Despite significant improvements in our understanding of brain diseases, many barriers remain. Cognitive neuroscience faces four major challenges: complex structure–function associations; disease phenotype heterogeneity; the lack of transdiagnostic models; and oversimplified cognitive approaches restricted to the laboratory. Here, we propose a synergetics framework that can help to perform the necessary dimensionality reduction of complex interactions between the brain, body, and environment. The key solutions include low-dimensional spatiotemporal hierarchies for brain-structure associations, whole-brain modeling to handle phenotype diversity, model integration of shared transdiagnostic pathophysiological pathways, and naturalistic frameworks balancing experimental control and ecological validity. Creating whole-brain models with reduced manifolds combined with ecological measures can improve our understanding of brain disease and help identify novel interventions. Synergetics provides an integrated framework for future progress in clinical and cognitive neuroscience, pushing the boundaries of brain health and disease toward more mature, naturalistic approaches.

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