Decreased Hand Motor Resting-State Functional Connectivity in Patients with Glioma: Analysis of Factors including Neurovascular Uncoupling

Abstract

R esting-state functional MRI is a technique that allows for the generation of functional MRI data while the patient is at rest (1). This technique depicts low-frequency blood oxygenation level-dependent (BOLD) signal fluctuation in the brain at rest and extracts regions with highly correlated resting-state time courses to form larger-scale "resting-state networks" that correspond to known functional networks and anatomic areas, including visual, motor, and language pathways (2,3). Resting-state functional MRI offers substantial potential as a clinical tool for the treatment of patients with brain tumors. Compared with traditional paradigm-driven functional MRI, resting-state functional MRI obviates task compliance from patients who are functionally impaired, allows the parallel assessment of functional networks in place of serial assessment across lengthy imaging sessions (2), and has been shown to more accurately identify anatomic correlates of functional regions (4,5). Resting-state functional MRI has also been successfully piloted in periand intraoperative settings (6-8).BOLD functional MRI studies have shown that brain tumors exert local effects that reduce BOLD functional MRI activation, through a hypothesized uncoupling of tumor vascular responses and neural activity:

Glioma-Induced Disruption of Resting-State Functional Connectivity and Amplitude of Low-Frequency Fluctuations in the Salience Network

“…Higher glioma grades were associated with decreased overall SN RSFC compared with controls, possibly due to a combination of factors including true-positive changes due to increased tumor infiltration and disrupted functional reorganization, 9,20 as well as false-negative signals due to tumorinduced neurovascular uncoupling that may have artifactually decreased RSFC due to altered hemodynamics. 22,36 These findings warrant cautious clinical interpretation of rsfMRI findings in high-grade gliomas.…”

“…We hypothesized that there would be decreased average SN RSFC and altered ALFF in patients with gliomas compared with healthy controls. Recent studies have acknowledged that gliomas have variable effects on network integrity based on lesion location and proximity to network ROIs, [20][21][22] and unilateral gliomas can be associated with plasticity in both the ipsilateral and contralateral hemispheres. 11,17 Research also supports differences in resting-state network reorganization in aggressive high-grade gliomas compared with slower-growing low-grade gliomas.…”

Asymmetric tumor‐related alterations of network‐specific intrinsic functional connectivity in glioma patients

“…A further limitation is the fact that neurovascular uncoupling occurs in tumor patients, which is known to impact the Blood‐Oxygenation Level Dependent (BOLD) signal by tumor related changes of the neurovasculature and brain perfusion (Sun et al, 2020). Thus, it should be considered that RSFC alterations in patients might be an expression of tumor‐related alterations of brain perfusion and neurovascular uncoupling.…”

Inhibitory Effect of miR-339-5p on Glioma through PTP4A1/HMGB1 Pathway

“…Glioma is a process of multifactor participation and multistep accumulation, with potential risk factors including genetic factors, specific gene polymorphism, viral infection, carcinogens of the nervous system, and ionizing radiation [3]. For patients with glioma of different grades, low-grade glioma usually has good prognoses, with a 10-year OS rate of 47% [4]. However, the prognosis is usually poor for high-grade glioma, especially for glioblastoma multiforme, with a high degree of malignancy and a 5-year OS rate of less than 3% [5].…”