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.
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.
- Huiling Tan
- Peter J Magill
- Andrew Sharott
- Huiling Tan
- Huiling Tan
- Peter J Magill
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Nicole C Swann, University of Oregon, United States
© 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.
Acid-sensing ion channels (ASICs) are trimeric proton-gated sodium channels. Recent work has shown that these channels play a role in necroptosis following prolonged acidic exposure like occurs in stroke. The C-terminus of ASIC1a is thought to mediate necroptotic cell death through interaction with receptor interacting serine threonine kinase 1 (RIPK1). This interaction is hypothesized to be inhibited at rest via an interaction between the C- and N-termini which blocks the RIPK1 binding site. Here, we use two transition metal ion FRET methods to investigate the conformational dynamics of the termini at neutral and acidic pH. We do not find evidence that the termini are close enough to be bound while the channel is at rest and find that the termini may modestly move closer together during acidification. At rest, the N-terminus adopts a conformation parallel to the membrane about 10 Å away. The distal end of the C-terminus may also spend time close to the membrane at rest. After acidification, the proximal portion of the N-terminus moves marginally closer to the membrane whereas the distal portion of the C-terminus swings away from the membrane. Together these data suggest that a new hypothesis for RIPK1 binding during stroke is needed.
Decisions under uncertainty are often biased by the history of preceding sensory input, behavioral choices, or received outcomes. Behavioral studies of perceptual decisions suggest that such history-dependent biases affect the accumulation of evidence and can be adapted to the correlation structure of the sensory environment. Here, we systematically varied this correlation structure while human participants performed a canonical perceptual choice task. We tracked the trial-by-trial variations of history biases via behavioral modeling and of a neural signature of decision formation via magnetoencephalography (MEG). The history bias was flexibly adapted to the environment and exerted a selective effect on the build-up (not baseline level) of action-selective motor cortical activity during decision formation. This effect added to the impact of the current stimulus. We conclude that the build-up of action plans in human motor cortical circuits is shaped by dynamic prior expectations that result from an adaptive interaction with the environment.