Functional reconfiguration of task-active frontoparietal control network facilitates abstract reasoning.

While the brain's functional network architecture is largely conserved between resting and task states, small but significant changes in functional connectivity support complex cognition. In this study, we used a modified Raven's Progressive Matrices Task to examine symbolic and perceptual reasoning in human participants undergoing fMRI scanning. Previously, studies have focused predominantly on discrete symbolic versions of matrix reasoning, even though the first few trials of the Raven's Advanced Progressive Matrices task consist of continuous perceptual stimuli. Our analysis examined the activation patterns and functional reconfiguration of brain networks associated with resting state and both symbolic and perceptual reasoning. We found that frontoparietal networks, including the cognitive control and dorsal attention networks, were significantly activated during abstract reasoning. We determined that these same task-active regions exhibited flexibly-reconfigured functional connectivity when transitioning from resting state to the abstract reasoning task. Conversely, we showed that a stable network core of regions in default and somatomotor networks was maintained across both resting and task states. We propose that these regionally-specific changes in the functional connectivity of frontoparietal networks puts the brain in a "task-ready" state, facilitating efficient task-based activation.

Functional network reconfiguration supporting memory-guided attention.

Studies have identified several brain regions whose activations facilitate attentional deployment via long-term memories. We analyzed task-based functional connectivity at the network and node-specific level to characterize large-scale communication between brain regions underlying long-term memory guided attention. We predicted default mode, cognitive control, and dorsal attention subnetworks would contribute differentially to long-term memory guided attention, such that network-level connectivity would shift based on attentional demands, requiring contribution of memory-specific nodes within default mode and cognitive control subnetworks. We expected that these nodes would increase connectivity with one another and with dorsal attention subnetworks during long-term memory guided attention. Additionally, we hypothesized connectivity between cognitive control and dorsal attention subnetworks facilitating external attentional demands. Our results identified both network-based and node-specific interactions that facilitate different components of LTM-guided attention, suggesting a crucial role across the posterior precuneus and restrosplenial cortex, acting independently from the divisions of default mode and cognitive control subnetworks. We found a gradient of precuneus connectivity, with dorsal precuneus connecting to cognitive control and dorsal attention regions, and ventral precuneus connecting across all subnetworks. Additionally, retrosplenial cortex showed increased connectivity across subnetworks. We suggest that connectivity from dorsal posterior midline regions is critical for the integration of external information with internal memory that facilitates long-term memory guided attention.

Gated transformations from egocentric to allocentric reference frames involving retrosplenial cortex, entorhinal cortex, and hippocampus.

This paper reviews the recent experimental finding that neurons in behaving rodents show egocentric coding of the environment in a number of structures associated with the hippocampus. Many animals generating behavior on the basis of sensory input must deal with the transformation of coordinates from the egocentric position of sensory input relative to the animal, into an allocentric framework concerning the position of multiple goals and objects relative to each other in the environment. Neurons in retrosplenial cortex show egocentric coding of the position of boundaries in relation to an animal. These neuronal responses are discussed in relation to existing models of the transformation from egocentric to allocentric coordinates using gain fields and a new model proposing transformations of phase coding that differ from current models. The same type of transformations could allow hierarchical representations of complex scenes. The responses in rodents are also discussed in comparison to work on coordinate transformations in humans and non-human primates.

Theta oscillations support active exploration in human spatial navigation.

