The hippocampus is necessary for binding and reconstituting information in relational memory. These essential memory functions are supported by the distinct cytoarchitecture of the hippocampal subfields. Magnetic resonance elastography is an emerging tool that provides sensitive estimates of microstructure vis-à-vis tissue mechanical properties. Here, we report the first in vivo study of human hippocampal subfield viscoelastic stiffness and damping ratio. Stiffness describes resistance of a viscoelastic tissue to a stress and is thought to reflect the relative composition of tissue at the microscale; damping ratio describes relative viscous-to-elastic behavior and is thought to generally reflect microstructural organization. Measures from the subiculum (combined with presubiculum and parasubiculum), cornu ammonis (CA) 1–2, and CA3-dentate gyrus (CA3-DG) were collected in a sample of healthy, cognitively normal men ( n = 20, age = 18–33 years). In line with known cytoarchitecture, the subiculum demonstrated the lowest damping ratio, followed by CA3-DG and then combined CA1–CA2. Moreover, damping ratio of the CA3-DG—potentially reflective of number of cells and their connections—predicted relational memory accuracy and alone replicated most of the variance in performance that was explained by the whole hippocampus. Stiffness did not differentiate the hippocampal subfields and was unrelated to task performance in this sample. Viscoelasticity measured with magnetic resonance elastography appears to be sensitive to microstructural properties relevant to specific memory function, even in healthy younger adults, and is a promising tool for future studies of hippocampal structure in aging and related diseases.

Declarative memory is supported by distributed brain networks in which the medial-temporal lobes (MTLs) and pFC serve as important hubs. Identifying the unique and shared contributions of these regions to successful memory performance is an active area of research, and a growing literature suggests that these structures often work together to support declarative memory. Here, we present data from a context-dependent relational memory task in which participants learned that individuals belonged in a single room in each of two buildings. Room assignment was consistent with an underlying contextual rule structure in which male and female participants were assigned to opposite sides of a building and the side assignment switched between buildings. In two experiments, neural correlates of performance on this task were evaluated using multiple neuroimaging tools: diffusion tensor imaging (Experiment 1), magnetic resonance elastography (Experiment 1), and functional MRI (Experiment 2). Structural and functional data from each individual modality provided complementary and consistent evidence that the hippocampus and the adjacent white matter tract (i.e., fornix) supported relational memory, whereas the ventromedial pFC/OFC (vmPFC/OFC) and the white matter tract connecting vmPFC/OFC to MTL (i.e., uncinate fasciculus) supported memory-guided rule use. Together, these data suggest that MTL and pFC structures differentially contribute to and support contextually guided relational memory.

It is well established that the hippocampus is critical for memory. Recent evidence suggests that one function of hippocampal memory processing is to optimize how people actively explore the world. Here we demonstrate that the link between the hippocampus and exploration extends even to the moment-to-moment use of eye movements during visuospatial memory encoding. In Experiment 1, we examined relationships between study-phase eye movements in healthy individuals and subsequent performance on a spatial reconstruction test. In addition to quantitative measures of viewing behaviors (e.g., how many fixations or saccades were deployed during study), we used the information–theoretic measure of entropy to assess the amount of randomness or disorganization in participants' scanning behaviors. We found that the use of scanpaths during study that were lower in entropy (e.g., more organized, less random) predicted more accurate spatial reconstruction both within and between participants. Scanpath entropy was a better predictor of reconstruction accuracy than were the quantitative measures of viewing. In Experiment 2, we found that individuals with hippocampal amnesia tended to engage in viewing patterns that were higher in entropy (less organized) relative to healthy comparisons. These findings reveal a critical role of the hippocampus in guiding eye movement exploration to optimize visuospatial relational memory.

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.

The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study–test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains.

Health factors such as an active lifestyle and aerobic fitness have long been linked to decreased risk of cardiovascular disease, stroke, and other adverse health outcomes. Only more recently have researchers begun to investigate the relationship between aerobic fitness and memory function. Based on recent findings in behavioral and cognitive neuroscience showing that the hippocampus might be especially sensitive to the effects of exercise and fitness, the current study assessed hippocampal-dependent relational memory and non-hippocampal-dependent item memory in young adults across a range of aerobic fitness levels. Aerobic fitness was assessed using a graded exercise test to measure oxygen consumption during maximal exercise (VO 2 max), and relational and item memory were assessed using behavioral and eye movement measures. Behavioral results indicated that aerobic fitness was positively correlated with relational memory performance but not item memory performance, suggesting that the beneficial effects of aerobic fitness selectively affect hippocampal function and not that of the surrounding medial temporal lobe cortex. Eye movement results further supported the specificity of this fitness effect to hippocampal function, in that aerobic fitness predicted disproportionate preferential viewing of previously studied relational associations but not of previously viewed items. Potential mechanisms underlying this pattern of results, including neurogenesis, are discussed.

