Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin

BACKGROUND: Serotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesized to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood. METHODS: We used resting-state functional magnetic resonance images collected during a randomized, double-blind, placebo-controlled clinical trial of 24 healthy adults under 0.2 mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and 3 large-scale resting-state networks involved in cognition. These networks are the default mode network, the salience network, and the central executive network. RESULTS: We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the default mode network and salience network but increased within the central executive network. These changes in effective connectivity were statistically associated with behavioral measures of altered cognition and emotion under the in ﬂ uence of psilocybin. CONCLUSIONS: Our ﬁ ndings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are signi ﬁ cant for altered cognition and perception and suggest targets for research investigating the ef ﬁ cacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the brain ’ s hierarchical organization using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences.

Empirical investigations of amygdala response under psychedelics have primarily focused on emotional stimuli.Reduced response to fearful stimuli associated with reduced amygdala activity has been found in healthy adults under the acute effects of psilocybin and has been linked to increased positive (9) and decreased negative affect lasting up to 1 month (43).Similar effects have been observed under the semisynthetic serotonergic psychedelic lysergic acid diethylamide (LSD) and the psychedelic herbal brew ayahuasca, which contains DMT (44,45).In contrast, responses to emotional stimuli were increased 1 day post psilocybin treatment, and these responses were associated with increased amygdala activity in participants with treatment-resistant depression and correlated with reduced depressive symptoms (46).These acute and postacute psychedelic activation differences were related to improved outcomes, suggesting that the behavioral significance of amygdala activation may be contextualized by connectivity with other brain regions.
Amygdala abnormalities have been shown to involve integrated connectivity with midline cortical regions, which can mediate the perception and intensity of positive and negative emotions (34,47,48).For example, altered connectivity with the prefrontal cortex (PFC), a region that is integrally linked to amygdala activity and central in modulating emotional responses (49,50) and reward processing (51,52), has been extensively documented in various psychiatric disorders (53,54).
Several studies have provided evidence that psilocybin modulates top-down midline cortical control of limbic regions involved in emotional processing (43,44,55), with changes to the amygdala and cortical regions remaining for up to 1 month after administration (43).Supporting these findings, a recent study revealed that psilocybin modulated amygdala-frontal pole connectivity during tasks involving emotional face discrimination.Notably, this modulation manifested as decreased connectivity during tasks that involved distinguishing happy faces, highlighting that psilocybin may modulate amygdala circuits toward positive emotions (56).Moreover, cortical-amygdala changes have been associated with improved psychological well-being, as evidenced by decreased rumination 1 week after psilocybin administration (57).Cortical-amygdala modulation has also been associated with alterations in emotional empathy (58)(59)(60), including under psilocybin (61,62), and the amygdala has a demonstrated role in higher-order cognitive processes, such as decision making (63) and memory (64).Preclinical studies have also shown that psychedelic administration enhances the neuroplastic potential of the PFC (65)(66)(67)(68), implicating PFC connectivity changes with the amygdala as a factor in remediated emotional states and cognitive processing.
Emotional regulation in the amygdala relies on top-down and bottom-up modulation of hierarchically organized directed connections (69,70).For example, the acute effects of psilocybin have been shown to alter directed connectivity in healthy adults, causing reduced effective connectivity from the amygdala to the primary visual cortex that coincided with reduced threat processing (71).In this context, we investigated the impact of psilocybin on the effective connectivity of resting-state network (RSN) interactions with the amygdala to understand the neural mechanisms that underlie cognition and emotion and their potential therapeutic significance for the treatment of internalizing disorders.While this study focused on the acute effects of psilocybin, understanding these immediate neural changes is critical for exploring their enduring therapeutic effects.Our examination focused on the amygdala's role in adding an emotional component to the top-down connectivity that forms the frontal and anterior nodes of distinct large-scale RSNs, which are involved in cognition and are abundant in 5-HT 2A receptors (72,73).The RSNs include the default mode network (DMN), associated with selfreflective and introspective mental activity (74)(75)(76)(77); the salience network (SN), responsible for detecting and appraising irregularities in the environment and modulating network activity (78); and the central executive network (CEN), which performs various cognitive processes related to attention, working memory, and decision making (79,80).Analyzing cognitive regions in the current study as part of their respective RSNs helped us to interpret the functional significance of the effective connectivity changes and provided a detailed spatial description of the effective connectivity underlying the functional organization of brain connectivity involved in cognition and emotion.See the Supplement for additional context on RSN inclusion in this study.
We also examined the association between changes in effective connectivity and psychological changes, using subjective measures of altered states to assess the psychological significance of changes in network region interactions with the amygdala under psilocybin.Consistent with evidence of psilocybin's modulation of limbic connectivity and the reduced amygdala response under psychedelics, we hypothesized that increased top-down inhibition of the amygdala contributes to the subjective effects of psilocybin.

