Increased thalamic resting state connectivity as a core driver of LSD-induced hallucinations
Following oral administration of 100 μg LSD to 20 healthy participants, resting‑state fMRI showed increased thalamic functional connectivity to multiple cortical regions, with thalamus–right fusiform and thalamus–insula connectivity correlating with subjective visual and auditory effects. These findings suggest enhanced thalamocortical coupling—likely via 5‑HT2A receptor mechanisms—may underlie LSD‑induced hallucinations by facilitating cortical excitability.
Authors
- Stefan Borgwardt
- Patrick Dolder
- Matthias Liechti
Published
Abstract
Objective
It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system.Method100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI‐to‐ROI and ROI‐to‐voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects.
Results
LSD caused significant alterations in all dimensions of the 5D‐ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD‐induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects.
Conclusion
Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5‐HT2A‐receptor in altered states of consciousness.
Research Summary of 'Increased thalamic resting state connectivity as a core driver of LSD-induced hallucinations'
Introduction
Hallucinogenic drugs produce distinctive alterations in perception, cognition and emotion, and understanding their neural correlates may illuminate mechanisms of altered consciousness. Prior models and empirical work have implicated the thalamus as an important site of action for hallucinogens: one influential idea is that hallucinogens disrupt thalamic gating of internal and external signals, permitting increased passage of information to cortex. Neuroimaging studies have reported mixed effects of hallucinogens on thalamic metabolism and blood flow, and some recent resting-state fMRI work has suggested increased thalamocortical functional connectivity after psilocybin or LSD, but these findings had not been investigated in detail. This study tested the acute effects of a single oral dose of LSD (100 µg) on thalamic resting-state functional connectivity (rFC) in healthy volunteers using a placebo-controlled, double-blind cross-over design. The investigators hypothesised that LSD would increase thalamocortical connectivity relative to placebo and that those connectivity changes would relate to subjective LSD-induced visual and auditory alterations measured with the 5D-ASC questionnaire. The work aims to clarify whether altered thalamocortical interactions are a core neural correlate of LSD-induced hallucinations and altered consciousness.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Müller, F., Lenz, C., Dolder, P., Lang, U., Schmidt, A., Liechti, M., & Borgwardt, S. (2017). Increased thalamic resting state connectivity as a core driver of LSD-induced hallucinations. Acta Psychiatrica Scandinavica, 136(6), 648-657. https://doi.org/10.1111/acps.12818
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