Increased cortico-cortical functional connectivity in early-stage Parkinson's disease: An MEG study

Abstract

We set out to determine whether changes in resting-state corticocortical functional connectivity are a feature of early-stage Parkinson's disease (PD), explore how functional coupling might evolve over the course of the disease and establish its relationship with clinical deficits.Whole-head magnetoencephalography was performed in an eyesclosed resting-state condition in 70 PD patients with varying disease duration (including 18 recently diagnosed, drug-naive patients) in an "OFF" medication state and 21 controls. Neuropsychological testing was performed in all subjects. Data analysis involved calculation of three synchronization likelihood (SL, a general measure of linear and non-linear temporal correlations between time series) measures which reflect functional connectivity within (local) and between (intrahemispheric and interhemispheric) ten major cortical regions in five frequency bands.Recently diagnosed, drug-naive patients showed an overall increase in alpha1 SL relative to controls. Cross-sectional analysis in all patients revealed that disease duration was positively associated with alpha2 and beta SL measures, while severity of parkinsonism was positively associated with theta and beta SL measures. Moderately advanced patients had increases in theta, alpha1, alpha2 and beta SL, particularly with regard to local SL. In recently diagnosed patients, cognitive perseveration was associated with increased interhemispheric alpha1 SL.Increased resting-state cortico-cortical functional connectivity in the 8-10 Hz alpha range is a feature of PD from the earliest clinical stages onward. With disease progression, neighboring frequency bands become increasingly involved. These findings suggest that changes in functional coupling over the course of PD may be linked to the topographical progression of pathology over the brain.

MEG resting state functional connectivity in Parkinson’s disease related dementia

“…In very early stage, untreated, non-demented patients, we recently found increased alpha1 synchronization (Stoffers et al 2008). In moderately advanced patients, the increase in functional connectivity involved a more extended frequency range, also including the theta, alpha2 and beta bands (Stoffers et al 2008).…”

“…However, for the UPDRS OFF scores, there were no significant results nor even a trend towards significance for any of the SL parameters in the ANOVA with repeated-measures in both the demented and non-demented PD group. Furthermore, previous studies have shown that impaired motor function in early as well as more advanced stage, non-demented PD patients is associated with increases in synchronization (Silberstein et al 2005;Stoffers et al 2008)). Since, in the present study, we mainly report significant reductions in the demented patients, it seems highly unlikely that our results can be explained by worse motor function in our demented patients.…”

“…In moderately advanced patients, the increase in functional connectivity involved a more extended frequency range, also including the theta, alpha2 and beta bands (Stoffers et al 2008). In advanced stage nondemented PD patients receiving deep brain stimulation, Silberstein et al found a correlation between higher cortico-cortical coupling in the beta band and more impaired motor function (Silberstein et al 2005).…”

“…Using MEG and a general measure of synchronization, the synchronization likelihood (SL) , in early stage, untreated PD patients, we recently demonstrated increased synchronization for both local and long distance connections in the alpha1 frequency range compared to healthy controls (Stoffers et al 2008). In advanced, but non-demented PD patients, higher levels of cortico-cortical synchronization in the 10-35 Hz frequency range were correlated with more severe parkinsonism and could be attenuated by treatment with levodopa or deep brain stimulation of the subthalamic nucleus, in parallel with clinical motor improvement, suggesting an association between increased synchronization and impaired motor function (Silberstein et al 2005).…”

Complexity of resting-state EEG activity in the patients with early-stage Parkinson’s disease

“…Here the brain was described as a complex network, and graph theory was used to characterize the structure and dynamics of relevant networks. With such methods, Stoffers et al (2008) observed that the increased resting-state functional connectivity in alpha range was a feature of PD from the earliest clinical stages, and the increases in theta or beta bands appeared later in the disease; Utianski et al (2016) recently found that the network alteration and breakdown was the robust attribute of the pathophysiology of PD cortical dysfunction.…”