Psilocybin enhances insightfulness in meditation:... — Research Summary & Context | Blossom

Neuroimaging & Brain MeasuresPsilocybinPlacebo

Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation

Using Mapper-based topological data analysis of fMRI during focused-attention and open-monitoring meditation before and after a five-day psilocybin versus placebo retreat in experienced meditators, the study shows that whole-brain activity topology — quantified by optimal transport distance — differentiates meditation styles and psilocybin-induced changes. Crucially, psilocybin-induced positive derealisation paired with enhanced open-monitoring correlated with increased OT distance between open-monitoring and resting state and with greater reported insightfulness, suggesting potential brain markers of beneficial synergy between mindfulness practice and psilocybin.

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Authors

Erich Seifritz
Milan Scheidegger
Franz Vollenweider

Published

March 26, 2024

Scientific Reports

individual Study

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Abstract

In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin.

Related Clinical Trial

CompletedPhase NA

Beyond the Self and Back: Neuropharmacological Mechanisms Underlying the Dissolution of the Self

Randomized, double-blind, placebo-controlled multi-group study (n=140) using single oral doses of psilocybin (0.20–0.315 mg/kg) to probe neural and phenomenological signatures of self-dissolution in healthy volunteers and meditators.

Started: October 1, 2013
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT03736980

References (31)

Papers cited by this study that are also in Blossom

Trends in the Top-Cited Articles on Classic Psychedelics

Lawrence, D. W., Sharma, B., Griffiths, R. R. et al. · Journal of Psychoactive Drugs (2021)

Introduction

Berit and colleagues situate their work at the intersection of two rapidly expanding literatures: meditation neuroscience and psychedelic research. Earlier studies have documented overlapping phenomenology and some shared neurophysiological signatures between meditation and classical serotonergic psychedelics (e.g. changes in self-consciousness, reduced default mode network activity, altered functional connectivity and increased markers of plasticity). However, most prior work has used conventional measures such as functional connectivity, resting‑state networks, signal variability and entropy. The authors identify a gap: more holistic, geometry‑aware approaches that capture the global spatiotemporal organisation of whole‑brain activity during different meditation styles and under psychedelic influence have not been widely applied to these states. This study applies a topological data analysis (TDA) method based on the Mapper algorithm to fMRI collected before and after a five‑day psilocybin‑assisted meditation retreat in experienced meditators. The authors aim to characterise the ‘‘topological landscape’’ of meditative brain states (focused attention, open monitoring, resting state), test whether psilocybin modulates that landscape, and relate topological descriptors (for example optimal transport distances and graph centrality measures) to subjective reports from an altered‑states questionnaire. They hypothesise that psilocybin will alter the organisation of meditative brain states (consistent with increased informational richness) and that topological measures will relate to experiential dimensions such as meta‑awareness, insightfulness and positive derealization.

