Maladaptive Brain-state Locking as a Lifespan Framework for Neurodevelopmental, Psychiatric, and Neurodegenerative Disorders: A Hypothesis

Neurodevelopmental, psychiatric, and neurodegenerative disorders are traditionally studied as distinct disease categories, yet they show overlapping disturbances in systems that regulate neural function and resilience. This article proposes maladaptive brain-state locking (MBSL) as a lifespan framework for examining whether otherwise distinct disorders may converge, in some contexts, on impaired biological-state reversibility. MBSL is defined as a failure of adaptive state-transition or recovery dynamics in which a maladaptive state becomes insufficiently reversible and the nervous system loses its normal capacity to terminate, recalibrate, or transition away from that state. Locking is therefore distinguished from persistence alone: an abnormal state maintained solely by a continuing pathological driver does not, by itself, constitute MBSL. Candidate operational features include abnormal persistence, impaired transition toward an adaptive state, delayed or incomplete recovery after perturbation reduction or removal, and history-dependent loss of flexibility. Lifespan timing, regional context, disease stage, severity, duration, and resilience are proposed to modify phenotypic consequences rather than assign disorder classes exclusively to specific age periods. Existing evidence is compatible with components of the hypothesis, but direct demonstration of MBSL will require longitudinal or perturbational evidence of impaired recovery or state-transition dynamics. Major limitations include etiological and pathological heterogeneity, nonspecific biomarkers, unresolved causality, and challenges in operationalizing multiscale state dynamics. If validated, the framework could support research focused on measurable reversibility, longitudinal monitoring, and interventions designed to restore adaptive state regulation rather than symptom improvement alone.