Neural Activity Signatures of Tumor Infiltration in the Human Brain

ABSTRACT In brain cancer, tumor cells form complex interactions with cells in the brain. Recent studies have revealed a complex interaction between brain cells, or neurons, and tumor cells. Specifically, tumor cells infiltrate healthy brain tissue inducing increased neuron activity and connectivity, particularly among a one class of brain cells (excitatory neurons), making brain tissue more excitable in the process. This increase in excitability is thought to act as an accelerant for increased tumor infiltration into healthy neural tissue. Conversely, another class of neurons, inhibitory neurons, are degraded during tumor cell infiltration. This feedback loop leads to further spread of tumor into healthy brain tissue, particularly as the excitation- inhibition balance essential for normal brain function is tipped toward excitation. This imbalance is thought to be a reason for 40-80% of glioma patients developing epilepsy. However, this detailed, intricate, and devastating process of tumor infiltration has only been detailed through studies in non-human animals and in surgically removed tissue samples, with little to no information on how tumor-induced changes alter activity in the intact human brain. In addition to FDA-approved clinical electrodes, we propose using cutting edge high-resolution microelectrodes we pioneered for use in the human operating room to sample brain activity in, around, and far from tumor. We will use two types: 1) microelectrodes with 1000 channels printed on ultrathin materials to conforming to the surface of the brain; and 2) Neuropixels probes which are microelectrodes which can record single cell activity across >300 channels along a probe close to the thickness of a human hair. Recording neural activity altered by tumor infiltration therefore not only offers unprecedented temporal and spatial resolution relative to current clinical technologies but also fills a scientific gap in capturing ongoing tumor-induced changes in brain activity in the intact human brain. The goal is to provide a high-resolution dynamic physiological map of the tumor and the tumor boundary to better understand tumor infiltration in the intact brain working with patients already scheduled for neurosurgery for the treatment of tumor following fully informed consent. We predict the tumor boundary can be identified by physiological signatures possibly providing new diagnostic tools providing high resolution information for clinical decisions in the future.