Fig. 4: HFO induced by therapeutic 130 Hz DBS is present even after removal of evoked waveform between stimulation pulses.

a The overlay plot of raw data aligned with respect to the stimulus pulses (0.5 ms pre-onset was used to avoid edge artifacts). The large biphasic stimulation artifact at 0 ms masks both ECA and other LFP activity. b, c The same segment in a shown with 1 mV amplitude scale before and after denoising, to better demonstrate the removal of ECA waveform between pulses (thicker lines indicate the average waveform). The residual was obtained by subtraction of reconstructed segments from the raw data and it is devoid of stimulus pulse and inter-pulse evoked activity. d The amplitude range of the denoised (residual) data is similar to the baseline levels, except the first 3 s seconds of transient period. This segment, denoted with the dashed lines, was removed from overlay plots for clarity and excluded from spectral plots as well. e The root-mean-square (RMS) amplitude of the baseline segment before stimulation as well as raw and residual traces during stimulation. There was no significant difference between baseline and the denoised stimulation segment (n = 16). The first 1 ms including the large stimulation artifact was omitted from the RMS calculations to capture the amplitude levels associated with the evoked response. f TFM of the raw and residual segments and the template trace that was removed, as well as g their PSD plots from two representative patients illustrate that the denoising primarily removes the artifacts at the sub-harmonics of stimulation frequency while keeping the enhanced HFO intact. The varying power levels of the sub-harmonics throughout the spectrum are due to the leakage from the background activity to the extracted template trace and do not affect the overall peak and power characteristics of the HFO activity when removed. The color scale of the TFMs is same as limits of y-axis of their corresponding PSD plots. The dashed lines on TFMs denote the transition artifacts associated with turning the stimulator on and off. On each box in the boxplots, the central mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme data points not considered outliers, and the outliers are plotted individually using the “+” symbol. The individual data points are also plotted as red circles. *** denotes significance <0.001.