Methods

Design and participants: This was a double‑blind, randomised, placebo‑controlled parallel study of a five‑day silent meditation retreat (sesshin) in experienced meditators. Thirty‑eight participants were enrolled and two were excluded from analysis, yielding 36 subjects (18 per group: psilocybin and placebo). Participants were matched on age, sex, lifetime meditation experience and dispositional mindfulness; mean age reported was 51.66 ± 8.32 years. Psilocybin was administered on the fourth day at a dose of 315 µg/kg body weight (mean absolute dose 21.82 ± 3.7 mg); placebo was lactose. The Five‑Dimensional Altered States of Consciousness (5D‑ASC) questionnaire and 11 lower‑order scales (11‑ASC) were collected 360 minutes after ingestion as retrospective measures of subjective effects. Imaging and experimental tasks: Each participant underwent two fMRI sessions: one day before and one day after the retreat. Each session comprised three fixed, eyes‑closed 7‑minute blocks (resting state, focused attention (FA), then open monitoring (OM)), producing 21 minutes (600 frames after slicing) per session after concatenation and exclusion of transition frames. FA instructions focused on breath, OM on open observation without attachment; during resting state subjects were instructed to rest but not meditate. MRI acquisition used a 3T Philips Achieva scanner with standard structural and T2*-weighted functional sequences (TR = 2000 ms, TE = 35 ms). Preprocessing followed a standard pipeline (C‑PAC) including motion correction, skull stripping, ANTs registration to MNI152 template, aCompCor nuisance regression, temporal bandpass (0.009–0.08 Hz), spatial smoothing (FWHM 4 mm) and z‑scoring. Topological pipeline and graph measures: The Mapper algorithm (using UMAP for the filter function) was applied to subject‑specific concatenated fMRI time series (middle 100 frames of each labeled block). The projected space was covered with overlapping bins (30 bins, 50% overlap), DBSCAN clustering of slices produced nodes representing clusters of similar fMRI frames, and nodes were connected when clusters shared frames, yielding a Mapper shape graph per subject. Nodes were annotated by meditation state labels. From each graph the investigators computed several topological descriptors per state: degree centrality (weighted mean degree of nodes for a label), closeness centrality (weighted mean reciprocal shortest path length), diameter of the set of nodes for a label, and pairwise optimal transport (OT) distances between label distributions on the graph (1‑Wasserstein / Earth Mover’s distance). The OT distance quantifies the minimum transport cost to transform one label’s node distribution into another given graph geodesic distances. Statistics and associations with phenomenology: Primary inferential tests were two‑way repeated‑measures ANOVAs with group (psilocybin vs placebo) as between‑subject factor and session (pre vs post retreat) as within‑subject factor, applied separately to each graph measure and state (or tuple of states). For OT distances comparing a state pre vs post (d(*1,*2)) only paired t tests were used to test drug effects. Correlations between graph measures and psychometric scales (35 measures) used Kendall or Pearson correlations as appropriate, with multiple comparisons correction: Benjamini‑Yekutieli for t‑tests and an eigenvalue‑based estimate of 10 effective tests for psychometric correlations. Significant correlations informed mixed linear models (session and psychometric measure as fixed effects, subject as random effect) and linear regression models examining insightfulness with predictors such as positive derealization and d(OM1,OM2).

Results

Sample and scans: Thirty‑six experienced meditators (18 psilocybin, 18 placebo) completed fMRI one day before and one day after the five‑day retreat. Psilocybin dosing averaged 21.82 ± 3.7 mg (315 µg/kg). Each session included three 7‑minute blocks (RS, FA, OM) and graphs were constructed from concatenated middle frames to reduce transition noise. Main topological findings: The global effect of the retreat was a shift in resting‑state fMRI activity across all three states, evidenced by nontrivial OT distances d(OM1,OM2), d(RS1,RS2) and d(FA1,FA2). This retreat‑induced shift tended to be larger than differences between meditation styles measured within the same day. Specific psilocybin effects were concentrated on OT distances involving open monitoring and resting state. Optimal transport distances and subjective experience: The OT distance d(OM2,RS2) (open monitoring vs resting state after the retreat) showed a significant group difference, with greater mean and variance in the psilocybin group (independent t test t20.6 = -2.7, p = 0.010). Across subjects, d(OM2,RS2) correlated positively with the ASC subscale positive derealization (Kendall r = 0.379, p = 0.00118; corrected p = 0.0118). Mixed linear models for outcome d(OM*,RS*) with positive derealization and session as predictors showed a significant main effect of retreat (t = -2.624, p = 0.0129) and a significant interaction between retreat and positive derealization (t = 2.315, p = 0.0268); analogous models run in the psilocybin group yielded comparable significant retreat and interaction terms (retreat t = -2.293, p = 0.0358; interaction t = 2.446, p = 0.0264). A median split showed that for participants with low positive derealization, d(OM*,RS*) decreased due to the retreat (t = 2.3348, p = 0.03207), whereas no retreat effect appeared in the high derealization subgroup. Pre/post changes and drug modulation of OM and RS: Psilocybin increased the OT distances comparing the same state pre vs post: d(OM1,OM2) was larger in the psilocybin group (t25.7 = -2.2, p = 0.037), and d(RS1,RS2) showed a similar group difference (t26.6 = -2.2, p = 0.04). Additionally, the OT distance measures d(OM1,OM2), d(RS1,RS2) and d(OM2,RS2) were strongly intercorrelated and exhibited significant drug effects. Relations with insightfulness and ASC: Insightfulness correlated strongly with positive derealization (Pearson r = 0.82, p = 6.56e-10). Linear models predicting insightfulness with positive derealization and d(OM1,OM2) were significant and explained substantial variance: for the whole sample the model F(3,31) = 25.1, p = 1.96e-08 with multiple and adjusted R‑squared 0.7084 and 0.6802; in the psilocybin subgroup F(3,13) = 7.061, p = 0.00464 with multiple and adjusted R‑squared 0.6197 and 0.5319. Interaction terms between positive derealization and d(OM1,OM2) trended toward significance (p ≈ 0.075–0.081). Changes in graph centrality and diameter: Across both groups, retreat produced significant increases in measures for the OM node: degree centrality (ANOVA F1,34 = 24.8, p corr = 5.5e-5; paired t t35 = -5.04, p corr = 4.2e-5), closeness centrality (ANOVA F1,35 = 20.8, p corr ≈ 9e-5; paired t t35 = 4.6, p corr = 1.5e-4), and diameter (ANOVA F1,35 = 8.7, p corr = 0.017; paired t t35 = 2.97, p corr = 0.016). The OT distance between FA and OM decreased after the retreat across subjects (session effect F1,34 = 9.7, p = 0.0038; paired t t35 = 3.14, p = 0.0034). No significant effects were found for FA–RS OT distances. An exploratory group difference showed greater FA degree centrality post‑retreat in the psilocybin group, but this effect was near nonsignificant and appeared present pre‑retreat as well. Timing and acute effects: Importantly, post‑retreat fMRI was acquired approximately 48 hours after drug administration, so the observed psilocybin‑related topological differences are described as persisting beyond acute intoxication in this setting.