Active navigation seems to yield better spatial knowledge than passive navigation, but it is unclear how active decision-making influences learning and memory. Here, we examined the contributions of theta oscillations to memory-related exploration while testing theories about how they contribute to active learning. Using electroencephalography (EEG), we tested individuals on a maze-learning task in which they made discrete decisions about where to explore at each choice point in the maze. Half the participants were free to make active decisions at each choice point, and the other half passively explored by selecting a marked choice (matched to active exploration) at each intersection. Critically, all decisions were made when stationary, decoupling the active decision-making process from movement and speed factors, which is another prominent potential role for theta oscillations. Participants were then tested on their knowledge of the maze by traveling from object A to object B within the maze. Results show an advantage for active decision-making during learning and indicate that the active group had greater theta power during choice points in exploration, particularly in midfrontal channels. These findings demonstrate that active exploration is associated with theta oscillations during human spatial navigation, and that these oscillations are not exclusively related to movement or speed. Results demonstrating increased theta oscillations in prefrontal regions suggest communication with the hippocampus and integration of new information into memory. We also found evidence for alpha oscillations during active navigation, suggesting a role for attention as well. This study finds support for a general mnemonic role for theta oscillations during navigational learning.

Dynamic Network Analysis Demonstrates the Formation of Stable Functional Networks During Rule Learning.

Variations in the functional connectivity of large-scale cortical brain networks may explain individual differences in learning ability. We used a dynamic network analysis of fMRI data to identify changes in functional brain networks that are associated with context-dependent rule learning. During fMRI scanning, naïve subjects performed a cognitive task designed to test their ability to learn context-dependent rules. Notably, subjects were given minimal instructions about the task prior to scanning. We identified several key network characteristics associated with fast and accurate rule learning. First, consistent with the formation of stable functional networks, a dynamic community detection analysis revealed regionally specific reductions in flexible switching between different functional communities in successful learners. Second, successful rule learners showed decreased centrality of ventral attention regions and increased assortative mixing of cognitive control regions as the rules were learned. Finally, successful subjects showed greater decoupling of default and attention communities throughout the entire task, whereas ventral attention and cognitive control regions became more connected during learning. Overall, the results support a framework by which a stable ventral attention community and more flexible cognitive control community support sustained attention and the formation of rule representations in successful learners.

Evidence for a gradient within the medial temporal lobes for flexible retrieval under hierarchical task rules.

A fundamental question in memory research is how the hippocampus processes contextual cues to retrieve distinct mnemonic associations. Prior research has emphasized the importance of hippocampal-prefrontal interactions for context-dependent memory. Our fMRI study examined the human medial temporal lobes (MTL) and their prefrontal interactions when retrieving memories associated with hierarchically organized task contexts. Participants learned virtual object-location associations governed by subordinate and superordinate task rules, which could be independently cued to change. On each fMRI trial, participants retrieved the correct object for convergent rule and location contextual information. Results demonstrated that hippocampal activity and hippocampal-prefrontal functional interconnectivity distinguished retrieval under different levels of hierarchically organized task rules. In explicit contrast to the hippocampal tail, anterior (body and head) regions were recruited specifically for superordinate changes in the contextual hierarchy. The hippocampal body also differed in its functional connectivity with the prefrontal cortex for superordinate versus subordinate changes. Our findings demonstrate a gradient in MTL for associative retrieval under changing task rules, and advance understanding of hippocampal-prefrontal interactions that support flexible contextual memory.

Cardiorespiratory fitness and mnemonic discrimination across the adult lifespan.

With a rising aging population, it is important to develop behavioral tasks that assess and track cognitive decline, and to identify protective factors that promote healthy brain aging. Mnemonic discrimination tasks that rely on pattern separation mechanisms are a promising metric to detect subtle age-related memory impairments. Behavioral performance on these tasks rely on the integrity of the hippocampus and surrounding circuitry, which are brain regions known to be adversely affected in aging and neurodegenerative disorders. Aerobic exercise, which improves cardiorespiratory fitness (CRF), has been shown to counteract aging-related decreases in structural and functional brain integrity and attenuate decline of cognitive performance. Here, we tested the hypothesis that higher CRF attenuates age-related deficits in mnemonic discrimination in both a nonspatial mnemonic discrimination (Mnemonic Similarity Task) and a virtual navigation task (Route Disambiguation Task). Importantly, we included individuals across the lifespan (aged 18-83 yr), including the middle-age range, to determine mnemonic discrimination performance across adulthood. Participants completed two mnemonic discrimination tasks and a treadmill test to assess CRF. Our results demonstrate robust negative age-related effects on mnemonic discrimination performance across both the nonspatial and spatial domains. Critically, higher CRF mitigated age-related attenuation in spatial contextual discrimination task performance, but did not show an attenuation effect on performance for object-based mnemonic discrimination. These results suggest that performance on spatial mnemonic discrimination may be a useful tool to track vulnerability in older individuals at risk for cognitive decline, and that higher CRF may lead to cognitive preservation across the adult lifespan, particularly for spatial disambiguation of similar contexts.

