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Functional Connectivity of the Anterior and Posterior Hippocampus: Differential Effects of Glucose in Younger and Older Adults.

ABSTRACT: The hippocampus features structurally and functionally distinct anterior and posterior segments. Relatively few studies have examined how these change during aging or in response to pharmacological interventions. Alterations in hippocampal connectivity and changes in glucose regulation have each been associated with cognitive decline in aging. A distinct line of research suggests that administration of glucose can lead to a transient improvement in hippocampus-dependent memory. Here, we probe age, glucose and human cognition with a special emphasis on resting-state functional connectivity (rsFC) of the hippocampus along its longitudinal axis to the rest of the brain. Using a randomized, placebo-controlled, double-blind, crossover design 32 healthy adults (16 young and 16 older) ingested a drink containing 25 g glucose or placebo across two counter balanced sessions. They then underwent resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive testing. There was a clear dissociation in the effects of glucose by age. Magnitude change in rsFC from posterior hippocampus (pHPC) to medial frontal cortex (mPFC) was correlated with individual glucose regulation and gains in performance on a spatial navigation task. Our results demonstrate that glucose administration can attenuate cognitive performance deficits in older adults with impaired glucose regulation and suggest that increases in pHPC-mPFC rsFC are beneficial for navigation task performance in older participants.

SUBMITTER: Peters R

PROVIDER: S-EPMC7004964 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSubjective cognitive decline (SCD) is a putative Alzheimer's disease (AD) precursor without objective neuropsychological deficits. The hippocampus plays an important role in cognitive function and emotional responses and is generally aberrant in SCD. However, previous studies have mainly focused on static functional connectivity (sFC) by resting-state functional magnetic resonance imaging (fMRI) in SCD individuals, and it remains unclear whether hippocampal dynamic functional connectivity (dFC) changes exist in SCD and whether those changes are associated with subtle changes in cognitive function or affect.MethodsSeventy SCD patients and 65 healthy controls were recruited. Demographic data, comprehensive neuropsychology assessments, and resting-state fMRI data were collected. The bilateral anterior and posterior hippocampi were selected as seeds to investigate the static and dynamic functional connectivity alterations in SCD.ResultsCompared to healthy controls, subjects with SCD exhibited: (1) decreased sFC between the left caudal hippocampus and left precuneus; (2) decreased dFC variability between the bilateral caudal hippocampus and precuneus; (3) increased dFC variability between the bilateral rostral hippocampus and caudate nucleus; and (4) increased dFC variability between the left rostral hippocampus and left olfactory cortex. Additionally, the attention scores were positively correlated with dFC variability between the left posterior hippocampus and left precuneus, and the dFC variability between the bilateral anterior hippocampus and caudate nucleus was positively correlated with depression scores and negatively correlated with global cognition scores.ConclusionSCD individuals exhibited abnormal sFC and dFC in the anterior-posterior hippocampus, and abnormal dFC was more widespread than abnormal sFC. A combination of sFC and dFC provides a new perspective for exploring the brain pathophysiological mechanisms in SCD and offers potential neuroimaging biomarkers for the early diagnosis and intervention of AD.

Project description:While age-related volumetric changes in human hippocampal subfields have been reported, little is known about patterns of subfield functional connectivity (FC) in the context of healthy ageing. Here we investigated age-related changes in patterns of FC down the anterior-posterior axis of each subfield. Using high resolution structural MRI we delineated the dentate gyrus (DG), CA fields (including separating DG from CA3), the subiculum, pre/parasubiculum, and the uncus in healthy young and older adults. We then used high resolution resting state functional MRI to measure FC in each group and to directly compare them. We first examined the FC of each subfield in its entirety, in terms of FC with other subfields and with neighboring cortical regions, namely, entorhinal, perirhinal, posterior parahippocampal, and retrosplenial cortices. Next, we analyzed subfield to subfield FC within different portions along the hippocampal anterior-posterior axis, and FC of each subfield portion with the neighboring cortical regions of interest. In general, the FC of the older adults was similar to that observed in the younger adults. We found that, as in the young group, the older group displayed intrinsic FC between the subfields that aligned with the tri-synaptic circuit but also extended beyond it, and that FC between the subfields and neighboring cortical areas differed markedly along the anterior-posterior axis of each subfield. We observed only one significant difference between the young and older groups. Compared to the young group, the older participants had significantly reduced FC between the anterior CA1-subiculum transition region and the transentorhinal cortex, two brain regions known to be disproportionately affected during the early stages of age-related tau accumulation. Overall, these results contribute to ongoing efforts to characterize human hippocampal subfield connectivity, with implications for understanding hippocampal function and its modulation in the ageing brain.

Project description:In older adults, motor sequence learning (MSL) is largely intact. However, consolidation of newly learned motor sequences is impaired compared to younger adults, and there is evidence that brain areas supporting enhanced consolidation via sleep degrade with age. It is known that brain activity in hippocampal-cortical-striatal areas is important for sleep-dependent, off-line consolidation of motor-sequences. Yet, the intricacies of how both age and sleep alter communication within this network of brain areas, which facilitate consolidation, are not known. In this study, 37 young (age 20-35) and 49 older individuals (age 55-75) underwent resting state functional magnetic resonance imaging (fMRI) before and after training on a MSL task as well as after either a nap or a period of awake rest. Young participants who napped showed strengthening of functional connectivity (FC) between motor, striatal, and hippocampal areas, compared to older subjects regardless of sleep condition. Follow-up analyses revealed this effect was driven by younger participants who showed an increase in FC between striatum and motor cortices, as well as older participants who showed decreased FC between the hippocampus, striatum, and precuneus. Therefore, different effects of sleep were observed in younger vs. older participants, where young participants primarily showed increased communication in the striatal-motor areas, while older participants showed decreases in key nodes of the default mode network and striatum. Performance gains correlated with FC changes in young adults, and this association was much greater in participants who napped compared to those who stayed awake. Performance gains also correlated with FC changes in older adults, but only in those who napped. This study reveals that, while there is no evidence of time-dependent forgetting/deterioration of performance, older adults exhibit a completely different pattern of FC changes during consolidation compared to younger adults, and lose the benefit that sleep affords to memory consolidation.

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Functional Connectivity of the Anterior and Posterior Hippocampus: Differential Effects of Glucose in Younger and Older Adults.

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