Hippocampal theta coordinates memory processing during visual exploration.

The hippocampus supports memory encoding and retrieval, which may occur at distinct phases of the theta cycle. These processes dynamically interact over rapid timescales, especially when sensory information conflicts with memory. The ability to link hippocampal dynamics to memory-guided behaviors has been limited by experiments that lack the temporal resolution to segregate encoding and retrieval. Here, we simultaneously tracked eye movements and hippocampal field potentials while neurosurgical patients performed a spatial memory task. Phase-locking at the peak of theta preceded fixations to retrieved locations, indicating that the hippocampus coordinates memory-guided eye movements. In contrast, phase-locking at the trough of theta followed fixations to novel object-locations and predicted intact memory of the original location. Theta-gamma phase amplitude coupling increased during fixations to conflicting visual content, but predicted memory updating. Hippocampal theta thus supports learning through two interleaved processes: strengthening encoding of novel information and guiding exploration based on prior experience.

Distinguishing the precision of spatial recollection from its success: Evidence from healthy aging and unilateral mesial temporal lobe resection.

Successful episodic recollection can vary in the precision of the information recalled. The hypothesis that recollection precision requires functional neuroanatomical contributions distinct from those required for recollection success remains controversial. Some findings in individuals with hippocampal lesions have indicated that precision is dependent on the hippocampus. However, other neuroimaging and lesion studies have implicated regions outside of the mesial temporal lobe (MTL) in precision, such as parietal cortex. To further elucidate distinctions of recollection precision versus success, we examined whether they were differentially sensitive to aging and to unilateral MTL lesions. Precision and success were measured using a novel task that required memory for item-location associations across different spatial contexts. We found impairments in recollection precision, but not success, in older adults (59-80 years) relative to younger adults (18-33 years). Recollection precision was also selectively impaired in individuals with unilateral MTL resections made to treat refractory epilepsy. Moreover, recollection precision was significantly worse when resections included the hippocampus compared to when only non-hippocampal MTL tissue was resected. These findings suggest that the MTL is critically involved in the high-resolution binding required to support spatial recollection precision, and thus provide evidence for functional neuroanatomical differences between recollection success and precision.

Prefrontal θ-Burst Stimulation Disrupts the Organizing Influence of Active Short-Term Retrieval on Episodic Memory.

Dorsolateral prefrontal cortex (DLPFC) is thought to organize items in working memory and this organizational role may also influence long-term memory. To causally test this hypothesized role of DLPFC in long-term memory formation, we used θ-burst noninvasive stimulation (TBS) to modulate DLPFC involvement in a memory task that assessed the influence of active short-term retrieval on later memory. Human subjects viewed three objects on a grid and then either actively retrieved or passively restudied one object's location after a brief delay. Long-term memory for the other objects was assessed after a delay to evaluate the beneficial role of active short-term retrieval on subsequent memory for the entire set of object locations. We found that DLPFC TBS had no significant effects on short-term memory. In contrast, DLPFC TBS impaired long-term memory selectively in the active-retrieval condition but not in the passive-restudy condition. These findings are consistent with the hypothesized contribution of DLPFC to the organizational processes operative during active short-term retrieval that influence long-term memory, although other regions that were not stimulated could provide similar contributions. Notably, active-retrieval and passive-restudy conditions were intermixed, and therefore nonspecific influences of stimulation were well controlled. These results suggest that DLPFC is causally involved in organizing event information during active retrieval to support coherent long-term memory formation.

A Closer Look at the Hippocampus and Memory.

Current interpretations of hippocampal memory function are blind to the fact that viewing behaviors are pervasive and complicate the relationships among perception, behavior, memory, and brain activity. For example, hippocampal activity and associative memory demands increase with stimulus complexity. Stimulus complexity also strongly modulates viewing. Associative processing and viewing thus are often confounded, rendering interpretation of hippocampal activity ambiguous. Similar considerations challenge many accounts of hippocampal function. To explain relationships between memory and viewing, we propose that the hippocampus supports the online memory demands necessary to guide visual exploration. The hippocampus thus orchestrates memory-guided exploration that unfolds over time to build coherent memories. This new perspective on hippocampal function harmonizes with the fact that memory formation and exploratory viewing are tightly intertwined.

Distinct Hippocampal versus Frontoparietal Network Contributions to Retrieval and Memory-guided Exploration.

