Altered Resting-State Functional Connectivity in the Hand Motor Network in Glioma Patients

Abstract

To examine the functional connectivity of the primary and supplementary motor areas (SMA) in glioma patients using resting-state functional MRI (rfMRI). To correlate rfMRI data with tumor characteristics and clinical information to characterize functional reorganization of resting-state networks (RSN) and the limitations of this method. This study was IRB approved and in compliance with Health Insurance Portability and Accountability Act. Informed consent was waived in this retrospective study. We analyzed rfMRI in 24 glioma patients and 12 age- and sex-matched controls. We compared global activation, interhemispheric connectivity, and functional connectivity in the hand motor RSNs using hemispheric voxel counts, pairwise Pearson correlation, and pairwise total spectral coherence. We explored the relationship between tumor grade, volume, location, and the patient's clinical status to functional connectivity. Global network activation and interhemispheric connectivity were reduced in gliomas (p < 0.05). Functional connectivity between the bilateral motor cortices and the SMA was reduced in gliomas (p < 0.01). High-grade gliomas had lower functional connectivity than low-grade gliomas (p < 0.05). Tumor volume and distance to ipsilateral motor cortex demonstrated no association with functional connectivity loss. Functional connectivity loss is associated with motor deficits in low-grade gliomas, but not in high-grade gliomas. Global reduction in resting-state connectivity in areas distal to tumor suggests that radiological tumor boundaries underestimate areas affected by glioma. Association between motor deficits and rfMRI suggests that rfMRI may accurately reflect functional changes in low-grade gliomas. Lack of association between rfMRI and clinical motor deficits implies decreased sensitivity of rfMRI in high-grade gliomas, possibly due to neurovascular uncoupling.

Resting-state Functional Magnetic Resonance Imaging in Presurgical Functional Mapping

“…It has been suggested that altered RS-fMRI functional connectivity in the SM network can occur on the same basis in patients with brain tumors 49 . Although neurovascular uncoupling could be a contributor in the cases that fail our RS-fMRI analysis, our overall failure rate is low, and, in most cases, we can identify a specific cause for this failure, typically, patient motion or sedation.…”

The Resting-State Functional Magnetic Resonance Imaging Regional Homogeneity Metrics—Kendall's Coefficient of Concordance-Regional Homogeneity and Coherence-Regional Homogeneity—Are Valid Indicators of Tumor-Related Neurovascular Uncoupling

“…Very recently, a few publications (Agarwal et al, 2016a(Agarwal et al, , 2016bMallela et al, 2016) have demonstrated similar impaired BOLD responses in rsfMRI due to brain tumor-induced NVU. Studies by Agarwal et al (2016b) have demonstrated that tumor-related NVU can adversely affect the restingstate BOLD signal similar to its effect on task-based BOLD activation.…”

“…Another study demonstrated that brain tumor-related NVU may also similarly affect rsfMRI at ultrahigh field (7 Tesla) despite the higher signal-to-noise ratio afforded by higher field strength (Agarwal et al, 2016a). Mallela et al (2016) have examined the correlation of rsfMRI data with tumor characteristics and clinical information to characterize functional reorganization of resting-state networks (RSNs) and the limitations of this method in high-grade gliomas due to NVU. Thus, practical application of rsfMRI for presurgical planning should take into account the possibility of NVU to ensure mapping accuracy.…”

Limitations of Resting-State Functional MR Imaging in the Setting of Focal Brain Lesions

“…51 Because of its easy implementation and less stringent requirements for patient compliance, rsfMRI has been attracting wide attention for use as a preoperative mapping tool. 52,53 However, rsfMRI also suffers from similar important clinical limitations of false negative BOLD signals due to brain-tumor related NVU; 54–56 thus, to use rsfMRI as a reliable pre-surgical tool, it becomes all the more important to study NVU in cases of focal resectable brain lesions such as tumors to evaluate its effects on rsfMRI.…”

“…56 Mallela and colleagues examined the correlation of rsfMRI data with tumor characteristics and clinical information to characterize functional reorganization of RSNs and the limitations of rsfMRI in high-grade gliomas due to NVU. 54 …”