The Metacontinuum: Bridging cellular composition to cognitive functions in brain organization.
Gustavo Guzmán, Elsa Magaña-Cuevas, Rocío Hernández-Rizo, Malinalli López-Medina, Omar Cano-Garcia, Omar Paredes
Bio Systems September 1, 2025 DOI: 10.1016/j.biosystems.2025.105550 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Keywords | Brain gradients Code biology Connectomics Metacontinuum hypothesis Molecular codes Multi-scale integration Neural codes |
| Key points | Proposes that molecular and neural codes are coupled through bidirectional regulatory mechanisms, forming a 'metacontinuum' that integrates biological information processing across scales. |
Abstract
Brain organization emerges from molecular, cellular, and systems-level processes that together generate cognitive function. While individual biological codes have been characterized at specific scales, their integration across levels remains poorly understood. Existing theories of consciousness recognize diverse electrophysiological signatures but fail to explain the continuity linking molecular and neural codes. We propose the metacontinuum hypothesis as a unifying framework that connects these layers of biological information processing. Molecular codes establish cellular identity and circuit properties, while neural codes organize these circuits into systems supporting cognition. Evidence from connectomics, transcriptomics, and neuroimaging reveals mechanistic links between these levels, including gene expression gradients aligned with functional connectivity patterns. These findings suggest molecular and neural codes are coupled through bidirectional regulatory mechanisms. The metacontinuum hypothesis offers a roadmap for understanding biological information flow-from molecular interactions to neural computations-addressing the fragmentation problem in Code Biology and supporting the development of an integrated, multi-scale theory of life's coding architecture.