A region of the brain called the perirhinal cortex represents both what things look like and what they mean.

The ability to remember our past depends critically on the hippocampus and ventromedial prefrontal cortex (vmPFC), but their respective roles are debated. Contrary to classic theories, recent work (McCormick et al.) has shown that vmPFC drives the hippocampus during memory retrieval, irrespective of how old the recalled memories are.

Everyday experience requires processing external signals from the world around us and internal information retrieved from memory. To do both, the brain must fluctuate between states that are optimized for external versus internal attention. Here, we focus on the hippocampus as a region that may serve at the interface between these forms of attention and ask how it switches between prioritizing sensory signals from the external world versus internal signals related to memories and thoughts. Pharmacological, computational, and animal studies have identified input from the cholinergic basal forebrain as important for biasing the hippocampus toward processing external information, whereas complementary research suggests the dorsal attention network (DAN) may aid in allocating attentional resources toward accessing internal information. We therefore tested the hypothesis that the basal forebrain and DAN drive the hippocampus toward external and internal attention, respectively. We used data from 29 human participants (17 female) who completed two attention tasks during fMRI. One task (memory-guided) required proportionally more internal attention, and proportionally less external attention, than the other (explicitly instructed). We discovered that background functional connectivity between the basal forebrain and hippocampus was stronger during the explicitly instructed versus memory-guided task. In contrast, DAN-hippocampus background connectivity was stronger during the memory-guided versus explicitly instructed task. Finally, the strength of DAN-hippocampus background connectivity was correlated with performance on the memory-guided but not explicitly instructed task. Together, these results provide evidence that the basal forebrain and DAN may modulate the hippocampus to switch between external and internal attention.SIGNIFICANCE STATEMENT How does the brain balance the need to pay attention to internal thoughts and external sensations? We focused on the human hippocampus, a region that may serve at the interface between internal and external attention, and asked how its functional connectivity varies based on attentional states. The hippocampus was more strongly coupled with the cholinergic basal forebrain when attentional states were guided by the external world rather than retrieved memories. This pattern flipped for functional connectivity between the hippocampus and dorsal attention network, which was higher for attention tasks that were guided by memory rather than external cues. Together, these findings show that distinct networks in the brain may modulate the hippocampus to switch between external and internal attention.

Multiple types of memory guide attention: Both long-term memory (LTM) and working memory (WM) effectively guide visual search. Furthermore, both types of memories can capture attention automatically, even when detrimental to performance. It is less clear, however, how LTM and WM cooperate or compete to guide attention in the same task. In a series of behavioral experiments, we show that LTM and WM reliably cooperate to guide attention: Visual search is faster when both memories cue attention to the same spatial location (relative to when only one memory can guide attention). LTM and WM competed to guide attention in more limited circumstances: Competition only occurred when these memories were in different dimensions - particularly when participants searched for a shape and held an accessory color in mind. Finally, we found no evidence for asymmetry in either cooperation or competition: There was no evidence that WM helped (or hindered) LTM-guided search more than the other way around. This lack of asymmetry was found despite differences in LTM-guided and WM-guided search overall, and differences in how two LTMs and two WMs compete or cooperate with each other to guide attention. This work suggests that, even if only one memory is currently task-relevant, WM and LTM can cooperate to guide attention; they can also compete when distracting features are salient enough. This work elucidates interactions between WM and LTM during attentional guidance, adding to the literature on costs and benefits to attention from multiple active memories.

Goal-directed attention is usually studied by providing individuals with explicit instructions on what they should attend to. But in daily life, we often use past experiences to guide our attentional states. Given the importance of memory for predicting upcoming events, we hypothesized that memory-guided attention is supported by neural preparation for anticipated attentional states. We examined preparatory coding in the human hippocampus and mPFC, two regions that are important for memory-guided behaviors, in two tasks: one where attention was guided by memory and another in which attention was explicitly instructed. Hippocampus and mPFC exhibited higher activity for memory-guided vs. explicitly instructed attention. Furthermore, representations in both regions contained information about upcoming attentional states. In the hippocampus, this preparation was stronger for memory-guided attention, and occurred alongside stronger coupling with visual cortex during attentional guidance. These results highlight the mechanisms by which memories are used to prepare for upcoming attentional goals.

