Trends in Neurosciences
Review
INMED/TINS special issuePathological synchronization in Parkinson's disease: networks, models and treatments
INMED/TINS special issue
Section snippets
Parkinson's disease and its treatment
Parkinson's disease (PD) is a progressive age-related neurodegenerative disorder, second in frequency only to Alzheimer's disease. It affects tens of millions of people worldwide, and the frequency and associated socioeconomic burden of the condition are set to increase as the elderly population grows. The disease is characterized by poverty of voluntary movements (akinesia), slowness and impaired scaling of voluntary movement (bradykinesia), muscle rigidity and tremor of the limbs at rest. The
Cellular and network basis for oscillations in the basal ganglia
The operation of the basal ganglia network in health and disease is heavily determined by its dual composition: the striatum on the one hand and, on the other, all the other basal ganglia nuclei, comprising the globus pallidus pars externa (GPe) and interna (GPi), STN and the substantia nigra pars reticulata (SNr) (Figure 1). These two neuronal populations have different membrane properties and different organizational principles. Inside the second network, STN deserves a special mention, given
Excessive synchrony in animal models of PD
Monkeys treated with the toxin MPTP show an increase in the fraction of basal ganglia neurons that discharge in bursts. These bursts are either irregular or oscillatory (Figure 2) and have been found in STN, GPe and GPi [18]. In most cases, the bursts follow the frequency of tremor or its higher harmonics. Both STN inactivation [19] and dopamine replacement therapy [20] significantly ameliorate the MPTP tremor and other motor symptoms and reduce 8–20-Hz oscillations in GPi, supporting the
Excessive synchrony in patients with PD
LFPs are more readily recorded from the basal ganglia than the activity of single neurons in patients because the former recordings can also be made in the interval between surgical implantation of the STN or globus pallidus and connection of macroelectrodes to a subcutaneous stimulator a few days later (Figure 3a–c). LFP recordings in patients withdrawn from their antiparkinsonian medication have consistently revealed prominent oscillations between 8 Hz and 30 Hz 26, 27, 28, 29, 30, 31, 32, 33,
How might excessive synchrony impair motor processing?
Information theoretic studies reveal that the information encoded by the simultaneous activity of neurons can be independent, redundant or synergistic 39, 40. These activity modes are strongly, but not simply, related to the level of pairwise correlations between the neuronal elements of the network [41]. Usually, one can assume that a correlated network is redundant, offering stability against the possible results of the extinction of one or several neurons in the network. In that case, the
Do therapies for PD suppress excessive synchrony?
PD is treated today mainly by dopaminergic drugs, particularly levodopa, deep-brain stimulation or lesioning of the basal ganglia. The latter suppresses spontaneous beta synchrony at the operation target, but what of the other therapeutic approaches? As already stated, treatment with dopaminergic drugs suppresses beta synchrony, particularly that at lower frequencies within this band. This relationship is a graded one, with the amount of drug-induced suppression in the STN [27] and cerebral
Conclusion and future research
There are increasing amounts of data linking excessive synchrony at low beta frequencies in basal ganglia-cortical loops to impaired motor processing in PD. Nevertheless, this evidence remains correlative in nature and is notably challenged by a recent model of basal ganglia function that suggests that action selection is impaired before the appearance of oscillations [66], although interpretation of this model in the context of PD assumes that failure of action selection leads to bradykinesia.
Acknowledgements
P.B. was supported by the Medical Research Council, UK; H.B. was supported by the ‘Fighting against Parkinson’ Foundation of the Hebrew University Netherlands Association (HUNA); C.H. was supported by CNRS, Inserm and Fondation de France. C.H. thanks Liliana Garcia, Rachida Ammari and Bernard Bioulac.
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