Participants
The data analyzed for this paper were collected as part of group 2 of a previous study (registered at ClinicalTrials.gov[NCT03736980]), which is reported in Preller et al. (81) and was approved by the Cantonal Ethics Committee of Zurich.Twenty-four participants (12 men and 11 women; mean age = 26.3years; range = 20 to 40 years; 1 participant did not complete the study) were recruited through advertisements at universities in Zurich, Switzerland.All participants were deemed healthy after screening for medical history, physical examination, blood analysis, and electrocardiography.See the Supplement for more details.

Design
A double-blind, randomized, placebo-controlled, crossover study was performed.Testing days occurred 2 weeks apart, and participants were orally administered either psilocybin (0.2 mg/kg orally) or placebo (179 mg mannitol and 1 mg colloidal silicon dioxide).Resting-state functional magnetic resonance imaging (fMRI) scans (10 minutes) taken 70 minutes following administration were analyzed.Participants were asked not to engage in repetitive thoughts such as counting and were instructed to close their eyes during the resting-state scan.

MRI Data Acquisition and Preprocessing
MRI data were acquired on a Philips Achieva 3T whole-body scanner.A 32-channel receive head coil and MultiTransmit parallel radio frequency transmission were used.Images were acquired using a whole-brain gradient echo-planar imaging sequence (repetition time = 2430 ms).A total of 265 volumes were acquired per resting-state scan, which resulted in a scan duration of 10 minutes.See the Supplement for more details.The acquired images were analyzed using SPM12 (https:// www.fil.ion.ucl.ac.uk).The preprocessing of the images consisted of slice-timing correction, realignment, spatial normalization to the standard echo-planar imaging template of the Montreal Neurological Institute, and spatial smoothing using a Gaussian kernel of 6-mm full width at half maximum.Head motion was investigated for any excessive movement.Three participants were excluded due to head motion, and 1 participant did not complete the scan at 70 minutes.

Measurement of Subjective Effects
Subjective experience was assessed using the retrospective 5-Dimensional Altered States of Consciousness questionnaire.Participants completed the 5-Dimensional Altered States of Consciousness questionnaire 360 minutes following psilocybin administration.Behavioral change under psilocybin was measured using subdimension scales that assessed the subjective experience of emotional bliss and change to the meaning of percepts (11).Changed meaning of percepts refers to a cognitive shift in perception, interpretation, and significance of the environment.The questions used to assess the subjective effect scores and the scores across conditions can be found in the Supplement.

Dynamic Causal Modeling
Dynamic causal modeling (DCM) estimates dynamic fluctuations in brain activity, assessing how selected brain regions influence others through the generative modeling of directed connectivity.Using model selection procedures, DCM determines the set of parameters that are best suited for a causal interpretation of time series data.We employed DCM in this study to elucidate the mechanistic, causal relationships among selected brain regions that underlie the effects of psilocybin.DCM is capable of deciphering hierarchical connectivity patterns, which can be inferred only by modeling the directed connectivity, and has provided a comprehensive framework for understanding the change and influence of brain network states.Specifically, we used spectral DCM, which is designed for resting-state fMRI analysis (82).Spectral DCM infers the effective connectivity that best explains the observed crossspectral density, a data feature related to functional connectivity (83).

Independent RSN-Amygdala DCM Models
We investigated the amygdala's effective connectivity with the DMN, CEN, and SN, 3 networks that are involved in cognition and emotion (35,84,85).These 3 analyses were performed independently to reduce model complexity and focus on the connections of interest (i.e., those between each network and the amygdala rather than those among the networks).

