Brain state theory as a comprehensive model for addressing the "non-eloquent" brain in glioma surgery.

Glioma surgery often results in significant cognitive deficits that magnify patient morbidity and mortality. Traditional classifications of brain regions as "eloquent" or "non-eloquent" can oversimplify the complexity of cortical and sub-cortical function and its structure-function relationships, preventing our ability to limit the cognitive footprint of brain surgery. The notion that everything is eloquent in the brain is impractical, as deeming the entire brain off-limits is an unrealistic stance that would render glioma surgery unfeasible. However, even interventions in the 'non-eloquent' areas can result in personality changes and cognitive dysfunction. The Brain State Theory provides a more nuanced perspective by emphasizing that brain activity is governed by distinct brain states: patterns of neuronal firing that reflect cognitive and neurological function. While there are nearly countless possible brain states, only a fraction are utilized in normal physiology, influenced by structural connectivity, neurotransmitters, and energy constraints. Highly connected hub regions, which facilitate multiple brain states, align closely with areas traditionally considered "eloquent." Resection of these brain hubs hinders the ability to maintain certain states, often leading to cognitive and neurological deficits that may not be immediately apparent in standard postoperative assessments but emerge in real-life scenarios. Factors such as structural connectivity, neurotransmitters, and energetic landscape impact the probability of brain states, as some require extensive coordination and more energy. Highly connected regions, or hubs, are crucial in various states. The surgical preservation of brain function should extend beyond a binary classification of eloquence. Instead, surgical planning should prioritize protecting key hubs and networks to sustain the maximum number of brain states and minimize long-term morbidity. Here, we provide a significant discussion of brain states as it relates to clinical neuroscience and for the operative neurosurgeon. Understanding these principles will refine neurosurgical decision-making, optimizing patient outcomes by balancing oncological control with functional preservation.