The selfish network: how the brain preserves behavioral function through shifts in neuronal network state.

Neuronal networks possess the ability to regulate their activity states in response to disruptions. How and when neuronal networks turn from physiological into pathological states, leading to the manifestation of neuropsychiatric disorders, remains largely unknown. Here, we propose that neuronal networks intrinsically maintain network stability even at the cost of neuronal loss. Despite the new stable state being potentially maladaptive, neural networks may not reverse back to states associated with better long-term outcomes. These maladaptive states are often associated with hyperactive neurons, marking the starting point for activity-dependent neurodegeneration. Transitions between network states may occur rapidly, and in discrete steps rather than continuously, particularly in neurodegenerative disorders. The self-stabilizing, metastable, and noncontinuous characteristics of these network states can be mathematically described as attractors. Maladaptive attractors may represent a distinct pathophysiological entity that could serve as a target for new therapies and for fostering resilience.