Pagni, B. | bioRxiv Science

bioRxiv2024

Human brain changes after first psilocybin use

Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1- and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin placebo dose.

neuroscience↗

bioRxiv2021

Sex-Related Neurocircuitry Supporting Camouflaging in Adults with Autism: Female Protection Insights

The male preponderance in autism led to the hypothesis that aspects of female biology are protective against autism. Females with autism report engaging in more compensatory behaviors (i.e., "camouflaging") to overcome autism-related social differences, which may be a downstream result of protective pathways. No studies have examined sex-related brain pathways supporting camouflaging in females with autism, despite its potential to inform mechanisms underlying the sex bias in autism. This case-control design included 45 non-intellectually-disabled adults with autism (male/female: 21/24) and 40 neurotypical adults (male/female: 19/21) ages 18-71. We used group multivariate voxel pattern analysis to conduct a data-driven, connectome-wide characterization of "sex-atypical" (sex-by-diagnosis) and "sex-typical" (sex) brain functional connectivity features linked to camouflaging, and validated findings in females with autism multi-modally via structural connectometry. Exploratory associations with cognitive control, memory, emotion recognition, and depression/anxiety examined the adaptive nature of functional connectivity patterns supporting camouflaging in females with autism. We found 1) "sex-atypical" functional connectivity patterns predicting camouflaging in the hypothalamus and precuneus and 2) "sex-typical" patterns in the anterior cingulate and right anterior parahippocampus. Higher hypothalamic functional connectivity with a limbic reward cluster was the strongest predictor of camouflaging in females with autism (a "sex-atypical" pattern), and also predicted better cognitive control/emotion recognition. Structural connectometry validated functional connectivity results with consistent brain pathways/effect patterns implicated across multi-modal findings in females with autism. This data-driven, connectome-wide characterization of "sex-atypical" and "sex-typical" brain connectivity features supporting compensatory social behavior in autism suggests hormones may play a role in the autism sex bias. Furthermore, both "male-typical" and "female-typical" brain connectivity patterns are implicated in camouflaging in females with autism in circuits associated with reward, emotion, and memory processing. "Sex-atypical" results are consistent with the fetal steroidogenic hypothesis, which would result in masculinized brain features in females with autism. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging.

neuroscience↗