Topological Phase Transitions in Whole-Brain Dynamics Driven by Spatially Heterogeneous Receptor Gain Modulation: A Receptor-Constrained Dynamical Topology (RCDT) Hypothesis

Abstract

The mechanistic link between molecular pharmacology and global brain dynamics remains unresolved--a "scale bridge" problem central to consciousness research. We propose the Receptor-Constrained Dynamical Topology (RCDT) hypothesis: that the functional impact of neuromodulatory drugs propagates from local ligand-receptor binding events through spatially heterogeneous gain modulation to produce qualitative reorganizations of the whole-brain dynamical attractor. Using a biophysically grounded whole-brain model--Wilson- Cowan excitatory-inhibitory dynamics on structural connectivity with axonal delays--we implement pharmacology via gain modulation weighted by 5-HT2A receptor density (Be-liveau et al., 2017). Topological state-space analysis via Takens embedding and persistent homology reveals a mapping from molecular receptor distribution to the global topological manifold. We define ego dissolution operationally as a breakdown of low-dimensional Betti-1 stability: a transition from a single dominant 1-cycle (constrained dynamics) to fragmented or higher-dimensional topological structure. The RCDT hypothesis is explicitly falsifiable: receptor-shuffling controls and concentration-topology response curves provide clear failure criteria. This work establishes a formal framework for bridging pharmacology, dynamics, and topology without invoking phenomenological experience as a premise.