Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/517847

Serotonergic Psychedelics LSD & Psilocybin Increase theFractal Dimension of Cortical Brain Activity in Spatial and Temporal Domains

Varley, T.·Carhart-Harris, R.·Roseman, L.·Menon, D.·Stamatakis, E.
View original source ↗Export metadata ↓

Abstract

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers in-vestigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attentional network. These results show that psychedelic drugs increase the fractal character of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.\n\nAuthor SummaryThe unique state of consciousness produced by psychedelic drugs like LSD and psilocybin (the active component in magic mushrooms) are potentially useful tools for discovering how specific changes in the brain are related to differences in perception and thought patterns. Past research into the neuroscience of psychedelics has led to the proposal of a general theory of brain function and consciousness: the Entropic Brain Hypothesis proposes that consciousness emerges when the brain is sitting near a critical tipping point between order and chaos and that the mind-expanding elements of the psychedelic experience are caused by the brain moving closer to that critical transition point. Physicists have discovered that near this critical point, many different kinds of systems, from magnets to ecosystems, take on a distinct, fractal structure. Here, we used two measures of fractal-quality of brain activity, as seen in fMRI, to test whether the activity of the brain on psychedelics is more fractal than normal. We found evidence that this is the case and interpret that as supporting the theory that, psychedelic drugs are move the brain towards a more critical state.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Varley, T., Carhart-Harris, R., Roseman, L., Menon, D., Stamatakis, E.. 2019-01-11. Serotonergic Psychedelics LSD & Psilocybin Increase theFractal Dimension of Cortical Brain Activity in Spatial and Temporal Domains. https://doi.org/10.1101/517847

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Circuit and cell-type mechanisms of the spectrolaminar motif of cortical oscillations

Oscillations are a key feature of cortical activity, coordinating spike timing across areas, layers, and cell types. Recent work suggests these rhythms follow a stereotyped organization across cortical depth, the spectrolaminar (SL) motif, with higher-frequency gamma prominent in superficial layers and lower-frequency alpha/beta in deep layers, yet the mechanisms generating it remain poorly understood. Using a bio-realistic model of mouse primary visual cortex, we reproduced the SL motif and found it preserved across diverse visual stimuli. Systematic cell-type- and layer-resolved perturbations showed that the alpha/beta component was intrinsic to every layer, whereas the 50-80 Hz gamma component was predominantly generated within layer 4 (L4) and propagated network-wide through inter-laminar connections. Pvalb interneurons were the principal regulators of gamma, Sst cells shaped low-frequency power, and Vip cells controlled oscillation magnitude. The temporal properties of L4 Pvalb-to-excitatory synapses were especially influential in generating the SL motif. These models and simulation results thus offer a plausible description of circuit mechanisms underlying cortical oscillations and the SL motif and are publicly available to facilitate further studies.

neuroscience↗
bioRxiv2026

Personalized Prediction of Differences in fMRI Connectivity Estimates Across Preprocessing Pipelines

Longitudinal functional MRI of the human brain is valuable for tracking changes in functional connectivity (FC) associated with disease progression or treatment response. Even so, measured FC values depend on preprocessing, and nuisance regression and temporal filtering affect individuals differently. We examined whether we could use earlier scans to predict how preprocessing would affect a later scan. In 69 ADNI (Alzheimers Disease Neuroimaging Initiative) participants scanned three times, we measured how nuisance regression and filtering, alone and in sequence, changed the measured FC. A ridge regression model combined these responses with baseline FC from the third scan to predict the effect of reversing the processing order. Just four coefficients were shared across 79,800 connections. In leave-one-participant-out testing, mean squared error was 0.012, compared with 0.017 for predicting the same average response for everyone. It outperformed the best of seven alternative predictions chosen for each participant (0.013; normalized gain 0.069, 95% bootstrap interval 0.006-0.134), with lower error in 44 of 69 participants. About half the benefit of using each persons earlier responses, rather than the average across participants, came from which connections changed. This advantage persisted after accounting for acquisition variables. The ADNI-trained model reduced mean error in ten Midnight Scan Club participants without refitting. These results support using personal preprocessing history to predict changes in connectivity estimates on newly acquired scans.

neuroscience↗
bioRxiv2026

Temporal Structure in Resting-State fMRI under Marginal and Cross-Spectral Surrogate Controls

Resting-state functional MRI is commonly analyzed using correlations between regional signals and their frequency spectra, which characterize average connectivity and spectral properties but may miss other aspects of temporal organization. Measures of temporal complexity offer complementary information about the recurrence of signal patterns, how fluctuations vary across timescales, and signal roughness. These properties may reveal disease-related alterations in brain activity, offering opportunities for biomarker discovery and insights into mechanisms of neurological and psychiatric disorders. Here we examined sample entropy (SampEn), multifractal de-trended fluctuation analysis (MFDFA), and Higuchi curve shapes in 732 scans from 270 ADNI participants, including cognitively normal individuals, people with mild cognitive impairment, and people with dementia. Using the seven Yeo resting-state networks (Yeo-7), we compared recordings with randomized signals preserving either each networks amplitude distribution and approximate spectrum (IAAFT), or the complete cross-spectrum across networks. If these properties fully explained temporal complexity, real recordings should resemble their randomized references. We therefore counted how often each real recording was the strongest outlier among itself and 20 references. This occurred in 21.7%, 12.7%, and 44.2% of 5,124 network-visits for SampEn, MFDFA, and Higuchi, versus 5.5%, 5.1%, and 6.3% in surrogate-only controls. Cross-spectrum-preserving references yielded 39.8%, 17.5%, and 49.8%. Simulations showed that changes in sampling or signal processing, including abrupt changes in signal amplitude, can produce similar differences without changing the underlying dynamics. The measures showed repeatability across visits but did not improve retrospective prediction of changes in Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. These findings identify temporal features not reproduced by the tested spectral controls and provide a basis for evaluating their potential as disease biomarkers.

neuroscience↗