerebellum, these two cortical areas seem to be dominated by basal ganglia input.
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The authors studied the possible involvement of the cerebellum in nonexecutive motor functions needed for a normal performance of complex motor patterns by analyzing (using chronometric evaluation) finger movement sequences and their respective motor imagery (a mental simulation of motor patterns). Patients suffering from a cerebellar stroke (n=11) were compared with aged-matched control volunteers (n=11). Patients that had apparently recovered from a unilateral cerebellar stroke showed a marked slowing of motor performance in both hands (ipsi- and contralateral to lesion). This effect was accompanied by a similar slowing of motor imagery, suggesting that the cerebellum, traditionally implicated in the control of motor execution, is also involved in nonexecutive motor functions such as the planning and internal simulation of movements.
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The cerebellum has a critical role in control of timing and coordination of movement, acquisition of skills, and cognitive and affective functions. It participates in motor control via both immediate online adjustments of motor performance and long-term adaptive motor learning, referred to as supervised or error-based learning. Most of the cerebellum is interconnected with association areas of the cerebral cortex. The cerebellum is a major target of genetic, degenerative, metabolic, and immune disorders. Experimental evidence indicates that disrupted Purkinje cell pacemaking activity and synaptic plasticity in the cerebellum have a major role in the pathophysiology of ataxia. The cerebellar circuits also have a major role in the pathophysiology of different types of tremor.
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