Functional MRI studies of working memory maintenance and long-term encoding

The main focus of this thesis was to further our understanding of interactions between working memory (WM) and long-term memory (LTM). In a series of three experiments this thesis investigated the role of medial temporal lobes (MTL) and prefrontal cortex (PFC) in the active maintenance of visual-nonspatial and visual-spatial information and its relationship to long-term encoding using functional magnetic resonance imaging and delayed match-to-sample (DMS) tasks in healthy young human adults.; Experiment #1 elucidates the role of previous stimulus experience (novel vs. familiar objects) and of stimulus domain (spatial locations vs. visual objects) in delay-period activity. The results of this experiment indicate that actively maintaining novel objects during brief memory delays recruits MTL areas. Activity in the PFC is greater during maintenance of familiar compared to novel objects, and maintenance of spatial and nonspatial information recruits different subregions within the PFC. These results support the hypothesis that MTL regions are critical for the active maintenance of stimuli that have no previous representation in the brain. In addition, the findings support the idea that the PFC is recruited when familiar stimuli need to be monitored (i.e., when interference is high among them).; Experiment #2 combines a DMS task with a post-scan subsequent recognition memory assessment to test the hypothesis that during WM maintenance, novel sample stimuli are encoded into long-term memory. The results showed that delay activity in the MTL is correlated with subsequent memory, and support the idea that sustained activity in the MTL is required for long-term encoding.; Experiment #3 tests the hypothesis that encoding-related activity during the delay-period (experiment #2) is modulated by the neurotransmitter acetylcholine. The results of this experiment demonstrate that fMRI activity within the MTL is attenuated in individuals who received an injection of the cholinergic antagonist scopolamine.; In conclusion, these three experiments provide strong support for a role of the MTL in WM maintenance of novel information for which no previous representation exists in the brain, and for a role in long-term encoding during WM. In contrast, the PFC is critical for the maintenance of familiar stimuli, for which LTM representations already exist.