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Ozenne, B.

Publications and source records attributed to Ozenne, B..

6 recordsLinked to original sources

Psilocybin acutely reduces low-frequency BOLD power and frequency-specific connectivity

Psilocybin and other serotonergic drugs acutely alter human brain function and large-scale connectivity as measured with BOLD fMRI, but whether these effects are frequency-specific remains unknown. We applied multitaper spectral and cross-spectral analyses to resting-state fMRI data from 28 healthy volunteers scanned multiple times acutely following oral psilocybin administration (0.2 - 0.3 mg/kg), together with plasma psilocin measurements, to estimate psilocin associations with temporal frequency-specific activity and connectivity. Psilocybin produced a selective reduction in low-frequency spectral power (0.01 - 0.06Hz) and an increase in spectral entropy, with the strongest effects in transmodal networks. We also observed a reduction in low-frequency connectivity energy explained by the unimodal/transmodal axis. These findings demonstrate that psilocin induces spatially distributed, frequency-dependent alterations, suggesting that broadband fMRI analyses may obscure low-frequency dynamics. Frequency-resolved approaches may offer greater sensitivity for characterizing psychedelic effects on brain activity.

neuroscience↗

Pitfalls of mapping functional and molecular human brain imaging data from separate cohorts

It has become increasingly common to probe correlations between human brain imaging measures of receptor/protein binding and function using population-level brain maps drawn from independent cohorts, estimating correlations across regions. This strategy raises issues of interpretation that we highlight here with a multimodal brain imaging dataset and simulation studies. Twenty-four healthy participants completed neuroimaging with both [11C]Cimbi-36 positron emission tomography and magnetic resonance imaging scans to estimate receptor binding potential (BP) and cerebral blood flow (CBF), respectively, in 18 cortical/subcortical regions. Correlations between BP and CBF were estimated in three ways: 1) Pearson correlation across regions of mean regional BP and CBF ({rho}l), to mimic studies using data from independent cohorts; 2) Pearson correlation between BP and CBF across participants in each region ({rho}2); or 3) the correlation between BP and CBF across participants across all regions within a single linear mixed effects model ({rho}3). We observed a significant positive correlation across regions ([Formula]l = 0.672; p = 0.0023). Region-specific correlations across participants were substantively lower and not statistically significant ([Formula]2: mean = 0.140, range = -0.112 to 0.336; all p > 0.10), nor when estimated simultaneously within a linear mixed model ([Formula]3 = 0.138, p = 0.26). Our simulation study illustrated that regional differences in BP or CBF mean and variance can bias across regions correlations by 1000% or create a type-1 error of 100%. Our observations that both the estimated correlation and the statistical significance can differ greatly highlights that inferring across region correlation as evidence for correlation across participants is erroneous. Without validated methods that limit confounding and other biases, we discourage future studies from inferring across region correlation of population-level brain maps from independent cohorts in this manner.

neuroscience↗

The association between brain serotonin 2A receptor binding and neuroticism in healthy individuals: A Cimbi database independent replication study

BackgroundUsing the [18F]altanserin tracer to image serotonin 2A receptors (5-HT2AR), we previously showed that there exists a positive association between cortical 5-HT2AR binding and the inward facets of neuroticism, namely depression, anxiety, self-consciousness, and vulnerability. Fairly recently, the [11C]Cimbi-36 tracer was also shown to be a suitable radioligand for imaging 5-HT2A receptors in the human brain. In the present study, we examined whether our previously reported finding of the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent sample of healthy individuals scanned using the newer [11C]Cimbi-36 tracer. Furthermore, to determine whether this association of 5-HT2AR binding with neuroticism merely reflects its known relation to stress-coping related indices such as cortisol dynamics. The present study also investigated the potential role of cortisol awakening response on the association between 5-HT2AR binding and the inward facets of neuroticism. MethodsSixty-nine healthy volunteers underwent a [11C]CIMBI-36 scan for the assessment of 5-HT2AR binding, completed the standardized NEO-PI-R personality questionnaire, and provided salivary samples for the determination of cortisol awakening response. A linear latent variable model (LVM) was used to examine the association between 5-HT2AR binding and the inward facets of neuroticism with adjustment for age, sex, cortisol awakening response, and MR scanner. A second latent variable model examined the potential moderating effect of cortisol awakening response on the association between 5-HT2AR binding and the inward facets of neuroticism. ResultsWe replicated a positive association between 5-HT2AR binding and the inward facets of neuroticism (r=0.37, p=0.015). We saw no moderating effect of the cortisol awakening response on this association (p=0.98). ConclusionsIn an independent cohort of healthy individuals imaged with the [11C]CIMBI-36 tracer, we confirm the link between serotonin 2A receptor binding and the inward-directed facets of neuroticism that is independent of cortisol dynamics.