Memory can profoundly influence new learning, presumably because memory optimizes exploration of to-be-learned material. Although hippocampus and frontoparietal networks have been implicated in memory-guided exploration, their specific and interactive roles have not been identified. We examined eye movements during fMRI scanning to identify neural correlates of the influences of memory retrieval on exploration and learning. After retrieval of one object in a multiobject array, viewing was strategically directed away from the retrieved object toward nonretrieved objects, such that exploration was directed toward to-be-learned content. Retrieved objects later served as optimal reminder cues, indicating that exploration caused memory to become structured around the retrieved content. Hippocampal activity was associated with memory retrieval, whereas frontoparietal activity varied with strategic viewing patterns deployed after retrieval, thus providing spatiotemporal dissociation of memory retrieval from memory-guided learning strategies. Time-lagged fMRI connectivity analyses indicated that hippocampal activity predicted frontoparietal activity to a greater extent for a condition in which retrieval guided exploration occurred than for a passive control condition in which exploration was not influenced by retrieval. This demonstrates network-level interaction effects specific to influences of memory on strategic exploration. These findings show how memory guides behavior during learning and demonstrate distinct yet interactive hippocampal-frontoparietal roles in implementing strategic exploration behaviors that determine the fate of evolving memory representations.

Stimulation of the Posterior Cortical-Hippocampal Network Enhances Precision of Memory Recollection.

Episodic memory is thought to critically depend on interaction of the hippocampus with distributed brain regions [1-3]. Specific contributions of distinct networks have been hypothesized, with the hippocampal posterior-medial (HPM) network implicated in the recollection of highly precise contextual and spatial information [3-6]. Current evidence for HPM specialization is mostly indirect, derived from correlative measures such as neural activity recordings. Here we tested the causal role of the HPM network in recollection using network-targeted noninvasive brain stimulation in humans, which has previously been shown to increase functional connectivity within the HPM network [7]. Effects of multiple-day electromagnetic stimulation were assessed using an object-location memory task that segregated recollection precision from general recollection success. HPM network-targeted stimulation produced lasting (∼24 hr) enhancement of recollection precision, without effects on general success. Canonical neural correlates of recollection [8-10] were also modulated by stimulation. Late-positive evoked potential amplitude and theta-alpha oscillatory power were reduced, suggesting that stimulation can improve memory through enhanced reactivation of detailed visuospatial information at retrieval. The HPM network was thus specifically implicated in the processing of fine-grained memory detail, supporting functional specialization of hippocampal-cortical networks. These findings demonstrate that brain networks can be causally linked to distinct and specific neurocognitive functions and suggest mechanisms for long-lasting changes in memory due to network-targeted stimulation.

Binding among select episodic elements is altered via active short-term retrieval.

Of the many elements that comprise an episode, are any disproportionately bound to the others? We tested whether active short-term retrieval selectively increases binding. Individual objects from multiobject displays were retrieved after brief delays. Memory was later tested for the other objects. Cueing with actively retrieved objects facilitated memory of associated objects, which was associated with unique patterns of viewing behavior during study and enhanced ERP correlates of retrieval during test, relative to other reminder cues that were not actively retrieved. Active short-term retrieval therefore enhanced binding of retrieved elements with others, thus creating powerful memory cues for entire episodes.

Active retrieval facilitates across-episode binding by modulating the content of memory.

The contents of memory can be updated when information from the current episode is bound with content retrieved from previous episodes. Little is known regarding factors that determine the memory content that is subject to this across-episode binding. We tested whether across-episode binding preferentially occurs for memory content that is currently "active" and identified relevant neural correlates. After studying objects at specific locations on scene backgrounds, subjects performed one of two retrieval tasks for the objects on different scene backgrounds. In an active condition, subjects recalled object locations, whereas subjects merely dragged objects to predetermined locations in a passive condition. Immediately following each object-location retrieval event, a novel face appeared on a blank screen. We hypothesized that the original episode content would be active in memory during face encoding in the active condition, but not in the passive condition (despite seeing the same content in both conditions). A ramification of the active condition would thus be preferential binding of original episode content to novel faces, with no such across-episode binding in the passive condition. Indeed, memory for faces was better when tested on the original background scenes in the active relative to passive condition, indicating that original episode content was bound with the active condition faces, whereas this occurred to a lesser extent for the passive condition faces. Likewise, early-onset negative ERP effects reflected binding of the face to the original episode content in the active but not the passive condition. In contrast, binding in the passive condition occurred only when faces were physically displayed on the original scenes during recognition testing, and a very similar early-onset negative ERP effect signaled binding in this condition. ERP correlates of binding were thus similar for across-episode and within-episode binding (and were distinct from other encoding and retrieval ERP signals in both cases), indicating that active retrieval modulated when binding occurred, not the nature of the binding process per se. These results suggest that active retrieval promotes binding of new information with contents of memory, whereas without active retrieval, these unrelated pieces of information might be bound only when they are physically paired.

Hippocampal binding of novel information with dominant memory traces can support both memory stability and change.