Discussion

The investigators interpret their findings as demonstrating that TDA, operationalised via the Mapper algorithm and OT distances, provides a useful, complementary lens on the organisation of whole‑brain activity across meditation states and how this organisation is modulated by a psilocybin‑assisted meditation retreat. They argue that OT distance quantifies similarity or overlap of whole‑brain activation patterns between labelled states and can be read conceptually as a measure of information flow or geometric dissimilarity between state distributions on the Mapper graph. Authors emphasise that the retreat produced a consistent shift in resting‑state activity across FA, OM and RS that exceeded within‑day differences between meditation styles, indicating that the Mapper approach is sensitive to broad retreat effects. Superimposed on this stable topology were specific psilocybin‑related alterations, notably larger OT distances between OM and RS post‑retreat that correlated with positive derealization. The authors link these observations to the experiential construct of insightfulness: psilocybin increased positive derealization, which associated with larger OM–RS dissimilarity, and insightfulness was best explained by positive derealization together with the magnitude of OM pre/post change (d(OM1,OM2)). From this pattern they propose a mechanistic interpretation in which meditation‑trained increases in meta‑awareness and ‘‘aperture’’ (represented by increases in OM centrality and diameter) combined with psilocybin‑induced enrichment of informational content support greater insightfulness. In placing results relative to prior work, the authors note convergences with studies reporting increased brain entropy with psychedelics and changes in default‑mode and task‑positive network dynamics with both meditation and psychedelics. They suggest the combined state may be ‘‘divergent yet synergistic’’: psilocybin increases informational richness while meditation provides a stabilising meta‑awareness that preserves the capacity for reflection. The paper proposes that topological graph measures could serve as candidate brain markers for beneficial psychological processes in psychedelic‑assisted interventions. The authors acknowledge several limitations reported in the extracted text. These include the novelty and evolving nature of the TDA pipeline (choice of UMAP as filter may affect results), comparatively short fMRI block durations (7 minutes per condition), concatenation of blocks and exclusion of transitions, and the challenge of defining and controlling ‘‘task performance’’ in meditation settings. Additional limitations noted are the lack of a non‑meditator control group and absence of a psilocybin‑without‑retreat arm, which limit inferences about the necessity of the meditation context. The authors recommend future work to annotate Mapper graphs with intrinsic network labels and entropic measures, and to combine topological analysis with richer first‑person phenomenological methods (neurophenomenology) to deepen understanding of how changes in entropy and topology relate to conscious experience.

