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LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm.

Christopher Timmermann, Meg J. Spriggs, Mendel Kaelen, Robert Leech, David Nutt, Rosalyn J. Moran, Robin Carhart-Harris, Suresh Muthukumaraswamy

Neuropharmacology November 20, 2017 DOI: 10.1016/j.neuropharm.2017.10.039 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 20
Population Healthy participants
Intervention LSD
Topics LSD
Keywords LSD LSD Neuroscience brain Neural adaptation Brain network dynamics Unexpected sounds Sensory processing
Citations 83
Key findings LSD reduces neural adaptation to familiar stimuli and blunts the neural surprise response to novel stimuli, and modulates backward connectivity within a fronto-temporal network.

Abstract

Under the predictive coding framework, perceptual learning and inference are dependent on the interaction between top-down predictions and bottom-up sensory signals both between and within regions in a network. However, how such feedback and feedforward connections are modulated in the state induced by lysergic acid diethylamide (LSD) is poorly understood. In this study, an auditory oddball paradigm was presented to healthy participants (16 males, 4 female) under LSD and placebo, and brain activity was recorded using magnetoencephalography (MEG). Scalp level Event Related Fields (ERF) revealed reduced neural adaptation to familiar stimuli, and a blunted neural 'surprise' response to novel stimuli in the LSD condition. Dynamic causal modelling revealed that both the presentation of novel stimuli and LSD modulate backward extrinsic connectivity within a task-activated fronto-temporal network, as well as intrinsic connectivity in the primary auditory cortex. These findings show consistencies with those of previous studies of schizophrenia and ketamine but also studies of reduced consciousness - suggesting that rather than being a marker of conscious level per se, backward connectivity may index modulations of perceptual learning common to a variety of altered states of consciousness, perhaps united by a shared altered sensitivity to environmental stimuli. Since recent evidence suggests that the psychedelic state may correspond to a heightened 'level' of consciousness with respect to the normal waking state, our data warrant a re-examination of the top-down hypotheses of conscious level and suggest that several altered states may feature this specific biophysical effector. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.

Comparable studies

Other randomized controlled trials on LSD, most cited first.

Study Year Design Participants
Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases 2014 Randomized controlled trial n = 12
Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users 1994 Double-blind, saline placebo-controlled, randomized study n = 12
Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) 2014 Double-blind, randomized, placebo-controlled, crossover study n = 16
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants 2018 Double-blind, randomized, counterbalanced, cross-over study n = 24
LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults 2016 Balanced-order, placebo-controlled study n = 19

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Explore topics

LSD Addiction Altered states of consciousness Ketamine Philosophy of mind