- Proposes the High Processing Cost Phenotypes framework: neurodevelopmental profiles reflect a shared ECM-based developmental substrate, not discrete diagnostic entities.
- Describes Island, Desert, Bridge topology: local high-gain Islands, weakly stabilised Deserts for serial tasks, and costly Bridges enabling compensatory connectivity.
- Interprets burnout-like states thermodynamically: when bridging allostatic cost exceeds metabolic tolerance, functional throughput collapses; introduces Functional Iron Blockade hypothesis.
Neurosci Biobehav Rev. 2026 Sep 20:106992. doi: 10.1016/j.neubiorev.2026.106992. Online ahead of print.
ABSTRACT
BACKGROUND: Current neurodevelopmental classifications partition autism, ADHD, developmental coordination disorder (DCD), dyslexia, twice-exceptionality, and high-ability phenotypes into ostensibly separate clinical entities.
AIMS: This narrative conceptual review aims to develop the phenotype-level clinical implications of an extracellular matrix (ECM)-based mechanobiological account of atypical neural topology, formulated in prior work, through the High Processing Cost Phenotypes (HPCPh) framework: these presentations are proposed to be phenotype-specific topological expressions of a shared developmental substrate.
PROPOSALS: Within this model, a more permissive and insufficiently stabilized neural architecture is proposed to give rise to a recurrent geometry of Islands (high-gain domains of efficient local capture and integration), Deserts (weakly stabilized domains of serial implementation, gating, timing, and sensorimotor translation), and Bridges (energetically expensive compensatory pathways linking them). This Island-Desert-Bridge (IDB) topology is used to organize recurrent clinical paradoxes across neurodivergent presentations, including sensory talent with severe overload, preserved intention with dyspraxic execution, semantic richness with reading bottlenecks, salience-driven hyperfocus with routine failure, and high abstract capacity sustained by exhausting masking. The framework proposes a thermodynamic interpretation of some burnout- and depression-like states as load-related reductions in functional throughput when the allostatic cost of bridging exceeds metabolic and autonomic tolerance; this formulation does not exclude primary mood disorders and requires empirical differentiation. Functional Iron Blockade (FIB) is introduced as one candidate, hypothesis-level containment mechanism.
CONCLUSIONS: By shifting emphasis from symptom-based deficits to topological cost, the HPCPh framework provides a falsifiable, transdiagnostic account that reconnects neurodevelopmental phenotypes with developmental biology, systems neuroscience, and allostatic physiology.
PMID:42764047 | DOI:10.1016/j.neubiorev.2026.106992
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