neuroscience↗

Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

The emerging novel therapeutic psilocybin produces psychedelic effects via engagement of cerebral serotonergic targets by psilocin (active metabolite). The serotonin 2A receptor critically mediates these effects by altering distributed neural processes that manifest as increased entropy, reduced functional connectivity (FC) within discrete brain networks (i.e., reduced integrity) and increased FC between networks (i.e., reduced segregation). Reduced integrity of the default mode network (DMN) is proposed to play a particularly prominent role in psychedelic phenomenology, including perceived ego-dissolution. Here, we investigate the effects of a psychoactive oral dose of psilocybin (0.2-0.3 mg/kg) on plasma psilocin level (PPL), subjective drug intensity (SDI) and their association in fifteen healthy individuals. We further evaluate associations between these measures and resting-state FC, measured with functional magnetic resonance imaging, acquired over the course of five hours after psilocybin administration. We show that PPL and SDI correlate negatively with measures of network integrity (including DMN) and segregation, both spatially constrained and unconstrained. We also find that the executive control network and dorsal attention network desegregate, increasing connectivity with other networks and throughout the brain as a function of PPL and SDI. These findings provide direct evidence that psilocin critically shapes the time course and magnitude of changes in the cerebral functional architecture and subjective experience following psilocybin administration. Our findings provide novel insight into the neurobiological mechanisms underlying profound perceptual experiences evoked by this emerging transnosological therapeutic and implicate the expression of network integrity and segregation in the psychedelic experience and consciousness.

neuroscience↗

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

BackgroundPsilocybin 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. AimsEvaluate changes in resting-state functional connectivity (RSFC) at one-week and three-months after one psilocybin dose in 10 healthy psychedelic-naive volunteers and explore associations between change in RSFC and related measures. MethodsParticipants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state fMRI scans at baseline, one-week and three-months post-administration and [11C]Cimbi-36 PET scans at baseline and one-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. ResultsPsilocybin was well tolerated and produced positive changes in well-being. At one-week only, executive control network (ECN) RSFC was significantly decreased (Cohens d=-1.73, pFWE=0.010). We observed no other significant changes in RSFC at one-week or three-months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at one-week predicted increased mindfulness at three-months (r =-0.65). ConclusionsThese 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 three-months, when personality changes are observed, remain to be identified.

neuroscience↗

Comparison of classification methods for tissue outcome after ischemic stroke

In acute ischemic stroke, identifying brain tissue at high risk of infarction is important for clinical decision-making. This tissue may be identified with suitable classification methods from magnetic resonance imaging (MRI) data. The aim of the present study was to assess comparatively the performance of five popular classification methods (Adaptive Boosting (ADA), Logistic Regression (LR), Artificial Neural Networks (ANN), Random Forest (RF), and Support Vector Machine (SVM)) in identifying tissue at high risk of infarction on human voxel-based brain imaging data. The classification methods were used with eight MRI parameters including diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) obtained in 55 patients. Sensitivity, specificity, the area under the receiver operating curve (ROC) as well as the area under the precision-recall curve criteria were used to compare the method performances. The methods performed equally in terms of sensitivity and specificity while the results of the area under the ROC were significantly better for ADA, LR, ANN and RF. However, there was no statistically significant difference between the performances of these five classification methods regarding the area under the precision-recall curve, which was the main comparison metric.

neuroscience↗