A neural circuit model for a contextual association task inspired by recommender systems.

Behavioral data shows that humans and animals have the capacity to learn rules of associations applied to specific examples, and generalize these rules to a broad variety of contexts. This article focuses on neural circuit mechanisms to perform a context-dependent association task that requires linking sensory stimuli to behavioral responses and generalizing to multiple other symmetrical contexts. The model uses neural gating units that regulate the pattern of physiological connectivity within the circuit. These neural gating units can be used in a learning framework that performs low-rank matrix factorization analogous to recommender systems, allowing generalization with high accuracy to a wide range of additional symmetrical contexts. The neural gating units are trained with a biologically inspired framework involving traces of Hebbian modification that are updated based on the correct behavioral output of the network. This modeling demonstrates potential neural mechanisms for learning context-dependent association rules and for the change in selectivity of neurophysiological responses in the hippocampus. The proposed computational model is evaluated using simulations of the learning process and the application of the model to new stimuli. Further, human subject behavioral experiments were performed and the results validate the key observation of a low-rank synaptic matrix structure linking stimuli to responses.

Improving fitness increases dentate gyrus/CA3 volume in the hippocampal head and enhances memory in young adults.

Converging evidence suggests a relationship between aerobic exercise and hippocampal neuroplasticity that interactively impacts hippocampally dependent memory. The majority of human studies have focused on the potential for exercise to reduce brain atrophy and attenuate cognitive decline in older adults, whereas animal studies often center on exercise-induced neurogenesis and hippocampal plasticity in the dentate gyrus (DG) of young adult animals. In the present study, initially sedentary young adults (18-35 years) participated in a moderate-intensity randomized controlled exercise intervention trial (ClinicalTrials.gov; NCT02057354) for a duration of 12 weeks. The aims of the study were to investigate the relationship between change in cardiorespiratory fitness (CRF) as determined by estimated V˙O2MAX , hippocampally dependent mnemonic discrimination, and change in hippocampal subfield volume. Results show that improving CRF after exercise training is associated with an increased volume in the left DG/CA3 subregion in young adults. Consistent with previous studies that found exercise-induced increases in anterior hippocampus in older adults, this result was specific to the hippocampal head, or most anterior portion, of the subregion. Our results also demonstrate a positive relationship between change in CRF and change in corrected accuracy for trials requiring the highest level of discrimination on a putative behavioral pattern separation task. This relationship was observed in individuals who were initially lower-fit, suggesting that individuals who show greater improvement in their CRF may receive greater cognitive benefit. This work extends animal models by providing evidence for exercise-induced neuroplasticity specific to the neurogenic zone of the human hippocampus.

Cortical and Subcortical Contributions to Long-Term Memory-Guided Visuospatial Attention.

