Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson’s disease

Abstract

1Parkinson's disease motor symptoms are associated with an increase in subthalamic 2 nucleus beta band oscillatory power. But these oscillations are phasic, and there is a 3 growing body of evidence suggesting that beta burst duration may be of critical 4 importance to motor symptoms, making insights into the dynamics of beta bursting 5 generation valuable. In this study, we ask the question "Can average burst duration 6 reveal how dynamics change between the ON and OFF medication states?". Our 7 analysis of local field potentials from the subthalamic nucleus demonstrates using linear 8 surrogates that the system generating beta oscillations acts in a more non-linear regime 9 OFF medication and that the change in the degree of non-linearity is correlated with 10 motor impairment. Further, we pinpoint specific dynamical changes responsible for 11 changes in the temporal patterning of beta oscillations between medication states by 12 fitting to data biologically inspired models, and simpler beta envelope models. Finally, 13 we show that the non-linearity can be directly extracted from average burst duration 14 profiles under the assumption of constant noise in envelope models. This reveals that 15 average burst duration profiles provide a window into burst dynamics, which may 16 underlie the success of burst duration as a biomarker. In summary, we demonstrate a 17 relationship between average burst duration profiles, dynamics of the system generating 18 beta oscillations, and motor impairment, which puts us in a better position to 19 understand the pathology and improve therapies such as deep brain stimulation. 20 April 27, 2020 1/39 65 OFF medication states to changes in dynamical properties of the system generating 66 beta oscillations? 67In previous studies, STN beta bursts have been mostly studied based on one 68 arbitrary threshold of the beta envelope as events above the threshold, potentially with 69April 27, 2020 2/39 a minimum duration condition (examples of various thresholds shown in Fig 1A). 70Average burst duration and amplitude profiles describing the average burst duration 71 and amplitude for a range of thresholds (see Fig 1A and Fig 1B for an illustration of 72 average burst duration profiles) have been introduced [13,14]. However, they played a 73 minor role and have not been considered systematically on an individual patient basis. 74 Here, we leave behind the arbitrary choice of a threshold by relying on profiles across 75 thresholds to provide an unbiased characterisation of beta oscillation temporal 76 patterning. It has been established that STN beta burst duration is a better metric 77 than burst amplitude to distinguish between the healthy and pathological states in an 78 animal model of PD [19]. We begin our study by investigating in STN recordings of PD 79 patients whether average burst duration profiles are better at distinguishing between the 80 ON and OFF medication states than average burst amplitude profiles. We only observe 81 changes in temporal patterning of beta oscillations in...

Sub-harmonic Entrainment of Cortical Gamma Oscillations to Deep Brain Stimulation in Parkinson’s Disease: Model Based Predictions and Validation in Three Human Subjects

“…Model parameters were then optimised to best match the selected data features (Figure 3B1-3). This process follows a fitting methodology similar to [28, 37]. It begins by generating random sets of parameters, and selecting parameter sets with a PSD broadly similar to that of the data (the first loop of Figure 3C), i.e.…”

Changes in non-oscillatory features of the cortical sensorimotor rhythm in Parkinson’s disease across age

“…[34][35][36][37] Functionally, the transient bursts appear to play a pivotal role in sensorimotor processing through the basal ganglia-thalamic-cortical network. For instance, the presence of a beta burst in the sensorimotor cortex close to a tactile stimulation decreased the likelihood of tactile detection 38 , and the rate of beta bursts is shown to decrease in the time leading up to a movement both in STN [39][40][41] and in the sensorimotor cortex. 42,43 In PD, quantification of beta-band burst activity from recordings in the STN has shown that beta-burst rate and duration are reduced by dopaminergic medication 44,45 and deep brain stimulation.…”

Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit

“…To do this, we compared fingerprints of the predefined network states (see Materials and Methods section “Definition of Discrete Network States”) with the outcomes of phase locked stimulation. To compare fingerprints between network states and phase stimulation we used a pooled R 2 measure [ 102 ]: where N f is the number of features (i.e., N f = 2: one vector from concatenated spectra and one vector from the flattened connectivity matrices), y n the feature under consideration, N n the length of y n and the mean of the n th data feature. varies between -∞ and 1, with 1 indicating a perfect fit, and negative coefficients indicating that the average fit is worse than that of a straight line going through the mean.…”

“…To do this, we compared fingerprints of the predefined network states (see section "Definition of Discrete Network States") with the outcomes of phase locked stimulation. To compare fingerprints between network states and phase stimulation we used a pooled R 2 measure [102]:…”