Thackery I. Brown

Which Way Was I Going? Contextual Retrieval Supports the Disambiguation of Well Learned Overlapping Navigational Routes

Groundbreaking research in animals has demonstrated that the hippocampus contains neurons that distinguish between overlapping navigational trajectories. These hippocampal neurons respond selectively to the context of specific episodes despite interference from overlapping memory representations. The present study used functional magnetic resonance imaging in humans to examine the role of the hippocampus and related structures when participants need to retrieve contextual information to navigate well learned spatial sequences that share common elements. Participants were trained outside the scanner to navigate through 12 virtual mazes from a ground-level first-person perspective. Six of the 12 mazes shared overlapping components. Overlapping mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required the retrieval of contextual information relevant to the current navigational episode. Results revealed greater activation during the successful navigation of the overlapping mazes compared with the non-overlapping mazes in regions typically associated with spatial and episodic memory, including the hippocampus, parahippocampal cortex, and orbitofrontal cortex. When combined with previous research, the current findings suggest that an anatomically integrated system including the hippocampus, parahippocampal cortex, and orbitofrontal cortex is critical for the contextually dependent retrieval of well learned overlapping navigational routes.

Hippocampus and retrosplenial cortex combine path integration signals for successful navigation.

The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals.

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 individuals 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.

Prospective representation of navigational goals in the human hippocampus

Brain activity to represent the future How do humans navigate from A to B? Brown et al. developed a virtual reality task to investigate the neural representations that support human navigational planning. Highly specific activity of the hippocampus and related brain areas represented the future locations to which participants eventually moved. Network-level interactions of the hippocampus with the prefrontal cortex thus enable flexible representation of planned destinations. Science, this issue p. 1323 The human hippocampus and hippocampal-cortical interactions simulate navigational events during goal-directed planning. Mental representation of the future is a fundamental component of goal-directed behavior. Computational and animal models highlight prospective spatial coding in the hippocampus, mediated by interactions with the prefrontal cortex, as a putative mechanism for simulating future events. Using whole-brain high-resolution functional magnetic resonance imaging and multi-voxel pattern classification, we tested whether the human hippocampus and interrelated cortical structures support prospective representation of navigational goals. Results demonstrated that hippocampal activity patterns code for future goals to which participants subsequently navigate, as well as for intervening locations along the route, consistent with trajectory-specific simulation. The strength of hippocampal goal representations covaried with goal-related coding in the prefrontal, medial temporal, and medial parietal cortex. Collectively, these data indicate that a hippocampal-cortical network supports prospective simulation of navigational events during goal-directed planning.

Cooperative interactions between hippocampal and striatal systems support flexible navigation

Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually dependent navigation.

Contributions of Medial Temporal Lobe and Striatal Memory Systems to Learning and Retrieving Overlapping Spatial Memories

Many life experiences share information with other memories. In order to make decisions based on overlapping memories, we need to distinguish between experiences to determine the appropriate behavior for the current situation. Previous work suggests that the medial temporal lobe (MTL) and medial caudate interact to support the retrieval of overlapping navigational memories in different contexts. The present study used functional magnetic resonance imaging (fMRI) in humans to test the prediction that the MTL and medial caudate play complementary roles in learning novel mazes that cross paths with, and must be distinguished from, previously learned routes. During fMRI scanning, participants navigated virtual routes that were well learned from prior training while also learning new mazes. Critically, some routes learned during scanning shared hallways with those learned during pre-scan training. Overlap between mazes required participants to use contextual cues to select between alternative behaviors. Results demonstrated parahippocampal cortex activity specific for novel spatial cues that distinguish between overlapping routes. The hippocampus and medial caudate were active for learning overlapping spatial memories, and increased their activity for previously learned routes when they became context dependent. Our findings provide novel evidence that the MTL and medial caudate play complementary roles in the learning, updating, and execution of context-dependent navigational behaviors.

