Connections within a network that supports semantic memory matures early, but connectivity between this network and hippocampus does not mature until at least 7-years of age, identifies 7-years as a developmental inflection point in both hippocampal signaling and hippocampal-cortical memory interactions that may support multiple memory systems.
Abstract
Decades of developmental memory research has mainly reported linear and protracted changes in both human hippocampal function and connectivity between the hippocampus and cortex. While foundational, very few studies have interrogated the reliability of hippocampal signals across age, and how this coincides with (or diverges from) age-related changes in connectivity to broader cortical networks supporting multiple memory systems. Here, utilizing movie-watching fMRI data in children 3-12 years and adults, we assessed hippocampal response stability using an inter-subject functional correlation (ISFC) approach, and then measured functional connectivity between the hippocampus and the Posterior Medial (PM) - Anterior Temporal (AT) cortical memory networks proposed to support episodic-like (PM) and semantic-like (AT) memory respectively. Results showed that hippocampal responses are stable in the youngest children, but bifurcate in 7-year-olds –– with half the subjects correlating most highly with younger and half with older age groups. Likewise, we found that while functional connectivity within the AT network is stable across development, connections between the anterior hippocampus and this network did not reach adult levels until around 7-years. Thus, while brain networks supporting semantic memory may be in place early, interactions with the hippocampus may not develop until after middle childhood –– with an inflection point around 7-years of age. Significance Statement The development of the hippocampus, a key-region in episodic memory behaviors, extends well into adolescence. However, little is known about the stability of hippocampal responses across age and how this might impact communication with cortical brain networks supporting episodic and semantic memory. Here, we show that connectivity within a network that supports semantic memory matures early, but connectivity between this network and hippocampus does not mature until at least 7-years of age. Unlike all other ages, 7-year-olds’ hippocampal responses are not stable: half of the subjects’ responses appear immature and half mature for their age. This work identifies 7-years as a developmental inflection point in both hippocampal signaling and hippocampal-cortical memory interactions that may support multiple memory systems.
The hippocampus is increasingly recognized for its role in working memory representations and goal-directed behavior, yet whether these functions share common neural substrates remains unclear. We investigated short-term memory performance in 27 patients (21 males and 6 females) with LGI1-antibody limbic encephalitis, a condition with predominant hippocampal involvement, compared to 27 age- and gender-matched healthy controls, using an object–location continuous report task with Bayesian mixture-modeling. Patients exhibited predominantly elevated misbinding errors—incorrectly associating objects with non-target locations—with unaltered guessing and only marginally reduced precision. Critically, apathy was positively associated with misbinding exclusively in patients, independent of depression and global cognition. Neuroimaging in a subset of patients (n = 12) revealed reduced hippocampal volumes and preliminary evidence for diminished hippocampal—medial prefrontal connectivity, which was associated with both higher apathy and increased misbinding at short retention intervals. These findings demonstrate that hippocampal dysfunction produces convergent deficits in memory binding and motivation, potentially reflecting disruption of a common brain mechanism linking working memory processing to goal-directed behavior.
B. Attaallah, M. Maio, Y. Tabi et al.· Journal of Neuroscience· 0 citations
Introduction Fidelity of detailed information retrieved from long-term memory (LTM) declines in aging due to changes affecting learning and remembering processes. Such behavioral deficits correspond with functional alterations in the hippocampal formation. However, it is unclear whether age-related decline in high-fidelity retrieval alters functional connections between hippocampal and cortical regions. Methods Twenty-two cognitively intact older adults (69.4 ± 4.4 years) completed mnemonic discrimination tasks during fMRI indicating, whether previously encoded targets, lures, or novel objects were old or new. Results Participants’ high-fidelity memory, measured by the lure discrimination index (the proportion of “new” responses to lures minus the proportion of “old” responses to novel objects), was 0.45 ± 0.04 – lower than previously reported scores in young adults. High-fidelity LTM in older adults engaged a hippocampal formation region in the left entorhinal cortex with trial-wise beta-series connections to the right angular gyrus and the left precuneus. Discussion Taken together, we characterize the distribution of medial temporal lobe (MTL)-cortical networks in older adults that underlies high-fidelity memory.
