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

TY - JOUR

T1 - LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm

AU - Timmermann, Christopher

AU - Spriggs, Meg J.

AU - Kaelen, Mendel

AU - Leech, Robert

AU - Nutt, David J.

AU - Moran, Rosalyn J.

AU - Carhart-Harris, Robin L.

AU - Muthukumaraswamy, Suresh D.

PY - 2018/11

Y1 - 2018/11

N2 - 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'.

AB - 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'.

KW - Attention/drug effects

KW - Auditory Perception/drug effects

KW - Brain/drug effects

KW - Brain Mapping/methods

KW - Female

KW - Hallucinogens/pharmacology

KW - Humans

KW - Lysergic Acid Diethylamide/pharmacology

KW - Magnetoencephalography

KW - Male

KW - Neural Pathways/drug effects

KW - Random Allocation

U2 - 10.1016/j.neuropharm.2017.10.039

DO - 10.1016/j.neuropharm.2017.10.039

M3 - Article

C2 - 29101022

SN - 0028-3908

VL - 142

SP - 251

EP - 262

JO - Neuropharmacology

JF - Neuropharmacology

ER -