The hippocampus is involved in mental navigation for a recently learned, but not a highly familiar environment: a longitudinal fMRI study

Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that memory for a large-scale environment is initially dependent on the hippocampus but is later supported by extra-hippocampal structures (e.g., precuneus, posterior parahippocampal cortex, and lingual gyrus) once the environment is well-learned. Participants were scanned during mental navigation tasks initially when they were newly arrived to the city of Toronto, and later after having lived and navigated within the city for 1 yr. In the first session, activation was observed in the right hippocampus, left precuneus, and postcentral gyrus. The second session revealed activation in the caudate and lateral temporal cortex, but not in the right hippocampus; additional activation was instead observed in the posterior parahippocampal cortex, lingual gyrus, and precuneus. These findings suggest that the right hippocampus is required for the acquisition of new spatial information but is not needed to represent this information when the environment is highly familiar.     

Dissociable neural responses in the hippocampus to the retrieval of facial identity and emotion: an event-related fMRI study

In studies with brain-damaged patients and experimental animals, the medial temporal lobe, including the hippocampus and parahippocampal gyrus, has been found to play a critical role in establishing declarative or episodic memory. We measured the neural response in these structures, using event-related functional magnetic resonance imaging, while six healthy subjects performed the retrieval task for facial identity and emotion, respectively. Under the identity condition, the subjects participated in a yes/no recognition test for neutral faces learned before the scanning. Under the emotion condition, the subjects learned the faces with positive or negative expression and retrieved their expressions from neutral cue faces. The results showed that the left hippocampus is primarily involved in the identification of learned faces, and that the adjacent parahippocampal gyrus responds more to target than to distracter events. These results indicate a specific engagement of the left hippocampal regions in conscious recollection and identification of physiognomic facial features. The activity in the right hippocampus increased under both the identity and emotion conditions. The present results may relate with the functional model of face recognition in which the left hemisphere contributes to the processing of detailed features and the right hemisphere is efficient in the processing of global features.     

Memory for familiar environments learned in the remote past: fMRI studies of healthy people and an amnesic person with extensive bilateral hippocampal lesions

Preserved remote spatial memory in amnesic people with bilateral hippocampal damage, including the well-studied case K.C., challenges spatial theories, which assume that the hippocampus is needed to support all allocentric spatial representations, old or new. It remains possible, however, that residual hippocampal tissue is functional and contributes to successful performance. Here, we examine brain activity with fMRI during the retrieval of spatial information in K.C. and in healthy controls using landmark and route stimuli from a premorbidly familiar neighborhood that K.C. can navigate normally. In all participants, activity was found in the parahippocampal cortex, but not in the hippocampus itself, during all navigational tasks on which K.C. performs well, even though part of his hippocampus remains viable. The opposite pattern was observed on a house recognition task, which is inconsequential to navigation, and on which K.C. performed poorly. On that task, K.C. recruited the right hippocampus presumably because even "familiar" houses were treated as novel by him, whereas controls recruited occipitotemporal cortex, including parahippocampal cortex. The distinction between recent and remote memory, therefore, may apply as much to spatial theories of hippocampal function as it does to theories emphasizing the role of the hippocampus in other types of explicit memory.     

Novelty responses to relational and non-relational information in the hippocampus and the parahippocampal region: a comparison based on event-related fMRI

We conducted two functional magnetic resonance imaging (fMRI) experiments that examined novelty responses in the human medial temporal lobe (MTL) to determine whether the hippocampus makes contributions to memory processing that differ from those of structures in the adjacent parahippocampal region. In light of proposals that such differential contributions may pertain to relational processing demands, we assessed event-related fMRI responses in the MTL for novel single objects and for novel spatial and non-spatial object relationships; subjects were asked to detect these different types of novelties among previously studied items, and they successfully performed this task during scanning. A double dissociation that emerged from the response pattern of regions in the hippocampus and perirhinal cortex provided the strongest support for functional specialization in the MTL. A region in the right middle hippocampus responded to the novelty of spatial and non-spatial relationships but not to the novelty of individual objects. By contrast, a region in right perirhinal cortex, situated in the anterior collateral sulcus, responded to the novelty of individual objects but not to that of either type of relationship. Other MTL regions that responded to novelty in the present study showed no reliable difference in their response to the various novelty types; these regions included anterior parts of the hippocampus and posterior aspects of parahippocampal cortex. Together, our findings indicate that relational processing demands are a critical determinant of functional specialization in the human MTL. They also suggest, however, that a neuroanatomical framework that only distinguishes between the hippocampus and the parahippocampal region is not sufficiently refined to account for all functional differences and similarities observed with respect to relational processes in the human MTL.     

