The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism: a cross-species study in vivo

Abstract

Periodic features of neural time series data, such as local field potentials (LFP), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically-relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in neuronal populations. Here, we used a cross-species in vivo electrophysiological approach to test the E/I hypothesis in the context of experimental and idiopathic Parkinsonism. We demonstrate in dopamine-depleted rats that aperiodic exponents and power at 30-100 Hz in subthalamic nucleus (STN) LFPs reflect defined changes in basal ganglia network activity; higher aperiodic exponents tally with lower levels of STN neuron firing and a balance tipped towards inhibition. Using STN-LFPs recorded from awake Parkinson's patients, we show that higher exponents accompany dopaminergic medication and deep brain stimulation (DBS) of STN, consistent with untreated Parkinson's manifesting as reduced inhibition and hyperactivity of STN. These results suggest that the aperiodic exponent of STN-LFPs in Parkinsonism reflects E/I balance, and might be a candidate biomarker for adaptive DBS.

Subthalamic Nucleus Stimulation–Induced Local Field Potential Changes in Dystonia

“…Recently, the aperiodic exponent (1/F slope of the PSD) was suggested as a marker for E/I balance 24,26,27 . We extracted the aperiodic exponent between 5 and 50 Hz to avoid a spectral plateau at ~50 Hz and found that aperiodic exponents in STN increase with increasing DBS currents (Linear mixed‐effect model (LME): estimate = 0.006, t = 8.15, P < 0.001, n = 11 hemispheres), consistent with the hypothesis that high‐frequency stimulation inhibits STN (Fig.…”

“…The lower bound was selected to avoid the impact of low‐frequency oscillations, and the upper bound was selected to avoid the impact of spectral plateaus at high DBS intensity 23 . The same FoooF settings were used to identify meaningful changes in the aperiodic exponent of STN‐LFPs with dopaminergic medication and high‐frequency stimulation 24 …”

“…23 The same FoooF settings were used to identify meaningful changes in the aperiodic exponent of STN-LFPs with dopaminergic medication and highfrequency stimulation. 24…”

“…DBS (deep brain stimulation)-induced power suppression in STN-LFPs (subthalamic nucleus-local field potential) of dystonic patients. (A) When stimulating contacts C2 to C7 at 2 mA and recording from the adjacent contact pair, average power (mean AE standard error of the mean) in the beta(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and gamma (36-80 Hz) range was suppressed compared to baseline in the most inferior contact only (in STN). Significant clusters are highlighted in green (cluster-based permutation test, P < 0.001).…”