Project 3

Cortico-subcortical interactions and local neuronal dynamics in Parkinson’s Disease

Summary

Numerous studies have established an association between Parkinson’s Disease (PD) and abnormal neuronal oscillations in cortico-basal ganglia (BG) networks. While the main emphasis was on the demonstration of the fact that excessively strong beta oscillations in subthalamic nucleus (STN) relate to motor deficits in PD, the relevance of ongoing cortical activity and cortico-BG coherence to PD still awaits deeper investigation. In particular, methods commonly used to study neuronal oscillations and interactions in cortico-BG had intrinsic limitations owing to the lack of spatial specificity and analytic restrictions, being primarily based on investigating linear interactions in cortico-BG.

In the present proposal we plan to use a complementary set of newly developed multivariate techniques (such as Spatio-Spectral Decomposition, Cross-Frequency Decomposing, Regression Coherence) to characterize linear and non-linear neuronal interactions between cortex and BG in patients with PD. We will put a particular emphasis on cross-frequency neuronal interactions in cortico-BG networks with the idea to identify mechanisms through which a major cortical oscillatory activity, represented by alpha oscillations, can modulate beta oscillations representing the most dominant rhythm in BG.

Specifically, such non-linear interactions could further our understanding of cortical contributions to the therapeutic effects of STN-DBS. Moreover, in order to address causal implications of changes in cortico-BG oscillatory activity for movement impairment in PD, we plan to study a link between instantaneous changes in the parameters of neuronal oscillations, evoked responses, and concurrent movement parameters.

Main results from the previous funding period (2011–2013)

  • Demonstration of the existence of long-range temporal correlations in local field potential recordings (LFP) from STN of patients with PD. The long-range temporal correlations were decreased after levodopa withdrawal in 13–35 Hz and ~300 Hz oscillations (Hohlefeld et al., 2012).
  • Demonstration of genuine functional and effective connectivity (i.e., not due to volume conduction) in STN-LFP recordings of patients with PD. Increased functional connectivity (10–30 Hz oscillations) after levodopa administration correlated with motor improvement in UPDRS (Hohlefeld et al., 2013a).
  • Demonstration of long-range temporal correlations in electroencephalographic recordings (6–30 Hz oscillations) of patients with essential tremor. Thalamic deep brain induced-changes in cortical long-range temporal correlations correlated with the tremor severity and disease duration (Hohlefeld et al., 2013b).
  • Development of a novel method (Source Power Correlation) that maximizes the correlation between the amplitude of neural oscillations and cognitive-motor variables, thus allowing the extraction of neural components that most strongly predict behavioral parameters, e.g., movement parameters in PD (Dähne et al., 2014).

Website:

https://sites.google.com/site/neurophysicsgroup/

Dr. rer. nat. Vadim V. Nikulin, Principal Investigator
Charité – Campus Benjamin Franklin
Department of Neurology / AG Neurophysik
Hindenburgdamm 30
12203 Berlin
Tel.: +49-30 8445 4706
Fax: +49-30 8445 4264
vadim.nikulin@charite.de

Prof. Dr. med. Gabriel Curio, Principal Investigator
Charité – Campus Benjamin Franklin
Department of Neurology / AG Neurophysik
Hindenburgdamm 30
12203 Berlin
Tel.: +49-30 8445 2276
Fax: +49-30 8445 4264
gabriel.curio@charite.de

Dr. phil. Friederike U. Hohlefeld, Postdoc
Charité – Campus Benjamin Franklin
Department of Neurology / AG Neurophysik
Hindenburgdamm 30
12203 Berlin
Tel.: +49-30 8445 4703
Fax: +49-30 8445 4264
friederike.hohlefeld@gmx.de