Adult survivors of pediatric brain tumors are likely to experience disrupted cognitive functions [1]. Currently, the specific neural and functional substrates associated with pediatric brain tumor and its treatment is not well understood in the adult survivors. Additional examination of the interruption or reorganization of communications among the regions involving the specific cognitive functions is needed. In this study, resting-state functional MRI (rs-fMRI) was used to investigate the functional connectivity (FC) of adult survivors of pediatric brain tumors using independent component analysis (ICA) to further elucidate FC changes associated to the observed lower cognitive performance [2].

Participants: Sixteen adult survivors of pediatric brain tumors (10 females, 17~34 years) participated in this study. All survivors were diagnosed and had been treated for pediatric posterior fossa brain tumors on average 14.9 years prior to the exam. Written consent was obtained from all adult participants. None of the survivors was found to have the history of tumor progression or recurrence, neurofibromatosis or other significant neurological insult. Sixteen healthy volunteers with matched age and gender (10 females, 18~34 years) were recruited as controls. MRI: MRI data were collected on a 3T MR scanner (Siemens Tim/Trio) using a 12-channel head coil. A routine clinical protocol was applied for each participant to assess for any abnormalities. In addition, T1-weighted sagittal anatomic images were acquired using a 3D MP-RAGE sequence. rs-fMRI data were acquired with a gradient-recalled T2*-weighted EPI sequence with a total of 129 volumes. Imaging parameters included: FOV=240 mm, 40 slices, 3-mm slice thickness and no slice gap, TR=2130 ms, TE=30 ms, FA =90 degrees and resolution=3 x 3 x 3 mm3. Image Processing and Analysis: All rs-fMRI data were preprocessed using the software of Data Processing Assistant for Resting-State fMRI with the approach of subject order independent group ICA (SOI-GICA [3]). We selected independent components (ICs) of interest based on the priori knowledge of the brain regions that are considered to be the parts of executive functional network (Fig. 1). Each selected IC was given its own mask generated based on the respective network. ROIs were defined based on the observation of the significant difference between the survivor and control groups. Two sample t-test analysis was performed on Z maps of each IC to obtain significantly difference between the two groups. The selected ROIs were used to the subsequent functional network analysis [4]. Calculation of Functional Connectivity: Functional Connectivity Toolkit in the REST software [5] was used to compute FC. The correlation coefficient of the time series between each pair of regions of interest (ROIs) was used to describe the strength of each set of FC. To evaluate FC within each group, one sample t-test (p<0.01) was carried out on each pair of ROIs in the survivor and control groups, respectively. When the average correlation coefficient between a pair of ROIs was greater than 0.3, it was considered that there is a significant or effective FC between two brain regions.Statistically significant differences between survivor and control groups were found in all five selected frontal functional networks, i.e. right executive control network (RECN), left executive control network (L-ECN), salience network (SN), anterior (ADMN) and posterior (PDMN) portions of default-mode network (DMN), respectively. 11 ROIs exhibited statistically significant differences between the two groups (Fig. 2). Furthermore, increased z-scores were found in 7 ROIs in survivors compared with controls. We further examined the reorganization of FCs in survivors in terms of the number of connected areas and the extent of the activation in these connected regions. Fig. 3 shows the averaged numbers of FCs in survivors and controls, respectively. There are 10 effective FCs observed in controls. In comparison, 25 effective FCs were observed in the survivor group. Among these 25 effective FCs, 16 were only found in the survivors but not in the control group, while only one effective FC found in the control group but not seen in the survivor group. Therefore, 9 effective FCs were found in both groups, in which 7 have increased strength, or increased level of the correlations, in survivors, while the other 2 FCs showed decreased strength.Adult survivors of pediatric brain tumors exhibited altered FC in the frontal region. The number of effective FC observed in survivors was higher compared to the controls, with increased strength in survivors. The hyperconnectivity may be attributed to the continuous need of a higher level of effort in the survivors which may result in recruiting more brain regions through the connectivity of frontal functional network.