The retrieval of learned sequences engages the hippocampus: Evidence from fMRI

Computational models suggest that the hippocampus plays an important role in the retrieval of sequences. However, empirical evidence supporting hippocampal involvement during sequence retrieval is lacking. The current study used functional magnetic resonance imaging (fMRI) to examine the role of the human hippocampus during the learning and retrieval of sequences. Participants were asked to learn four sequences comprised of six faces each. An overlapping condition, where sequences shared common elements, was comprised of two sequences in which two identical faces were shown as the middle images of both sequences. A nonoverlapping condition contained two sequences that did not share any faces between them. A third random condition contained two sets of six faces that were always presented in a random order. The fMRI data were split into a learning phase and an experienced phase based upon each individual's behavioral performance. Patterns of hippocampal activity during presentation, delay, and choice periods were assessed both during learning (learning phase) and after subjects learned the sequences to criteria (experienced phase). The results revealed hippocampal activation during sequence learning, consistent with previous findings in rats and humans. Critically, the current results revealed hippocampal activation during the retrieval of learned sequences. No difference in hippocampal activation was seen between the overlapping and nonoverlapping sequences during either sequence learning or retrieval of sequences. The results extend our current knowledge by providing evidence that the hippocampus is active during the retrieval of learned sequences, consistent with current computational models of sequence learning and retrieval. © 2009 Wiley‐Liss, Inc.     

Differential contributions of the parahippocampal place area and the anterior hippocampus to human memory for scenes

Past neuroimaging research has identified a parahippocampal place area (PPA) in the posterior medial temporal lobe (MTL), which responds preferentially to visual scenes and plays a role in episodic memory for this class of stimuli. In the present positron emission tomography study, we examined to what extent the functional characteristics of the PPA resemble those of other, more anterior MTL regions across various learning and recognition-memory tasks. We also determined whether the involvement of the PPA in recognition of previously studied scenes is specific to a particular type of scene information. We found that, like the PPA, anterior hippocampal regions showed a novelty response (higher activation for novel than repeated scenes) and a stimulus-related response (higher activation for scenes than objects) during learning, indicating that MTL structures other than the PPA contribute to the encoding of novel stimulus relationships in scenes. However, these anterior hippocampal regions showed no involvement during recognition of either spatial or nonspatial information contained in scenes. The PPA, by contrast, was consistently involved in recognition of all types of scene details, presumably through interactions with co-activated parietal and occipitotemporal cortices. We suggest that MTL contributions from the PPA are sufficient to support recognition of scenes when the task can be based on a perceptually based familiarity process.     

Characterizing the role of the hippocampus during episodic simulation and encoding

The hippocampus has been consistently associated with episodic simulation (i.e., the mental construction of a possible future episode). In a recent study, we identified an anterior‐posterior temporal dissociation within the hippocampus during simulation. Specifically, transient simulation‐related activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. In line with previous theoretical proposals of hippocampal function during simulation, the posterior hippocampal activity was interpreted as reflecting a transient retrieval process for the episodic details necessary to construct an episode. In contrast, the sustained anterior hippocampal activity was interpreted as reflecting the continual recruitment of encoding and/or relational processing associated with a simulation. In the present study, we provide a direct test of these interpretations by conducting a subsequent memory analysis of our previously published data to assess whether successful encoding during episodic simulation is associated with the anterior hippocampus. Analyses revealed a subsequent memory effect (i.e., later remembered > later forgotten simulations) in the anterior hippocampus. The subsequent memory effect was transient and not sustained. Taken together, the current findings provide further support for a component process model of hippocampal function during simulation. That is, unique regions of the hippocampus support dissociable processes during simulation, which include the transient retrieval of episodic information, the sustained binding of such information into a coherent episode, and the transient encoding of that episode for later retrieval.     