Long-term memory (LTM) helps to efficiently direct and deploy the scarce resources of the attentional system; however, the neural substrates that support LTM-guidance of visual attention are not well understood. Here, we present results from fMRI experiments that demonstrate that cortical and subcortical regions of a network defined by resting-state functional connectivity are selectively recruited for LTM-guided attention, relative to a similarly demanding stimulus-guided attention paradigm that lacks memory retrieval and relative to a memory retrieval paradigm that lacks covert deployment of attention. Memory-guided visuospatial attention recruited posterior callosal sulcus, posterior precuneus, and lateral intraparietal sulcus bilaterally. Additionally, 3 subcortical regions defined by intrinsic functional connectivity were recruited: the caudate head, mediodorsal thalamus, and cerebellar lobule VI/Crus I. Although the broad resting-state network to which these nodes belong has been referred to as a cognitive control network, the posterior cortical regions activated in the present study are not typically identified with supporting standard cognitive control tasks. We propose that these regions form a Memory-Attention Network that is recruited for processes that integrate mnemonic and stimulus-based representations to guide attention. These findings may have important implications for understanding the mechanisms by which memory retrieval influences attentional deployment.

Predictability matters: role of the hippocampus and prefrontal cortex in disambiguation of overlapping sequences.

Previous research has demonstrated that areas in the medial temporal lobe and prefrontal cortex (PFC) show increased activation during retrieval of overlapping sequences. In this study, we designed a task in which degree of overlap varied between conditions in order to parse out the contributions of hippocampal and prefrontal subregions as overlap between associations increased. In the task, participants learned sequential associations consisting of a picture frame, a face within the picture frame, and an outdoor scene. The control condition consisted of a single frame-face-scene sequence. In the low overlap condition, each frame was paired with two faces and two scenes. In the high overlap condition, each frame was paired with four faces and four scenes. In all conditions the correct scene was chosen among four possible scenes and was dependent on the frame and face that preceded the choice point. One day after training, participants were tested on the retrieval of learned sequences during fMRI scanning. Results showed that the middle and posterior hippocampus (HC) was active at times when participants acquired information that increased predictability of the correct response in the overlapping sequences. Activation of dorsolateral PFC occurred at time points when the participant was able to ascertain which set of sequences the correct response belonged to. The ventrolateral PFC was active when inhibition was required, either of irrelevant stimuli or incorrect responses. These results indicate that areas of lateral PFC work in concert with the HC to disambiguate between overlapping sequences and that sequence predictability is key to when specific brain regions become active.

A Working Memory Buffer in Parahippocampal Regions: Evidence from a Load Effect during the Delay Period.

Computational models have proposed that the entorhinal cortex (EC) is well suited for maintaining multiple items in working memory (WM). Evidence from animal recording and human neuroimaging studies show that medial temporal lobe areas including the perirhinal (PrC), EC, and CA1 hippocampal subfield may contribute to active maintenance during WM. Previous neuroimaging work also suggests CA1 may be recruited transiently when encoding novel information, and EC and CA1 may be involved in maintaining multiple items in WM. In this study, we tested the prediction that a putative WM buffer would demonstrate a load-dependent effect during a WM delay. Using high-resolution fMRI, we examined whether activity within the hippocampus (CA3/DG, CA1, and subiculum) and surrounding medial temporal cortices (PrC, EC, and parahippocampal cortex-PHC) is modulated in a load-dependent manner. We employed a delayed matching-to-sample task with novel scenes at 2 different WM loads. A contrast between high- and low-WM load showed greater activity within CA1 and subiculum during the encoding phase, and greater EC, PrC, and PHC activity during WM maintenance. These results are consistent with computational models and suggest that EC/PrC and PHC act as a WM buffer by actively maintaining novel information in a capacity-dependent manner.

Cognitive Control Network Contributions to Memory-Guided Visual Attention.

Visual attentional capacity is severely limited, but humans excel in familiar visual contexts, in part because long-term memories guide efficient deployment of attention. To investigate the neural substrates that support memory-guided visual attention, we performed a set of functional MRI experiments that contrast long-term, memory-guided visuospatial attention with stimulus-guided visuospatial attention in a change detection task. Whereas the dorsal attention network was activated for both forms of attention, the cognitive control network(CCN) was preferentially activated during memory-guided attention. Three posterior nodes in the CCN, posterior precuneus, posterior callosal sulcus/mid-cingulate, and lateral intraparietal sulcus exhibited the greatest specificity for memory-guided attention. These 3 regions exhibit functional connectivity at rest, and we propose that they form a subnetwork within the broader CCN. Based on the task activation patterns, we conclude that the nodes of this subnetwork are preferentially recruited for long-term memory guidance of visuospatial attention.

