The DMN mask consisted of the medial prefrontal cortex, the hippocampus, and the IPL (specifically, the angular

gyrus and supramarginal gyrus). The SMN mask consisted of the precentral and postcentral gyri, the supplementary motor area (SMA), and the paracingulate cortex. The FPN mask consisted of the precentral gyrus and middle frontal gyrus. FMRI data sellectchem processing was carried out using FEAT Version 5.98. Higher level analysis was carried out using OLS (ordinary least squares) simple mixed effects. We thresholded Z-statistic images using clusters determined Inhibitors,research,lifescience,medical by Z > 2.0 and a (corrected) cluster significance threshold of P= 0.05 (Worsley 2001). We used a lower statistical threshold (Z > 2.0) for the PPI analysis because of the low power inherent to this type of analysis due to possible multicollinearity Inhibitors,research,lifescience,medical between the physiological and/or psychological regressors and the 17-DMAG interaction term. Results Participant demographics (Table S1) Thirteen participants were initially enrolled. One participant was disqualified because he could feel the stimulation at the lowest possible current of 10 μA. Another potential participant was unable Inhibitors,research,lifescience,medical to perform the fMRI experiment due to claustrophobia. Data were therefore collected and analyzed for eleven participants. Behavioral

data (Table S1) Mean ratings on the STAI did not differ significantly before and after the experiment (before: 21.9 ± 3.9; after: 22.6 ± 3.1; t18= .428 P= .674). Only one participant reported awareness of any sensation during the scan; she felt a constant “sensation” on her

left earlobe during the entire duration of the scan, at the location where Inhibitors,research,lifescience,medical the headphones pressed on her earlobe (but not at the electrode site). “On” versus baseline voxel-wise analysis (Figs. 1, ​,22 and Table 1) Figure 1 Regions of decreased brain activity as a result of cranial electrotherapy stimulation (CES) for 0.5-Hz stimulation (blue), 100-Hz stimulation (yellow), and regions of overlap between the two frequencies Inhibitors,research,lifescience,medical (green). Figure 2 Regional brain deactivation Anacetrapib (BOLD percentage signal change ± SEM) associated with 0.5- and 100-Hz “on” CES stimulation versus baseline, based on local maxima from the voxel-wise analysis. Table 1 Local maxima for regional deactivation from cranial electrotherapy stimulation (CES). At both frequencies, participants exhibited deactivation in frontal, parietal, and posterior midline regions. A total of 0.5-Hz stimulation was associated with decreased activation in regions including the left SMA, bilateral precentral and postcentral gyri, right posterior cingulate cortex, right lateral occipital cortex, and bilateral precuneus. A total of 100-Hz stimulation was associated with decreased activation in regions including the right/left SMA, right supramarginal gyrus, right superior parietal lobule, and left superior frontal gyrus.