Neural circuits, cognition, and behavior in diffuse glioma

Diffuse gliomas arise within and become functionally integrated into neural circuits, establishing bidirectional interactions between malignant cells and the surrounding brain. Neuronal activity promotes glioma growth and progression, while glioma cells remodel the excitability, connectivity, and functional organization of the neural circuits they infiltrate. Pathological excitation-inhibition imbalance can impair cortical information processing, while tumor infiltration simultaneously disrupts, preserves, and induces adaptive reorganization of distributed functional networks. Language processing provides a well defined framework for examining these competing effects because language processing depends on distributed cortical and subcortical networks whose organization can be interrogated using neuroimaging, electrophysiology, and direct cortical stimulation. The pattern and severity of glioma-associated language dysfunction reflect the interaction among tumor location, growth kinetics, molecular and histopathological features, white matter involvement, and the capacity for adaptive redistribution of function within ipsilateral and contralateral networks. Slowly growing gliomas can permit substantial functional reorganization, whereas rapidly infiltrating tumors may constrain the time and biological substrate available for effective network adaptation. In this review, we examine reciprocal glioma-neural circuit interactions, with particular emphasis on the mechanisms of glioma-associated neuronal hyperexcitability and the disruption, preservation, and adaptive remodeling of language networks.