Effective Connectivity of Thalamocortical Interactions Following d-Amphetamine, LSD, and MDMA Administration.

Mihai Avram, Felix Müller, Katrin H Preller, Adeel Razi, Helena Rogg, Alexandra Korda, Friederike Holze, Patrick Vizeli, Laura Ley, Matthias E Liechti, Stefan Borgwardt

Journal: Biological psychiatry. Cognitive neuroscience and neuroimaging 2024;9(5):522-532

PMID: 37532129

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Abstract

BACKGROUND

While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain.

METHODS

We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions.

RESULTS

Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity.

CONCLUSIONS

The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes.

Address: Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany; Center of Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany. Electronic address: [email protected].; Department of Psychiatry, University of Basel, Basel, Switzerland.; Pharmaco-Neuroimaging and Cognitive-Emotional Processing, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland.; Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia.; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany; Center of Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany.; Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.

DOI: 10.1016/j.bpsc.2023.07.010

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MeSH Terms: Humans, Lysergic Acid Diethylamide, N-Methyl-3,4-methylenedioxyamphetamine, Thalamus, Male, Double-Blind Method, Adult, Magnetic Resonance Imaging, Hallucinogens, Dextroamphetamine, Cross-Over Studies, Female, Cerebral Cortex, Young Adult, Neural Pathways, Connectome