Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness

Classical serotonergic hallucinogens such as psilocybin produce a characteristic altered state of consciousness that combines marked subjective changes (for example ego dissolution, altered perception, hyper-associative cognition and changes in time and selfhood) with measurable shifts in brain activity and connectivity. Previous neuroimaging work has reported both averaged effects — including increased global connectivity and reduced modularity, and region-specific alterations (for example in the posterior cingulate cortex and default mode network) — and dynamic effects, with the brain visiting transient, less-stable connectivity patterns more frequently under psychedelics. However, the relationship between these time-varying neural patterns and the rich, multi-dimensional phenomenology of the psychedelic state has generally been treated separately and remains incompletely characterised. Mortaheb and colleagues set out to bridge that gap by adopting a neurophenomenological approach: they administered a single moderate dose of psilocybin or placebo to healthy adults and used ultra-high-field 7T resting-state fMRI acquired at the peak subjective effect together with the 5‑Dimensional Altered States of Consciousness (5D-ASC) questionnaire to link dynamic whole-brain functional connectivity patterns to detailed self-reported experiential dimensions. The analysis combined phase-based, time-resolved connectivity, clustering into recurrent connectivity patterns, Markov modelling of state transitions, and canonical correlation analysis to relate transition dynamics to phenomenological measures.

Forty-nine healthy volunteers with prior but not recent psychedelic experience were randomised to receive either psilocybin (0.17 mg/kg; n=22, 12 male, mean age 23±2.9 years) or a placebo bittering agent (n=27, 15 male, mean age 23.1±3.8 years). Six minutes of eyes‑open resting-state fMRI were acquired on a 7T scanner during the peak subjective effect (102 minutes after dosing). Retrospective phenomenology was assessed with the 5D-ASC at 360 minutes post-dose. Phenomenology: Scores on the 5D-ASC and its 11 subscales violated normality and were compared with non-parametric tests. The psilocybin group showed significantly greater effects than placebo across all dimensions and subscales (Mann–Whitney U tests, Bonferroni-corrected), with large effect sizes; reported changes included increased oceanic boundlessness (OBN), visionary restructuralization (VRS), dread of ego dissolution and other altered-state features. Averaged connectivity and BOLD amplitude: Using the Schaefer 100-region parcellation and Pearson correlations between regional time series, whole-brain average functional connectivity was higher after psilocybin (independent t-test: t=3.087, p=0.004). A cortex-wide elevation in pairwise connectivity values was observed after multiple-comparison correction. Regional BOLD signal amplitude, quantified as the Euclidean norm of each ROI's time series, decreased in anterior and posterior cortical regions in the psilocybin group (FDR-corrected independent t-tests). The largest amplitude reductions were centred on the posterior cingulate cortex and parietal regions of the executive control network; somatomotor, limbic and temporal DMN regions did not show significant changes. Time-varying connectivity and state structure: Instantaneous phase-based coherence was computed at each time point and concatenated across subjects, then summarised by k-means clustering (500 repetitions, 200 iterations) into four recurrent connectivity centroids. The four patterns were described as: Pattern 1 — a mix of correlations and anti-correlations; Pattern 2 — anti-correlation of the DMN with other networks; Pattern 3 — global, cortex-wide positive connectivity (a hyperconnected state); and Pattern 4 — generally low inter‑areal connectivity. Pattern 3 occurred significantly more often in the psilocybin group than in placebo (independent t-test: t=3.731, p=0.001; Bonferroni-corrected α=0.0125). State transitions: Treating the four centroids as states in a Markov model, the investigators estimated transition probabilities for each subject. Compared with placebo, the psilocybin group showed higher transition probabilities towards Pattern 3 from Pattern 1 (Wilcoxon rank-sum: z=2.744, p=0.006), from Pattern 3 itself (z=2.291, p=0.022), and from Pattern 4 (z=2.000, p=0.045). Conversely, the probability of remaining in Pattern 2 (Pattern 2→Pattern 2) was lower in the psilocybin group (z=-2.452, p=0.014). Neurophenomenological associations: Canonical correlation analysis (CCA) was used to relate the set of between‑state transition probabilities to the 11-ASC phenomenological factors. The first canonical correlation was very strong (r=0.97, p<0.001). In the neural set, the transition probability from Pattern 1 to Pattern 3 showed the highest loading on the first canonical variate (r=0.86, p<0.001), with smaller but significant loadings for Pattern 2→1 (r=0.47, p=0.015) and Pattern 4→3 (r=0.40, p=0.048). In the phenomenological set, OBN-related subscales had the largest correlations with the first canonical variate: experience of unity (r=0.80, p<0.001), blissful state (r=0.74, p<0.001), insightfulness (r=0.68, p<0.001), spiritual experience (r=0.62, p<0.001) and disembodiment (r=0.35, p=0.036). VRS subscales also loaded on the variate (elementary imagery r=0.67, audio–video synesthesia r=0.61, complex imagery r=0.50, changed meaning of percept r=0.50; p-values ≤0.001 for many). A validation CCA using the 5D-ASC dimensions produced a similar pattern: the neural 1→3 transition showed highest correlation with the neural canonical variate (r=0.89, p<0.001) and OBN dominated the phenomenological variate (r=0.93, p<0.001). These results indicate that the brain's increased tendency to enter the global hyperconnected pattern under psilocybin is primarily associated with reports of oceanic boundlessness and, to a lesser extent, visionary restructuralization.