A High‐resolution study of hippocampal and medial temporal lobe correlates of spatial context and prospective overlapping route memory

When navigating our world we often first plan or retrieve an ideal route to our goal, avoiding alternative paths that lead to other destinations. The medial temporal lobe (MTL) has been implicated in processing contextual information, sequence memory, and uniquely retrieving routes that overlap or “cross paths.” However, the identity of subregions of the hippocampus and neighboring cortex that support these functions in humans remains unclear. The present study used high‐resolution functional magnetic resonance imaging (hr‐fMRI) in humans to test whether the CA3/DG hippocampal subfield and parahippocampal cortex are important for processing spatial context and route retrieval, and whether the CA1 subfield facilitates prospective planning of mazes that must be distinguished from alternative overlapping routes. During hr‐fMRI scanning, participants navigated virtual mazes that were well‐learned from prior training while also learning new mazes. Some routes learned during scanning shared hallways with those learned during pre‐scan training, requiring participants to select between alternative paths. Critically, each maze began with a distinct spatial contextual Cue period. Our analysis targeted activity from the Cue period, during which participants identified the current navigational episode, facilitating retrieval of upcoming route components and distinguishing mazes that overlap. Results demonstrated that multiple MTL regions were predominantly active for the contextual Cue period of the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal cortex being consistently recruited across trials for Cue periods of both novel and familiar mazes. During early trials of the task, both CA3/DG and CA1 were more active for overlapping than non‐overlapping Cue periods. Trial‐by‐trial Cue period responses in CA1 tracked subsequent overlapping maze performance across runs. Together, our findings provide novel insight into the contributions of MTL subfields to processing spatial context and route retrieval, and support a prominent role for CA1 in distinguishing overlapping episodes during navigational “look‐ahead” periods.

Structural Differences in Hippocampal and Prefrontal Gray Matter Volume Support Flexible Context-Dependent Navigation Ability

Spatial navigation is a fundamental part of daily life. Humans differ in their individual abilities to flexibly navigate their world, and a critical question is how this variability relates to differences in underlying brain structure. Our experiment examined individual differences in the ability to flexibly navigate routes that overlap with, and must be distinguished from, previously learned trajectories. We related differences in flexible navigation performance to differences in brain morphology in healthy young adults using voxel-based morphometry. Our findings provide novel evidence that individual differences in gray matter volume in the hippocampus and dorsolateral prefrontal cortex correlate with our ability rapidly to learn and flexibly navigate routes through our world.

Cognitive control, attention, and the other race effect in memory

People are better at remembering faces from their own race than other races–a phenomenon with significant societal implications. This Other Race Effect (ORE) in memory could arise from different attentional allocation to, and cognitive control over, same- and other-race faces during encoding. Deeper or more differentiated processing of same-race faces could yield more robust representations of same- vs. other-race faces that could support better recognition memory. Conversely, to the extent that other-race faces may be characterized by lower perceptual expertise, attention and cognitive control may be more important for successful encoding of robust, distinct representations of these stimuli. We tested a mechanistic model in which successful encoding of same- and other-race faces, indexed by subsequent memory performance, is differentially predicted by (a) engagement of frontoparietal networks subserving top-down attention and cognitive control, and (b) interactions between frontoparietal networks and fusiform cortex face processing. European American (EA) and African American (AA) participants underwent fMRI while intentionally encoding EA and AA faces, and ~24 hrs later performed an “old/new” recognition memory task. Univariate analyses revealed greater engagement of frontoparietal top-down attention and cognitive control networks during encoding for same- vs. other-race faces, stemming particularly from a failure to engage the cognitive control network during processing of other-race faces that were subsequently forgotten. Psychophysiological interaction (PPI) analyses further revealed that OREs were characterized by greater functional interaction between medial intraparietal sulcus, a component of the top-down attention network, and fusiform cortex during same- than other-race face encoding. Together, these results suggest that group-based face memory biases at least partially stem from differential allocation of cognitive control and top-down attention during encoding, such that same-race memory benefits from elevated top-down attentional engagement with face processing regions; conversely, reduced recruitment of cognitive control circuitry appears more predictive of memory failure when encoding out-group faces.

Noninvasive Functional and Anatomical Imaging of the Human Medial Temporal Lobe

The ability to remember lifes events, and to leverage memory to guide behavior, defines who we are and is critical for everyday functioning. The neural mechanisms supporting such mnemonic experiences are multiprocess and multinetwork in nature, which creates challenges for studying them in humans and animals. Advances in noninvasive neuroimaging techniques have enabled the investigation of how specific neural structures and networks contribute to human memory at its many cognitive and mechanistic levels. In this review, we discuss how functional and anatomical imaging has provided novel insights into the types of information represented in, and the computations performed by, specific medial temporal lobe (MTL) regions, and we consider how interactions between the MTL and other cortical and subcortical structures influence what we learn and remember. By leveraging imaging, researchers have markedly advanced understanding of how the MTL subserves declarative memory and enables navigation of our physical and mental worlds.