Joseph C. C. Chen, A. Gazzaley, Peter E. Wais· Frontiers in Aging Neuroscie...· 0 citations
Episodic memory and spatial navigation are often viewed as interlinked, in part due to their shared reliance on medial-temporal lobe (MTL) structures. At the same time, there are important differences, for example, natural spatial navigation requires moving one's body through space while episodic memory does not. We investigated whether naturalistically encoded memories that were either episodic or additionally embedded in a navigational experience relied on overlapping or distinct neural networks. Children ages 8-13 years old and young adults viewed pictures of objects that they had previously encountered in real-world experiences, either on a tour of a new environment or seated in a room, along with novel objects. Univariate fMRI analyses revealed tour-related activity in entorhinal (ERC) and perirhinal (PRC) cortices that differed between early adolescents and adults. Functional connectivity between ERC and PRC for episodic memory decreased with age. Exploratory findings suggested behavior-driven connectivity among the hippocampus, ERC, and lateral occipital cortex to support reconstruction of the spatial context. Naturalistic episodic and spatial contexts are processed in the MTL, but these regions may interact somewhat differently in episodic and navigational contexts, and in late childhood and early adolescence versus early adulthood.
Kim V. Nguyen, L. Skalaban, Büşra Tanrıverdi et al.· Journal of Cognitive Neurosc...· 0 citations
How memories reorganize across brain circuits as they age remains a central question in systems neuroscience. Systems consolidation is thought to progressively shift memory reliance from the hippocampus to distributed cortical networks, yet the contribution of cortical regions beyond the prefrontal cortex and the nature of this shift remains unclear. Here we define the circuit-level organization of remote memory recall across entorhinal, prefrontal, and hippocampal subregions. Using high-resolution activity mapping combined with causal manipulations that leverage natural memory decay, we adapted a murine object-location paradigm to examine memory recall across the lifespan. We find that recall of early remote memories (1 month) selectively depends on a LEC-hippocampal (CA1/CA3) circuit, whereas recall of older memories (6-12 months) recruits a distinct and broader network involving both LEC and MEC together with ACC and CA1. These findings reveal a temporally ordered, circuit-specific reconfiguration of hippocampo-cortical networks and identify the EC as a dynamic hub in remote memory retrieval. Our results refine prevailing systems consolidation theories by showing that memory consolidation is a circuit-specific and temporally ordered process, rather than a passive gradual phenomenon, and position the EC as a central and dynamic component of remote memory retrieval alongside the PFC. Graphical abstract
BACKGROUND
Reliable detection of hippocampal engagement is critical in presurgical memory fMRI, yet the extent to which different paradigms differentially recruit anterior and posterior hippocampal regions at the individual level remains unclear. This study systematically compares hippocampal engagement across three commonly used memory fMRI tasks-autobiographical memory (AUT), picture encoding (PIC) and hometown walking (HTW)- at the individual level, with a particular emphasis on anterior versus posterior hippocampal regions.
METHODS
A total of 113 presurgical patients completed at least one memory fMRI task (AUT: n = 41; PIC: n = 53; HTW: n = 60). Hippocampal regions of interest were anatomically defined and subdivided into anterior/posterior and ipsilesional/contralesional segments. Individual-level suprathreshold activation detectability of hippocampal ROIs was assessed using standardized statistical criteria (p < 0.01, uncorrected).
RESULTS
All tasks showed high global hippocampal detection rates. However, regional differences were observed in the anterior hippocampus, where AUT demonstrated higher detectability, particularly contralesionally (88.9 %), compared with PIC (60 %) and HTW (64.7 %) (Cramér's V = 0.259). In contrast, posterior hippocampal detection was high and comparable across tasks, with PIC showing the highest rates (80.6-97.8 %). Whole-brain analyses revealed stronger engagement of default mode network regions for AUT.
CONCLUSIONS
Memory fMRI paradigms show distinct regional hippocampal engagement profiles and are not interchangeable for presurgical mapping at the individual level. These findings may inform task selection in presurgical memory fMRI depending on the anatomical region of interest and clinical context.
Eva Calderón-Rubio, A. Miró-Padilla, Jesús Adrián-ventura et al.· Epilepsy & Behavior· 0 citations
Healthy aging is associated with structural and functional brain changes. However, cognitive abilities vary in how they change with age: executive functions decline, while aspects of linguistic processing remain relatively preserved. This heterogeneity predicts differences among brain networks in whether and how they change with age. To evaluate this prediction, we used precision fMRI to examine the language-selective network and the Multiple Demand (MD) network, which supports executive functions, in older adults (N = 64) relative to young controls (N = 483). The MD network of older adults shows weaker, less spatially extensive, and more topographically variable activations during an executive function task and reduced within-network functional connectivity. In contrast, we find remarkable preservation of the language network in older adults: it responds during language comprehension as strongly and selectively as in younger adults, with similar left-hemispheric lateralization and within-network functional connectivity. These findings align with behavioral preservation of language comprehension in healthy aging. Here, the authors show that aging affects brain networks differently, with neural changes mirroring the preservation or decline of the cognitive functions they support. The multiple demand network exhibits age-related decline while the language network remains stable with age.
A. Billot, Niharika Jhingan, M. Varkanitsa et al.· Nature Communications· 0 citations
