Structuring time in human lateral entorhinal cortex

Episodic memories consist of event information linked to spatio-temporal context. Notably, the hippocampus is involved in the encoding, representation and retrieval of temporal relations that comprise a context, but it remains largely unclear how coding for elapsed time arises in the hippocampal-entorhinal region. The entorhinal cortex (EC), the main cortical input structure of the hippocampus, has been hypothesized to provide temporal tags for memories via contextual drift and recent evidence demonstrates that time can be decoded from population activity in the rodent lateral EC. Here, we use fMRI to show that the anterior-lateral EC (alEC), the human homologue region of rodent lateral EC, maps the temporal structure of events. Participants acquired knowledge about temporal and spatial relationships between object positions - dissociated via teleporters - along a fixed route through a virtual city. Multi-voxel pattern similarity in alEC changed through learning to reflect elapsed time between event memories. Furthermore, we reconstructed the temporal structure of object relationships from alEC pattern similarity change. In contrast to the hippocampus, which maps the subjective time between event memories in this task, the temporal map in alEC reflected the objective time elapsed between events. Our findings provide evidence for the notion that alEC represents the temporal structure of memories, putatively derived from slowly-varying population signals during learning. Further, our findings suggest a dissociation between objective and subjective temporal maps in EC and hippocampus; thereby providing novel evidence for the role of the hippocampal-entorhinal region in representing time for episodic memory

Mapping sequence structure in the human lateral entorhinal cortex

Remembering event sequences is central to episodic memory and presumablysupported by the hippocampal-entorhinal region. We previously demonstrated that thehippocampus maps spatial and temporal distances between events encountered along a routethrough a virtual city (Deuker et al., 2016), but the content of entorhinal mnemonic representationsremains unclear. Here, we demonstrate that multi-voxel representations in the anterior-lateralentorhinal cortex (alEC) — the human homologue of the rodent lateral entorhinal cortex —specifically reflect the temporal event structure after learning. Holistic representations of thesequence structure related to memory recall and the timeline of events could be reconstructedfrom entorhinal multi-voxel patterns. Our findings demonstrate representations of temporalstructure in the alEC; dovetailing with temporal information carried by population signals in thelateral entorhinal cortex of navigating rodents and alEC activations during temporal memoryretrieval. Our results provide novel evidence for the role of the alEC in representing time forepisodic memory

Rapid encoding of task regularities in the human hippocampus guides sensorimotor timing

The brain encodes the statistical regularities of the environment in a task-specific yet flexible and generalizable format. Here, we seek to understand this process by bridging two parallel lines of research, one centered on sensorimotor timing, and the other on cognitive mapping in the hippocampal system. By combining functional magnetic resonance imaging (fMRI) with a fast-paced time-to-contact (TTC) estimation task, we found that the hippocampus signaled behavioral feedback received in each trial as well as performance improvements across trials along with reward-processing regions. Critically, it signaled performance improvements independent from the tested intervals, and its activity accounted for the trial-wise regression-to-the-mean biases in TTC estimation. This is in line with the idea that the hippocampus supports the rapid encoding of temporal context even on short time scales in a behavior-dependent manner. Our results emphasize the central role of the hippocampus in statistical learning and position it at the core of a brain-wide network updating sensorimotor representations in real time for flexible behavior

Valence-specific Enhancements in Visual Processing Regions Support Negative Memories:

