Nature communications
October 3, 2022
S Parker Singleton, Andrea I Luppi, Robin L Carhart-Harris et al.
156 citations
Psychedelics like LSD and psilocybin temporarily alter subjective experience by acting on serotonin 2a (5-HT2a) receptors, increasing the diversity (entropy) of brain activity. This increase may arise from a flattening of the brain's control energy landscape. Using fMRI data, the authors show that these compounds reduce the control energy needed for transitions between brain states compared to placebo. Across individuals, lower control energy correlates with more frequent state transitions and higher entropy. Incorporating PET data on 5-HT2a receptor distribution under non-drug conditions, the analysis links these receptors to reduced control energy. The findings demonstrate that receptor-informed network control theory can model how neuropharmacological manipulation affects brain dynamics.
Frontiers in psychiatry
January 1, 2022
S Parker Singleton, Julie B Wang, Michael Mithoefer et al.
36 citations
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy (MDMA-AT) did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, showing only a trend. After treatment, brain activation during trauma memory recall decreased in the cuneus. Recovery from PTSD correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that amygdala, hippocampus, and insula functional connectivity may be a target of MDMA-AT, highlighting regions involved in memory processes.
Communications biology
April 18, 2025
S Parker Singleton, Christopher Timmermann, Andrea I Luppi et al.
7 citations
After DMT injection, the brain requires less control energy to transition between states compared to placebo, indicating a more flexible and less constrained brain dynamic. These energy changes track with EEG signal diversity and subjective intensity of the drug experience. The regional pattern of DMT's effects aligns with serotonin 2a receptor density, and a model using receptor distribution and pharmacokinetics can predict the drug's impact on brain energy trajectories.