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

Summary

Across humans and three other mammals, diverse anesthetics consistently disrupted integrated information and made brain dynamics harder to control, an effect reversed by thalamic deep-brain stimulation in macaques. Spatial patterns of disruption aligned with PVALB gene expression maps, and computational models combining species-specific connectivity and transcriptomics explained control of integration.

Key Findings

• Diverse anesthetics cause a convergent breakdown of integrated information across humans, macaques, marmosets, and mice.
• As integration breaks down, brain dynamics become harder to control; both effects are reversed by thalamic DBS in macaques.
• Regional disruption aligns with PVALB/Pvalb expression maps; models integrating connectivity and transcriptomic gradients recapitulate control of information integration.

Clinical Implications

Findings suggest transcriptomic and network markers (e.g., PVALB topography) could inform monitoring targets or agent selection, and highlight thalamic circuits as potential levers to reverse anesthetic-induced unresponsiveness in selected contexts.

Limitations

• Limited immediate clinical translatability; outcomes focus on mechanistic biomarkers rather than patient endpoints
• Gene expression alignment analyses are correlational; direct molecular manipulation was not performed in vivo across species

Future Directions

Develop bedside-compatible metrics of information integration linked to transcriptomic signatures; test targeted neuromodulation strategies to restore integration during anesthesia or disorders of consciousness.