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Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but research in humans has been constrained by the difficulty of examining hippocampal function during early development. In the present study, we assessed 48 2-year-olds with a novel paradigm in which participants completed two games on a tablet that required remembering associations between unique characters, the places they visited, and the temporal order with which they did so. At the completion of each game, a unique, novel song played. Toddlers remembered spatial locations better than temporal order during an immediate test, after a 20-minute delay, and after a week delay. After the last behavioral session, toddlers underwent an fMRI task during natural nocturnal sleep evaluating hippocampal activation in response to learned and novel songs. We found that the extent of hippocampal activation for learned songs compared to novel songs during sleep was correlated with memory for temproal order across all time delays, but not with memory for spatial locations. The results confirm that that the functional contribution of the hippocampus to early memory can be assessed during sleep and suggest that assessment of temporal aspects of memory in the current task best capture this contribution.

Accurate memories are often associated with vivid experiences of recollection. However, the neural mechanisms underlying subjective recollection and their unique role in decision making beyond accuracy have received limited attention. We dissociated subjective recollection from accuracy during a forced-choice task. Distractors corresponded either to non-studied exemplars of the targets (A-A' condition) or to non-studied exemplars of different studied items (A-B' condition). The A-A' condition resulted in higher accuracy and greater activation in the superior parietal lobe, whereas the A-B' condition resulted in higher subjective recollection and greater activation in the precuneus and retrosplenial regions, indicating a dissociation between objective and subjective memory. Activation in insular, cingulate, and lateral prefrontal regions was also associated with subjective recollection; however, during a subsequent decision phase, activation in these same regions was greater for discarded than for selected responses in anticipation of a social reward, underscoring their role in evaluating memory evidence flexibly based on current goals.

Relational memory improves during middle childhood and adolescence, yet the neural correlates underlying those improvements are debated. Although memory for spatial, temporal, and other associative relations requires the hippocampus, it is not established whether within-individual changes in hippocampal structure contribute to memory improvements from middle childhood into adolescence. Here, we investigated how structural changes in hippocampal head, body, and tail subregions predict improvements in the capacity to remember item-space, item-time, and item-item relations. Memory for each relation and volumes of hippocampal subregions were assessed longitudinally in 171 participants across 3 time points (Mage at T1 = 9.45 years; Mage at T2 = 10.86 years, Mage at T3 = 12.12 years; comprising 393 behavioral assessments and 362 structural scans). Among older children, volumetric growth in: (a) head and body predicted improvements in item-time memory, (b) head predicted improvements in item-item memory; and (c) right tail predicted improvements in item-space memory. The present research establishes that changes in hippocampal structure are related to improvements in relational memory, and that sub-regional changes in hippocampal volume differentially predict changes in different aspects of relational memory. These findings underscore a division of labor along the anterior-posterior axis of the hippocampus during child development.

IntroductionHeterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.MethodsOur international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption.ResultsThis progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures.DiscussionA harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but methodological challenges have hindered assessments of this possibility in humans. Here, we delivered a previously learned song and a novel song to 2-year-old toddlers during natural nocturnal sleep and, using functional magnetic resonance imaging, found that hippocampal activation was stronger for the learned song compared with the novel song. This was true regardless of whether the song was presented intact or backwards. Toddlers who remembered where and in the presence of which toy character they heard the song exhibited stronger hippocampal activation for the song. The results establish that hippocampal activation in toddlers reflects past experiences, persists despite some alteration of the stimulus, and is associated with behavior. This research sheds light on early hippocampal and memory functioning and offers an approach to interrogate the neural substrates of early memory.

Introduction: Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence., Methods: Our international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption., Results: This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures., Discussion: A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.