CNSC-12. PATHOLOGY SPECIFIC, PHARMACOLOGICALLY REVERSIBLE LOSS OF NEURONAL FUNCTION IN HUMAN GLIOMAS

Abstract

Abstract Prior evidence has demonstrated that neuronal activity is preserved within glioma-infiltrated cortex and maintains the ability to engage in task specific computations albeit with information loss. These findings support a potential therapeutic target to rescue cognitive impairments seen in nearly all afflicted patients if neuronal activity can be recovered. We developed an in vivo human behavioral and electrophysiological model to assess neuronal population tuning responses within primary sensory cortex including the decodability of stimuli and task-related changes in population spiking in a cohort of 14 human patients undergoing awake resection. We placed high-density electrode arrays to record human local field potentials from gliomas projecting to the cortical surface. We next designed a static sensory detection threshold task, stimulating with a tachometer at two different face and hand sites totaling 11,200 trials while recording from macroelectrode cortical contacts over both tumor-infiltrated (50 electrodes) and normal appearing cortex (52 electrodes). In tumor-infiltrated cortex, the ability to decode the site of stimulation using the oscillatory power in both theta (4-8 Hz) and gamma (32-70 Hz) bands was reduced compared to normal appearing cortex. However, tumor-infiltrated cortex-maintained selectivity between hand and face stimulation. Targeted next-generation tumor sequencing uncovered novel molecular targets of glioma-neuronal integration. The degree of loss of selectivity correlated with WHO grade and pathology. WHO grade 4 tumors and oligodendrogliomas compared to astrocytomas demonstrating greater loss of selectivity. Gabaergic agonist has been postulated to restore neuronal selectivity in aging and neurodegenerative disease. Therefore, we next computed GABA agonist dose (estimated by time off Propofol and beginning of behavioral testing). Higher concentrations of GABA agonist correlated with improved theta band selectivity and decodability. These results suggest that loss of neuronal computations in glioma-infiltrated cortex is caused by loss of neuronal selectivity and is both tumor selective and pharmacologically reversible.