Structure’s Role in Function During Psychedelic States: Insights from MEG and Diffusion Imaging
Poster No:
1713
Submission Type:
Abstract Submission
Authors:
Venkatesh Subramani1, Giulia Lioi2, Annalisa Pascarella3, Suresh Muthukumaraswamy4, Nicolas Farrugia2, Karim Jerbi5
Institutions:
1Université de Montréal, Montreal, Québec, 2IMT Atlantique, Brest, Bretagne, 3Institute for Computational Applications, CNR, Rome, Rome, 4University of Auckland, Auckland, Auckland, 5Université de Montréal, Montréal, Québec
First Author:
Co-Author(s):
Introduction:
Just as the pitch and timbre of music from a flute are tied to its design, the brain's function is shaped by its structure. The interplay between anatomy and function underpins cognition and behavior (Fotiadis et al., 2024). This relationship can be explored using Connectome Harmonics (CH) (Atasoy et al., 2017), harmonic modes of the structural connectome that characterize brain functions. CH, rooted in Graph Signal Processing (GSP; Ortega et al., 2018), links brain activity to the structural graph and reveals how structure shapes activity.
Previous research has applied CH to investigate normal and altered consciousness under anesthesia (Luppi et al., 2023), ketamine (Luppi et al., 2023), and psychedelics such as LSD (Atasoy et al., 2017) and psilocybin (Atasoy, Vohryzek et al., 2018). These studies reveal that low-frequency CH dominates in anesthetic states, while high-frequency CH is elevated in psychedelic states. However, these studies have primarily focused on BOLD activity to demonstrate the functional repertoire expansion under psychedelics. It remains unclear, however, how the brain's anatomical structure underpins electrophysiological activity during psychedelics compared to the normal wakeful state (Subramani et al 2024).
We hypothesize that the functional activity becomes more decoupled from anatomical connectivity during LSD-induced altered states than in waking consciousness. The rationale here is that the structural networks serve as priors for functional activity in the brain. Under LSD, this relationship weakens, as LSD increases the range of brain states (Atasoy et al., 2017) and entropy (Carhart-Harris et al., 2014), leading to less constrained functional activity.
Previous research has applied CH to investigate normal and altered consciousness under anesthesia (Luppi et al., 2023), ketamine (Luppi et al., 2023), and psychedelics such as LSD (Atasoy et al., 2017) and psilocybin (Atasoy, Vohryzek et al., 2018). These studies reveal that low-frequency CH dominates in anesthetic states, while high-frequency CH is elevated in psychedelic states. However, these studies have primarily focused on BOLD activity to demonstrate the functional repertoire expansion under psychedelics. It remains unclear, however, how the brain's anatomical structure underpins electrophysiological activity during psychedelics compared to the normal wakeful state (Subramani et al 2024).
We hypothesize that the functional activity becomes more decoupled from anatomical connectivity during LSD-induced altered states than in waking consciousness. The rationale here is that the structural networks serve as priors for functional activity in the brain. Under LSD, this relationship weakens, as LSD increases the range of brain states (Atasoy et al., 2017) and entropy (Carhart-Harris et al., 2014), leading to less constrained functional activity.
Methods:
In this study, we utilize the consensus structural graph derived from the DWI scans of 56 subjects (Preti and Van de Ville 2019). We analyze MEG data (N=10) collected during music-listening, and movie-watching (Carhart-Harris et al 2016) while subjects are under LSD or Placebo. After preprocessing to remove cardiac, movement, and ocular artifacts, we perform source localization using dSPM and employ a metric called the Structural-Decoupling Index (SDI; Preti & Van de Ville, 2019) to assess structure-function associations. Our analysis pipeline, established in previous studies of wakeful conscious state (Subramani et al., 2024), is employed to quantify the relationship between anatomical connectivity and functional brain states during LSD.
Results:
Our preliminary results suggest a significantly stronger coupling between functional activity and anatomical connectivity during LSD-induced altered states (paired t-test between LSD and Placebo; p<0.05, uncorrected), potentially reflecting more constrained brain dynamics. This trend is observed in both music (Fig. 1a) and video-watching (Fig. 1b) conditions, with some regions showing weaker coupling, such as the vmPFC in the music condition and the entorhinal cortex in video-watching.
Conclusions:
These findings provide novel insights complementary to fMRI-based studies that reported greater flexibility and stronger functional decoupling under LSD (e.g., Atasoy et al., 2017). Notably, while fMRI-based observations have shown that BOLD activity becomes decoupled from brain structure under LSD, our findings suggest that electrophysiological brain activity, as measured with MEG, may reveal stronger coupling to anatomy in certain contexts. The differences between these modalities may arise from 1) the relatively smooth nature of electrophysiological activity on the cortical surface compared to fMRI, and 2) region-specific interplays between the brain's anatomy and function, which are highlighted by our region-resolved analysis. These results offer preliminary evidence for LSD-induced brain dynamics and structure-function relationships, highlighting novel perspectives that, when integrated with previous work, may deepen our understanding of psychedelic effects on the brain.
Higher Cognitive Functions:
Music
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 1
Novel Imaging Acquisition Methods:
Diffusion MRI
MEG 2
Keywords:
Consciousness
MEG
Tractography
White Matter
Other - Music, Video
1|2Indicates the priority used for review
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Provide references using APA citation style.
Atasoy, S., Vohryzek, J., Deco, G., Carhart-Harris, R. L., & Kringelbach, M. L. (2018). Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition. Progress in Brain Research, 242, 97-120.
Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., ... & Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in human neuroscience, 8, 55875.
Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., ... & Nutt, D. J. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences, 113(17), 4853-4858.
Fotiadis, P., Parkes, L., Davis, K. A., Satterthwaite, T. D., Shinohara, R. T., & Bassett, D. S. (2024). Structure–function coupling in macroscale human brain networks. Nature Reviews Neuroscience, 25(10), 688-704.
Luppi, A. I., Vohryzek, J., Kringelbach, M. L., Mediano, P. A., Craig, M. M., Adapa, R., ... & Stamatakis, E. A. (2023). Distributed harmonic patterns of structure-function dependence orchestrate human consciousness. Communications biology, 6(1), 117.
Ortega, A., Frossard, P., Kovačević, J., Moura, J. M., & Vandergheynst, P. (2018). Graph signal processing: Overview, challenges, and applications. Proceedings of the IEEE, 106(5), 808-828.
Preti, M. G., & Van De Ville, D. (2019). Decoupling of brain function from structure reveals regional behavioral specialization in humans. Nature communications, 10(1), 4747
Subramani, V., Lioi, G., Jerbi, K., & Farrugia, N. (2024). Structure-function coupling and decoupling during movie-watching and resting-state: Novel insights bridging EEG and structural imaging. bioRxiv, 2024-04.