The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism
- University of Oxford, United Kingdom
- University Medical Center of the Johannes Gutenberg University Mainz, Germany
- King's College London, United Kingdom
- St. George's University, United Kingdom
- CNRS UMR5293, Université de Bordeaux, France
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.
Data availability
The code was uploaded directly to eLife and in addition can be found here https://doi.org/10.5287/bodleian:rJ7jyjX97. The animal data (Mallet et al., 2022) used for this project is available at the Medical Research Council Brain Networks Dynamics Unit (MRC BNDU) Data Sharing Platform at the University of Oxford https://data.mrc.ox.ac.uk/stn-rat and DOI: https://doi.org/10.5287/bodleian:wx6D7oenk. The human data (Wiest et al., 2022) is also available at the MRC BNDU Data Sharing Platform https://data.mrc.ox.ac.uk/stn-lfp-on-off-and-dbs and DOI: https://doi.org/10.5287/bodleian:mzJ7YwXvo.
-
Wideband recordings from silicon probes in the subthalamic nucleus of 6-OHDA hemi-lesioned rats during anaesthesiaOxford University Research Archive, doi:10.5287/bodleian:wx6D7oenk.
-
STN local field potential recordings from awake patients with Parkinson's, ON and OFF meds, and during 130 Hz DBSOxford University Research Archive, doi:10.5287/bodleian:mzJ7YwXvo.
Article and author information
Author details
Muthuraman Muthuraman
Funding
Medical Research Council (MC_UU_00003/2)
- Huiling Tan
Medical Research Council (MC_UU_00003/5)
- Peter J Magill
Medical Research Council (MC_UU_00003/6)
- Andrew Sharott
National Institute for Health Research Oxford Biomedical Research Centre
- Huiling Tan
Rosetrees Trust
- Huiling Tan
Parkinson's UK (G-0806)
- Peter J Magill
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were performed on adult male Sprague Dawley rats (Charles River), and were conducted in accordance with the Animals (Scientific Procedures) Act, 1986 (UK) and the provisions of the Society for Neuroscience Policies on the Use of Animals in Neuroscience Research. Animal data that was analysed in this paper has been generated under the project licence numbers 30/2131 and 30/2629. All details on the 6-OHDA lesion and electrophysiological recordings were published before (Mallet et al., 2008a).
Human subjects: This protocol was approved by the Health Research Authority UK, the National Research Ethics Service local Research Ethics Committee (IRAS: 46576) and the local ethics committee at the University of Mainz (837.208.17(11042)). Patients were recruited at St. George's University Hospital NHS Foundation Trust, London, King's College Hospital NHS Foundation Trust, London, and the University Medical Center Mainz. Written informed consent, and consent to publish, was obtained before surgery in line with the Declaration of the Principles of Helsinki. We analysed data from 24 patients from these 3 centres.
Copyright
© 2023, Wiest et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,523
- views
-
- 369
- downloads
-
- 51
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism
eLife 12:e82467.
https://doi.org/10.7554/eLife.82467
Further reading
-
- Neuroscience
Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.
-
- Neuroscience
When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.
