The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism

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.

Broadband aperiodic components of local field potentials reflect inherent differences between cortical and subcortical activity

“…These results are reproducible across patients, two medical centers, electrode types, recording systems, referencing montages, diagnoses, and subcortical structures. Furthermore, the value for the aperiodic exponent in the STN we measured is consistent with recent studies that estimated this parameter (Huang et al, 2020; Wiest et al, 2022).…”

“…This could be due to less sensitivity or higher variability for the UPDRS-OFF score (as compared to the ON score) for the clinical population undergoing DBS treatment, which is biased to high symptom severity. There were no significant correlations of the STN LFP aperiodic exponent with UPDRS-III score (ON nor OFF levodopa), consistent with a recent report (Wiest et al, 2022).…”

“…Due to the different morphology of cortical versus thalamic and basal ganglia neurons, this could contribute to the difference in 1/ f χ slope observed. However, the aperiodic slope in the STN has been shown to change with Propofol anesthesia (Huang et al, 2020), dopaminergic medication and DBS treatment (Wiest et al, 2022), demonstrating that this parameter depends on dynamical aspects of neural activity and cannot be fully explained by morphology and cytoarchitecture.…”

Changes in electrophysiological aperiodic activity during cognitive control in Parkinson’s disease

“…46 Regarding STN-DBS, a systematic increase was also found in both exponent and offset of the aperiodic spectrum 18-month follow-up after surgery in PD patients. 47 More recently, Wiest 34 evidenced that the aperiodic exponent of subthalamic field potentials reflects E:I ratio in PD. Five other studies were based on non-invasive scalp EEG recordings.…”

Non-linear input-output relationships in the subthalamic nucleus of Parkinson’s patients

“…Thus, power changes of frequency bands can result from: changes in true oscillatory power, shifts in oscillatory center frequency, or changes in aperiodic parameters (offset and exponent) 23 . Extracting the periodic oscillations and aperiodic component from the signals of interest by Fitting Oscillations and One Over F (FOOOF) analysis can overcome the limitation of traditional narrowband analyses 23, 24 .…”