Multiscale analysis of the mechanisms of cortical information loss in diffuse glioma

Project Summary/Abstract Recent years have seen the simultaneous eruption of the field of cancer neuroscience and the expansion of the role of intraoperative neurophysiological monitoring to guide safe maximal neurosurgical resection of intracranial pathologies, including gliomas. This enables an unprecedented study of the effects of tumors on the electrophysiological correlates of human cognition. Breakthrough translational technologies such as microelectrode arrays and the Neuropixel probe have only improved our investigations' granularity, narrowing the capabilities gap between rodent and human researchers. Despite the nascent ascendancy of cancer neuroscience as a field, we know very little, in humans and generally, about the electrophysiologic mechanisms by which gliomas affect neuronal information processing on either population or single neuron levels and how this is affected by tumor grade and pathology. We do, however, clinically observe that cognitive dysfunction is present in most glioma patients, which is an independent predictor of worsened outcomes, highlighting the pressing need better to understand glioma cells’ functional integration into cortical circuits. Thus, by answering the central question of our project proposal – what are the population and single neuron level mechanisms by which various gliomas affect cognition? – we can potentially satisfy the dual purpose of the NINDS, furthering our fundamental understanding of neurophysiology and generating ideas for potential novel therapeutics for gliomas. We aim to accomplish this by administering a newly developed somatosensory discrimination task to patients with gliomas undergoing awake brain surgery for resection while recording brain activity with both macroelectrode grids and microelectrode arrays. We will then employ established and novel electrophysiologic techniques to probe the electrophysiologic signature of the glioma-neuron interface. Our institutional environment is uniquely positioned to answer these questions due to its status as an international referral center for glioma surgery and its current nation-leading efforts in translating novel recording technologies for human intraoperative experimentation. During my fellowship, I will participate in fine-tuning intraoperative data acquisition and have the personnel and computing resources to perform electrophysiological analyses on the recorded signals. This will advance my understanding of lab management, novel electrode technology, and data science, with the end goal of increasing my capabilities of running my own lab as an independent surgeon-scientist in the near future.