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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Synchronization of neuronal activity evident in the local field potential (LFP) recorded in the subthalamic region of patients with Parkinson's disease occurs at low frequencies (〈 30 Hz) and, in some patients following treatment with levodopa, at high frequencies between 65 and 85 Hz. Here we investigate the functional relationship between these different activities by determining whether spontaneous fluctuations in their strength are correlated across time. To this end, we analysed recordings of LFPs from macroelectrodes inserted in the subthalamic area of 16 patients with Parkinson's disease, after treatment with anti-parkinsonian medication. Time-evolving autospectra of LFPs with significant 65–85 Hz peaks (from 21 sides) were computed and correlations between frequency components determined over time. LFP activity in the 5–32 Hz band was significantly negatively correlated with that in the 65–85 Hz band in data averaged across all 21 sides, as well as in 15 (71%) of the individual records. Negative correlations were relatively selective for interactions between these frequency bands and occurred over time epochs of as little as 40 s. They occurred about 50 min after levodopa and were recorded concurrently with contralateral levodopa-induced dyskinesias in all but four cases. Positive correlations were not seen between activities in the 5–32 Hz and 65–85 Hz bands. The spontaneous negative correlations suggest a reciprocal relationship between population synchrony in the high- and low-frequency ranges, and raise the possibility that spontaneous fluctuations in the balance between these activities may contribute to levodopa-induced dyskinesias.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Averaging techniques have demonstrated that movement preparatory cues and movement itself are associated with marked reductions in the oscillatory synchrony of local neuronal populations in the area of the human parkinsonian subthalamic nucleus (STN), as indexed by 8–30 Hz local field potential (LFP) activity. In order to examine the detailed nature and strength of the relationship between reductions in oscillatory activity and movement we examined single-trial LFP activity recorded from the STN area of parkinsonian subjects engaged in a choice reaction task. In this task an initial warning cue was either fully predictive or non-predictive of the hand required to make a later motor response. This motor response was elicited by a second go cue to which data were aligned. We observed a significant linear relationship between the onset time of oscillation reduction after go cues and subsequent motor response time across single trials within subjects. Consistent with this observation we also found a positive correlation of power with response time following go cues. In addition, we observed shorter durations of suppression in fully predictive trials where selection of the response could precede go cue presentation. The results are consistent with the hypothesis that reductions in 8–30 Hz population synchrony in the STN area are related to the processing required for motor preparation, particularly response selection.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The human disease hyperekplexia is characterized by excessive startle reactions to auditory and cutaneous stimuli. In its familial form, hyperekplexia has been associated with both dominant and recessive mutations of the GLRA1 gene encoding the glycine receptor α1 subunit (GlyRα1), which mediates inhibitory transmission in the spinal cord and brainstem. Here we have examined the functional consequences of two amino acid substitutions found in a compound heterozygous family, R252H and R392H, to investigate the mechanisms determining this inheritance pattern. When expressed in Xenopus laevis oocytes, both mutations were non-functional. Neither mutant affected the electrophysiological properties of wild type GlyRα1 when co-expressed. We introduced a green fluorescent protein tag to mutant subunits and found that both mutant proteins were detectable. Evidence that subcellular localization differed from wild type was significant for one of the mutants. Thus, an effective loss of functional GlyRα1-mediated current underlies hyperekplexia in this family, whereas a partial loss is asymptomatic.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 38 (2006), S. 801-806 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) α1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic ...
    Type of Medium: Electronic Resource
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