For many brain disorders, the progression of pathological changes at the molecular and cellular level poorly correlates with their phenotypic presentation. There are many examples for which behavioral functionality is maintained even following drastic regional neural loss. Neural networks can undergo fundamental changes very early in neurodegenerative, neuro-immunological as well as psychiatric disorders in a disease-transcending manner, even in regions not yet affected by the underlying molecular and cellular pathophysiology. These early changes are often maladaptive and associated with hyperactive neurons, which marks the starting point for activity-dependent neurodegeneration. Networks undergo plastic changes not necessarily aiming at optimizing the phenotypic outcome, but by systems dynamics governed in a stability retaining manner. These states can be formalized as self-balancing attractors, based on systems-theoretical framework. These early neural network changes are a distinct (patho-)physiological entity which offers new therapeutic targets for preventing the manifestation of disease and fostering resilience.
