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

LSD and ketamine produce altered brain states through different underlying mechanisms. In rodents, ketamine increased neuronal activity (indicated by shifts in local field potential power) but reduced connectivity between brain structures, while LSD also reduced connectivity but without a change in broadband power. The findings help bridge human imaging studies, which show altered functional connectivity, with invasive animal recordings that reveal high-frequency oscillations. Understanding these distinct neurophysiological signatures may clarify how classic psychedelics and dissociative anesthetics affect the brain, informing their potential therapeutic uses for psychiatric conditions.

Study at a glance

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.