Medial temporal lobe (MTL) contributions to the brief maintenance of visual representations were evaluated by studying a group of patients with MTL damage. Eye movements of patients and healthy comparison subjects were tracked while performing a visual search for a target among complex stimuli of varying similarity to that target. Despite the task having no imposed delays, patients were impaired behaviorally, and eye movement measures showed abnormally rapid degradation of target representations in the patients. Eye movement data showed a modulation of the duration of fixations as a function of the similarity of fixated array lures to the target, but the effect was attenuated in patients during long fixation paths away from the sample target. This effect manifested despite patients' shorter searches and more frequent fixations of the sample target. Novel techniques provided unique insight into visual representation without healthy MTL, which may support maintenance of information through hippocampal-dependent relational binding.

The influence of cardiorespiratory fitness on the modulation of cognitive control was assessed in preadolescent children separated into higher- and lower-fit groups. Participants completed compatible and incompatible stimulus–response conditions of a modified flanker task, consisting of congruent and incongruent arrays, while ERPs and task performance were concurrently measured. Findings revealed decreased response accuracy for lower- relative to higher-fit participants with a selectively larger deficit in response to the incompatible stimulus–response condition, requiring the greatest amount of cognitive control. In contrast, higher-fit participants maintained response accuracy across stimulus–response compatibility conditions. Neuroelectric measures indicated that higher-fit, relative to lower-fit, participants exhibited global increases in P3 amplitude and shorter P3 latency, as well as greater modulation of P3 amplitude between the compatible and incompatible stimulus–response conditions. Similarly, higher-fit participants exhibited smaller error-related negativity (ERN) amplitudes in the compatible condition, and greater modulation of the ERN between the compatible and incompatible conditions, relative to lower-fit participants who exhibited large ERN amplitudes across both conditions. These findings suggest that lower-fit children may have more difficulty than higher-fit children in the flexible modulation of cognitive control processes to meet task demands.

Little is known about the mechanisms by which memory for relations is accomplished, or about the time course of the critical processes. Here, eye movement measures were used to examine the time course of subjects' access to and use of relational memory. In four experiments, participants studied faces superimposed on scenic backgrounds and were tested with three-face displays superimposed on the scenes viewed earlier. Participants exhibited disproportionate viewing of the face originally studied with the scene, compared to other equally familiar faces in the test display. When a preview of a previously viewed scene was provided, permitting expectancies about the to-be-presented face to emerge, disproportionate viewing was manifested within 500–750 msec after test display onset, more than a full second in advance of explicit behavioral responses, and occurred even when overt responses were not required. In the absence of preview, the viewing effects were delayed by approximately 1 sec. Relational memory effects were absent in the eye movement behavior of amnesic patients with hippocampal damage, suggesting that these effects depend critically on the hippocampal system. The results provide an index of memory for face-scene relations, indicate the time by which retrieval and identification of these relations occur, and suggest that retrieval and use of relational memory depends critically on the hippocampus and occurs obligatorily, regardless of response requirements.

Various lines of evidence suggest that memory for the relations among arbitrarily paired items acquired prior to testing can influence early processing of a probe stimulus. The event-related potential experiment reported here was designed to explore how early in time memory for a previously established face-scene relationship begins to influence processing of faces, under sequential presentation conditions in which a preview of the scene can promote expectancies about the to-be-presented face. Prior to the current work, the earliest component documented to be sensitive to memory for the relations among arbitrarily paired items was the late positive complex (LPC), but here relational memory effects were evident as early as 270–350 msec after face onset. The latency of these relational memory effects suggests that they may be the precursor to similar effects observed in eye movement behavior. As expected, LPC amplitude was also affected by memory for face-scene relationships, and N400 amplitude reflected some combination of memory for items and memory for the relations among items.

The brain's attentional system identifies and selects information that is task-relevant while ignoring information that is task-irrelevant. In two experiments using functional magnetic resonance imaging, we examined the effects of varying task-relevant information compared to task-irrelevant information. In the first experiment, we compared patterns of activation as attentional demands were increased for two Stroop tasks that differed in the task-relevant information, but not the task-irrelevant information: a color-word task and a spatial-word task. Distinct subdivisions of dorsolateral prefrontal cortex and the precuneus became activated for each task, indicating differential sensitivity of these regions to task-relevant information (e.g., spatial information vs. color). In the second experiment, we compared patterns of activation with increased attentional demands for two Stroop tasks that differed in task-irrelevant information, but not task-relevant information: a color-word task and color-object task. Little differentiation in activation for dorsolateral prefrontal and precuneus regions was observed, indicating a relative insensitivity of these regions to task-irrelevant information. However, we observed a differentiation in the pattern of activity for posterior regions. There were unique areas of activation in parietal regions for the color-word task and in occipito-temporal regions for the color-object task. No increase in activation was observed in regions responsible for processing the perceptual attribute of color. The results of this second experiment indicate that attentional selection in tasks such as the Stroop task, which contain multiple potential sources of relevant information (e.g., the word vs. its ink color), acts more by modulating the processing of task-irrelevant information than by modulating processing of task-relevant information.