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.

The dopaminergic mechanisms that control reward-motivated behavior are the subject of intense study, but it is yet unclear how, in humans, neural activity in mesolimbic reward-circuitry and its functional neuroimaging correlates are related to dopamine release. To address this question, we obtained functional magnetic resonance imaging (fMRI) measures of reward-related neural activity and

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...