Mild traumatic brain injury (MTBI) is a substantial public health problem, representing 75% of traumatic brain injury cases [1]. Difficulty in working memory (WM) and attention is frequently reported in patients with TBI [2]. The default mode network (DMN), typically comprises the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and medial prefrontal cortex (mPFC) nodes, is a well-established network that is active at rest and suppressed during tasks that require attention and decision making [3]. Several functional MRI (fMRI) studies revealed disruption of resting state DMN connectivity and alterations of brain activation during WM task in MTBI patients, but very few studies addressed on the task-related deactivation in MTBI [4]. In this study, we investigated the MTBI effect on the DMN, by means of both resting state functional connectivity and task-related deactivation, in a group of MTBI patients and further evaluated the rest-task relationship in these patients.This study was approved by the local research ethics committee. All participants provided written informed consent. 36 patients (male/female: 11/25; age: 33.6±8.6; 22-49 years) fulfilling the MTBI criteria by the American Congress of Rehabilitative Medicine [5] and 24 control subjects (male/female: 7/17; age: 34.5±8.9; 21-49 years) were recruited. All participants underwent resting state fMRI and task fMRI (1-back verbal working memory task; block design; 30 trials) sequentially in a 3T MRI scanner (Discovery MR750; GE Healthcare, Milwaukee, Wis) within 1 month after injury. The fMRI scans used T2*-weigthed echo-planar imaging with the following parameters: TR/TE, 3000/35 msec; flip angle, 90°; FOV, 230 mm² ; matrix size, 64 x 64; slice thickness, 3 mm; 40 slices; intersection gap, 1 mm; 320 brain volumes for resting state fMRI; 70 brain volumes for task fMRI). Resting state DMN connectivity was estimated by a seed-based correlation method [7] with the seed defined by a 5-mm diameter sphere centered at PCC (table 1) [6]. The brain activity (represented by beta values) during the 1-back WM condition was obtained by using the general linear model approach in SPM8 package. The areas showing negative beta values were considered as deactivation regions. ROI analysis was carried at the core regions of the DMN, including PCC, IPL and mPFC (table 1) [8,9] within the functional connectivity maps and 1-back brain activity maps. We used one sample t test for the first level group analysis, two sample t test for the second level group comparison and Pearson’s correlation coefficient for correlation analysis in the study.The resting state DMN connectivity in MTBI patients and normal controls were presented in the first two rows of Figure 1. Voxel wise group comparison indicates that the patients had increased connectivity to the left inferior frontal gyrus compared to the normal controls (Figure 1B). However, ROI analysis of the connectivity within the PCC, MPFC and bilateral IPCs revealed no significant difference between patients and healthy controls. Figure 2 shows that the brains deactivate predominantly in the DMN regions during 1-back WM condition both in the patients and healthy controls. The patients had more pround deactivation compared to the healthy controls by visual comparison. ROI analysis confirmed that the patients had more deactivation in right IPL (p = 0.047) and left IPL (p = 0.00012). Correlation analysis revealed that there was significant correlation (r = -0.638, p = 0.00079) between the mean connectivity and the mean deactivation within the 4 DMN ROIs in healthy controls, while no correlation was found in the MTBI patients (r = 0.143, p = 0.405).In the study, we found differences in both resting state DMN connectivity and task-related deactivation between MTBI patients and healthy controls. Although no significant within-network difference was found in the DMN connectivity between patients and controls, there was increased extra-network connection to the left inferior frontal gyrus in the patients. Significantly more profound task-related deactivation was found in the patients, especially in bilateral IPCs. Increased task-related deactivation may imply the patients need more attention on performing the WM tasks. Furthermore, significant correlation between resting state connectivity and task-related deactivation of DMN was found in healthy controls and this rest-task correlation was disrupted in the patients.