| Method: |
Design and Procedure
fMRI
After obtaining informed consent, participants were placed on the MR scanner table and fitted with MRI compatible headphones, and a mirror fitted into the head coil, which projected a visual display from an external projector (Sanyo ProX, Multiverse Projector, maximum 60 Hz). Once inside the scanner, participants received instructions through headphones. Participants performed an auditory oddball task in which auditory stimuli were presented binaurally through headphones with foam inserts. Twenty target tones (15%) were presented in a pseudo-random sequence of 105 standard tones (85%) with a fixed interstimulus interval of 3.59 seconds. Targets were auditory tones of 1000 Hz and standard tones were 500 Hz. All stimuli were presented at 75 dB and were of 50ms duration, with a rise and fall time of 5 ms. The number of standard tones preceding targets was randomized between 2 and 9 stimuli. The minimal inter-target interval was 10.72 seconds to ensure recovery of task-related signal intensity change to baseline, which is known to take approximately 10 seconds (Yoshiura et al., 1999). Stimuli were presented after three dummy scans to familiarize participants with scanning noise and to ensure blood oxygen level dependent (BOLD) saturation. Subjects were instructed to button-press simultaneously with their left and right thumbs (to counterbalance for motor activity) to target tones as quickly and accurately as possible and not to respond to the standard tones. Accuracy ratings of 100% were required in practice trials before proceeding to the task. Reaction times were computed on trials for which the participant responded correctly within 100 - 1000 ms post-stimulus.
fMRI Image Acquisition
125 T2*-weighted volumes depicting blood oxygenation level dependent (BOLD) contrast were acquired with a Siemens Magnetom VISION plus 1.5 Tesla Scanner, fitted with a standard quadrature head coil. One T2* weighted image was obtained per stimulus using a gradient echoplanar sequence. 15 axial non-contiguous slices of 6mm thickness (0.6mm interslice gap) were measured, positioned parallel to the intercommisural (AC-PC) line: TR: 3.5 secs, TE: 80mecs, matrix 128 x 128. FOV 24cm x 24 cm, flip angle 90º. These slices covered the whole cerebrum providing whole-brain coverage.
fMRI Analysis
Pre-processing and statistical analysis of the fMRI data was performed using Statistical Parametric Mapping software (SPM2; Wellcome Department of Cognitive Neurology; http://www.fil.ion.ucl.ac.uk/spm).
Pre-processing
In order to control for movement during the scanning, all T2* weighted volumes were realigned to the first in the time series and unwarped. Images were normalized into standardized MNI space and then smoothed with a 8mm full width at half maximum isotropic Gaussian kernal.
Voxel-wise Analysis
An HRF-convolved event-related model was created in order to correspond to the pseudo-randomized target and background stimuli. A high pass filter was applied to remove low frequency fluctuations in the BOLD signal. Individual contrast files were created for each subject to examine voxel-wise effects of signal changes, defined for target versus background stimuli. We subsequently applied a random effects analysis, using related sample t-tests to examine the significance of BOLD responses during presentation of targets relative to background stimuli.
ROI analysis was conducted on 3 regions, the anterior cingulate cortex (ACC), hippocampus (HIP), and supramarginal gyrus (SMG). These regions were selected as they have been implicated in the healthy response to oddball target stimuli (Stevens et al., 2000; Yoshiura et al., 1999). Further, the ACC attentional shifting and amygdala are thought involved in attention and attributing salience to stimuli (Bush et al., 2000; Davis & Whalen, 2001). Anatomical regions of interest included both the left and right hemispheres. A statistical threshold of p |