Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior-posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC.

Emotional experiences are typically remembered with a greater sense of recollection than neutral experiences, but memory benefits for emotional items do not typically extend to their source contexts. Item and source memory have been attributed to different subregions of the medial temporal lobes (MTL), but it is unclear how emotional item recollection fits into existing models of MTL function and, in particular, what is the role of the hippocampus. To address these issues, we used high-resolution functional magnetic resonance imaging (fMRI) to examine MTL contributions to successful emotional item and context encoding. The results showed that emotional items were recollected more often than neutral items. Whereas amygdala and perirhinal cortex (PRC) activity supported the recollection advantage for emotional items, hippocampal and parahippocampal cortex activity predicted subsequent source memory for both types of items, reflecting a double dissociation between anterior and posterior MTL regions. In addition, amygdala activity during encoding modulated the relationships of PRC activity and hippocampal activity to subsequent item recollection and source memory, respectively. Specifically, whereas PRC activity best predicted subsequent item recollection when amygdala activity was relatively low, hippocampal activity best predicted source memory when amygdala activity was relatively high. We interpret these findings in terms of complementary compared to synergistic amygdala-MTL interactions. The results suggest that emotion-related enhancements in item recollection are supported by an amygdala-PRC pathway, which is separable from the hippocampal pathway that binds items to their source context.

Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here we used fMRI to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- and low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high-reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high-reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation.

The hippocampus plays a critical role in supporting episodic memory, in large part by binding together experiences and items with surrounding contextual information. At present, however, little is known about the roles of different hippocampal subfields in supporting this item-context binding. To address this question, we constructed a task in which items were affiliated with differing types of context-cognitive associations that vary at the local, item level and membership in temporally organized lists that linked items together at a global level. Participants made item recognition judgments while undergoing high-resolution fMRI. We performed voxel pattern similarity analyses to answer the question of how human hippocampal subfields represent retrieved information about cognitive states and the time at which a past event took place. As participants recollected previously presented items, activity patterns in the CA23DG subregion carried information about prior cognitive states associated with these items. We found no evidence to suggest reinstatement of information about temporal context at the level of list membership, but exploratory analyses revealed representations of temporal context at a coarse level in conjunction with representations of cognitive contexts. Results are consistent with characterizations of CA23DG as a critical site for binding together items and contexts in the service of memory retrieval.