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Figure 1. Behavioral tasks. (A) Episodic retrieval task. Participants first studied 36 objects (18 red/18 green). After a 1-hr delay, during scanning, participants viewed all 36 pictures again in black and white during the experimental blocks and indicated the color at study with a left or right button press. The control condition was a visual size- discrimination task. (B) The high-load working memory task is depicted here. The low-load condition was the same except that the study set contained four letters.

scanner. Subjects viewed the 36 pictures in black and white (2800 msec stimulus duration, 700 msec intertrial interval [ITI]) and made left/right button presses to indicate whether the picture had been red or green at study. Blocks of pictures alternated with blocks of a simple visual size-discrimination baseline task. This con- sisted of a central fixation cross with a shape (circles or squares) presented on either side of the cross. Partic- ipants were instructed to press a button to indicate which side (left or right) was larger. This baseline task was chosen because it required both visual encoding and a motor response, but no memory processes were engaged. Each run consisted of six blocks of each condition with six trials in each block.

Verbal Item Recognition Working Memory Task

This task has been shown to elicit dorsolateral PFC activations in older people when a high-load condition is used (Rypma & D’Esposito, 1999, 2000). In this study, we used two different load conditions, a four-letter version as the low load and a six-letter version as the high load. Separate functional MRI (fMRI) runs were used for each load. A schematic of the task is depicted in Figure 1B. Participants viewed the study letter set (2500 msec) followed by a short delay (1500 msec). A probe letter then appeared (2500 + 1500 msec ITI) and participants responded to indicate whether the probe letter matched any letter in the study set. The baseline condition consisted of a single letter in the study set, substantially reducing the memory load. Each run con- sisted of four blocks of each condition with four trials in each block.

Visual Sensory Control Task

We used this task as a control to assess whether vascular abnormalities associated with WMH fundamentally alter the fMRI BOLD signal. The task consisted of alternating blocks of a flickering checkerboard (16 sec) followed by

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Journal of Cognitive Neuroscience

fixation (16 sec). Each run consisted of eight blocks of each condition. Participants were instructed to fixate on the screen for the duration of the run.

Procedures

All participants gave informed consent to participate in the study. After completing an MRI screening question- naire, subjects were familiarized with the behavioral tasks in a practice session outside of the scanner. Participants were then fitted with scanner-compatible eyeglasses if necessary.

Each scanning session consisted of collection of structural images followed by six functional scans: the episodic retrieval task, two runs each of the low- and high-load working memory task (for a total of four runs of the working memory task), followed by the visual sensory task. The order of the structural and functional scans was the same for every participant. Stimuli were presented using Presentation v.7.0 (nbs.neuro-bs.com), projected onto a screen located at the end of the MRI gantry, and viewed by means of a mirror inset in the head coil. Participants made left-/right-hand responses using two fiber-optic button press boxes, one in each hand. Due to technical difficulties, data from one run of the high load working memory task is missing for one subject and data from the visual task is missing for two subjects.

MRI Data Acquisition

All MRI data for each subject were acquired in a single session on a 1.5T GE Signa scanner at the UC Davis Imaging Research Center. Functional imaging was per- formed using a gradient echo-planar imaging (EPI) sequence (TR = 2000, TE = 50, FOV = 24 cm, 64 64 matrix, 22 axial slices, 5 mm thick). Structural imaging sequences included a fluid-attenuated inversion recov- ery (FLAIR) (FOV = 24 cm, 48 slices, 3 mm thick)

Volume 18, Number 3

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