Thesis advisor: Elizabeth A. KensingerResearch in four parts examines the effects of valence on the neural processes that support emotional memory formation and retrieval. Results show a consistent valence-specific enhancement of visuocortical engagement along the ventral visual stream and occipital cortex that supports negative memories to a greater extent than positive memories. Part I investigated the effects of valence on the interactions between trial-level physiological responses to emotional stimuli (i.e., heart rate deceleration) during encoding and subsequent memory vividness. Results showed that negative memory vividness, but not positive or neutral memory vividness, is tied to arousal-related enhancements of amygdala coupling with early visual cortex during encoding. These results suggest that co-occurring parasympathetic arousal responses and amygdala connectivity with early visual cortex during encoding influence subsequent memory vividness for negative stimuli, perhaps reflecting enhanced memory-relevant perceptual enhancements during encoding of negative stimuli. Part II examined links between individual differences in post-encoding increases is amygdala functional connectivity at rest and the degree and direction of emotional memory biases at retrieval. Results demonstrated that post-encoding increases in amygdala resting state functional connectivity with visuocortical and frontal regions predicted the degree of negative memory bias (i.e., better memory for unpleasant compared to pleasant stimuli) and positive memory bias, respectively. Further, the effect of amygdala-visuocortical post-encoding coupling on behavioral negative memory bias was completely mediated by greater retrieval-related activity for negative stimuli in visuocortical areas. These findings suggest that those individuals with a negative memory bias tend to engage visual processing regions across multiple phases of memory more than individuals with a positive memory bias. While Parts I-II examined encoding-related memory processes, Part III examined the effects of valence on true and false subjective memory vividness at the time of retrieval. The findings showed valence-specific enhancements in regions of the ventral visual stream (e.g., inferior temporal gyrus and parahippocampal cortex) support negative memory vividness to a greater extent than positive memory vividness. However, activation of the parahippocampal cortex also drove a false sense of negative memory vividness. Together, these findings suggest spatial overlap in regions that support negative true and false memory vividness. Lastly, Part IV utilized inhibitory repetitive transcranial magnetic stimulation (rTMS) to test if a portion of occipito-temporal cortex that showed consistent valence-specific effects of negative memory in Parts I-III was necessary for negative memory retrieval. Although some participants showed the hypothesized effect, there was no group-level evidence of a neuromodulatory effect of occipito-temporal cortex rTMS on negative memory retrieval. Together, the results of the current dissertation work highlight the importance of valence-based models of emotional memory and consistently implicated enhanced visuosensory engagement across multiple phases of memory. By identifying valence-specific effects of trial-level physiological arousal during encoding, post-encoding amygdala coupling during early consolidation, and similarities and differences between true and false negative memories, the present set of work has important implications for how negative and positive memories are created and remembered differently.Thesis (PhD) — Boston College, 2019.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Psychology

The ghosts of the past and future: the propagation of anxious beliefs in episodic memory

Anxiety disorders are characterized by the heightened anticipation of future threat. People with anxiety can go to extremes to avoid feared situations, and fear can spread to related situations. For example, being mocked by a friend may over time lead to someone becoming anxious to engage in social situations in general. In this thesis, I aim to elucidate the mechanisms that drive the anticipation and generalization of future threats by utilizing insights from episodic memory. First, I examined how memory for unique experiences can generalize. Across two experiments, I show that we can memorize an event in high levels of detail. However, with repeated experience we also learn what to expect. This knowledge biases our memory towards what we think is generally true, making it less accurate. This bias is enhanced when we experience high levels of stress. This means that for feared situations, your memory may be more negative than it was because you expected a negative outcome. Beyond memory of your past experiences, episodic memory also enables the imagination of potential future events. In two further experiments, we first showed that while non-anxious people had better memory for imagined emotional future events, anxious people did not and tended to forget more details. Second, we showed that when people imagined positive future events similar to a feared situation they were about to engage in, their memory for that feared event was more positive than when they imagined random positive events. Together, these findings suggest that in anxiety emotional (future) memories may become more generalized and biased towards negative expectations, but that positive future thinking can help reduce negative expectations and ease engaging in feared experiences

Hippocampal-entorhinal codes for space, time and cognition

Contains fulltext : 207524.pdf (publisher's version ) (Open Access)Radboud University, 9 oktober 2019Promotor : Doeller, C.F. Co-promotor : Deuker, Lorena225 p