Long-term potentiation in the hippocampus can be enhanced and prolonged by dopaminergic inputs from midbrain structures such as the substantia nigra. This improved synaptic plasticity is hypothesized to be associated with better memory consolidation in the hippocampus. We used a condition that reliably elicits a dopaminergic response, reward anticipation, to study the relationship between activity of dopaminergic midbrain areas and hippocampal long-term memory in healthy adults. Pictures of object drawings that predicted monetary reward were associated with stronger fMRI activity in reward-related brain areas, including the substantia nigra, compared with non-reward-predicting pictures. Three weeks later, recollection and source memory were better for reward-predicting than for non-reward-predicting pictures. FMRI activity in the hippocampus and the midbrain was higher for reward-predicting pictures that were later recognized compared with later forgotten pictures. These data are consistent with the hypothesis that activation of dopaminergic midbrain regions enhances hippocampus-dependent memory formation, possibly by enhancing consolidation.

We report a human electrophysiological brain state that predicts successful memory for events before they occur. Using magnetoencephalographic recordings of brain activity during episodic memory encoding, we show that amplitudes of theta oscillations shortly preceding the onsets of words were higher for laterrecalled than for later-forgotten words. Furthermore, single-trial analyses revealed that recall rate in all 24 participants tested increased as a function of increasing prestimulus theta amplitude. This positive correlation was independent of whether participants were preparing for semantic or phonemic stimulus processing, thus likely signifying a memory-related theta state rather than a preparatory task set. Source analysis located this theta state to the medial temporal lobe, a region known to be critical for encoding and recall. These findings provide insight into state-related aspects of memory formation in humans, and open a perspective for improving memory through theta-related brain states.hippocampus ͉ magnetoencephalography ͉ memory ͉ oscillations ͉ prestimulus T he neurocognitive processing that is instantiated by an event determines the longevity and quality of memory for that event. Studies using electrophysiological (1-3) and hemodynamic (4-9) techniques have shown that episodic memory-the ability to recollect an event and its spatiotemporal context-is associated with specific patterns of brain activity during the time the event is originally experienced. Recent observations that perception of a stimulus can be influenced by prestimulus brain activity (10, 11) raise the additional possibility that the brain state immediately preceding an event could predict later episodic memory. This possibility is supported by findings in rodents that the amplitude of hippocampal theta (3-8 Hz) oscillations, which are held to be important modulators of the induction of synaptic plasticity (12)(13)(14), is associated with enhanced learning in classical conditioning even before stimulus onset (15)(16)(17). Because the medial temporal lobe (MTL) and, in particular, the hippocampus are also critical for episodic memory encoding in humans (18)(19)(20), prestimulus mediotemporal theta states might be linked to effective episodic memory encoding.For prestimulus brain activity to qualify as a general encodingrelated state, it should be associated with encoding success independent of preparatory factors related to the cognitive control of particular task demands. A recent event-related potential (ERP) study of episodic memory showed that prestimulus, frontal-negative slow shifts predicted successful encoding of words 250 ms before the onset of word presentation (21). Critically, this prestimulus effect was observed only if the prestimulus task cue required a semantic judgment on the word and not when the task cue required an orthographic judgment (21). Therefore, this prestimulus ERP difference depended on a specific task set and is unlikely to reflect a general encodingrelated state.To examine whether prestimulus the...

Evidence from animal studies points to the importance of the parahippocampal region (PHR) [including entorhinal, perirhinal, and parahippocampal (PHC) cortices] for recognition of visual stimuli. Recent findings in animals suggest that PHR may also be involved in visual associative recognition memory for configurations of stimuli. Thus far, however, such involvement has not been demonstrated in humans. In fact, it has been argued that associative recognition in humans is critically dependent on the hippocampal formation (HF). To better understand the division of function between HF and PHR during recognition memory in humans, we measured the activity of both areas in healthy young adults during an associative recognition memory task using functional magnetic resonance imaging. To more precisely characterize the nature of the associations that might be coded by the HF and PHR during recognition, subjects were required to learn and were later tested for associations based on either the spatial arrangements of two stimuli or the identity of two stimuli (a face and a tool). An area in the PHC was found to be more active for recognized old configurations than new configurations in both the spatial and identity conditions. The HF, on the other hand, was more active for recognition of new configurations than old configurations and also more active in the spatial than the identity condition. These data highlight the involvement of PHR in the long-term coding of associative relationships between stimuli and help to clarify the nature of its functional distinction from the HF.

No abstract

One functional aspect of theta oscillations that recent studies have begun to explore in humans is their role for the recollection of personal events. A specific role of theta for recollection but not for stimulus-familiarity would support links between cortical theta oscillations and hippocampal functioning, given that the hippocampus seems to be more critical for recollection than for stimulus-familiarity. During recollection, theta oscillations might mediate a dynamic link between hippocampal and neocortical areas, thereby allowing to recruit and bind distributed cortical representations. We recorded theta oscillations using whole-head magnetoencephalography while nine healthy subjects made recognition memory judgments on previously studied and unstudied pictures of faces. For each recognized face, subjects indicated whether they also recollected the background image in front of which that face was studied. Theta oscillations were higher in amplitude during recollection than during recognition in the absence of accurate memory for the background. These theta oscillations were induced in nature, meaning that they showed considerable phase variability from trial to trial. To nevertheless extract the field distribution of coherent theta oscillations from single trials, we calculated phase differences between sensor pairs at each time point of each single trial. This field information was used to localize the brain sources of synchronized theta-generators. The results suggest that recollection is associated with induced activity increase in a distributed synchronous theta network, including prefrontal, mediotemporal, and visual areas. These findings are compatible with the notion that theta oscillations are related to the binding of distributed cortical representations during recollection.