Common neural signatures of psychedelics : Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition, Selen Atasoy et al., 2018

Common neural signatures of psychedelics : Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition

Selen Atasoy, Jakub Vohryzek, Gustavo Deco, Robin L. Carhart-Harris, Morten L. Kringelbach

Progress in Brain Research, 2018, Volume 242,97-

ISSN 0079-6123 © 2018 Elsevier B.V. All rights reserved.


The search for the universal laws of human brain function is still on-going but progress is being made. Here we describe the novel concepts of connectome harmonics and connectomeharmonic decomposition, which can be used to characterize the brain activity associated with any mental state. We use this new frequency-specific language to describe the brain activity elicited by psilocybin and LSD and find remarkably similar effects in terms of increases in total energy and power, as well as frequency-specific energy changes and repertoire expansion. In addition, we find enhanced signatures of criticality suggesting that the brain dynamics tune toward criticality in both psychedelic elicited states. Overall, our findings provide new evidence for the remarkable ability of psychedelics to change the spatiotemporal dynamics of the human brain.

Keywords : Connectome harmonics, Brain, Psychedelics, Psilocybin, LSD



If you want to understand the secrets of the universe, think in terms of energy, frequency and vibration Attributed to Nikola Tesla Science has made spectacular progress in elucidating the fundamental laws of nature; generating elegant mathematical equations describing the detailed interactions between many of the forces governing the spatiotemporal distribution of matter and energy in the universe. Yet, one of the most exciting challenges remains, namely to understand the dynamical complexity of the human brain, and specifically how mental states arise through the complex interplay of structural and functional brain connectivity.

The invention of non-invasive neuroimaging techniques with ever more precise spatiotemporal information on human brain activity has given rise to a growing field of neuroscientific research, which is starting to bring about new fundamental insights into the brain dynamics of integration and segregation of information over time (Deco et al., 2015; Dehaene et al., 1998; Tononi et al., 1994). Here we focus on the important progress in using a promising mathematical framework (Atasoy et al., 2016) for decoding the brain activity in any mental state (whether awake, in deep sleep, under anesthesia, or in a psychedelic state) as a combination of harmonic brain modes (Atasoy et al., 2017, 2018). These harmonic brain modes can be determined as the harmonic modes of structural connectivity yielding fully synchronous neural activity patterns with different frequency oscillations. The complex spatiotemporal patterns of brain activity during a mental state can be expressed in terms of these elementary building blocks of brain activity, i.e., connectome harmonics, using a connectome-harmonic decomposition. More generally, the mathematical framework of connectome harmonics is directly related to the fundamental principle of harmonic patterns, which are ubiquitous in nature— emerging in physical, as well as biological phenomena ranging from acoustics, optics, electromagnetic interactions to morphogenesis (Atasoy et al., 2018). Here, we used this mathematical framework to elucidate the brain activity in a special mental state, namely the altered states elicited by psychedelics, currently enjoying a renaissance in terms of scientific study (Sessa, 2012). Over millennia, people have been using psychedelics derived from indigenous plants including Peyote and the subspecies of the Psilocybin mushroom (Pollan, 2018; Whybrow, 1962). Often, these have been central to healing rituals but also to expand the mind. The scientific study of psychedelics started with the chemical characterization of mescaline in 1898 by Arthur Heffer and the synthesizing of LSD by Albert Hoffmann in 1938 (Hoffmann, 1980). Subsequent research in the 1950s and 1960s revealed the powerful potential of psychedelics to treat addiction and anxiety,
but this research was eventually curtailed worldwide (Nichols, 2016). Yet, with the identification of the 5HT2A receptor as a main target of LSD in the 1980s and the advent of brain imaging, the study of the brain correlates of psychedelics has slowly been gathering pace (Halberstadt, 2015; Kyzar et al., 2017). There is a clear need for a better understanding of the underlying mechanisms in order to potentially harness the power of psychedelics for treating brain disorder and for exploring the limits of consciousness.

In the following, we first describe the fundamental principles of harmonic patterns and the mathematical framework of connectome harmonics as brain states. We then review the existing literature on the neural correlates of psychedelics and finally discuss how the effect of psychedelics can be understood in this frequency-specific language of cortical activity, and can be studied in terms of different expressions of these harmonic brain states. Analogous to how different combinations of elementary particles form various atoms and molecules or combinations of musical notes comprise different melodies or even symphonies, connectome harmonics provide the elementary building blocks to express complex spatiotemporal patterns of neural activity. Here, we demonstrate how the expressions of these building blocks, the connectome harmonics, change in the psychedelic state. Furthermore, beyond reviewing the existing evidence on the LSD-induced changes in the expression of these harmonic brain states, we present new findings demonstrating common connectomeharmonic signatures of two different psychedelic substances, LSD and psilocybin. Finally, we discuss the implications of these findings in the context of deepening our understanding of mental states.