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RESULTS

Thirty-six experienced meditators completed two fMRI brain imaging sessions one day before and after a 5-day psilocybin-assisted meditation retreat following a double-blind, randomized, placebo-controlled, parallel-group study design. Placebo or psilocybin (315µg/kg body weight; absolute dose, 21.82±3.7 mg) was administered on the fourth day of the retreat, and the 11D-ASC questionnairefor ratings of altered states of consciousness (see Methods ) was administered 360 minutes after drug intake as a retrospective measure of subjective effects. Each scan session (one day before and one day after retreat) consisted of 21 min of resting-state, focused attention, and open monitoring sequences (fixed order), with each meditation lasting 7 min. For each subject both scan sessions were concatenated (with transition times excluded) and Mapper shape graphs were generated and analyzed (see Methods and Statistics below). The abbreviations used throughout this paper are shown in Table1. To analyze the topological landscape of meditative brain states at the subject level we computed topological descriptors for the Mapper shape graphs of all 36 subjects, including degree centrality, closeness centrality and diameter for each experimental condition FA, OM, and RS), OT distances for each pair of experimental conditions within the same day of measurement (e.g. d(OM1,FA1)), and OT distances between pre-and post-intervention under the same experimental conditions (e.g. d(OM1,OM2)). Subsequently we compared these topological descriptors for the drug (psilocybin vs. placebo) and retreat (pre vs. post) effects (Fig.) and identified correlations with psychometric measures (Fig.). For OT distances before vs. after treatment under the same experimental conditions (e.g. d(OM1,OM2)) we analyzed only the drug effect, as the retreat effect is intrinsic to this measure. An example of a Mapper shape graph for one representative subject is provided in Fig.. Although the appearance of Mapper shape graphs varies for each subject, they share topological principles of organization that are similar for both groups and hence show the effect of meditation. Additionally, alterations in specific topological measures (within a similar overall topology) can be observed and linked to psilocybin induced alterations of consciousness. Figure1b provides a schematic representation of the average topological organization of Mapper shape graphs across all 36 subjects. We observe a shift of all three mediation states (i.e. nontrivial d(OM1, OM2), d(RS1, RS2), and d(FA1, FA2), visualized by the shift of the triangle FA2-OM2-RS2 with regard to FA1-OM1-RS1) in both groups due to the retreat, which was greater than the differences between mediation styles (e.g. OM vs. FA) within the same day of measurement. (For example, d(OM2, FA2) is shorter than d(FA1, FA2).) Moreover, the shift in the open monitoring and resting state was significantly greater in the Ppsilocybin group. (Fig., which also provides all p values.) Most interestingly, the main significant differences between the psilocybin and placebo groups were changes in and variances in OT distances (between OM and RS) that were related to Table. Notations used for the Mapper shape graphs and the figures, as well as for the statistics section and the discussion. For precise definitions, refer to the Methods section.. Each color represents the distribution of an MS (Table) in the subject-specific landscape of brain states. (b) The network is a schematic picture of the average topological organization of Mapper shape graphs that are shared across all subjects. The nodes are labeled according to the six meditation states (MS), (Table). For example, we found that the closeness centrality of the OM significantly increased postretreat, which is represented by the central position of the OM post-node. The length of the edges represents the average OT distance (over all subjects) between the MSs. For example, the OT distance between FA2 and OM2 is smaller than the OT distance between FA1 and OM1. Finally, the diameter of the node represents the diameter of the corresponding MS. Significant increases in the measurements due to retreat and drug effects are annotated by blue and red stars, respectively. Similarly, decreases are annotated by blue and red accidentals, respectively. The star in the bracket near node FA2 indicates that the effect is most likely neglectable. psilocybin-induced positive derealization and similar psychometric ratings. Since the other topological features were stable across the groups, this finding shows that the model in Fig.reliably describes the effect of the retreat, specifying the psilocybin-induced alterations of the topology and linking them to psychometric experience ratings. Notably, the model is more sensitive to the overall effect of the retreat on resting-state fMRI (rsfMRI) changes (i.e., in all three states FA,OM, and RS) than to the differences between meditation styles (on the same day of measurement). Moreover, our results exemplify (with the help of extensive methodological development in) the potential of these methods to provide novel topological brain markers related to meditation and psychometric experience of altered states of consciousness. The main topological organizations of meditation are visualized in Fig., statistics are summarized in Figs.and. Main results are further emphasized in Fig.and interpreted in Fig.. First, we found a significant difference in the OT distance d(OM2, RS2) according to drug treatment (placebo vs. psilocybin), with higher median values and variance in the psilocybin group. Correlation analyses with altered states of consciousness ratings showed that the OT distance d(OM2, RS2) was positively associated with positive states of consciousness, such as positive derealization (Fig.and), which are commonly enhanced by psilocyin (Fig.). Moreover, we observed a significant retreat and interaction effect of positive derealization and retreat on d(OM * , RS * ) for the whole group as well as for the psilocybin group. We found that d(OM * , RS * ) decreased significantly due to retreat in those subjects whose positive derealization was below the mean (Fig.). However, psilocybin increased positive derealization, which was linked to higher d(OM2, RS2) compared to placebo (Fig.). Notably, these observations on d(OM * , RS * ) were not due to acute effects of psilocybin, as the fMRI scans taken post-retreat (i.e. 48 hours after drug administration). Moreover, insightfulness was strongly correlated with psilocybin-induced positive derealization during meditation, and the latter relation tended to be stronger for higher d(OM1, OM2) (Fig.and) Second, we observed that the optimal transport distances d(OM1, OM2) and d(RS1, RS2) were significantly greater in the psilocybin group than in the placebo group (Fig.). Third, we observed that FA and OM became more similar (i.e., decreased d(FA, OM)) after the retreat across all subjects (Fig.). Finally, the degree centrality, closeness centrality and diameter of the OM increase over the retreat for both groups (Fig.).

