Functional MRI of Attention in Normal Volunteers Using a Modified PASAT Test: Effect of Test Difficulty on Activation

R.C. Platenberg, V.N. Starbuck, C.S. Lin, C. Morris, K.M. Ward, S.S. Rajan, D. Schellinger

Georgetown University Medical Center, Washington, D.C.

Introduction:

Functional MRI (fMRI) using the BOLD (Blood Oxygen Level Dependant) technique has demonstrated localized brain activation associated with regional changes in blood flow that imply neuronal activation (1,2). We performed fMRI to evaluate activation in the cerebral hemispheres in volunteers during the performance of three modified versions of the Paced Auditory Serial Addition Test (PASAT). The PASAT test requires subjects to perform mental calculation (addition) on a continuous string of numbers and is a test of attention as well as working memory. It was hypothesized that, like other tasks that demonstrate increased activation with a higher degree of difficulty (3), the more difficult the addition task the more activation might be identified.

Methods:

Eight normal right handed volunteers were studied on a 1.5 T actively shielded whole body imaging system (Vision, Siemens, Erlangen Germany) with a quadrature circularly polarized head coil. Single-shot gradient echo EPI pulse sequences were used to acquire images. Sequence parameters were: TE = 50msec, TR = 3 to 4 secs, flip angle = 90, FOV = 230x230mm2, slice thickness = 4mm, matrix size = 64x64, acquisition time per measurement = 100msec. The slice positions were angled 20 (Transverse/Coronal) which allowed for coverage of the frontal, temporal, parietal, and occipital regions of the brain.

The funcitonal stimulation pattern involved a 2 minute scan of 28 images at each slice position with a 7-5-5-5-6 protocol of alternating task/rest conditions. The pre and post stimulation images were analyzed using a trapezoid wave funtion. The funcional maps were obtained using a coefficient threshold of 0.65 which corresponds to a p < 0.001. These functional maps were then overlaid on an anatomical image. The numbers of activated pixels were evaluated by region and by task. Results were obtained using non-parametric statistical analysis due to the variability of the data and the small sample size. A Wilcoxin Ranked-Sum Signed-Pairs test was performed on the regions of interest.

Volunteers were first presented with an auditory string of numbers and were asked to add the most recent number to the number presented 1 item back (PASAT test). The task was repeated using higher integers, thus increasing the task difficulty. The third version of the task was even more difficult and required subjects to carry numbers to three places. Many individuals expressed they were unable to complete the addition sequence in the time allotted.

Each volunteer practiced the PASAT test outside of the MRI to gain familiarity with the concept. In addition, individuals demonstrated a level of proficiency indicative of the absence of impairment, prior to participation in our study.

Figure 1: BOLD activation superimposed on EPI data during the performance if the easy PASAT test. Note activity in temporal regions in the primary auditory cortex. This was demonstrated on all volunteers. Right frontal activity is present in the dorsal lateral prefrontal cortex. Left frontal-periventricular activity is also seen.

Figure 2: Easy PASAT test processed using MEDEX Software courtesy of Tom Zeffiro, M.D., PhD. Sensor Systems, Reston, VA. The EPI data is superimposed on a hight resolution anatomic image. Note activation in the left dorsal lateral prefrontal cortex as well as the right medial frontal area.

Figure 3: Bilateral primary auditory cortex activity, during the performance of the easy PASAT test, is characterized by colored pixels in the temporal lobes superimposed on an EPI image. Signal changes in the left temporal lobe, which correlate with the rest-task-rest-task-rest paradigm, are indicated by the graph.

PASAT Test

Figure 4: Upper images illustrate the activation seen during the performance of the medium PASAT test with more frontal pixels activated than in the lower images of easy PASAT.

Results:

During all three of the PASAT tests, activation was present in all subjects in the primary auditory cortex located in the posterior temporal region. Bilateral activation was identified with no hemispheric laterlization. BOLD effect was present in the left or right medial frontal and dorsal lateral pre-frontal cortex in 6 of 8 volunteers during the easy verbal addition test. Three volunteers had activity in both right and left frontal areas, two had activity in right>left frontal, one had only left frontal activity and two showed no activity.

During the medium difficulty PASAT test, 7 of 8 demonstrated frontal BOLD activity. Two each were seen with bilateral, right>left frontal and right frontal only. One each was seen with left only and no activity.

During the difficult PASAT test two volunteers each showed left>right frontal, bilateral frontal, left only and right only activity.

All individuals were noted to have frontal activation during the most difficult addition task compared to the, easy, single integer PASAT test. During the easy PASAT test, two individuals did not demonstrate frontal activation however, BOLD effect was seen in these volunteers with the more difficult task.

Increased task difficulty elicited two to three times the number of pixels activated in 5 of 8 volunteers in the left frontal area. In two other individuals, the nimber of pixels activated were unchanged in the left frontal area and one was decreased with the more difficult task.

In the right frontal lobe, 4 of 8 had increased and two each had no change or decreased frontal activity with the difficult task compared to the easy task. This may reflect the small number of volunteers studied, or the complex nature of increasingly difficult cognitive tasks and brain activation.

Conclusions:

We have noted activation in the primary auditory cortex and in frontal areas in volunteers performing serial addition tasks when given verbal stimuli. The frontal activation is located in the medial frontal lobe and/or in the dorsal lateral pre-frontal cortex in either the right or left frontal region. More pixel activation is seen with increasing task difficulty in some individuals. The most difficult task demonstrated frontal activity to some degree in all volunteers. These results suggest that an increasingly difficult cognitive task may assist in demonstrating subtle activation in a more robust manner. Variability of activation is noted from one frontal lobe to the other in the more difficult task. This may reflect the small numbers of volunteers studied, or the complex nature of difficult cognitive tasks and brain activation. Comparison of attention and working memory using the PASAT test in fMRI within the same individual may be valueable in grading response to therapy or in following the natural recovery of cognitive function in individuals with deficits. Comparison between individuals may be problematic because of variable response to task.

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