UC San Diego

As individuals navigate the world, they encounter a constant stream of stimuli, some of which are important to attend to, encode, and associate with other stimuli separated in time. How does the brain attempt to form and succeed in forming associative memories for temporally- discontiguous stimuli? Does using different associative strategies influence which brain regions are engaged in encoding, and could this have clinical implications for potential treatment approaches in patients with neurological damage and disease? The studies described in this dissertation were designed to address these questions using functional magnetic resonance imaging and behavioral memory testing. Using a novel memory paradigm, in which subjects encoded and formed associations between temporally-discontiguous sequentially-presented stimuli, the established involvement of prefrontal and medial temporal regions in associative encoding was disentangled, as these regions were found to subserve different functions in maintaining and binding visual stimuli. Successful associative encoding of object pairs involved coordination of frontoparietal working memory regions and the hippocampus. Frontoparietal regions were also engaged in visuospatial encoding, where the spatial cue preceded the centrally-presented object; however, parietal regions were modulated by attempted visuospatial binding while frontal responses predicted successful binding. Additionally, when examining the timing of associative memory formation with a temporal delay between visual objects, positive modulation of frontal, lateral occipital, and anterior medial temporal regions were found to predict success at binding and not during maintenance. Besides exploring the natural processes involved in associating and encoding temporally-discontiguous stimuli, another primary goal of this dissertation was to examine the influence of encoding strategy on regional memory effects. Encoding object pairs using a visual versus verbal strategy engaged similar regions as those reported in prior studies of visual- versus verbal-stimulus encoding. Such findings suggest a driving effect of strategy, not stimulus-type, on regional involvement in associative memory formation, which has implications for future development both in basic memory research and for potential clinical treatments. Together, the studies that comprise this dissertation addressed existing unknowns in the field of human memory formation and contributed to the understanding of how individuals with intact and impaired cognitive function form associative memories