CONCLUSION

This is the first brain imaging study combining topological data analysis (TDA) of BOLD signal fluctuations (fMRI) in a sample of thirty-six experienced meditators before and after a 5-day psilocybin-assisted meditation group retreat. This is also the first study of the modulatory effects of psilocybin on the topological landscape of meditative brain states using a novel, previously established approachbased on Mapperand TDA. We found that organizational principles in the topological landscape of meditative states were associated with meditation retreat effects and that specific topological measures correlate with enhanced positive experiential effects of psilocybin combined with meditation. The latter processes reflect a modulation of the topological properties in the landscape of meditative brain states, which in turn can be used to better understand the beneficial psychological processes underlying synergistic effects of psilocybin and meditation. The OT distance provides a tool for studying the relationships and interactions of different meditation states in terms of the similarity and overlap of their whole-brain activation patterns. For example, if two different meditation states correspond to similar combinations of activated brain regions, the OT distance between them is small. In contrast, if complementary regions are activated during the two meditation states, the OT distance increases. The OT distances can then potentially be related to changes in perception, cognition and consciousness. Conceptually, the OT distance can be thought as a measure of information flow on the level of brain activity between two distributions of mediation states, i.e. labels on the nodes in a Mapper shape graph. This can be illustrated by the analogy of optimizing the transport cost of a product from a collection of suppliers to a collection of vendors; the transport cost is optimized while taking into account the underlying distributions of suppliers and vendors as well as all pairwise distances between them. Hence, the optimal transport distance is a measure that not only is a distance but also entails a rich geometric structure in the space of the underlying probability distributions. Overall, we observed a shift in rsfMRI activity in all three states -open monitoring, focused attention, and resting state -due to retreat (i.e., nontrivial OT distances d(OM1, OM2), d(RS1, RS2), and d(FA1, FA2)). These effects were greater than the OT distances between different mediation states within the same day of measurement (e.g. d(OM2, FA2) is shorter than d(FA1, FA2)). This effect is illustrated by the shift of the triangle FA2-OM2-RS2 with respect to FA1-OM1-RS1. This is most likely due to an overall (i.e., affecting all states, [FA, OM and RS]) change in rsfMRI activity due to the mediation retreat. Hence, the method is more sensitive to the overall retreat effect on rsfMRI activity than it is to differences between meditation states. The characteristics of the topological landscape were relatively stable across the groups, revealing the reliable effect of the retreat. Most interestingly, specific topological alterations (discussed below) in the psilocybin group, can be linked to positive psychometric ratings (see Fig.and the next paragraph). Together, these findings indicate differential effects of psilocybin on the topological architecture of brain networks underlying different meditation states. Moreover this approach could be used to extract topological markers (using graph theoretic measures) for identifying beneficial psychological processes underlying the synergistic effects of psilocybin and meditation. Among the 35 ASC ratings that showed significant correlations with one of the distances, insightfulness is the most likely to have therapeutic potential because it can serve as a reference point for reflecting and integrating positive experiences. For topological interpretation d(OM * , RS * ) is most interesting because it describes the relation between two different states of consciousness and how the latter is affected by meditation and psilocybin. It was hypothesizedthat oceanic self-boundlessness (OSB) , of which positive derealization is a subscale, would predict outcomes of psilocybin-assisted therapy for treatment-resistant depression. Combined effects of mediation and psilocybin-induced alterations in consciousness, such as positive alterations in the perception of the external world and positive derealization, were associated with greater OT distances between OM and RS postretreat (Fig.). Moreover, positive derealization had the most significant correlation with d(OM2, RS2) and was most prominent in the correlation matrix. Hence, in our analysis, we focused on investigating the effect of the retreat and the drug on positive derealization and, subsequently, how positive derealization may be related to insightfulness. First, we found that psilocybin supports insightfulness in meditation and that insightfulness correlates with greater changes in open monitoring meditation (i.e., d(OM1, OM2)). Moreover, insightfulness correlated with positive derealization (which was linked to increased OT distance between OM and RS, i.e., d(OM * , RS * ) ) , and notably , the latter