Effects of an Oral Contraceptive on Dynamic Brain States and Network Modularity in a Serial Single-Subject Study.

Hormonal contraceptive drugs are used by adolescent and adult women worldwide. Increasing evidence from human neuroimaging research indicates that oral contraceptives can alter regional functional brain connectivity and brain chemistry. However, questions remain regarding static whole-brain and dynamic network-wise functional connectivity changes. A healthy woman (23 years old) was scanned every day over 30 consecutive days during a naturally occurring menstrual cycle and again a year later while using a combined hormonal contraceptive. Here we calculated graph theory-derived, whole-brain, network-level measures (modularity and system segregation) and global brain connectivity (characteristic path length) as well as dynamic functional brain connectivity using Leading Eigenvector Dynamic Analysis and diametrical clustering. These metrics were calculated for each scan session during the serial sampling periods to compare metrics between the subject's natural and contraceptive cycles. Modularity, system segregation, and characteristic path length were statistically significantly higher across the natural compared to contraceptive cycle scans. We also observed a shift in the prevalence of two discrete brain states when using the contraceptive. Our results suggest a more network-structured brain connectivity architecture during the natural cycle, whereas oral contraceptive use is associated with a generally increased connectivity structure evidenced by lower characteristic path length. The results of this repeated, single-subject analysis allude to the possible effects of oral contraceptives on brain-wide connectivity, which should be evaluated in a cohort to resolve the extent to which these effects generalize across the population and the possible impact of a year-long period between conditions.

Psychedelic resting-state neuroimaging: A review and perspective on balancing replication and novel analyses.

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.

Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report.

Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 × 10-5). Moreover, the MEQ subscales "Positive Mood" (pcorr = 4.1 × 10-4) and "Mysticality" (pcorr = 2.0 × 10-4) are associated with positive PEQ whereas the subscales "Transcendence of Time and Space" (pcorr = 0.38) and "Ineffability" (pcorr = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects.

Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals.

BACKGROUND: Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. AIM: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures. METHODS: Participants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding. RESULTS: Psilocybin was well tolerated and produced positive changes in well-being. At 1 week only, executive control network (ECN) RSFC was significantly decreased (Cohen's d = -1.73, pFWE = 0.010). We observed no other significant changes in RSFC at 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months (r = -0.65). CONCLUSIONS: These findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic 'afterglow' period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.