Multidimensional Hippocampal Connectivity Gradients Support Memory Across the Adult Lifespan

Core Concepts

Distinct dimensions of hippocampal-neocortical functional connectivity, organized along the hippocampus longitudinal axis, contribute to episodic memory function across the adult lifespan. Maintaining a youth-like gradient profile in older age supports preserved mnemonic functioning.

Abstract

The study examined the multidimensional functional organization of the hippocampus across the adult lifespan and its relevance for memory function. Using resting-state fMRI data, the authors identified three principal gradients of hippocampal-neocortical connectivity: The principal anteroposterior gradient (G1) conveyed gradual change in connectivity along the hippocampus longitudinal axis, linking medial orbitofrontal, temporolimbic, and medial parietal regions at the anterior end with occipital and frontoparietal regions at the posterior end. G1 corresponded to a cortical gradient separating task-negative and task-positive networks. The second-order gradient (G2) expressed a secondary long-axis gradient organized from the middle hippocampus towards anterior and posterior ends. G2 reflected the principal unimodal-transmodal gradient of cortical function and showed spatial correspondence with the distribution of hippocampal dopamine D1 receptors. The third-order gradient (G3) reflected variation along the hippocampus transverse axis, separating inferior-lateral from medial-superior parts, particularly in the anterior hippocampus. Older age was associated with less distinct transitions in connectivity along G1 and G2, an effect that was exacerbated in a subgroup of older adults exhibiting an "aged" gradient profile. In contrast, older adults maintaining a "youth-like" gradient profile displayed superior episodic memory performance, with G1 topography predicting memory in this group. These findings underscore the importance of disentangling multiple dimensions of hippocampal-neocortical integration in understanding memory-related behavior across the adult lifespan.

Stats

"Older age was associated with less distinct transitions in connectivity along G1 and G2." "Older adults maintaining a "youth-like" gradient profile displayed superior episodic memory performance."

Quotes

"Maintaining a youth-like gradient profile in older age supports preserved mnemonic functioning." "Distinct dimensions of hippocampal-neocortical functional connectivity, organized along the hippocampus longitudinal axis, contribute to episodic memory function across the adult lifespan."

Key Insights Distilled From

Two long-axis dimensions of hippocampal-cortical integration support memory function across the adult lifespan

by Nordin,K., P... at www.biorxiv.org 03-25-2023

https://www.biorxiv.org/content/10.1101/2023.03.24.534115v3

Deeper Inquiries

How do the identified hippocampal gradients relate to the heterogeneous vulnerability of hippocampal subregions to aging and disease?

The identified hippocampal gradients, particularly the principal anteroposterior gradient (G1) and the second-order gradient (G2), provide insights into the heterogeneous vulnerability of hippocampal subregions to aging and disease. These gradients reflect distinct dimensions of macroscale cortical organization and functional connectivity within the hippocampus. The G1 gradient, which conveys gradual anterior-to-posterior variation in cortical connectivity, aligns with the known anteroposterior differentiation in hippocampal connectivity. This gradient may play a role in differentiating task-negative and task-positive cortical areas, which are crucial for memory and cognitive functions. On the other hand, the G2 gradient, representing a secondary long-axis gradient from the middle hippocampus towards anterior and posterior ends, may reflect a unimodal-transmodal organization across cortex. In the context of aging and disease, the observed age-related changes in the topography of these gradients, with older age associated with less distinct transitions along the gradients, suggest a dedifferentiation of hippocampal connectivity patterns. This loss of specificity in connectivity change across gradients in older individuals, particularly those exhibiting an aged gradient profile, may contribute to functional isolation of hippocampal subregions from neocortical areas. This disconnection has been linked to cognitive decline, especially in memory-related functions, and is associated with conditions like Alzheimer's disease. Therefore, the identified hippocampal gradients provide a framework for understanding how age-related changes in connectivity patterns may underlie the vulnerability of hippocampal subregions to aging and disease.

How might the potential mechanisms underlying the maintenance of a youth-like gradient profile in older age, and its association with preserved memory function?

The maintenance of a youth-like gradient profile in older age, characterized by preserved distinctiveness of connectivity change along the gradients, may be linked to several potential mechanisms. One possible mechanism is the preservation of efficient communication and integration between hippocampal subregions and neocortical areas, which is essential for memory function. The youth-like gradient profile may indicate that older adults retain the ability to maintain differentiated functional connectivity patterns that support memory processes. This preservation could be attributed to factors such as cognitive engagement, neuroplasticity, and healthy aging practices that promote neural resilience and connectivity. Furthermore, the association between the youth-like gradient profile and preserved memory function suggests that maintaining distinct connectivity patterns within the hippocampus contributes to cognitive resilience in older age. Older adults with a youth-like gradient profile may exhibit more efficient neural processing, better cognitive flexibility, and enhanced memory encoding and retrieval mechanisms. These individuals may also benefit from a more integrated and coordinated neural network that supports memory consolidation and retrieval processes. Overall, the maintenance of a youth-like gradient profile in older age may reflect the preservation of optimal neural connectivity and function that underlies preserved memory performance.

How might the multidimensional hippocampal organization revealed in this study inform our understanding of hippocampal contributions to broader cognitive domains beyond memory, such as spatial navigation and social cognition?

The multidimensional hippocampal organization revealed in this study provides valuable insights into hippocampal contributions to broader cognitive domains beyond memory, including spatial navigation and social cognition. The identified hippocampal gradients, particularly the principal anteroposterior gradient (G1) and the second-order gradient (G2), reflect distinct patterns of functional connectivity that may play a role in supporting various cognitive functions. In the context of spatial navigation, the hippocampus is known to be crucial for spatial memory and navigation abilities. The identified gradients, especially G1, which differentiates task-negative and task-positive cortical areas, may contribute to the integration of spatial information and navigation-related processes. The spatial distribution of cortical networks along these gradients could influence the encoding and retrieval of spatial memories, as well as the navigation strategies employed by individuals. Regarding social cognition, the hippocampus is involved in processing social information, emotional memory, and social behavior. The multidimensional organization of hippocampal connectivity revealed in this study could shed light on how the hippocampus integrates social and emotional cues from the environment. The connectivity patterns along the identified gradients may influence social memory, emotional regulation, and the interpretation of social cues. Understanding how these gradients relate to social cognitive processes could provide insights into the neural mechanisms underlying social behavior and interactions. Overall, the multidimensional hippocampal organization uncovered in this study offers a comprehensive framework for investigating the hippocampus's role in diverse cognitive domains, including spatial navigation and social cognition. By elucidating the connectivity patterns and functional organization of the hippocampus, this research enhances our understanding of how the hippocampus contributes to a wide range of cognitive functions beyond memory.