0, Sony Pictures Digital Inc., TX). All three types of U0126 MAPK stimuli lasted 130 msec. The “Standard” stimulus was a sound with frequencies increasing linearly from 250 to 1000 Hz, while the “Target” stimulus was a sound with frequencies decreasing linearly from 1000 to 250 Hz. “Novel”

stimuli consisted of different 130 msec noises (e.g., onomatopoeia sound effects used in cartoons). Interstimulus intervals lasted 800 msec during which subjects Inhibitors,research,lifescience,medical could hear in background the protein inhibitors scanner noise. All stimuli were presented during a silent gap and baseline recorded in silent gaps without stimulus presentation. Participants were instructed to respond as quickly as possible with their right thumb (pushing a button) at the occurrence/recognition of every “Target” stimulus. The task thus demanded strong attention associated with a muscular reflex. During auditory Inhibitors,research,lifescience,medical stimulus presentation, subjects were instructed to watch a gray screen with a fixation point (black cross). Presentation®

software (http://www.neurobs.com/presentation) was used to present stimuli, to register the subject’s responses and to analyze the behavioral tests Inhibitors,research,lifescience,medical (i.e., reaction times, intrasubject reaction times variability, error rates). Before the actual start of the scans, subjects were trained outside the scanner in order to familiarize to stimuli and handling of the system. All subjects were able to perceive sounds and operate the response keys correctly. By contrast, tinnitus could not be perceived because masked by the experimental environment. In order to ensure comfortable hearing of stimuli in the noisy MRI environment, we performed some acoustic measures inside the scanner before optimizing the setup for the transmission of the auditory stimuli. The mean acoustic sound pressure Inhibitors,research,lifescience,medical level (SPL) during fMRI scans was 80 dB

SPL with a very narrow spectral peak of 120 dB SPL at 1.12 kHz. To reduce scanner noise, a passive sound-attenuating cylinder was inserted into the bore of the scanner. It was composed of two layers of 5-mm-thick sound-attenuating material (Plastison®, www.serenata.tm.fr) fixed on a rigid cylindrical support (Sonotube®, http://sonotube.com). Inhibitors,research,lifescience,medical Furthermore to improve hearing of the stimuli, Dacomitinib imaging slices were acquired in three stacks. Acquisition of each stack took 800 msec. Stacks were separated by a silent gap of 130 msec (gradient system “off”), during which period the auditory stimuli were presented. Subjects wore earplugs and stimuli were transmitted by home-made prototype earphones inserted in industrial hearing protectors (Bilsom®). The frequency range of the stimuli (250–1000 Hz) was below the peak frequency of the echo-planar imaging (EPI) sequence. fMRI protocol Blood oxygen-level-dependent (BOLD) images were acquired on a 3-Tesla whole body MR scanner (Brucker Medspec S300, Ettlingen, Germany) using gradient-echo planar imaging (EPI). Images of the whole brain, including cerebellum and brainstem, were obtained.