Abstracts

Rationale: In our clinical evaluation of memory in patients with epilepsy we use a pair of tests, one verbal and the other nonverbal, that are matched except for the material specificity of the stimuli. These tests reliably distinguish patients with unilateral left vs. right temporal-lobe epilepsy (TLE). They have also revealed an interesting pattern: patients with left TLE tend to learn verbal stimuli adequately, but show great loss after a delay, whereas patients with right TLE show slow learning of visual stimuli but retain what they successfully encode. To date in fMRI research, tests of nonverbal memory have had little success in demonstrating specific increases in activation of the right medial temporal-lobe structures. This is likely due to two factors: a lack of appropriately designed tests, and the vulnerability of the medial temporal lobe to susceptibility artifacts due to proximity to skull base structures. The aim of this study was to assess which medial temporal-lobe structures are important in these tasks that we know are differentially sensitive to left vs. right TLE, and to determine how involvement of these structures differs in patients compared to appropriate healthy subjects. Methods: The two matched tests each involve the same sequence of trials: initial encoding, initial recognition, second encoding, second recognition, and delayed recognition10 minutes later. A block design was used and runs were alternated with baseline stimuli to compare activations. Stimuli were designed to maximize lateralization: verbal items were pronounceable nonwords (not easily associated with an image) and nonverbal items were abstract designs (not easily named). We developed an fMRI protocol that minimizes the inhomogeneity in the temporal lobe and used 3 Tesla MRI to maximize spatial resolution. We tested healthy volunteers similar in age and education to our population of patients with unilateral TLE. Data were analyzed using SPM8, and an explicit mask of the hippocampus and parahippocampal region was applied. Results: Performance on the two tests was not significantly different, suggesting that they are of comparable difficulty. Neuroimaging results showed, compared to baseline, increased activations in the right hippocampus during encoding of both visual and verbal information. We also saw increased activation in the left hippocampus during recognition (immediate or delayed) of verbal information, and in the right hippocampus during recognition of the visual stimuli. Conclusions: We found activations specific to the right hippocampus during encoding and recognition of the abstract designs. The verbal task also involved the right hippocampus during encoding, but left during recognition. This is in keeping with clinical findings using these tests. These results also provide support for theories that the left and right medial temporal-lobe structures do not subserve identical memory functions; i.e., encoding may be predominantly a right hippocampal function and hippocampal involvement in learning may be less material-specific than previously thought.