Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

H2(15)O PET activation studies enable the brain systems involved in controlling different aspects of motor function to be defined. In Parkinson's disease (PD) freely chosen limb movements are performed slowly. This bradykinesia is associated with selective underactivity of the supplementary motor area and dorsal prefrontal cortex, frontal association areas that receive subcortical input principally from the basal ganglia. At the same time there is compensatory overactivity of the lateral premotor and parietal cortex, areas that have a primary role in facilitating motor responses to visual and auditory cues. This finding explains why PD patients find it easier to perform cued as opposed to freely chosen actions. Levels of activation of the supplementary motor area and dorsal prefrontal cortex in PD can be restored with dopaminergic medication, implants of fetal mesencephalic tissue, internal pallidotomy or high frequency electrical subthalamic stimulation. Activation studies suggest that Parkinsonian rest tremor arises from a combination of inappropriate overactivity of cerebellar connections and loss of dopaminergic function. When tremor is relieved by ventral thalamotomy or thalamic stimulation this cerebellar overactivity is corrected but at the expense of reducing levels of primary motor cortex activation. It has been hypothesised that dyskinesias in PD arise due to altered dopamine receptor binding following chronic exposure to levodopa stimulation. Functional imaging findings, however, are against this hypothesis and rather suggest that downstream increases in basal ganglia opioid neurotransmission are more likely to be relevant.
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PMID:Functional imaging of Parkinson's disease: is it possible to detect brain areas for specific symptoms? 1037 Sep 8

Current models about the organization of the basal ganglia have provided a resurgence of the surgical treatment of Parkinson's disease (PD). Surgical experience has served to corroborate many of the predictions supported by the model. For instance, hyperactivity of the subthalamopallidal pathway is the key feature in PD and its suppression is associated with an improvement of the cardinal signs and symptoms of the disease. Parkinsonian rest tremor may be related to the oscillatory activity of the subthalamic and pallidal neurons. However, some clinical observations can not be entirely explained by the model. The most important paradox is the disappearance of levodopa-induced dyskinesias after pallidal surgery. This review critically analyzes the validity of the current model based on the surgical observations.
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PMID:[Physiopathology of parkinsonism and dyskinesias: lessons from surgical observations]]. 1123 58

Classical Parkinsonian rest tremor typically fluctuates over time and can be provoked by stressful situations. We quantified and compared the influence of different provocation methods on classical rest tremor severity. The effect of counting backwards from 100, tapping of the contralateral foot and a Stroop test on the Unified Parkinson's Disease Rating Scale (UPDRS) III rest tremor scores and the accelerometrically measured tremor amplitudes (total power) were analyzed in 18 patients with Parkinson's disease and a Type I tremor. Each of the three provocation methods increased the UPDRS III rest tremor score by 1-2 and the total power by 1-2 orders of magnitude compared with baseline (P < 0.001). The maximal effect was reached on average after 2-3 minutes of provocation. The effects were not significantly different. Provocations clearly influence the result of clinical rest tremor ratings, with the kind of provocation being of minor importance. We therefore suggest that each assessment of Parkinsonian rest tremor should include a systematic provocation and this should be formally included in future versions of the UPDRS.
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PMID:Provocation of Parkinsonian tremor. 1838 37

Tremor in Parkinson's disease (PD) is generated by an oscillatory neuronal network consisting of cortex, basal ganglia and thalamus. The subthalamic nucleus (STN) which is part of the basal ganglia is of particular interest, since deep brain stimulation of the STN is an effective treatment for PD including Parkinsonian tremor. It is controversial if and how the STN contributes to tremor generation. In this study, we analyze neuronal STN activity in seven patients with Parkinsonian rest tremor who underwent stereotactic surgery for deep brain stimulation. Surface EMG was recorded from the wrist flexors and extensors. Simultaneously, neuronal spike activity was registered in different depths of the STN using an array of five microelectrodes. After spike-sorting, spectral coherence was analyzed between spike activity of STN neurons and tremor activity. Significant coherence at the tremor frequency was detected between EMG and neuronal STN activity in 76 out of 145 neurons (52.4%). In contrast, coherence in the beta band occurred only in 10 out of 145 neurons (6.9%). Tremor-coherent STN activity was widely distributed over the STN being more frequent in its dorsal parts (70.8-88.9%) than in its ventral parts (25.0-48.0%). Our results suggest that synchronous neuronal STN activity at the tremor frequency contributes to the pathogenesis of Parkinsonian tremor. The wide-spread spatial distribution of tremor-coherent spike activity argues for the recruitment of an extended network of subthalamic neurons for tremor generation.
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PMID:Tremor-correlated neuronal activity in the subthalamic nucleus of Parkinsonian patients. 1863 49

We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinson's disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within and between basal ganglia nuclei is very often accompanied by synchronization at Parkinsonian rest tremor frequencies (3-10 Hz). These oscillations have a profound influence on thalamic projections and impair the thalamic relaying of cortical input by generating rebound action potentials. Our model describes convergent inhibitory input received from basal ganglia by the thalamocortical cells based on characteristics of normal activity, and/or low-frequency oscillations (activity associated with Parkinson's disease). In addition to simulated input, we also used microelectrode recordings as inputs for the model. In the resting state, and without additional sensorimotor input, pathological rebound activity is generated for even mild Parkinsonian input. We have found a specific stimulation window of amplitudes and frequencies for periodic input, which corresponds to high-frequency DBS, and which also suppresses rebound activity for mild and even more prominent Parkinsonian input. When low-frequency pathological rebound activity disables the thalamocortical cell's ability to relay excitatory cortical input, a stimulation signal with parameter settings corresponding to our stimulation window can restore the thalamocortical cell's relay functionality.
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PMID:From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling. 2199 Jan 62