Distributed changes of the functional connectome in patients with glioblastoma

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.

Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival

“… 1 , 2 In addition to distally seeded cells, given the highly connected nature of the brain, changes in the tumor microenvironment may elicit subsequent functional changes in seemingly healthy regions. 3 , 4 These effects have been observed using resting-state functional MRI (rs-fMRI), which utilizes the fluctuations in blood-oxygen-level-dependent (BOLD) signals to identify brain regions that are temporally correlated. 3 , 4 This process, termed functional connectivity (FC), can reveal the network similarity of spatially noncontiguous areas, enabling their study in healthy and diseased brains.…”

“… 3 , 4 These effects have been observed using resting-state functional MRI (rs-fMRI), which utilizes the fluctuations in blood-oxygen-level-dependent (BOLD) signals to identify brain regions that are temporally correlated. 3 , 4 This process, termed functional connectivity (FC), can reveal the network similarity of spatially noncontiguous areas, enabling their study in healthy and diseased brains. 5–9 Few studies have focused on the global cortical impact of glioma using FC.…”

“… 5–9 Few studies have focused on the global cortical impact of glioma using FC. 3 , 4 , 10 , 11 However, recent studies have demonstrated bilateral FC disruptions in glioma patients. One study demonstrated whole-brain FC alterations related to underlying tumor biology and cognitive impairments, with higher grade glioma resulting in greater deficits.…”

“… 3 Another study suggested that FC changes in resting-state networks are due to localized within-network damage, but this remains poorly understood. 4 …”

Dissociation of structural and functional connectomic coherence in glioma patients

“…Nenning et al 51 recently showed in longitudinal rs-fMRI measurements of six patients with glioblastoma, that longitudinal whole-brain FC aberrations reflected even the disease course, with functional network deterioration preceding tumor reoccurrence by two months. Our study furthermore suggests that at the time of disease manifestation, structural connectomic aberrations might be more pronounced in glioma patients than functional connectomic alterations, which may relate to IDH-mutation status.…”