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First published online on January 12, 2006.
Copyright © 2006 by The Physiological Society
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jphysiol.2005.100271v1
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Received October 18, 2005
Revised November 29, 2005
Accepted after revision January 5, 2006

Dopamine-dependent non-linear correlation between subthalamic rhythms in Parkinson's disease

Sara Marceglia1, Guglielmo Foffani2, Annamaria Bianchi3, Giuseppe Baselli3, Filippo Tamma4, Marcello Egidi5, and Alberto Priori6*

1 Dipartimento di Scienze Neurologiche, Universit&agr di Milano, Fondazione IRCCS Ospedale Policlinico
2 1)Uni.di Milano2)Drexel Univ., Philadelphia3)Fundacion Hospital Nacional de Parapléjicos
3 Politecnico di Milano
4 Divisione di Neurologia, Ospedale San Paolo, Milano
5 Dipartimento di Scienze Neurologiche, IRCCS Ospedale Maggiore Policlinico, Milano
6 Dipartimento di Scienze Neurologiche, Universita&agrave di Milano, IRCCS Ospedale Maggiore di Milano

* To whom correspondence should be addressed. E-mail: alberto.priori{at}unimi.it.

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single-neurons in normal animals, suggesting a segregated parallel processing scheme. In MPTP-treated monkeys and in parkinsonian patients single-neurons become linearly correlated, thus leading to a loss of segregation between neurons. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13-20 Hz) and the high-beta rhythm (20-35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurons, but is not sufficient to induce correlated firing between neuron pairs. Conversely, loss of dopamine generates pathological linear correlation between neuron pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.


Key words: Basal ganglia • Motor control • Parkinson's disease




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