The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

Janne M Papma,Aad Van Der Lugt,Henri A Vrooman,Marion Smits,John C Van Swieten,Peter J Koudstaal,Niels D Prins,Frederik M Van Der Veen,Wiro J Niessen,Francesco U Mattace Raso,Marius De Groot

doi:10.1007/s00330-017-4768-1

Abstract

ObjectivesDiminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI).MethodMCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus.ResultsWe found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors.ConclusionsOur results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI.Key Points• PCC functioning during episodic memory relates to hippocampal functioning in MCI.• PCC functioning during episodic memory does not relate to hippocampal structure in MCI.• Functional network changes are an important predictor of PCC functioning in MCI.

Highlights

Mild cognitive impairment (MCI) is a clinical construct that identifies individuals with cognitive impairment and a high risk of dementia [1,2,3]
As the posterior cingulate cortex (PCC) is a key hub, and PCC dysfunctioning is shown to be an indicator for Alzheimer’s disease (AD) prodromal stages, examining the relationship between PCC functioning and hippocampus functioning, hippocampus structure and structural connectivity in MCI will provide further insight into the origin of PCC dysfunctioning in MCI
Our results indicate an association between PCC activation and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients

Summary

Introduction

Mild cognitive impairment (MCI) is a clinical construct that identifies individuals with cognitive impairment and a high risk of dementia [1,2,3]. While structural and functional MRI studies concerning memory functioning in MCI and AD, initially focused on the MTL or hippocampus [6], current neuroimaging studies examine patterns of deterioration in global functional and structural brain circuits or networks, e.g. the Papez circuit [7, 8], or the more recently described default mode network (DMN) [9,10,11,12] Within these networks though, the effects of medial temporal lobe degeneration on network functioning, or functioning of specific network nodes, is still unclear [8, 13]. In this multimodal MRI study we performed analyses on the association between PCC functioning during task-related episodic memory fMRI and (1) hippocampus activation (episodic memory fMRI), (2) hippocampus volume (automatic segmentation of hippocampus), and (3) structural connections subserving partly the connection between the hippocampus and PCC (diffusion tensor imaging; DTI), in patients with MCI

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