Extraction of Region Coordinates Across Participants
Neurosynth, a large-scale automated synthesis of functional neuroimaging data, was used to identify coordinates of the regions of interest (ROIs) (86).We chose Neurosynth due to its robust anatomical mapping, consistent with our focus on effective connectivity.More details can be found in the Supplement.Networks were composed of cardinal regions constituting core parts of the DMN (76,87), SN, and CEN.The DMN and SN followed the selection of regions in a related investigation by Zhou et al. (88).We also used global signal regression in our preprocessing pipeline consistent with our previous work (14) (see the Supplement for results without global signal regression and additional details).The time series for each ROI was computed as the first principal component of the voxel activity within a 6-mm radius sphere centered on the ROI coordinates (as listed in Table 1).

Specification and Inversion of DCM
Three independent, fully connected DCM models were specified for each network and the amygdala using the 11 ROIs defined in Table 1, without any exogenous inputs.The DCM for each participant was then inverted using spectral DCM (89) to infer the effective connectivity that best explained the observed cross-spectral density for each participant.This procedure was repeated for each testing condition.The explained variance averaged 90.9% for placebo conditions and 89.8% for psilocybin conditions, indicating a successful fit of the DCM model to the data.

Second-Level Analysis Using Parametric Empirical Bayes
The effective connectivity inferred by spectral DCM for each participant was taken to the second (group) level to test hypotheses concerning between-group effects.A general linear model was employed to decompose individual differences in effective connectivity into hypothesized group-average connection strengths and unexplained noise.Hypotheses on the group-level parameters were tested within the parametric empirical Bayes framework (90,91), where both the expected values and the covariance of the parameters were considered.That is, precise parameter estimates influenced the group-level result more strongly than uncertain estimates, which are downweighted.Bayesian model reduction is used as an efficient form of Bayesian model selection (90,91).
In DCM, effective connectivity is measured in the unit of hertz (Hz).The unit of Hz quantifies the rate of change in (neural states) per unit time that one brain region causes in another.Unit of Hz refers to directed connections.Self-connections are log scaled and therefore have no unit.
With reference to behavioral associations, statistical probabilities express the strength of association between neural connectivity estimates and behavioral scores.We applied a statistical threshold of posterior probability .0.99 to estimate the significance of meaningful relationships between observed neural patterns and measured behavioral outcomes.Please see the Supplement for additional technical details about parametric empirical Bayes.

RESULTS
Network effective connectivity change with the amygdala under psilocybin is presented as follows: Change of DMN effective connectivity to the amygdala under psilocybin is shown in Figure 1 and Table 2. Change of CEN effective connectivity to the amygdala under psilocybin is shown in Figure 2 and Table 3. Change of SN effective connectivity to the amygdala under psilocybin is shown in Figure 3 and Table 4. See the Supplement for network summary statistics.

