Just-in-Time Neuromodulation: A Precision, State-Dependent Paradigm for On-Demand Brain Intervention

Neuromodulation is commonly delivered on fixed schedules, whereas psychiatric and neurological symptoms fluctuate over time. Just-in-Time Neuromodulation (JiT-NM) offers a framework for aligning intervention with the emergence or escalation of clinically relevant neural or symptomatic states. We propose three essential components: targeting the desired state, a state-detection system, and a neuromodulatory intervention capable of acting within a clinically useful time window. A fourth, optional component, adaptive personalization, may refine detection models and stimulation parameters over time. JiT-NM may support self-initiated or autonomous delivery, open-loop or closed-loop control, informed by automated symptom recognition or self-report, physiological signals, digital phenotyping, or wearable neural sensing. Established responsive and adaptive implanted stimulation systems provide clinical precedents, while early investigations in psychiatric disorders support further exploration. We discuss how neuroimaging-derived targets and biomarkers might be translated into compact, individualized sensing-and-stimulation systems, emphasizing the need to validate reliable state detection with fewer sensors. Key challenges include demonstrating the added value of intervention timing, accommodating changing neural dynamics, establishing real-world usability, as well as addressing safety, privacy, and regulatory requirements. JiT-NM provides a framework for investigating whether on-demand, state-based stimulation can complement scheduled treatment or achieve superior outcomes while reducing unnecessary treatment burden.