correlation was stronger for greater changes in OM (i.e., greater d(OM1, OM2)). Conversely, we observed that OT distances between OM and RS (i.e., d(OM * , RS * ) ) decreased in the subgroup of participants with low ratings of positive derealization (Fig.) due to the retreat. Together , these findings could indicate that enhanced aperture and meta-awareness (which are commonly trained during OM) combined with psilocybin-induced positive derealization (through opposite effects on d(OM * , RS * ) ) fosters insightfulness. Second, we showed that meditation increased the degree-centrality, closeness-centrality, and diameter of the OM, which could be another indicator of increased aperture and meta-awareness (for a a conceptual description and discussion Figure). Third, a five-day meditation retreat for experienced mediators decreased the OT distance between OM and FA, which could indicate increased meta-awareness of monitoring attention. As apparent from previous analyses of the same dataset, psilocybin administered in a retreat setting supported by mindfulness practices, such as OM, significantly potentiated felt states of ego dissolution compared to the placebo; in particular, oceanic self-boundlessness (OSB) increased, of which insightfulness and positive derealization were substantial lower-order subscales. Furthermore, persistent positive effects after the meditation retreat were positively correlated with OSB scores during psilocybin administration. A hypothetical topological model (Fig.) of detailed experiential features in mindfulness-related practices delineates the interpretation of our results. Figureaims to explain how changes in perception, cognition, and consciousness may affect OT distances; in a way consistent with our findings. We start by identifying experiential similarities and differences between MSs and how they might affect OT distances. Enhanced OM (e.g., through practice) involves an increase in various phenomenological dimensions, such as increased meta-awareness, clarity, aperture, and dereification. Enhanced FA (e.g. through practice) involves phenomenological dimensions such as increased focus, decreased distraction, increased effortlessness, and increased stability and clarity. In direct contrast, a resting state typically involves mind-wandering, which is associated with low meta-awareness, clarity, aperture, and dereification. Notably, what distinguishes RS from OM is meta-awareness of the ongoing experience, and mind-wandering. However, as suggested by previous studiesit is expected that resting state brain activity is also substantially affected by 5-day meditation practice. In fact, as meta-awareness is the main target of mindfulness-based practices, which were trained during the retreat, an increase in meta-awareness capabilities over the retreat in all conditions (FA, OM, and RS) is plausible. Moreover, the increase in meta-awareness observed under all conditions is consistent with our findings, as explained below and in Fig.. Notably, certain changes in consciousness and perception may have effects on different MSs that cancel the effect on the level of their OT distances (Fig., e.g., the effect of meditation and positive derealization on d(OM * , RS * )). The profound modulatory effects on consciousness, perception and cognition 7 observed after psilocybin administration in our dataset are known to increase the entropy of spontaneous brain activity (examples include; for an overview see), which is hypothesized to indicate the informational richness of conscious states. Although the precise effect of meditation on the entropy of spontaneous brain activity is not well understood, it is plausible that mediation combined with psychedelics, such as psilocybin, is characterized by brain states with greater entropy than meditation combined with a placebo. Together with our results, these findings suggest that a psilocybin-induced state of enriched informational content manifests as a greater OT distance between OM and RS (compared to that in the control group), which persists even beyond the retreat, potentially contributing to the increased levels of insightfulness when combined with open monitoring meditation training (i.e. increased meta-awareness). This might indicate that increased entropy due to psilocybin benefits from a counterbalancing effect of meditation to prevent the brain from going beyond a state of criticality where the ability to consciously reflect is impaired. According to the entropic brain hypothesis, the combined effects of psilocybin and meditation could be described as divergent yet synergistic. Conceptually, the increased degree and closeness centrality of the OM postretreat (represented by the central position of the OM2 in Fig.) indicate that OM postretreat receives/exchanges information (with other MS in the Mapper shape) more frequently and at higher speeds). As meta-awareness is the ability to note the content of one's current mental state, increased closeness centrality of the OM observed across subjects could represent a neural correlate of increased meta-awareness. Aperture might be interpreted as the ability to bring into awareness more distinct contents of one's current mental state. Hence, the increased degree centrality