Characterizing thalamocortical (dys)connectivity following d-amphetamine, LSD, and MDMA administration

This neuroimaging study (n=28) investigated the effects of LSD, d-amphetamine and MDMA on thalamocortical intrinsic functional connectivity (iFC). Each substance elicited auditory-sensorimotor-thalamic-hyperconnectivity compared to placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD produced salience (SAL) hyperactivity whereas MDMA and amphetamine produced hypoconnectivity with SAL. This range of activity is similar to that seen in patients with psychotic disorders.

Abstract

“Background: Patients with psychotic disorders present alterations in thalamocortical intrinsic functional connectivity (iFC) as measured by resting-state functional magnetic resonance imaging (rs-fMRI). Specifically, thalamic iFC is increased with sensorimotor cortices (hyperconnectivity) and decreased with prefrontal-limbic cortices (hypoconnectivity). Intriguingly, psychedelics such as lysergic acid diethylamide (LSD) elicit similar thalamocortical-hyperconnectivity with sensorimotor areas in healthy volunteers. It is unclear whether LSD also induces thalamocortical-hypoconnectivity with prefrontal-limbic cortices as current findings are equivocal. Notably, thalamocortical-hyperconnectivity was associated with psychotic symptoms in patients and substance-induced altered states of consciousness in healthy volunteers. Thalamocortical dysconnectivity is likely evoked by altered neurotransmission, e.g., via dopaminergic excess in psychotic disorders and serotonergic agonism in psychedelic-induced states. It is unclear whether thalamocortical dysconnectivity is also elicited by amphetamine-type substances, broadly releasing monoamines (i.e., dopamine, norepinephrine) but producing fewer perceptual effects than psychedelics.

Methods: We administrated LSD, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers and investigated their effects on thalamic iFC with two brain networks (auditory-sensorimotor (ASM) and salience (SAL) – corresponding to sensorimotor and prefrontal-limbic cortices, respectively), using a double-blind, placebo-controlled, cross-over design.

Results: All active substances elicited ASM-thalamic-hyperconnectivity compared to placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD-induced effects correlated with subjective changes in perception, indicating a link between hyperconnectivity and psychedelic-type perceptual alterations. Unlike d-amphetamine and MDMA, which induced hypoconnectivity with SAL, LSD elicited hyperconnectivity. D-amphetamine and MDMA evoked similar thalamocortical dysconnectivity patterns.

Conclusions: Psychedelics, empathogens, and psychostimulants evoke thalamocortical-hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.”

Authors: Mihai Avram, Felix Müller, Helena Rogg, Alexandra Korda, Christina Andreou, Freiderike Holze, Laura Ley, Matthias Liechti & Stefan Borgwardt

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