Mortaheb and colleagues interpret their findings as evidence that a moderate dose of psilocybin increases the brain's propensity to enter a globally hyperconnected, low‑BOLD‑amplitude state and that this dynamical tendency maps onto specific subjective changes, especially oceanic boundlessness (OBN) and visionary restructuralization (VRS). Behaviourally, the study replicated prior dose‑dependent phenomenological effects of psilocybin across multiple 5D-ASC dimensions. Neurally, both averaged and dynamic analyses pointed to greater global integration: whole‑brain connectivity increased, and time-resolved analysis revealed a recurrent, functionally non‑specific hyperconnected pattern that occurred more often and was more readily entered under psilocybin. The authors situate these results within a dynamical systems framing commonly invoked in psychedelic research: psychedelics flatten the brain's attractor landscape so that functionally specific connectivity states become less dominant and transitions between states are easier. In this dataset, that interpretation is supported by higher transition probabilities into the hyperconnected state and by reduced occurrence of some self‑specific patterns (for example reduced self‑transition probability in Pattern 2). The hyperconnected pattern was accompanied by lower global signal (GS) amplitude as measured from the BOLD norm; retaining the GS was an explicit analytical choice and the authors note prior evidence that lower GS amplitude is associated with higher cortical arousal. From this perspective, the authors argue that the hyperconnected–low‑GS configuration reflects heightened cortical arousal and increased capacity for diverse mental associations, which plausibly underpins experiences such as unity, bliss and insight. Linking dynamics and phenomenology, canonical correlation analysis indicated that transitions into the global hyperconnected pattern were most strongly associated with OBN subscales (unity, bliss, insight) and then with VRS subscales. The authors emphasise that OBN — a positive, ego‑dissolution‑related dimension — may be the principal phenomenological driver of psilocybin's effects, a conclusion aligned with earlier work linking OBN to clinical outcomes in psilocybin‑assisted therapy and to neurochemical and connectivity markers. They suggest the hyperconnected pattern's combination of high integration and low segregation offers a mechanistic account for experiences that require loosening of self–world boundaries. Several limitations are acknowledged. The chosen dose was moderate and did not produce total ego dissolution in all participants; it was selected to be tolerable in the 7T scanner. The absence of concurrent physiological and electrophysiological recordings limits the ability to disambiguate vascular or peripheral contributions to the GS and to relate hyperconnected states to neuronal firing or arousal more directly. Finally, the authors note the data‑driven nature of the analyses and that findings may be specific to the recruited sample, although they point to prior work showing reproducible recurrent connectivity motifs across datasets. They recommend future studies include simultaneous physiological/electrophysiological measures and explore a range of doses and populations. In closing, the study concludes that psilocybin produces coordinated alterations in brain dynamics and subjective experience, with a recurrent global hyperconnected pattern most closely linked to feelings of oceanic boundlessness and visual restructuralization.