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Updated: Aug 19, 2025

A Comprehensive Protocol for Manual Segmentation of the Medial Temporal Lobe Structures
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Reduced structural connectivity of the medial temporal lobe including the perforant path is associated with aging and

Steven J Granger1, Luis Colon-Perez1, Myra Saraí Larson1

  • 1Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA; Department of Neurobiology and Behavior, University of California, Irvine, CA.

Neurobiology of Aging
|November 26, 2022
PubMed

Insights

Brain connectivity in the medial temporal lobe (MTL) declines with age, impacting memory. Reduced perforant path integrity, linking the entorhinal cortex to the hippocampus, is linked to cognitive decline in older adults.

Area of Science:

  • Neuroimaging
  • Cognitive Neuroscience
  • Aging Research

Background:

  • The perforant path, crucial for memory, degrades with age-related cognitive decline.
  • Previous MRI methods for assessing perforant path integrity have limitations in resolution and methodology.

Purpose of the Study:

  • To investigate the structural connectivity of the perforant path and other medial temporal lobe (MTL) pathways using advanced diffusion imaging.
  • To explore the relationship between age, cognitive function, and MTL structural connectivity.

Main Methods:

  • Utilized ultra-high resolution diffusion imaging (ZOOMit) with quantitative-anisotropy informed tractography.
  • Analyzed structural connectivity in 51 older adults (aged 63-98).

Main Results:

  • Medial temporal lobe (MTL) graph density decreases with age and correlates with poorer delayed recall.
  • Older age and lower delayed recall are associated with fewer streamlines in the putative perforant path (entorhinal cortex to dentate gyrus).

Conclusions:

  • Intra-MTL structural connectivity shows age-related decline and is associated with cognitive performance.
  • Reduced perforant path integrity may serve as a potential biomarker for age-related cognitive decline.
Keywords:
AgingDiffusion weighted MRIHigh resolutionMemoryPerforant path

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