Biology subjects

Safron, A.

Publications and source records attributed to Safron, A..

2 recordsLinked to original sources

bioRxiv2024

A dual-receptor model of serotonergic psychedelics: therapeutic insights from simulated cortical dynamics

Serotonergic psychedelics have been identified as promising next-generation therapeutic agents in the treatment of mood and anxiety disorders. While their efficacy has been increasingly validated, the mechanism by which they exert a therapeutic effect is still debated. A popular theoretical account is that excessive 5-HT2a agonism disrupts cortical dynamics, relaxing the precision of maladaptive high-level beliefs and making them more malleable and open to revision. We extend this perspective by developing a simple energy-based model of cortical dynamics based on predictive processing which incorporates effects of neuromodulation. Using this model, we propose and simulate hypothetical computational mechanisms for both 5-HT2a and 5-HT1a agonism. Results from our model are able to account for a number of existing empirical observations concerning serotonergic psychedelics effects on cognition and affect. Using the findings of our model, we provide a theoretically-grounded hypothesis for the clinical success of LSD, psilocybin, and DMT, as well as identify the design space of biased 5-HT1a agonist psychedelics such as 5-MeO-DMT as potentially fruitful in the development of more effective and tolerable psychotherapeutic agents in the future.

neuroscience↗

bioRxiv2024

Stable Individual Differences from Dynamic Patterns of Function: Brain Network Flexibility Predicts Openness/Intellect and Intelligence

Growing understanding of the nature of brain function has led to increased interest in interpreting the properties of large-scale brain networks. Methodological advances in network neuroscience provide means to decompose these networks into smaller functional communities and measure how they reconfigure over time as an index of their dynamic and flexible properties. Recent evidence has identified associations between flexibility and a variety of traits pertaining to complex cognition including creativity and working memory. The present study used measures of dynamic resting-state functional connectivity in data from the Human Connectome Project (N = 994) to test associations with Openness/Intellect and general intelligence, two traits that involve flexible cognition. Using a machine-learning cross-validation approach, we identified reliable associations of intelligence with cohesive flexibility of parcels in large communities across the cortex, and of Openness/Intellect with overall flexibility among parcels in smaller communities. These findings are reasonably consistent with previous theories of the neural correlates of intelligence and Openness/Intellect, and help to expand on previous associations of behavior and dynamic functional connectivity within the context of broader personality dimensions.

neuroscience↗