Convergent transcriptomic and connectomic controllers of information integration and its anaesthetic breakdown across mammalian brains.

Summary

Using fMRI across humans and three non-human species, the authors demonstrate that reduced integrated information under anesthesia is a convergent phenomenon linked to regional PVALB/Pvalb gene expression gradients. Brain dynamics become harder to control during disintegration, and thalamic deep brain stimulation reverses both the loss of integration and controllability in macaques.

Key Findings

• Anesthetic-induced breakdown of information integration is conserved across humans, macaques, marmosets, and mice.
• Loss of integration coincides with reduced controllability of brain dynamics and is reversed by thalamic deep brain stimulation in macaques.
• Regional susceptibility aligns with species-specific PVALB/Pvalb gene expression topography; models integrating connectivity and transcriptomics recapitulate these effects.

Clinical Implications

While not directly practice-changing, the identification of PVALB-linked regional susceptibility and the reversibility via thalamic stimulation inform future neuromodulation strategies, monitoring targets, and anesthetic agent development aimed at preserving network integration.

Limitations

• Single-center prospective cohorts and laboratory settings may limit generalizability to diverse clinical anesthetic contexts
• Indirect translation to clinical outcomes; no randomized clinical trials of monitoring or agent selection are provided

Future Directions

Define patient-level biomarkers (e.g., PVALB-informed EEG signatures) to guide anesthetic dosing, and test neuromodulatory strategies to preserve integration in vulnerable populations.