Encoding of novel picture pairs activates the perirhinal cortex: an fMRI study

It is well established in nonhuman primates that the medial temporal lobe (MTL) structures, the hippocampus and the entorhinal and perirhinal cortices, are necessary for declarative memory encoding. In humans, the neuropathological and neuropsychological changes in early Alzheimer's disease (AD) further support a role for the rhinal cortex in the consolidation of new events into long-term memory. Little is known, however, regarding the function of the rhinal cortex in humans in vivo. To examine the participation of the interconnected MTL structures as well as the whole-brain network of activated brain areas in visual associative long-term memory, functional magnetic resonance imaging (fMRI) was used to determine the brain regions that are activated during encoding and retrieval of paired pictures in 12 young control subjects. The most striking finding in the MTL activation pattern was the consistent activation of the perirhinal cortex in the encoding-baseline and encoding-retrieval comparisons with a strict statistical threshold (P < 0.00001). In contrast, no perirhinal cortex activation was detected in the retrieval-baseline or retrieval-encoding comparisons even with a low statistical threshold (P < 0.05). The location of the perirhinal activation area was in the transentorhinal part of the perirhinal cortex, in the medial bank of the collateral sulcus. The hippocampus and the more posterior parahippocampal gyrus were activated in both encoding and retrieval conditions. During the encoding processing, MTL activations were more consistent and the hippocampal activation area located more anteriorly than during retrieval. The frontal, parietal, temporal, and occipital association cortices were also activated in the encoding-baseline and retrieval-baseline comparisons. The data suggest that encoding, but not retrieval, of novel picture pairs activates the perirhinal cortex. To our knowledge, this is the first fMRI study reporting encoding activation in this transentorhinal part of the perirhinal cortex, the site of the very earliest neuropathological changes in AD.     

Understanding medial temporal activation in memory tasks: evidence from fMRI of encoding and recognition in a case of transient global amnesia

We used fMRI to examine the activation patterns of patient AE during encoding and recognition of visual scenes during an episode of transient global amnesia (TGA) and 3 months later. Controls (n = 5) showed bilateral (R > L) activation in parahippocampal and fusiform gyri during encoding and right-sided activation in the same regions associated with recognition of previously viewed scenes. AE showed a similar pattern at follow-up. During acute TGA, when performance was profoundly impaired, AE showed no medial temporal activation associated with encoding of new scenes or recognition of old scenes. In both contrasts, the percent signal change in relevant medial temporal regions was more than three standard deviations below the control sample mean. She did, however, show striking bilateral hippocampal activation for recognition attempts (old + new scenes > baseline) even though retrieval was unsuccessful (55% recognition accuracy). This finding was unique to AE on this occasion. This is the first study to document normalization of both encoding and recognition activation patterns in TGA. Furthermore, the strong hippocampal activation during unsuccessful retrieval highlights important issues in interpreting memory-related activations, particularly in dysfunctional systems.     

Encoding and retrieval along the long axis of the hippocampus and their relationships with dorsal attention and default mode networks: The HERNET model

The encoding of sensory input is intertwined with external attention, whereas retrieval is intrinsically related to internal attention. This study proposes a model in which the encoding of sensory input involves mainly the anterior hippocampus and the external attention network, whereas retrieval, the posterior hippocampus and the internal attention network. This model is referred to as the HERNET (hippocampal encoding/retrieval and network) model. Functional neuroimaging studies have identified two intrinsic large‐scale networks closely associated with external and internal attention, respectively. The dorsal attention network activates during any externally oriented mental activity, whereas the default mode network shows increased activity during internally oriented mental activity. Therefore, the HERNET model may predict the activation of the anterior hippocampus and the dorsal attention network during the encoding and activation of the posterior hippocampus and the default mode network during retrieval. To test this prediction, this study provides a meta‐analysis of three memory‐imaging paradigms: subsequent memory, laboratory‐based recollection, and autobiographical memory retrieval. The meta‐analysis included 167 individual studies and 2,856 participants. The results provide support for the HERNET model and suggest that the anterior–posterior gradient of encoding and retrieval includes amygdala regions. More broadly, humans continuously oscillate between external and internal attention and thus between encoding and retrieval processes. These oscillations may involve repetitive and spontaneous activity switching between the anterior hippocampus/dorsal attention network and the posterior hippocampus/default mode network. © 2014 Wiley Periodicals, Inc.