Hippocampal Resting-State Functional Connectivity Patterns are More Closely Associated with Severity of Subjective Memory Decline than Whole Hippocampal and Subfield Volumes

Zajac, Lauren; Koo, Bang‐Bon; Tripodis, Yorghos; Mian, Asim; Steinberg, Eric; Mez, Jesse; Alosco, Michael L.; Cervantes‐Arslanian, Anna M.; Stern, Robert; Killiany, Ronald

doi:10.1093/texcom/tgaa019

Cited by 11 publications

(11 citation statements)

References 68 publications

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“…Our work adds to a growing body of evidence suggesting that individual differences like intrinsic (i.e., task-free) functional connectivity (Elliott et al, 2019;Finn et al, 2020) and structural properties (Llera et al, 2019) relate to cognition in meaningful ways. Our results join prior research in highlighting the greater sensitivity of connectivity relative to volume-based measures (Yassa et al, 2010;Zajac et al, 2020). Here, we took a hypothesis-rather than a data-driven approach to asking these questions; our analysis was limited to just two hippocampal pathways of greatest expected significance: CA 3 -CA 1 as related to TSP, and ERC-CA 1 as related to MSP.…”

Section: Discussionmentioning

confidence: 54%

The structure of hippocampal circuitry relates to rapid category learning in humans

2021

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Prior work suggests that complementary white matter pathways within the hippocampus (HPC) differentially support the learning of specific versus general information. In particular, while the trisynaptic pathway (TSP) rapidly forms memories for specific experiences, the monosynaptic pathway (MSP) slowly learns generalities.However, despite the theorized significance of such circuitry, characterizing how information flows within the HPC to support learning in humans remains a challenge.We leveraged diffusion-weighted imaging as a proxy for individual differences in white matter structure linking key regions along with TSP (HPC subfields CA 3 and CA 1 ) and MSP (entorhinal cortex and CA 1 ) and related these differences in hippocampal structure to category learning ability. We hypothesized that learning to categorize the "exception" items that deviated from category rules would benefit from TSPsupported mnemonic specificity. Participant-level estimates of TSP-and MSP-related integrity were constructed from HPC subfield connectomes of white matter streamline density. Consistent with theories of TSP-supported learning mechanisms, we found a specific association between the integrity of CA 3 -CA 1 white matter connections and exception learning. These results highlight the significant role of HPC circuitry in complex human learning.

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Section: Discussionmentioning

confidence: 54%

The structure of hippocampal circuitry relates to rapid category learning in humans

2021

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“…Our work adds to a growing body of evidence suggesting that individual differences like intrinsic (i.e., task-free) functional connectivity (Elliott et al, 2019;Finn et al, 2020) and structural properties (Llera et al, 2019) relate to cognition in meaningful ways. Our results join prior research in highlighting the greater sensitivity of connectivity relative to volume-based measures (Yassa et al, 2010;Zajac et al, 2020). Here, we took a hypothesis-rather than data-driven approach to asking these questions; our analysis was limited to just two hippocampal pathways of greatest expected significance: CA3-CA1 as related to TSP, and ERC-CA1 as related to MSP.…”

Section: Discussionmentioning

confidence: 53%

The structure of hippocampal circuitry relates to rapid category learning in humans

Gumus

Zhu

Mack

2021

Preprint

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Prior work suggests that complementary white matter pathways within the hippocampus differentially support learning of specific versus general information. In particular, while the trisynaptic pathway (TSP) rapidly forms memories for specific experiences, the monosynaptic pathway (MSP) slowly learns generalities. However, despite the theorized significance of such circuitry, characterizing how information flows within hippocampus (HPC) to support learning in humans remains a challenge. We leveraged diffusion-weighted imaging as a proxy for individual differences in TSP and MSP white matter structure and related it to category learning ability. We hypothesized that learning to categorize the "exception" items that deviated from category rules would benefit from TSP-supported mnemonic specificity. Participant-level estimates of TSP and MSP integrity were constructed from HPC subfield connectomes of white matter streamline density. Consistent with theories of TSP-supported learning mechanisms, we found a specific association between TSP integrity and exception learning. These results highlight the significant role of HPC circuitry in complex human learning.

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“…To our knowledge, this is the first report of desynchronization between the ACC and hippocampus being linked with improved working memory performance in any animal model. Given that multiple reports have recently showed that patients with mild cognitive impairment and early AD symptomology have increased connectivity between the hippocampus and cingulate areas 99 , 100 , it is possible that our results provide a potential mechanistic window into how patients are able to overcome these effects during the prolonged prodromic phase of AD. It is possible that short spells of decreased oscillatory coherence are a neural adaptation that minimizes the cognitive impairments of increased connectivity.…”

Section: Discussionmentioning

confidence: 86%

Altered theta rhythm and hippocampal-cortical interactions underlie working memory deficits in a hyperglycemia risk factor model of Alzheimer’s disease

et al. 2021

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Diabetes mellitus is a metabolic disease associated with dysregulated glucose and insulin levels and an increased risk of developing Alzheimer’s disease (AD) later in life. It is thought that chronic hyperglycemia leads to neuroinflammation and tau hyperphosphorylation in the hippocampus leading to cognitive decline, but effects on hippocampal network activity are unknown. A sustained hyperglycemic state was induced in otherwise healthy animals and subjects were then tested on a spatial delayed alternation task while recording from the hippocampus and anterior cingulate cortex (ACC). Hyperglycemic animals performed worse on long delay trials and had multiple electrophysiological differences throughout the task. We found increased delta power and decreased theta power in the hippocampus, which led to altered theta/delta ratios at the end of the delay period. Cross frequency coupling was significantly higher in multiple bands and delay period hippocampus-ACC theta coherence was elevated, revealing hypersynchrony. The highest coherence values appeared long delays on error trials for STZ animals, the opposite of what was observed in controls, where lower delay period coherence was associated with errors. Consistent with previous investigations, we found increases in phosphorylated tau in STZ animals’ hippocampus and cortex, which might account for the observed oscillatory and cognitive changes.

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Hippocampal Resting-State Functional Connectivity Patterns are More Closely Associated with Severity of Subjective Memory Decline than Whole Hippocampal and Subfield Volumes

Cited by 11 publications

References 68 publications

The structure of hippocampal circuitry relates to rapid category learning in humans

The structure of hippocampal circuitry relates to rapid category learning in humans

The structure of hippocampal circuitry relates to rapid category learning in humans

Altered theta rhythm and hippocampal-cortical interactions underlie working memory deficits in a hyperglycemia risk factor model of Alzheimer’s disease

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