LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm
This single-blind, placebo-controlled, MEG (magnetoencephalography) study (n=20) used a clever auditory test to show decreased top-down information processing (more entropy, more bottom-up) under the influence of LSD (75μg).
Authors
- Suresh Muthukumaraswamy
- Robin Carhart-Harris
- David Nutt
Published
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.
Research Summary of 'LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm'
Introduction
Serotonergic psychedelics such as LSD act primarily at 5-HT2A receptors and are increasingly used to investigate the neural mechanisms of normal waking consciousness and psychopathology. Prior work suggests overlap between acute psychedelic states and early psychosis, with shared alterations in predictive coding mechanisms. The auditory oddball paradigm, which elicits a Mismatch Negativity (MMN) response to infrequent ‘deviant’ tones among repeated ‘standard’ tones, offers a well-established probe of perceptual learning and the balance between top-down predictions and bottom-up sensory signals. Timmermann and colleagues set out to characterise how LSD alters perceptual learning and effective connectivity within a fronto‑temporal network during an auditory oddball task recorded with magnetoencephalography (MEG). Using Dynamic Causal Modelling (DCM), the study tested whether LSD primarily modulates backward (top-down) extrinsic connections, intrinsic connectivity in primary auditory cortex (A1), or both, based on prior evidence that 5-HT2A receptors are located on neurons involved in backward projections and on earlier reports of psychedelic effects on effective connectivity.
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Study Details
- Study Typeindividual
- Journal
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- APA Citation
Timmermann, C., Spriggs, M. J., Kaelen, M., Leech, R., Nutt, D. J., Moran, R. J., Carhart-Harris, R. L., & Muthukumaraswamy, S. D. (2018). LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm. Neuropharmacology, 142, 251-262. https://doi.org/10.1016/j.neuropharm.2017.10.039
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