PLoS computational biology
February 1, 2023
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
28 citations
Brain dynamics under LSD become more disordered and complex, moving further from the critical point that characterizes healthy brain function. Using Ising spin models fitted to fMRI data from fifteen participants, the authors show that LSD reduces interhemispheric connectivity, especially between corresponding regions in opposite hemispheres. Ising temperatures were significantly higher under LSD than placebo, indicating a shift into a more disordered (paramagnetic) state. Algorithmic complexity of brain activity, measured by block decomposition, correlated with both Ising temperature and condition, supporting the entropic brain hypothesis that psychedelics increase neural disorder.
PLoS computational biology
June 6, 2025
Wiep Stikvoort, Eider Pérez-Ordoyo, Iván Mindlin et al.
3 citations
A person's level of consciousness can be assessed by how the brain reacts to stimulation, but this study shows that the brain's unperturbed activity already contains that information. Using personalized whole-brain models fitted to resting-state fMRI data from people in altered states of consciousness (deep sleep, disorders of consciousness), the researchers measured the brain's out-of-equilibrium dynamics—specifically, the asymmetry of effective connections and time irreversibility. They found that states with lower arousal or awareness had less asymmetric connectivity, less irreversibility, and lower complexity in simulated responses compared to controls. The asymmetry in connections drives the nonequilibrium state and, in turn, the differences in complexity.
PLoS computational biology
June 9, 2025
Jessie Rademacher, Tineke Grent-'t-Jong, Davide Rivolta et al.
2 citations
Ketamine, an NMDA receptor antagonist given at sub-anesthetic doses, flattens the aperiodic slope of brain activity and increases gamma-band power (30–90 Hz), especially in prefrontal and central regions. These effects correlate with gene expression of parvalbumin and GluN2D. A computational model of cortical layer 2/3 shows that reducing NMDA receptor activity in parvalbumin or somatostatin interneurons boosts pyramidal neuron firing, reproducing the gamma power increase but not the aperiodic slope change. This suggests parvalbumin and somatostatin interneurons drive the gamma power rise, while the aperiodic component involves other mechanisms, challenging current excitation/inhibition balance models.
PLoS computational biology
September 1, 2025
Jordy Peeters, Dimitri De Bundel, Kenno Vanommeslaeghe
The serotonin-2A receptor (5-HT2AR) is a target for antidepressants that could work quickly or in treatment-resistant cases, but activating it can cause hallucinations. Recent research suggests certain partial agonists might produce antidepressant effects without hallucinations, though the molecular details are unclear. This study used molecular dynamics simulations of the receptor bound to two antipsychotics, three potential non-hallucinogens, and two hallucinogens. Findings suggest modest receptor activation yields only antidepressant effects, while hallucinations result from excessive activation. Modest activation via a sufficiently weak partial agonist may offer a viable drug development pathway, whereas microdosing may be problematic due to abuse potential and narrow therapeutic windows.
PLoS computational biology
July 1, 2022
Michelle J Redinbaugh, Mohsen Afrasiabi, Jessica M Phillips et al.
Deep brain stimulation (DBS) of the central lateral thalamus in macaques can produce episodes of vacant staring with low-frequency brain oscillations, termed vacant, perturbed consciousness (VPC). The likelihood of VPC depended on stimulation frequency. During VPC, measures of neural complexity and integration decreased, and communication in cortico-striato-thalamic circuits changed substantially, with increased low-frequency power and coherence, especially in thalamo-parietal and cortico-striatal pathways. These features resembled absence epilepsy. The same DBS method, at different frequencies, can also increase consciousness in anesthetized macaques, offering a flexible tool to study consciousness with fewer confounds and to inform clinical research on consciousness disorders.