Pattern separation involves regions beyond the hippocampus in non-demented elderly individuals: A 7T object lure task...

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Neuroimaging

Background:

• Pattern separation, the mechanism for differentiating similar memories, has been primarily studied in the hippocampus.
• The roles of cortical regions and their interaction with the hippocampus in pattern separation remain unclear.

Purpose of the Study:

• To investigate the neural mechanisms of pattern separation in elderly individuals using high-resolution fMRI data.
• To examine the involvement of cortical regions, specifically the frontoparietal network (FPN), and their interaction with the hippocampus during a mnemonic similarity task (MST).

Main Methods:

• Analysis of whole-brain, high-resolution Mnemonic Similarity Task (MST) fMRI data from 55 non-demented elderly subjects using a 7-Tesla MR scanner.
• Utilized a general linear model on hippocampal regions of interest (ROIs) and whole-brain data, comparing conditions like lure correct rejection (LureCR) versus lure false alarm (LureFA) to identify pattern separation activity.
• Examined task-based functional connectivity between hippocampal ROIs and other regions, including the FPN, and correlated performance with brain activity and age.

Main Results:

• Left anterior CA3/DG showed greater activity in LureCR vs. LureFA, indicating pattern separation involvement.
• Better lure discrimination performance correlated with greater activity differences in left anterior CA3/DG and right anterior subiculum.
• Whole-brain analysis revealed left-hemisphere lateralization for pattern separation, with eleven clusters identified, including the left FPN, middle temporal lobe, and subcortical regions.
• The right FPN was associated with retrieving previously viewed objects, while the left FPN was preferentially involved in pattern separation.

Conclusions:

• Pattern separation in elderly individuals is lateralized to the left hemisphere, involving both hippocampal and frontoparietal network (FPN) regions.
• The left and right FPN exhibit distinct roles in the MST, with the left FPN crucial for pattern separation.
• The interaction between the FPN and hippocampus, potentially mediated by subcortical regions, is essential for pattern separation.