Patients with neurodegenerative syndromes who defined the five disease-vulnerable ROI sets were those studied previously as described (Seeley et al., 2009). Clinical diagnostic criteria and clinicopathological correlation data are detailed in the Supplemental

Experimental Procedures. In addition, we studied 16 healthy controls (8 females, all right-handed, mean age 65.4 (s.d. 3.2) years, psychoactive medication-free, Vemurafenib in vitro not included in our previous work (Seeley et al., 2009)) evaluated at the UCSF Memory and Aging Center. All subjects provided informed consent, and the procedures were approved by the UCSF Committee on Human Research. Healthy subjects were recruited from the local community through advertisements and underwent a comprehensive neuropsychological LY294002 nmr assessment and a neurological exam within 180 days of scanning. All controls met the criteria of having a Clinical Dementia Rating scale total score of 0, a mini-mental state examination score of 28 or higher, no significant history of neurological disease or structural lesions on MRI, and a consensus diagnosis of cognitively normal. All subjects underwent an eight-minute task-free or “resting-state” functional magnetic resonance (fMRI) scan after being instructed to remain awake with their eyes closed. Functional and structural images were acquired on a 3 Tesla Siemens MRI scanner at the Neuroscience Imaging Center, University

of California, San Francisco. Functional MRI scanning was performed using a standard 12-channel head coil. Thirty-six interleaved axial slices (3 mm thick with a gap of 0.6 mm) Rebamipide were imaged parallel to the

plane connecting the anterior and posterior commissures using a T2∗-weighted echo planar sequence (repetition time [TR]: 2,000 ms; echo time (TE): 27 ms; flip angle [FA]: 80°; field of view: 230 × 230 mm2; matrix size: 92 × 92; in-plane voxel size: 2.5 × 2.5 mm). For coregistration purposes, a volumetric magnetization prepared rapid gradient echo (MPRAGE) MRI sequence was used to obtain a T1-weighted image of the entire brain in sagittal slices in the same session (repetition time, 2300 ms; echo time, 2.98 ms; inversion time, 900 ms; flip angle, 9). The structural images were reconstructed as a 160 × 240 × 256 matrix with 1 mm3 spatial resolution. After discarding the first 16 s to allow for magnetic field stabilization, functional images were realigned and unwarped, slice-time corrected, coregistered to the structural T1-weighted image, normalized, and smoothed with a 4 mm full-width at half-maximum Gaussian kernel using SPM5 (http://www.fil.ion.ucl.ac.uk/spm/), resulting in images with a voxel size of 2 mm3. Coregistration was performed between each subject’s mean T2∗ image and that subject’s T1-weighted image, and normalization was carried out by calculating the warping parameters between the subject’s T1-weighted image and the MNI T1-weighted image template and applying those parameters to all functional images in the sequence.