Distributed changes of the functional connectome in patients with glioblastoma

Karl-Heinz Nenning,Martha Marko,Gregor Kasprian,Christoph Bock,Sophia Stoecklein,Adelheid Wöehrer ,Hesheng Liu,Ernst Schwartz,Georg Widhalm,Thomas Roetzer,Christine Marosi,Nikolaus Fortelny,Anna Grisold,Polina Golland,Julia Furtner,Daniela Prayer,Johannes A Hainfellner,Fritz Leutmezer,Barbara Kiesel,Georg Langs

doi:10.1038/s41598-020-74726-1

Abstract

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.

Highlights

The tumour edge within macroscopically normal brain p arenchyma[6,7,8]
Across all patients and for all seven resting-state networks, we found that functional proximity to the tumour correlated stronger with anomaly than spatial distance (Fig. 2b)
We found patterns of network alterations across all patients irrespective of tumour size or location

Summary

Introduction

The tumour edge within macroscopically normal brain p arenchyma[6,7,8]. In addition to structural imaging, taskbased functional MRI (fMRI) has been recognized as a relevant tool for preoperative mapping of eloquent cortical function[9]. Task-independent resting-state fMRI is gaining increased attention for its ability to evaluate functionally relevant areas even in impaired or non-compliant patients[12,13]. We hypothesized that network anomalies are not restricted to areas of spatial tumour involvement but distributed more globally and follow a functional rather than a spatial distance to the tumour. To answer this question, we quantified tumour-induced network anomalies of patients with GBM based on their deviation from network connectivity of a healthy control population (Fig. 1) and disentangled their spatial and functional relations to the brain tumour

Methods

Results

Conclusion