DISCUSSION
After administering psilocybin, we observed an increase in effective connectivity in the CEN and a decrease in the DMN and SN.These networks and their component regions are crucial in cognitive and emotional experiences.The connectivity changes under psilocybin align well with earlier clinical psychedelic neuroimaging studies (43,57).Importantly, we also found evidence of hierarchical modulation characterized by decreased effective connectivity from cortical regions to the amygdala (see the Supplement for hierarchical connectivity strength calculation), with the notable exception of the DMN, discussed below.The connectivity changes that we observed may have therapeutic relevance, suggested by their associations with subjective effects related to cognition and emotion.
In our DMN model, we identified bidirectional inhibitory effective connectivity changes between the posterior cingulate cortex (PCC), which orients information toward the self (75,77,92), and the left amygdala, along with an increased PCC synaptic gain as indicated by decreased self-inhibition.Notably, the bottom-up decreased effective connectivity between the left amygdala and the PCC was more substantial than the top-down decrease.The findings across all 3 network models generally support our initial hypothesis of increased top-down inhibition.However, the stronger inhibition from the amygdala to the PCC adds a layer of complexity to these results.The DMN-amygdala regulatory dynamics indicate a bidirectional feedback loop between higher-order cognitive centers like the PCC and emotional centers like the amygdala, suggesting the role of emotional inputs in cognitive processes.This interpretation is supported by the PCC self-connection association with a blissful state, the PCC to left amygdala association with both a blissful state and changed meaning of percepts, and the left amygdala to PCC association with changed meaning of percepts.These behavioral associations suggest that inhibition between the amygdala and the PCC may be an important connectivity change underlying emotion and altered meaning (i.e., everyday things gaining symbolic,  Cortical-Amygdala Mechanisms Under Psilocybin strange, or emotional meaning).These changes may in turn contribute to shifts in self-awareness.Our findings also indicate that decreased PCC inhibition facilitates blissful feelings.Together, these changes signify reduced top-down cognitive control and decreased bottom-up modulation, which may contribute to the cognitive and emotional features of dissolved self-boundaries.This is consistent with the PCC's known role in self-referential processing (75,92) and with previous evidence that PCC changes that occur under psychedelics affect self-boundaries (93).For example, previous findings found PCC self-inhibition under LSD and the PCC's association with diminished self-representation in social interaction, feelings of self, and self-other processing under psychedelics (8,14,94,95).
Examination of the DMN-amygdala connectivity changes under psilocybin did not find effective connectivity change involving the medial PFC, which has frequently been cited in association with emotion, such as emotional valence (85,96).
Left dorsolateral PFC and left lateral posterior parietal cortex inhibition to the amygdala were also observed and are situated within our CEN model.Connectivity in this network is believed to underlie the evaluative aspect of thought, with the dorsolateral PFC playing a central role in emotional regulation.One characterization of the observed activity may be its resemblance to hyperfrontality, which is associated with worry and anxiety (97) and acute psychosis (98).There is also evidence that CEN connectivity increases during cognitive control strategies and that amygdala connectivity decreases (99,100).However, it has been suggested that links between CEN activity and behavior are task and context dependent (84), and participants in this study reported nominal anxiety (see the Supplement).In other research, increased CEN and decreased amygdala activity of healthy adults were observed to increase during emotion introspection, while increased CEN and increased amygdala activity were associated with selfreflection and positive self-appraisal (100,101).While psilocybin experiences are commonly related to emotional introspection and align with our findings, the introspection during scans was not assessed, leaving the activity pattern in this network open to interpretation.Additional evidence demonstrating the therapeutic capacity of increased intrinsic CEN connectivity is presented in association with resilience (102).This evidence indicates the merit of further CEN-amygdala imaging research to investigate its function for revising beliefs under psilocybin and its therapeutic potential.See the Supplement for further interpretation.
The anterior cingulate cortex and anterior insula (AI) regions of our SN model serve essential functions in salience detection, and the integration of these regions with the amygdala may underwrite pathologically enhanced salience detection (80).These regions' inhibition of the right amygdala suggests that their role in salience detection could be diminished under psilocybin, with possible relevance for internalizing disorders.Notably, previous literature found that psilocybin acutely reduced the response in the right amygdala to negative stimuli, which may reflect decentering from one's emotion and thought that may facilitate reappraisal (103).However, inhibited salience detection also aligns with positive symptoms in schizophrenia (i.e., hallucinations and delusions) (80).At higher doses, psychedelics can induce a psychotic-like state in some individuals (5), which may be related to the effect of serotonergic psychedelics on salience detection (8).However, psychotic-like behavioral outcomes rarely occur in a controlled clinical setting (11,104,105).

