Ego dissolution as a collapse of integration, not a surge of entropy

Abstract
The “entropic brain” hypothesis holds that psychedelic and other ego-dissolving states correspond
to an increase in the entropy or signal diversity of spontaneous brain activity. Motivated by a
first-person report of a combined serotonergic–dissociative state (LSD/DMT together with nitrous
oxide, N2O), we asked a sharper question: when a 5-HT2A agonist and an NMDA antagonist act
together, is the resulting state dominated by a rise in local signal complexity, by a collapse of long
range functional integration, or by both? We address this in a validated whole-brain dynamic
mean-field (DMF) model (reduced Wong–Wang, Deco et al. 2014) implemented in The Virtual
Brain, on empirical human structural connectomes, with regional excitation/inhibition balanced
by analytic Feedback Inhibition Control (FIC). The two drug classes are represented by separable,
biophysically motivated parameters: 5-HT2A agonism as a density-weighted increase in excitatory
response gain, and sub-anaesthetic NMDA antagonism as interneuron-preferential disinhibition
(reduced excitatory→inhibitory NMDA conductance) plus reduced long-range NMDA coupling.
Crucially, because both perturbations shift mean firing rate — and both Lempel–Ziv complexity
(LZc) and functional connectivity (FC) co-vary with rate — we rate-match every condition back
to the ∼3 Hz physiological set-point before reading out the metrics, isolating mechanism from a
trivial rate confound. At matched rate, the combination produces a robust, dose-dependent,
topology-general collapse of functional integration (mean ΔFC = −56%±12% SD, nega
tive in 6/6 noise seeds and reproduced on a second 192-region connectome) together with a small
but statistically reproducible increase in signal complexity (ΔLZc = +0.9%±0.5% SD,
positive in 6/6 seeds, 𝑡 ≈ 4). These multi-seed values are the canonical results; single-run figures
quoted in the development log are individual noise realisations. The 5-HT2A entropy increase
(+5.4%) is largely cancelled by an N2O-driven hypersynchrony (−4.6%), so the net complexity
change is marginal while the integration collapse is large. We conclude that, in this model, the
combined ego-dissolving state is dissociation-dominated rather than entropy-dominated:
the brain loses its capacity to integrate, not its local richness. We discuss this as a refinement of
the entropic-brain framing for combined serotonergic–dissociative states, and report the analyses
transparently including a working-point artefact we explicitly reject.
Keywords: ego dissolution, entropic brain, dynamic mean-field model, The Virtual Brain, feed
back inhibition control, 5-HT2A, NMDA antagonist, nitrous oxide, functional integration, Lempel
Ziv complexity