The coupling between neuronal activity and adjacent microvascular responses is often disrupted by brain tumors or other focal brain lesions, resulting in false negative BOLD fMRI activation that can lead to inadvertent eloquent cortical resection and resultant postsurgical neurological disability.¹ This phenomenon of neurovascular uncoupling (NVU) is a limitation of clinical fMRI. In a previous study using task-based motor activation (tbfMRI) and breath hold cerebrovascular reactivity (BH CVR) mapping, BH CVR detected NVU in low-grade perirolandic tumors.² The objective of this study was to demonstrate that such NVU can be detected on resting state fMRI (rsfMRI) similar to previously noted findings on tbfMRI and BH CVR maps.Seven brain tumor patients undergoing routine clinical presurgical motor mapping with BOLD fMRI were included in this IRB-approved study. Each patient demonstrated evidence of potential NVU with abnormally decreased or absent tbfMRI activation and corresponding decreased BH CVR in the primary sensorimotor cortex of the ipsilesional) hemisphere without corresponding motor deficits.² Imaging was performed on a 3.0 T Siemens Trio MRI with a 12-channel head matrix coil. Imaging protocol included a 3D T1 MPRAGE (TR=2300 ms, TI= 900 ms, TE= 3.5 ms, 9° FA, 24-cm FOV, 256x 256x176 matrix, slice thickness 1 mm) for structural imaging and multiple 2D GE-EPI T2* weighted BOLD sequences for task, BH & resting functional imaging (TR=2000 ms, TE=30 ms, 90° FA, 24-cm FOV, 64x64x33 matrix, 4 mm slice thickness with 1 mm gap between slices, interleaved acquisition). 180 volumes were acquired in a 6 minute rsfMRI scan and 130 volumes were acquired in a 4 minute 20 sec BH scan. The motor tasks used were a vertical tongue movement task and a bilateral simultaneous sequential finger tapping task (each 3 minutes long with 30 seconds blocks of rest alternating with 30 seconds blocks of motion). The details of the BH task are described in a previous publication.² Instructions for all tasks were visually cued. Z-score maps for the motor and BH tasks were obtained using general linear model (GLM) analysis using AFNI software (reflecting motor activation vs. rest and hypercapnia vs. baseline, respectively). Motor activation maps were further analyzed using Amplitude Measured as a Percentage of Local Excitation (AMPLE) thresholding of 50% (i.e., only voxels with Z scores above 50% of a local cluster Z score maximum were considered “active”).³ Ipsilesional (IL) and mirror contralesional (CL) regions of interest (ROI) were used. Independent component analysis (ICA) of rsfMRI data was performed with MATLAB GIFT toolbox using 30 components to identify the sensorimotor network in each case. The same IL and CL ROIs were used for all three BOLD maps (i.e. tbfMRI, BH CVR, & ICA sensorimotor network component map) and a two-tailed t-test was performed to determine whether statistically significant differences between the two sides were present that were consistent with NVU. Group analysis revealed decreased motor activation (p=0.006) in IL compared to CL ROIs and similar IL signal decreases on BH CVR maps (p=0.02), consistent with NVU. Fewer voxels displaying synchronized resting state BOLD signal were seen in IL compared to CL ROIs within the ICA-derived sensorimotor component (p=0.004). Single subject data for one patient are provided in Figure 1.Our study demonstrates evidence of significantly decreased IL BOLD signal compared to CL mirror regions on tbfMRI, rsfMRI and BH CVR maps within the sensorimotor network in a group of perirolandic primary glioma patients. Since these patients did not exhibit corresponding clinical motor deficits, these IL BOLD signal decreases are indicative of NVU.Our study suggests that NVU in the sensorimotor network can be similarly detected on tbfMRI, rsfMRI and BH CVR maps. This is the first study, to our knowledge, that has demonstrated similar brain tumor-related NVU in both tbfMRI and rsfMRI.