Abstract

INTRODUCTION: It has been shown recently that infiltration of gliomas into healthy neural tissue alters local neuronal spiking patterns, leading to circuit dysfunction. It is unknown, however, if glioma infiltration also impacts the coordination of local neuronal computations with other networks during behavioral tasks. Cross-frequency coupling of high gamma (HG) (80-150 Hz) amplitude with theta (Th) (4-7Hz) phase is a well-established mechanism for this type of neural integration. METHODS: Patients (n = 13) with dominant hemisphere perisylvian gliomas were intraoperatively implanted with an ECoG grid and performed a picture naming task. Electrodes overlying regions of tumor infiltration and those overlying normal parenchyma were identified using the T2-FLAIR signal. Following a widely accepted method, Kullback–Leibler (KL) divergence of HG amplitude distribution over Th phases from a uniform distribution was used to quantify Th-HG coupling of each electrode during speech production. Statistical significance was determined by comparing to a null distribution of KL divergence values corresponding to the original HG time series randomly cut in ten places and permuted, while preserving the theta time series. This destroys the cyclostationarity of theta-gamma coupling while preserving other non-stationarities. RESULTS: 43 out of 114 electrodes overlying normal parenchyma and 104 out of 300 electrodes overlying tumor-infiltrated regions exhibited significant Th-HG coupling after FDR correction. Electrodes overlying tumor regions and normal parenchyma had similar spatial coverage at the group level. Electrodes with Th-HG coupling at a preferred theta phase of π radians exhibited greater coupling. No significant difference in KL divergence was found between tumor-overlying electrodes and non-tumor overlying electrodes at the group level. CONCLUSIONS: Th-HG phase-amplitude coupling is preserved in glioma-infiltrated brain tissue during speech production. This suggests that glioma-infiltrated tissue participates in the coordination of spatially and temporally distributed processes during complex behaviors.

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