Widespread cortical functional disconnection in gliomas: an individual network mapping approach

Abstract

Assessment of impaired/preserved cortical regions in brain tumours is typically performed via intraoperative direct brain stimulation of eloquent areas or task-based functional MRI. One main limitation is that they overlook distal brain regions or networks that could be functionally impaired by the tumour. This study aims: 1) to investigate the impact of brain tumours on the cortical synchronization of brain networks measured with resting-state functional magnetic resonance imaging (resting-state networks) both near the lesion and remotely; 2) to test whether potential changes in resting state networks correlate with cognitive status. The sample included twenty-four glioma patients (mean age 58.1 ± 16.4y) with different pathological staging. We developed a new method for single subject localization of resting state networks abnormalities. First, we derived the spatial pattern of the main resting state networks by means of the group guided independent component analysis. This was informed by a high-resolution resting state networks template derived from an independent sample of healthy controls. Second, we developed a spatial similarity index to measure differences in network topography and strength between healthy controls and individual brain tumour patients. Next, we investigated the spatial relationship between altered networks and tumour location. Finally, multivariate analyses related cognitive scores across multiple cognitive domains (attention, language, memory, decision making) with patterns of multi-network abnormality. We found that brain gliomas cause broad alterations of resting state networks topography that occurred mainly in structurally normal regions outside the tumour and oedema region. Cortical regions near the tumour often showed normal synchronization. Finally, multi-network abnormalities predicted attention deficits. Overall, we present a novel method for the functional localization of resting state networks abnormalities in individual glioma patients. These abnormalities partially explain cognitive disabilities and shall be carefully navigated during surgery.

Presurgical predictors of early cognitive outcome after brain tumor resection in glioma patients

“…This concept refers to the time the tumor growth permits to neuroplasticity processes to compensate for the functional consequences of the lesion ( Gempt et al, 2017 ), and could explain the differential pattern of cognitive impairment in HGG and LGG patients ( Bosma et al, 2007 ) with the latter showing milder deficits or even nearly-normal cognitive functioning for years ( Desmurget et al, 2006 ). Recent studies have found altered functional resting-state networks topography in structurally normal regions outside the tumor or the oedema in gliomas ( Silvestri et al, 2022 ), and impaired functional brain reorganization also in areas not directly related to the tumor or the neurosurgery act ( De Baene et al, 2019 , Jütten et al, 2020 ). In this perspective, clinical manifestation of cognitive deficits could be seen as the net result of the compensatory role of brain plasticity and functional network reorganization processes that have acted while tumor was infiltrating healthy brain tissue.…”

Structural Reorganization Following a Brain Tumor: A Machine Learning Study Considering Desynchronized Functional Oscillations

“…To try and compensate, BOLD correlations between regions would rearrange themselves to spare the functionality. Network similarities and topologies across subjects would change, as found by previous studies [1, 2, 35, 3], without significantly altering their complexity. However, DASs could not disentangle whether the tumor altered the signal and that alteration spread to the DMN or the opposite.…”

“…We also try to answer the origin of these desynchronizations. Current knowledge states that structural closeness is not sufficient to understand disruptions in patterns of functional disconnections [1, 2, 3]. In accordance with this, changes in BOLD dynamics are also not explainable by the spatial overlap nor distance between lesions and DMN (Fig.…”

“…The integrity of resting-state activity of the brain has been associated with cognitive function [6]. Based on this paradigm, numerous studies have explored how functional damage translates into cognitive impairment [4, 5, 1, 35, 3]. As a clear demonstration of the resilience of the brain to damage, all of them reported a continuous rather than binary decrease in cognitive performance.…”

“…Functional networks of brain tumor patients, as obtained from functional magnetic resonance imaging (fMRI), show clear altered patterns of local and global disconnections [1] that follow functional rather than spatial distance to tumor location [2]. Consistent with these findings, a separate study also reported functional abnormalities that overlap with unaffected structural areas [3]. Large-scale theoretical models of functional activity also report differences in inhibitory connections between networks having similar structural features [4, 5].…”