Cortical-Amygdala Mechanisms Under Psilocybin
Previous research has shown that increased functional connectivity between the AI and the amygdala is associated with relapse of addiction in preclinical studies ( 106) and behavioral habituation in healthy adults (107), and increased effective connectivity of this link has been associated with depression in clinical populations (108).The AI inhibition to the amygdala was associated with changed meaning of percepts, which suggests that it may be associated with therapeutic behavioral change.Previous task-based research has shown reduced dorsal anterior cingulate cortex activity in association with blunted response to social exclusion under psilocybin (61).Although our findings did not associate subjective effects with this connection, dorsal anterior cingulate cortex-related inhibition aligns with the inhibition of social pain (61,109), and previous findings of this circuit implicate top-down inhibition in resolving emotional conflict (110).DCM also estimated increased self-inhibition in the bilateral amygdala and right AI, suggesting reduced synaptic gain of the regions.LSD produced similar results that demonstrated hypoconnectivity of the right insula (95).However, the changes we observed were not associated with the measured psychedelic subjective effects.
Our results suggest that psilocybin induces changes to the effective connectivity of large-scale RSNs that serve functions in cognition and perception.These changes are accompanied by temporary attenuation of amygdala recruitment and diminished amygdala activation, which has previously been linked to emotional regulation (111).However, the functional significance of these changes remains tentative.We suggest that changes in RSN's reduced connectivity to the amygdala and altered within-RSN effective connectivity are likely to be important aspects of the subjective effects and emotionalcognitive changes that characterize a neurophenomenological transition away from the ordinary mode of thinking and feeling that underlie self-experience (see the Supplement for more details).Importantly, our results demonstrate that this connectivity contributes to the altered meaning of percepts and subjective emotion, and psilocybin may affect conditioned patterns of emotional, cognitive, and self-reflective responses.
The psilocybin-induced alterations in effective connectivity observed in our study are consistent with previous research that has investigated the impact of psilocybin on emotional processing and amygdala-cortical neural dynamics (43,44,46,57), indicating that the acute response to amygdala connectivity relates to psychedelic subjective effects, and are consistent with the broader findings in psychedelic research, which have consistently highlighted an increase in neural plasticity and network flexibility (112)(113)(114)(115)(116).This body of research suggests that psychedelics such as psilocybin facilitate a more fluid and adaptable neural architecture.Our research contributes a mechanistic view of the underlying effective connectivity modulation of the CEN, DMN, and SN by psilocybin, which likely indicate brain transitions between different states of consciousness and cognitive processes and the manifestation of increased neural plasticity at the network level.Adaptability is crucial for the nuanced processing of cognitive and emotional information and is consistent with the known effects of psychedelics in enhancing brain network flexibility and responsiveness (35,117).Importantly, the connectivity changes that we report are linked with measurable changes to positive emotion and altered cognitive meaning.
The change to hierarchical interactions that we identified (see the Supplement) may play a key role in cognitive processes, such as thoughts and appraisals, bypassing  Cortical-Amygdala Mechanisms Under Psilocybin conditioned patterns of amygdala response.This may be aided in turn by dampened bottom-up amygdala influence.In therapeutic contexts, this may promote more adaptive means of regulating the interplay between thoughts and feelings.These findings contribute to advancing the mechanistic understanding of neural connectivity associated with functional significance in cognition and emotion processes and have implications for the development of clinical research that seeks to analyze and improve emotional and cognitive processes that underlie maladaptive internalized patterns of responses and to understand therapeutic mechanisms of psychedelics.
Our investigation into the interplay between cognition and emotion in healthy individuals under the influence of psilocybin has limitations.While our study highlights the attenuation of amygdala signals, it did not employ task-based fMRI protocols typically used to elicit specific emotional responses.Instead, we focused on connectivity changes during rest under psilocybin, correlating these changes with behavioral scores.Furthermore, ethical constraints prevented us from imaging clinical populations under the effects of psychedelics, underscoring the value of our study in understanding neural mechanisms in a safe and controlled environment.While this research provides valuable insights into the mechanisms of action of psilocybin that are foundational for understanding psychedelic clinical effects, the generalizability of our results to clinical populations is constrained by the reliance on a small, healthy adult sample.The potential of these observed connectivity changes as diagnostic tools for internalizing disorders requires further exploration with clinical populations.See the Supplement for further discussion of limitations.
However, this study provides crucial insights into understanding psilocybin's effects on neural dynamics.While general trends in psychedelic research have suggested an increase in bottom-up connectivity (12,73), as exemplified by enhanced thalamic-cortical interactions (94,118), our findings present a more nuanced view.Specifically, we observed a singular excitatory bottom-up connection from the amygdala in our CEN model.This observation contrasts with the broader pattern of stronger inhibitory dynamics, particularly in top-down connections.This nuanced response to psilocybin underscores the varied and complex effects that psychedelics can have on neural connectivity.As psychedelic research advances, examining multiple limbic regions and their subnuclei connectivity to the cortex may uncover more precise and nuanced dynamics between the subcortex and cortex, thus moving our neurobiological understanding beyond previously theorized global patterns.Recent research that demonstrated the spatial specificity of entropic activity and thalamic connectivity associated with psychedelic subjective effects (119) underscores the need for nuanced exploration.