There and Back Again: Hippocampus and Retrosplenial Cortex Track Homing Distance during Human Path Integration.

Path integration, the updating of position and orientation during movement, often involves tracking a home location. Here, we examine processes that could contribute to successful location tracking in humans. In particular, we investigate a homing vector model of path integration, whereby a navigator continuously tracks a trajectory back to the home location. To examine this model, we developed a loop task for fMRI, in which participants viewed movement that circled back to a home location in a sparse virtual environment. In support of a homing vector system, hippocampus, retrosplenial cortex, and parahippocampal cortex were responsive to Euclidean distance from home. These results provide the first evidence of a constantly maintained homing signal in the human brain. In addition, hippocampus, retrosplenial cortex, and parahippocampal cortex, as well as medial prefrontal cortex, were recruited during successful path integration. These findings suggest that dynamic processes recruit hippocampus, retrosplenial cortex, and parahippocampal cortex in support of path integration, including a homing vector system that tracks movement relative to home. SIGNIFICANCE STATEMENT: Path integration is the continual updating of position and orientation during navigation. Animal studies have identified place cells and grid cells as important for path integration, but underlying models of path integration in humans have rarely been studied. The results of our novel loop closure task are the first to suggest that a homing vector tracks Euclidean distance from the home location, supported by the hippocampus, retrosplenial cortex, and parahippocampal cortex. These findings suggest a potential homing vector mechanism supporting path integration, which recruits hippocampus and retrosplenial cortex to track movement relative to home. These results provide new avenues for computational and animal models by directing attention to homing vector models of path integration, which differ from current movement-tracking models.

Influences of Long-Term Memory-Guided Attention and Stimulus-Guided Attention on Visuospatial Representations within Human Intraparietal Sulcus.

Human parietal cortex plays a central role in encoding visuospatial information and multiple visual maps exist within the intraparietal sulcus (IPS), with each hemisphere symmetrically representing contralateral visual space. Two forms of hemispheric asymmetries have been identified in parietal cortex ventrolateral to visuotopic IPS. Key attentional processes are localized to right lateral parietal cortex in the temporoparietal junction and long-term memory (LTM) retrieval processes are localized to the left lateral parietal cortex in the angular gyrus. Here, using fMRI, we investigate how spatial representations of visuotopic IPS are influenced by stimulus-guided visuospatial attention and by LTM-guided visuospatial attention. We replicate prior findings that a hemispheric asymmetry emerges under stimulus-guided attention: in the right hemisphere (RH), visual maps IPS0, IPS1, and IPS2 code attentional targets across the visual field; in the left hemisphere (LH), IPS0-2 codes primarily contralateral targets. We report the novel finding that, under LTM-guided attention, both RH and LH IPS0-2 exhibit bilateral responses and hemispheric symmetry re-emerges. Therefore, we demonstrate that both hemispheres of IPS0-2 are independently capable of dynamically changing spatial coding properties as attentional task demands change. These findings have important implications for understanding visuospatial and memory-retrieval deficits in patients with parietal lobe damage. SIGNIFICANCE STATEMENT: The human parietal lobe contains multiple maps of the external world that spatially guide perception, action, and cognition. Maps in each cerebral hemisphere code information from the opposite side of space, not from the same side, and the two hemispheres are symmetric. Paradoxically, damage to specific parietal regions that lack spatial maps can cause patients to ignore half of space (hemispatial neglect syndrome), but only for right (not left) hemisphere damage. Conversely, the left parietal cortex has been linked to retrieval of vivid memories regardless of space. Here, we investigate possible underlying mechanisms in healthy individuals. We demonstrate two forms of dynamic changes in parietal spatial representations: an asymmetric one for stimulus-guided attention and a symmetric one for long-term memory-guided attention.

Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: A voxel-based morphometry study.

Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests that exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF). This exercise-enhanced expression of growth hormones may boost synaptic plasticity, and neuronal survival and differentiation, potentially supporting function and structure in brain areas including but not limited to the hippocampus. Here, using voxel based morphometry and a standard graded treadmill test to determine cardio-respiratory fitness (Bruce protocol; ·VO2 max), we examined if entorhinal and hippocampal volumes were associated with cardio-respiratory fitness in healthy young adults (N=33). In addition, we examined if volumes were modulated by recognition memory performance and by serum BDNF, a putative marker of synaptic plasticity. Our results show a positive association between volume in right entorhinal cortex and cardio-respiratory fitness. In addition, average gray matter volume in the entorhinal cortex, bilaterally, was positively associated with memory performance. These data extend prior work on the cerebral effects of aerobic exercise and fitness to the entorhinal cortex in healthy young adults thus providing compelling evidence for a relationship between aerobic fitness and structure of the medial temporal lobe memory system.

Which way and how far? Tracking of translation and rotation information for human path integration.

Path integration, the constant updating of the navigator's knowledge of position and orientation during movement, requires both visuospatial knowledge and memory. This study aimed to develop a systems-level understanding of human path integration by examining the basic building blocks of path integration in humans. To achieve this goal, we used functional imaging to examine the neural mechanisms that support the tracking and memory of translational and rotational components of human path integration. Critically, and in contrast to previous studies, we examined movement in translation and rotation tasks with no defined end-point or goal. Navigators accumulated translational and rotational information during virtual self-motion. Activity in hippocampus, retrosplenial cortex (RSC), and parahippocampal cortex (PHC) increased during both translation and rotation encoding, suggesting that these regions track self-motion information during path integration. These results address current questions regarding distance coding in the human brain. By implementing a modified delayed match to sample paradigm, we also examined the encoding and maintenance of path integration signals in working memory. Hippocampus, PHC, and RSC were recruited during successful encoding and maintenance of path integration information, with RSC selective for tasks that required processing heading rotation changes. These data indicate distinct working memory mechanisms for translation and rotation, which are essential for updating neural representations of current location. The results provide evidence that hippocampus, PHC, and RSC flexibly track task-relevant translation and rotation signals for path integration and could form the hub of a more distributed network supporting spatial navigation. Hum Brain Mapp 37:3636-3655, 2016. © 2016 Wiley Periodicals, Inc.

Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson's Disease.

OBJECTIVES: Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. METHODS: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. RESULTS: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. CONCLUSIONS: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease.

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.

Functional connections between optic flow areas and navigationally responsive brain regions during goal-directed navigation.

Recent computational models suggest that visual input from optic flow provides information about egocentric (navigator-centered) motion and influences firing patterns in spatially tuned cells during navigation. Computationally, self-motion cues can be extracted from optic flow during navigation. Despite the importance of optic flow to navigation, a functional link between brain regions sensitive to optic flow and brain regions important for navigation has not been established in either humans or animals. Here, we used a beta-series correlation methodology coupled with two fMRI tasks to establish this functional link during goal-directed navigation in humans. Functionally defined optic flow sensitive cortical areas V3A, V6, and hMT+ were used as seed regions. fMRI data was collected during a navigation task in which participants updated position and orientation based on self-motion cues to successfully navigate to an encoded goal location. The results demonstrate that goal-directed navigation requiring updating of position and orientation in the first person perspective involves a cooperative interaction between optic flow sensitive regions V3A, V6, and hMT+ and the hippocampus, retrosplenial cortex, posterior parietal cortex, and medial prefrontal cortex. These functional connections suggest a dynamic interaction between these systems to support goal-directed navigation.