Systems-level analysis of local field potentials reveals differential effects of lysergic acid diethylamide and ketamine on neuronal activity and functional connectivity

Front Neurosci. 2023 May 23:17:1175575. doi: 10.3389/fnins.2023.1175575. eCollection 2023.

Abstract

Psychedelic substances have in recent years attracted considerable interest as potential treatments for several psychiatric conditions, including depression, anxiety, and addiction. Imaging studies in humans point to a number of possible mechanisms underlying the acute effects of psychedelics, including changes in neuronal firing rates and excitability as well as alterations in functional connectivity between various brain nodes. In addition, animal studies using invasive recordings, have suggested synchronous high-frequency oscillations involving several brain regions as another key feature of the psychedelic brain state. To better understand how the imaging data might be related to high-resolution electrophysiological measurements, we have here analyzed the aperiodic part of the local field potential (LFP) in rodents treated with a classic psychedelic (LSD) or a dissociative anesthetic (ketamine). In addition, functional connectivity, as quantified by mutual information measures in the LFP time series, has been assessed with in and between different structures. Our data suggest that the altered brain states of LSD and ketamine are caused by different underlying mechanisms, where LFP power shifts indicate increased neuronal activity but reduced connectivity following ketamine, while LSD also leads to reduced connectivity but without an accompanying change in LFP broadband power.

Keywords: LFP; dissociative anesthetics; in vivo; neurophysiology; psychedelics.

Grants and funding

This study was supported by grants from the Kempe Foundation, Insamlingsstiftelserna, Oskarfonden, Umeå University, the Swedish Brain Foundation, Vetenskapsrådet (VR) Grants 2018-02717 and 2021-01769, Olle Engkvist Foundation, the Parkinson Foundation, Kockska Foundation, Hedlund Foundation, Åhlén Foundation, Promobilia, LU Innovation, Wenner-Gren Foundation, Royal Physiological Society in Lund, BABEL (Erasmus Mundus), Crafoord Foundation, Barncancerfonden, Magnus Bergvall Foundation, Segerfalk Foundation, Sigur & Elsa Goljes Minne Foundation, Sven-Olof Jansons Livsverk, Svenska Sällskapet för Medicinsk Forskning (SSMF), and Thurings Foundation. The computations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at LUNARC partially funded by the Swedish Research Council through grant agreement no. 2016−07213.