Conclusions
In sum, we demonstrated altered within-RSN effective connectivity and reduced top-down RSN-amygdala effective connectivity associated with cognitive and emotional changes under psilocybin and the ability of effective connectivity analyses to advance our mechanistic understanding of hierarchically organized brain connectivity underlying alterations to consciousness.We revealed that change to the excitatoryinhibitory balance of amygdala-cortical connectivity affects cognitive appraisal and emotion, implicating potential mechanisms for reduced threat processing and enhanced subjective mood that may have relevance to the remediation of maladaptive cognitive and emotional characteristics of internalizing disorders.Our findings point to promising directions for future psychedelic imaging studies, suggesting corticalamygdala targets for analyses in task-based paradigms of healthy adults and postacute imaging of clinical populations.These lines of inquiry can help us discern the imperative of the psychedelic subjective experience to therapeutic outcomes and bridge gaps in our understanding of the relationships between brain connectivity and behavior.DS, AR, and FXV were responsible for conceptualization.DS, LN, and AR developed the methodology.DS, KHP, FXV, and AR were responsible for investigations.DS, LN, and AR were responsible for visualizations.AR supervised the study.DS wrote the original draft.DS, LN, AR, GFE, KHP, and FXV were responsible for writing, reviewing, and editing.

ACKNOWLEDGMENTS AND DISCLOSURES
All data are available in the main text or the Supplement or on request to the corresponding author.
The authors report no biomedical financial interests or potential conflicts of interest.

Figure 1 .
Figure 1.Default mode network effective connectivity change under psilocybin 70 minutes post administration.Connections show changes in effective connectivity compared with placebo.Values display effect sizes (posterior expectations) of connections in Hz (except the inhibitory self-connections, which are log scaled).Values linked to subjective effects represent their associations with effective connectivity and represent normalized b coefficients.Positive values represent positive associations; negative values represent negative associations.All results are for posterior probability .0.99 (amounting to very strong evidence).Those connections and associations not reported did not exceed this threshold.AMG, amygdala; l, left; mPFC, medial prefrontal cortex; PCC, posterior cingulate cortex; r, right.

Figure 2 .
Figure 2. Central executive network effective connectivity change under psilocybin 70 minutes post administration.Values display effect sizes (posterior expectations) of connections in Hz (except the inhibitory self-connections, which are log scaled).Values linked to subjective effects represent their associations with effective connectivity and represent normalized b coefficients.Positive values represent positive associations; negative values represent negative associations.All results are for posterior probability .0.99.Those connections and associations not reported did not exceed this threshold.AMG, amygdala; DLPFC, dorsolateral prefrontal cortex; l, left; LPCC, lateral posterior cingulate cortex; r, right.

Figure 3 .
Figure 3. Salience network effective connectivity change under psilocybin 70 minutes post administration.Connections show changes in effective connectivity compared to placebo.Values display effect sizes (posterior expectations) of connections in Hz (except the inhibitory self-connections, which are log scaled).Values linked to subjective effects represent their associations with effective connectivity and represent normalized b coefficients.Positive values represent positive associations; negative values represent negative associations.All results are for posterior probability .0.99.Those connections and associations not reported did not exceed this threshold.AI, anterior insula; AMG, amygdala; dACC, dorsal anterior cingulate cortex; l, left; r, right.
This work was supported by the Swiss Neuromatrix Foundation (Grant No. 2015-0103 [to FXV]), Usona Institute (Grant No. 2015-2056 [to FXV]), Australian Research Council Discovery Early Career Research Award Fellowship (No. DE170100128 [to AR]), Australian Research Council Discovery Project (Grant No. DP200100757 [to AR]), Australian National Health and Medical Research Council Investigator (Grant No. 1194910 [to AR]), and Wellcome Centre for Human Neuroimaging supported by core funding from Wellcome (Grant No. 203147/Z/16/Z [to AR]).

Table 2 .
Change of Default Mode Network Effective Connectivity to the AMG Under Psilocybin and Behavioral AssociationsBliss and percept refer to scores on the blissful state and changed meaning of percept subdimensions of the 5-Dimensional Altered States of Consciousness questionnaire.See TableS1for additional details.

Table 3 .
Change of Central Executive Network Effective Connectivity to the AMG Under Psilocybin and Behavioral AssociationsBliss and percept refer to scores on the blissful state and changed meaning of percept subdimensions of the 5-Dimensional Altered States of Consciousness questionnaire.See TableS1for additional details.

Table 4 .
Change of Salience Network Effective Connectivity to the AMG Under Psilocybin and Behavioral AssociationsPercept refers to score on the changed meaning of percept subdimensions of the 5-Dimensional Altered States of Consciousness questionnaire.See TableS1for additional details.