Abstract

Abnormal oscillatory activity in the basal ganglia is increasingly implicated in the pathophysiology of Parkinson's disease. Such activity is recorded in patients in the form of oscillations in the local field potential (LFP) picked up in the subthalamic nucleus. Previous studies have focused on correlations between features of the time averaged power or amplitude spectrum of the LFP and the clinical state, either off medication or in response to levodopa. However, average spectral densities do not take account of time variant spectral properties and we hypothesised that these dynamic properties of the spectrum of the LFP would contain additional information about clinical state. Here we assess the variability in LFP amplitude over time using the coefficient of variation (CV), evaluating this with regard to clinical state off medication and in response to levodopa in two datasets. The CV of activity in the high beta frequency band was found to be correlated with clinical state off levodopa (rho=−0.59, p<0.001) and this was shown to be complementary, rather than redundant, to spectral amplitude in a multiple regression analysis, selective for rigidity–bradykinesia and highly focal. Similarly, a strong correlation was found between change in clinical scores and change in high beta CV following levodopa (rho=−0.66, p=0.004). This too was selective for rigidity–bradykinesia and non-redundant to spectral power in a multiple regression model. Our results indicate that temporal stability in the beta band is correlated with rigidity–bradykinesia. It is suggested that loss of beta reactivity is deleterious to basal ganglia function over and above any concomitant change in absolute level of beta synchrony. The CV of LFP beta band amplitude may potentially provide an additional index of clinical state suitable for feedback control in closed loop stimulation therapy.

Highlights

  • There is an increase in correlative evidence suggesting that exaggerated oscillatory synchronisation in the beta frequency band may be related to motor impairment in patients with Parkinson's Disease (Jenkinson and Brown, 2011)

  • Such synchronisation is usually indirectly measured as the average spectral amplitude or power of beta frequency band activity in the local field potential (LFP) recorded in basal ganglia sites targeted during functional neurosurgery

  • This study demonstrates that the normalised variability (CV) of the beta frequency band component of the Subthalamic nucleus (STN) LFP over time strongly predicts the variance between patients in rigidity–bradykinesia

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Summary

Introduction

There is an increase in correlative evidence suggesting that exaggerated oscillatory synchronisation in the beta frequency band may be related to motor impairment in patients with Parkinson's Disease (Jenkinson and Brown, 2011). Such synchronisation is usually indirectly measured as the average spectral amplitude or power of beta frequency band activity in the LFP recorded in basal ganglia sites targeted during functional neurosurgery. The temporal stability of beta band amplitude might provide a faithful indicator of current motor state suitable as a feedback signal in the closed loop control of therapeutic deep brain

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