β band stability over time correlates with Parkinsonian rigidity and bradykinesia

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.

Fig. 1

Schematic showing amplitude variability in beta in one subject and corresponding instantaneous amplitude time series. [A] Filtered beta LFP signal from subject 12 (intraoperative rest data) demonstrating marked fluctuations in beta amplitude over time and a low hemibody UPDRS score = 23. [B] Instantaneous amplitude time series with mean amplitude (thick dashed line) and standard deviation also illustrated (thin dashed lines). Instantaneous amplitude is calculated by convolution of the LFP with an appropriately scaled/frequency specific wavelet to determine the amplitude of the selected frequency band at all points in time. The standard deviation of the instantaneous amplitude time series captures the variability of amplitude over time for that frequency. This is then normalised by the mean amplitude in that frequency band to derive a scale invariant measure of amplitude variability — the coefficient of variation of amplitude over time (CV), for each record.

Fig. 2

Spectral correlations. [A] Mean STN LFP amplitude spectral density across all subjects, shown as % of total in each 1 Hz frequency band. There are peaks at 16 and 25 Hz, in the beta 1 and beta 2 ranges, respectively. [B] and [C] show Spearman's correlation coefficient (rho) and its significance between the CV of STN LFP amplitude at a given frequency and contralateral hemibody (HB) motor UPDRS scores. There is a strong and broad correlation between the STN LFP CV at a given frequency and contralateral hemibody motor UPDRS scores in the beta 2 range.

Fig. 3

Scatter plot of CV and contralateral hemibody motor UPDRS off medication. Shown for the frequency (25 Hz) of the peak of activity in the Beta 2 range in the group mean spectrum (Fig. 2A). There is a negative correlation between CV and UPDRS off medication (rho = − 0.75, p < 0.001).

Fig. 4

Scatter plot of change in mean beta 2 CV and change in contralateral hemibody rigidity-bradykinesia score in response to levodopa. The patients with the best improvement (more negative % change) in rigidity-bradykinesia have the greater increase in beta 2 CV.