Repetition suppression in the medial temporal lobe and midbrain is altered by event overlap

Abstract

Repeated encounters with the same event typically lead to decreased activation in the medial temporal lobe (MTL) and dopaminergic midbrain, a phenomenon known as repetition suppression. In contrast, encountering an event that overlaps with prior experience leads to increased response in the same regions. Such increased responding is thought to reflect an associative novelty signal that promotes memory updating to resolve differences between current events and stored memories. Here, we married these ideas to test whether event overlap significantly modulates MTL and midbrain responses—even when events are repeated and expected—to promote memory updating through integration. While undergoing high-resolution functional MRI, participants were repeatedly presented with objects pairs, some of which overlapped with other, intervening pairs and some of which contained elements unique from other pairs. MTL and midbrain regions showed widespread repetition suppression for non-overlapping pairs containing unique elements; however, the degree of repetition suppression was altered for overlapping pairs. Entorhinal cortex, perirhinal cortex (PRc), midbrain, and PRc—midbrain connectivity showed repetition-related increases across overlapping pairs. Notably, increased PRc activation for overlapping pairs tracked individual differences in the ability to reason about the relationships among pairs—our behavioral measure of memory integration. Within hippocampus, activation increases across overlapping pairs were unique to CA1, consistent with its hypothesized comparator function. These findings demonstrate that event overlap engages MTL and midbrain functions traditionally implicated in novelty processing, even when overlapping events themselves are repeated. Our findings further suggest that the MTL—midbrain response to event overlap may promote integration of new content into existing memories, leading to the formation of relational memory networks that span experiences. Moreover, the results inform theories about the division of labor within MTL, demonstrating that the role of PRc in episodic encoding extends beyond familiarity processing and item-level recognition.

Functional connectivity between memory and reward centers across task and rest track memory sensitivity to reward

“…While this finding was not expected a priori, it is consistent with the proposal that interactions between midbrain and medial temporal regions are not unique to externally motivated rewards but support encoding and consolidation in general (Lisman et al, 2011). Consistent with this view, midbrain has been shown to interact with hippocampus in encoding tasks that do not involve reward (Duncan et al, 2014;Zeithamova, Manthuruthil, & Preston, 2016), with both background connectivity during encoding (Duncan et al, 2014) and rest connectivity after encoding (Tompary et al, 2015) tracking associative memory. Our findings suggest that midbrain connectivity during reward motivated encoding may be more relevant to overall associative memory than reward modulation of memory and potentially plays a distinct functional role in memory from other reward-related regions.…”

“…Resting state functional connectivity can change on a short time-scale in response to a task (Tambini et al, 2010;Urner, Schwarzkopf, Friston, & Rees, 2013), with learning-related connectivity changes relating to memory performance (Gruber et al, 2016;Murty et al, 2017;Tambini et al, 2010;Urner et al, 2013). During task performance, across-region coupling may change even more rapidly, differentiating between memory task conditions at the order of minutes or even from individual trial to individual trial (Kafkas & Montaldi, 2015;Rissman, Gazzaley, & D'Esposito, 2004;Zeithamova et al, 2012;Zeithamova et al, 2016). For example, Kafkas and Montaldi (2015) showed that hippocampal-VS connectivity was greater during encoding of unexpected versus expected stimuli.…”

Modulation of target recollection and recollection rejection networks due to retrieval facilitation and interference

“…Cold Spring Harbor Laboratory Press on August 31, 2020 -Published by learnmem.cshlp.org Downloaded from overlapping information in between item repetitions reduces repetition priming compared with repetition without interleaved related information (Zeithamova et al 2016), which indicates a need to re-parse target information in relationship to other recently experienced, similar information. In the case of L1 target recollections, a related lure is presented between the target's presentation at encoding and that at retrieval.…”

Effects of Repetition Learning on Associative Recognition Over Time: Role of the Hippocampus and Prefrontal Cortex

“…During encoding, multiple learning leads to decreased activation in stimulus-related cortical regions and the hippocampus when compared to learning once (for reviews, Grill-Spector et al, 2006 ; Segaert et al, 2013 ). The repetition suppression in the hippocampus is confirmed when the single stimuli (e.g., pictures, Suzuki et al, 2011 ; Manelis et al, 2013 ) and stimulus associations are repeatedly presented (e.g., face-name pairs, Rand-Giovannetti et al, 2006 ; Vannini et al, 2013 ; face-scene pairs, Kremers et al, 2014 and object pairs, Zeithamova et al, 2016 ). During retrieval, studies which focus on implicit retrieval suggested that the hippocampal activation increases when subjects retrieve repeated items (vs. new items) by explicit strategy (e.g., Schacter and Buckner, 1998 ; for reviews, see Segaert et al, 2013 ; Kim, 2017 ), but those studies did not directly manipulate retrieval processes to explore the role of the hippocampus for the learning effect.…”