BRAIN-TIME: Testing Whether Prospective Recovery Position Modifies the Benefit of the Same Intervention in Addiction

Addiction neuroscience has advanced the identification of vulnerability and mechanisms involving reward learning, salience, cognitive control, interoception, cue reactivity, and stress regulation. Yet a key translational question remains unresolved: when does an evolving post-perturbation brain–behavior trajectory become relevant to treatment benefit? Prediction models can estimate future craving, lapse, or deterioration, and adaptive-intervention systems can deliver support using prespecified tailoring variables, but neither dynamic treatment regimes, just-in-time adaptive interventions, nor causal machine learning specifies what evidence a temporal quantity must satisfy before it may serve as the tailoring variable itself. This Perspective asks whether prospective recovery position modifies the benefit of the same intervention, and introduces BRAIN-TIME as a falsifiable episode-level architecture for answering that question. It begins with a defined cue, stress, affective, or sleep-related perturbation, follows one prespecified recovery domain relative to an individualized reference, and separates retrospectively adjudicated sustained re-entry from a prospective estimate of incomplete recovery computed only from information available at the decision point, with no use of later observations. Its decisive Stage 1 test is treatment-effect moderation: at a common locked landmark, the benefit of the same intervention and dose must vary across prospectively estimated recovery positions by a prespecified, practically meaningful amount. A minimal proof of concept combines a standardized low-intensity challenge, repeated craving or autonomic sampling, an independent outward-function criterion, negative controls, and randomized fixed-content intervention. No original data are reported, and every quantity specified here is a proposed construct, estimand, or falsification criterion rather than an observed result. BRAIN-TIME is therefore neither a relapse classifier nor an autonomous treatment rule. Its central claim is deliberately narrow: temporal recovery information becomes relevant to treatment timing only when prospective episode position is shown to modify the benefit of the same intervention.