Memory stability and change are considered opposite outcomes. We tested the counterintuitive notion that both depend on one process: hippocampal binding of memory features to associatively novel information, or associative novelty binding (ANB). Building on the idea that dominant memory features, or "traces," are most susceptible to modification, we hypothesized that ANB would selectively involve dominant traces. Therefore, memory stability versus change should depend on whether the currently dominant trace is old versus updated; in either case, novel information will be bound with it, causing either maintenance (when old) or change (when updated). People in our experiment studied objects at locations within scenes (contexts). During reactivation in a new context, subjects moved studied objects to new locations either via active location recall or by passively dragging objects to predetermined locations. After active reactivation, the new object location became dominant in memory, whereas after passive reactivation, the old object location maintained dominance. In both cases, hippocampal ANB bound the currently dominant object-location memory with a context with which it was not paired previously (i.e., associatively novel). Stability occurred in the passive condition when ANB united the dominant original location trace with an associatively novel newer context. Change occurred in the active condition when ANB united the dominant updated object location with an associatively novel and older context. Hippocampal ANB of the currently dominant trace with associatively novel contextual information thus provides a single mechanism to support memory stability and change, with shifts in trace dominance during reactivation dictating the outcome.

Neural correlates of reactivation and retrieval-induced distortion.

Reactivation of recently acquired information can strengthen memory storage and likely contributes to memory consolidation. Retrieval (generating information about prior events) may improve memory storage because it entails reactivation. Alternatively, retrieval may promote storage of retrieved information, and, if retrieval is inaccurate, subsequent recall could be distorted by the retrieved information. If retrieval modifies memory storage, as hypothesized, neural signals associated with accurate retrieval at that time may be distinct from neural signals associated with the degree of repeated retrieval error evident at some later time. We tested this prediction using a 3-session protocol. During session 1, people learned object-location associations to criterion and completed a cued-recall test in which locations were recalled upon viewing objects. During session 2, an electroencephalogram (EEG) was recorded during cued recall for a subset of the associations. During session 3, cued recall was tested for all associations. Retrieval improved storage, in that recall at session 3 was superior for objects tested in session 2 compared with those not tested. Retrieval-induced distortion was revealed in session 3 for those objects tested in session 2, in that those objects were generally placed closer to locations retrieved at session 2 relative to original study locations. EEG analyses revealed positive potentials (400-700 ms) associated with relatively accurate recall at session 2. Memory updating was reflected in positive potentials after 700 ms that differentially predicted the degree to which recall promoted storage of the session-2-retrieved location. These findings demonstrate unique neurocognitive processing whereby memories are updated with information produced during retrieval.

Dynamic social power modulates neural basis of math calculation.

Both situational (e.g., perceived power) and sustained social factors (e.g., cultural stereotypes) are known to affect how people academically perform, particularly in the domain of mathematics. The ability to compute even simple mathematics, such as addition, relies on distinct neural circuitry within the inferior parietal and inferior frontal lobes, brain regions where magnitude representation and addition are performed. Despite prior behavioral evidence of social influence on academic performance, little is known about whether or not temporarily heightening a person's sense of power may influence the neural bases of math calculation. Here we primed female participants with either high or low power (LP) and then measured neural response while they performed exact and approximate math problems. We found that priming power affected math performance; specifically, females primed with high power (HP) performed better on approximate math calculation compared to females primed with LP. Furthermore, neural response within the left inferior frontal gyrus (IFG), a region previously associated with cognitive interference, was reduced for females in the HP compared to LP group. Taken together, these results indicate that even temporarily heightening a person's sense of social power can increase their math performance, possibly by reducing cognitive interference during math performance.

Emotional context at learning systematically biases memory for facial information.

Emotion influences memory in many ways. For example, when a mood-dependent processing shift is operative, happy moods promote global processing and sad moods direct attention to local features of complex visual stimuli. We hypothesized that an emotional context associated with to-be-learned facial stimuli could preferentially promote global or local processing. At learning, faces with neutral expressions were paired with a narrative providing either a happy or a sad context. At test, faces were presented in an upright or inverted orientation, emphasizing configural or analytical processing, respectively. A recognition advantage was found for upright faces learned in happy contexts relative to those in sad contexts, whereas recognition was better for inverted faces learned in sad contexts than for those in happy contexts. We thus infer that a positive emotional context prompted more effective storage of holistic, configural, or global facial information, whereas a negative emotional context prompted relatively more effective storage of local or feature-based facial information.

Neural representations of social status hierarchy in human inferior parietal cortex.

Mental representations of social status hierarchy share properties with that of numbers. Previous neuroimaging studies have shown that the neural representation of numerical magnitude lies within a network of regions within inferior parietal cortex. However the neural basis of social status hierarchy remains unknown. Using fMRI, we studied subjects while they compared social status magnitude of people, objects and symbols, as well as numerical magnitude. Both social status and number comparisons recruited bilateral intraparietal sulci. We also observed a semantic distance effect whereby neural activity within bilateral intraparietal sulci increased for semantically close relative to far numerical and social status comparisons. These results demonstrate that social status and number comparisons recruit distinct and overlapping neuronal representations within human inferior parietal cortex.