5 sec, echo time (TE) = 21 msec, flip angle = 75°, matrix = 64 × 64, field-of-view = 24 × 24 cm, in-plane voxel size 3.1 × 3.1 mm, slice thickness 3 mm, 1-mm intervening spaces, and 34 total slices). We obtained matched-bandwidth T2-weighted images for functional image registration. We also obtained higher resolution T1-weighted three-dimensional magnetic resonance images with 1-mm3 voxel size for each participant to provide detailed Inhibitors,research,lifescience,medical brain anatomy. For these, magnetization-prepared rapid gradient echo (MP-RAGE) sequences were used, with the parameters: TE = 2.26 msec, TR = 1900 msec, TI

= 900 msec, flip angle = 9.00°, field-of-view = 240 × 256, matrix = 240 × 256, slice thickness = 1 mm, 176 slices. Image processing included Inhibitors,research,lifescience,medical motion correction, skull stripping, spatial smoothing of 5-mm full-width/half-maximum

Gaussian kernel, mean-based intensity normalization of all volumes by the same factor, and high-pass temporal filtering. We coregistered functional images of each participant to corresponding matched-bandwidth structural images in native space, then performed a second-stage registration to Inhibitors,research,lifescience,medical their MP-RAGE scans, and finally registered these to structural standard images, defined by the Montreal Neurological Institute averaged 152 standard brain. Registration to high-resolution and standard images was carried out using FLIRT (Jenkinson and Smith 2001; Jenkinson et al. 2002). Statistical analysis Voxel-wise analysis For image analysis, we used FEAT software (FMRI Expert Analysis Tool) Version 5.98, part of the Oxford Centre for Functional Magnetic Resonance Imaging of

the Brain Software Library (FSL), http://www.fmrib.ox.ac.uk/fsl. Inhibitors,research,lifescience,medical FMRIB’s Improved Linear Model (FILM) was used for time-series statistical analysis, using local autocorrelation correction (Ibrutinib Woolrich et al. 2001). We thresholded Z-statistic images using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of P= 0.05 (Worsley 2001). For the first-level (individual subject) analysis, Inhibitors,research,lifescience,medical we modeled the hemodynamic response function using a convolution of the experimental paradigms of each “on” period versus baseline with the canonical hemodynamic response function and its temporal derivative (Aguirre et al. 1998). We analyzed the normalized data using CYTH4 regressors to model hemodynamic changes associated with the contrasts of “on” versus baseline for both the 0.5- and 100-Hz frequencies. For the “on” 22-sec blocks, we modeled only the two 10-sec periods that the device was actually on, and not the 2 sec intervening off period. The baseline consisted of the six “off” blocks plus the 33.5 sec of baseline at the end of the run. We tested both relative activation (modeled as “1”) and deactivation (modeled as “−1”).