Behaving adaptively requires selection of relevant memories and sensations and suppression of competing ones. We hypothesized that these mechanisms are linked, such that hippocampal computations that resolve competition in memory also shape the precision of sensory representations to guide selective attention. We leveraged f MRI-based pattern similarity, receptive field modeling, and eye tracking to test this hypothesis in humans performing a memory-dependent visual search task. In the hippocampus, differentiation of competing memories predicted the precision of memory-guided eye movements. In visual cortex, preparatory coding of remembered target locations predicted search successes, whereas preparatory coding of competing locations predicted search failures due to interference. These effects were linked: stronger hippocampal memory differentiation was associated with lower competitor activation in visual cortex, yielding more precise preparatory representations. These results demonstrate a role for memory differentiation in shaping the precision of sensory representations, highlighting links between mechanisms that overcome competition in memory and perception.

Attention and memory are intricately linked, but how attention modulates brain areas that subserve memory, such as the hippocampus, is unknown. We hypothesized that attention may stabilize patterns of activity in human hippocampus, resulting in distinct but reliable activity patterns for different attentional states. To test this prediction, we utilized high-resolution functional magnetic resonance imaging and a novel "art gallery" task. On each trial, participants viewed a room containing a painting, and searched a stream of rooms for a painting from the same artist (art state) or a room with the same layout (room state). Bottom-up stimulation was the same in both tasks, enabling the isolation of neural effects related to top-down attention. Multivariate analyses revealed greater pattern similarity in all hippocampal subfields for trials from the same, compared with different, attentional state. This stability was greater for the room than art state, was unrelated to univariate activity, and, in CA2/CA3/DG, was correlated with behavior. Attention therefore induces representational stability in the human hippocampus, resulting in distinct activity patterns for different attentional states. Modulation of hippocampal representational stability highlights the far-reaching influence of attention outside of sensory systems.

Learning about temporal structure is adaptive because it enables the generation of expectations. We examined how the brain uses experience in structured environments to anticipate upcoming events. During fMRI (functional magnetic resonance imaging), individuals watched a 90 s movie clip six times. Using a hidden Markov model applied to searchlights across the whole brain, we identified temporal shifts between activity patterns evoked by the first vs. repeated viewings of the movie clip. In many regions throughout the cortex, neural activity patterns for repeated viewings shifted to precede those of initial viewing by up to 15 s. This anticipation varied hierarchically in a posterior (less anticipation) to anterior (more anticipation) fashion. We also identified specific regions in which the timing of the brain's event boundaries was related to those of human-labeled event boundaries, with the timing of this relationship shifting on repeated viewings. With repeated viewing, the brain's event boundaries came to precede human-annotated boundaries by 1-4 s on average. Together, these results demonstrate a hierarchy of anticipatory signals in the human brain and link them to subjective experiences of events.

Attention to the relations between visual features modulates hippocampal representations. Moreover, hippocampal damage impairs discrimination of spatial relations. We explore a mechanism by which this might occur: modulation by the acetylcholine system. Acetylcholine enhances afferent input to the hippocampus and suppresses recurrent connections within it. This biases hippocampal processing toward environmental input, and should improve externally oriented, hippocampally mediated attention and perception. We examined cholinergic modulation on an attention task that recruits the hippocampus. On each trial, participants viewed two images (rooms with paintings). On "similar room" trials, they judged whether the rooms had the same spatial layout from a different perspective. On "similar art" trials, they judged whether the paintings could have been painted by the same artist. On "identical" trials, participants simply had to detect identical paintings or rooms. We hypothesized that cholinergic modulation would improve performance on the similar room task, given past findings that hippocampal representations predicted, and hippocampal damage impaired, behavior on this task. To test this, nicotine cigarette smokers took part in two sessions: one before which they abstained from nicotine for 12 hours, and one before which they ingested nicotine in the past hour. Individual differences in expired breath carbon monoxide levels-a measure of how recently or how much someone smoked-predicted performance improvements on the similar room task. This finding provides novel support for computational models that propose that acetylcholine enhances externally oriented attentional states in the hippocampus. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Memory for temporal structure enables both planning of future events and retrospection of past events. We investigated how the brain flexibly represents extended temporal sequences into the past and future during anticipation. Participants learned sequences of environments in immersive virtual reality. Pairs of sequences had the same environments in a different order, enabling context-specific learning. During fMRI, participants anticipated upcoming environments multiple steps into the future in a given sequence. Temporal structure was represented in the hippocampus and across visual regions (1) bidirectionally, with graded representations into the past and future and (2) hierarchically, with further events into the past and future represented in successively more anterior brain regions. Further, context-specific predictions were prioritized in the forward but not backward direction. Together, this work sheds light on how we flexibly represent sequential structure to enable planning over multiple timescales.