HYPOTHESIS AND THEORY article
Front. Neurol.
Sec. Headache and Neurogenic Pain
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1587296
This article is part of the Research TopicManagement of migraine in patients with coexistent conditions or comorbidities: from classic to novel therapiesView all 4 articles
A Hybrid Digital-4E Strategy for Migraine-Depression Therapy: A Medical Hypothesis on an AI-Driven, Neuroadaptive, and Exposome-Integrated Approach
Provisionally accepted
- Oslo Metropolitan University, Oslo, Norway
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The co-occurrence of migraines and depression presents a critical clinical challenge, affecting up to 50% of individuals with either condition. This comorbidity leads to greater disability, higher healthcare costs, and poorer treatment outcomes than either disorder alone. Despite a bidirectional pathophysiological relationship, current models remain static and fragmented, treating each condition separately. This paper proposes a Hybrid Digital-4E Strategy, deployed on an AI-driven neuroadaptive digital health platform, integrating closedloop therapy, digital phenotyping, and exposome tracking to enable real-time, personalized care.Grounded in the 4E cognition framework (Embodied, Embedded, Enactive, and Extended cognition), this strategy reconceptualizes migraine-depression as an interactive system rather than two separate conditions. The platform integrates real-time biomarker tracking, neuromorphic AI, and precision environmental analytics to dynamically optimize treatment.Adaptive chronotherapy, brain-computer interfaces (BCIs), and virtual reality (VR)-based neuroplasticity training further enhance intervention precision.A closed-loop, AI-driven neuroadaptive system could improve outcomes by enabling early detection, real-time intervention, and precision care tailored to individual neurophysiological and environmental profiles. Addressing AI bias, data privacy, and clinical validation is crucial for implementation. If validated, this Hybrid Digital-4E Strategy could redefine migraine-depression management, paving the way for precision neuropsychiatry.
Keywords: Migraine-Depression Comorbidity, 4E cognition, Digital Health, AI-driven Therapy, closed-loop systems, Exposome, precision medicine, Neuroadaptive
Received: 04 Mar 2025; Accepted: 29 Apr 2025.
Copyright: © 2025 Gazerani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Parisa Gazerani, Oslo Metropolitan University, Oslo, Norway
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.