Memory can often be triggered by retrieval cues that are quite different from the originally encoded events, but how different memory processes respond to variations in cue–target similarity is poorly understood. We begin by presenting simulations using a neurocomputational model of recognition memory (i.e., the complementary learning systems model), which proposes that the hippocampus supports recollection of associative information whereas the surrounding cortex supports assessments of item familiarity. The simulations showed that increases in the similarity between retrieval cues and learned items led to relatively linear increases in a cortex-based memory signal but led to steeper and more thresholded increases in the hippocampal signal. We then tested the predictions of the model by examining the effects of varying cue–target similarity in two recognition memory experiments in which participants studied a list of computer-generated faces and then, at test, gave confidence and remember/know responses to morphed faces. In both experiments, as cue–target similarity was increased, familiarity-based recognition increased in a gradual and relatively linear fashion, whereas recollection showed significantly steeper gradients. The results show that recollection and familiarity exhibit distinct similarity functions in recognition memory that correspond with predicted retrieval dynamics of the hippocampus and cortex, respectively.

Neural systems may be characterized by measuring functional interactions in the healthy brain, but it is unclear whether components of systems defined in this way share functional properties. For instance, within the medial temporal lobes (MTL), different subregions show different patterns of cortical connectivity. It is unknown, however, whether these intrinsic connections predict similarities in how these regions respond during memory encoding. Here, we defined brain networks using resting state functional connectivity (RSFC) then quantified the functional similarity of regions within each network during an associative memory encoding task. Results showed that anterior MTL regions affiliated with a network of anterior temporal cortical regions, whereas posterior MTL regions affiliated with a network of posterior medial cortical regions. Importantly, these connectivity relationships also predicted similarities among regions during the associative memory task. Both in terms of task-evoked activation and trial-specific information carried in multivoxel patterns, regions within each network were more similar to one another than were regions in different networks. These findings suggest that functional heterogeneity among MTL subregions may be related to their participation in distinct large-scale cortical systems involved in memory. At a more general level, the results suggest that components of neural systems defined on the basis of RSFC share similar functional properties in terms of recruitment during cognitive tasks and information carried in voxel patterns.

Perceptual judgments can be based on two kinds of information: state-based perception of specific, detailed visual information, or strength-based perception of global or relational information. State-based perception is discrete in the sense that it either occurs or fails, whereas strength-based perception is continuously graded from weak to strong. The functional characteristics of these types of perception have been examined in some detail, but whether state- and strength-based perception are supported by different brain regions has been largely unexplored. A consideration of empirical work and recent theoretical proposals suggests that parietal and occipito-temporal regions may be differentially associated with state- and strength-based signals, respectively. We tested this parietal/occipito-temporal state/strength hypothesis using fMRI and a visual perception task that allows separation of state- and strength-based perception. Participants made same/different judgments on pairs of faces and scenes using a 6-point confidence scale where “6” responses indicated a state of perceiving specific details that had changed, and “1” to “5” responses indicated judgments based on varying strength of relational match/mismatch. Regions in the lateral and medial posterior parietal cortex (supramarginal gyrus, posterior cingulate cortex, and precuneus) were sensitive to state-based perception and were not modulated by varying levels of strength-based perception. In contrast, bilateral fusiform gyrus activation was increased for strength-based “different” responses compared with misses and did not show state-based effects. Finally, the lateral occipital complex showed increased activation for state-based responses and additionally showed graded activation across levels of strength-based perception. These results offer support for a state/strength distinction between parietal and temporal regions, with the lateral occipital complex at the intersection of state- and strength-based processing.

Results from fMRI have strongly supported the idea that the ventrolateral PFC (VLPFC) contributes to successful memory formation, but the role the dorsolateral PFC (DLPFC) in memory encoding is more controversial. Some findings suggest that the DLPFC is recruited when one is processing relationships between items in working memory, and this processing specifically promotes subsequent memory for these relationships. However, previous studies could not rule out the possibility that DLPFC promotes memory during all elaborative encoding conditions and contributes to memory on all subsequent associative memory tests. To address this question directly, we used fMRI to examine activity during two encoding tasks that prompted participants to encode either relational or item-specific information. On relational trials, participants imagined pairs of items interacting, whereas on item-specific trials, participants imagined the items spatially separated and in different sizes. After scanning, we examined memory for relational information and item-specific information. fMRI results showed that DLPFC activity specifically promoted memory for relational information during relational encoding and not memory for item-specific information during item-specific encoding. In contrast, activity in the VLPFC predicted memory for both relational and item-specific information. The present results are consistent with the idea that the DLPFC specifically contributes to successful memory formation through its role in building relationships among items.

The medial temporal lobes (MTLs) are critical for episodic memory but the functions of MTL subregions are controversial. According to memory strength theory, MTL subregions collectively support declarative memory in a graded manner. In contrast, other theories assert that MTL subregions support functionally distinct processes. For instance, one view is that perirhinal cortex (PRc) processes item information, parahippocampal cortex (PHc) processes context information, and the hippocampus binds item and context. Here, we report two experiments that tested competing predictions from these models. In these studies, subjects encoded color–word associations by imagining color either as a contextual association (context detail condition) or as a feature of the item to be encoded (item detail condition). Results showed that encoding color information as an item detail improved source recognition in amnesic patients with recollection deficits. Furthermore, event-related fMRI data from healthy subjects revealed PRc activation associated with successful retrieval of item details, whereas activation in the hippocampus and PHc was associated with recollection-based source retrieval. The qualitatively different patterns of results observed in PRc and hippocampus/PHc are inconsistent with a memory strength account and are consistent with the idea that different MTL regions process different types of episodic information.

Changes in memory function in elderly individuals are often attributed to dysfunction of the prefrontal cortex (PFC). One mechanism for this dysfunction may be disruption of white matter tracts that connect the PFC with its anatomical targets. Here, we tested the hypothesis that white matter degeneration is associated with reduced prefrontal activation. We used white matter hyperintensities (WMH), a magnetic resonance imaging (MRI) finding associated with cerebrovascular disease in elderly individuals, as a marker for white matter degeneration. Specifically, we used structural MRI to quantify the extent of WMH in a group of cognitively normal elderly individuals and tested whether these measures were predictive of the magnitude of prefrontal activity (fMRI) observed during performance of an episodic retrieval task and a verbal working memory task. We also examined the effects of WMH located in the dorsolateral frontal regions with the hypothesis that dorsal PFC WMH would be strongly associated with not only PFC function, but also with areas that are anatomically and functionally linked to the PFC in a task-dependent manner. Results showed that increases in both global and regional dorsal PFC WMH volume were associated with decreases in PFC activity. In addition, dorsal PFC WMH volume was associated with decreased activity in medial temporal and anterior cingulate regions during episodic retrieval and decreased activity in the posterior parietal and anterior cingulate cortex during working memory performance. These results suggest that disruption of white matter tracts, especially within the PFC, may be a mechanism for age-related changes in memory functioning.