Access–Calibration–Amplification (ACA): A Compartmental Framework for Neurodevelopmental Divergence

Central thesis Developmental persistence is not sufficient for ACA admission. The framework asks which input was present, whether Access was actually required, whether a qualitative Calibration operation occurred, what persistent state it produced, how that state is maintained, whether later effects are recurrence, downstream propagation, or feedback Amplification, and which experiment would discriminate the remaining alternatives. Abstract Access–Calibration–Amplification (ACA) is the neurodevelopmental branch of Compartmental Decision Pathology (CDP). It addresses pathways in which a developing neural compartment maps intrinsic activity, instructive input, context, and prior state into a persistent functional organization. The programme-level grammar is Perturbation → [Access when required] → Calibration → Functional configuration → downstream propagation and, where a return relation is demonstrated, feedback Amplification → Phenotype, with modes of interference acting orthogonally. Access is optional and relational; ordinary sensory, social, or caregiving input is not Access. Calibration requires a qualitative organization or response relation rather than uniform gain, generic plasticity, binary activation, or residual damage. Functional configuration, maintenance, effector execution, downstream propagation, feedback Amplification, recurrence, and phenotype remain separate evidentiary claims; Amplification requires a demonstrated return relation. The experimental map contains one qualified operation-derived four-test Functional-configuration anchor in critical-period ocular-dominance/binocular-weighting plasticity, with adult chondroitinase-enabled recalibration; a qualified recurrent-Calibration anchor in sensory systems; and a qualified four-test GR/HPA state anchor whose provenance from a qualitatively distinct Calibration operation remains unresolved. Social-experience-dependent prefrontal myelination is a near-anchor state candidate. Prenatal valproate provides a strong disease-linked Calibration candidate: a temporally selective embryonic perturbation is followed by persistent, region-specific abnormalities of PV/PNN organization; adult chondroitinase can correct the PV state in VPA-exposed prefrontal cortex; and juvenile interventions identify a restricted postnatal window in which later behavioural and GABAergic outcomes can still be redirected. The specific VPA → PV/PNN → functional-phenotype rescue remains open, so this system is not classified as a four-test Functional-configuration anchor. The experimental programme makes the remaining causal tests explicit. In the Pb platform, Smith et al. themselves proposed a BBB-impermeable chelator or anti-inflammatory intervention to separate central from peripheral contributions; the selective mediation experiment remains open. In the GR/HPA system, modern locus- and cell-type-specific epigenome editing makes a more discriminating post-establishment test technically feasible. In the VPA system, the decisive gap is unusually narrow: manipulate PNN/plasticity architecture after the VPA-derived state is established, separate reopening from corrective experience, and test whether normalization of circuit organization and behaviour persists after the intervention ends. Schizophrenia, autism, ADHD, cerebral folate deficiency, and other human domains remain stress-tests rather than completed etiological chains. No full ACA chain is closed. ACA is presented as a living preprint whose claims are intended to move layer by layer as decisive experiments appear.