of the OM observed across subjects may bea neuronal surrogate marker for increased aperture. Furthermore , as the diameter of the OM measures the maximum dissimilarity of brain activity during OM, an increased diameter of the OM postretreat (represented by the diameter of the OM2 node in Fig.) might indicate broader diversity of the content of one's mental state during OM. In summary, these findings support the idea that meditation practice enhances OM by increasing meta-awareness and the aperture of the ongoing stream of consciousness, including a greater variety of mental contents and mental states. We conclude that, compared with meditation alone, psilocybin alters the perception of the external world, presumably by increasing informational richness, which is reflected by increased OT distances between OM and RS postretreat . Moreover, the retreat effects on open monitoring meditation (i.e., OT distance between OM before vs. after), which presumably indicates meta-awareness and aperture enhanced through meditation practice, reinforce insightfulness gained through psilocybin-induced positive derealization. In other words, meta-awareness may serve as a common mediating factor, that potentially explains how the altered state of consciousness induced by psilocybin enhances insightfulness in experienced meditators. The method has been extensively tested for reliability; however, different dimension reduction techniques have been used. Notably, the approach is novel and under rapid development. The specific dimension reduction method UMAPmay have an effect on the results. The fMRI scanning durations in our dataset were comparatively short, potentially limiting definitive conclusions. However, the total length of the scans was comparable to that of other studies with the same method that correlated task performance with OT distances. We obseved that the topology (Fig.) was relatively stable across the groups with differences that correlated with psilocybin-induced psychometric alterations. This finding supports the reliability of our results, despite the short scanning duration, the concatenation of the data and the many confounding factors in the fMRI data. Furthermore, while findings from previous studieson OT distance are based on dataset s with different levels of task performance, it is more challenging to define and control task performance in meditation, especially during rsfMRI scanning sessions (e.g., loss of concentration or distraction). However, since there is evidencethat novice practitioners can reliably report their experience, the reliability of experienced practitioners on meditation features can be assumed if they are trained to acknowledge and perform them. Hence a limitation in our dataset is the lack of a control group of naive or novice meditators. It would also be interesting to include a group of participants who take the psilocybin without participating in the meditation retreat. Moreover, 7 minutes could be too short to reach a significant meditation state effect, but the instructions during scanning were intended to simulate a natural way of entering into focus attention and open monitoring meditation. Meditation (such as OM) and psychedelics are both associated with reduced activation in the DMN and increased functional connectivity between DMN structures and certain task-positive networks. As an exception, there is preliminary evidence of increased anti-correlation between the DMN and TPN during FA. Various other brain networks, such as alerting, salience and orienting networks, were associated with meditation practice. Hence, annotating intrinsic brain network activity on the Mapper shape graphs (similar to resting states) could lead to neurophysiological explanations of the organizational principles observed in the Mapper shape graph of meditative states. Furhtermore, annotating nodes in the Mapper shape graph with entropic measures in regions of interest in the brain may reveal novel insight into how entropy changes the flow of information in the brain. For example, this could lead to a better understanding of how enriched informational content could affect the OT distance between OM and RS. To better understand the phenomenological or psychological implications of the organizational principles and potential modulations, this approach could be combined with more comprehensive phenomenological data. While most current experiential measurements are based on psychometric questionnaires (such as so-called "thin" measures), more recent studies have increasingly made a case for using "thicker" methods of phenomenological investigations that provide more refined and authentic qualitative accounts of experience. After this so-called neurophenomenological approach has originated as an offshoot of enactive cognitive science, it exhibited increasing influence on research on nonordinary states of consciousness, including meditation, psychedelics, and hypnosis. This neurophenomenological approach combining the topological analysis of thirdperson neuroimaging data and an in-depth phenomenological analysis of rigorous first-person experience reports might represent a promising direction for future research.

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