Abstract
Background: The “primacy effect,” i.e., increased memory recall for the first items of a series compared to the following items, is reduced in amnestic mild cognitive impairment (aMCI). Memory task-fMRI studies demonstrated that primacy recall is associated with higher activation of the hippocampus and temporo-parietal and frontal cortical regions in healthy subjects. Functional magnetic resonance imaging (fMRI) at resting state revealed that hippocampus functional connectivity (FC) with neocortical brain areas, including regions of the default mode network (DMN), is altered in aMCI. The present study aimed to investigate whether resting state fMRI FC between the hippocampus and cortical brain regions, especially the DMN, is associated with primacy recall performance in aMCI.Methods: A number of 87 aMCI patients underwent resting state fMRI and verbal episodic memory assessment. FC between the left or right hippocampus, respectively, and all other voxels in gray matter was mapped voxel-wise and used in whole-brain regression analyses, testing whether FC values predicted delayed primacy recall score. The delayed primacy score was defined as the number of the first four words recalled on the California Verbal Learning Test. Additionally, a partial least squares (PLS) analysis was performed, using DMN regions as seeds to identify the association of their functional interactions with delayed primacy recall.Results: Voxel-based analyses indicated that delayed primacy recall was mainly (positively) associated with higher FC between the left and right hippocampus. Additionally, significant associations were found for higher FC between the left hippocampus and bilateral temporal cortex, frontal cortical regions, and for higher FC between the right hippocampus and right temporal cortex, right frontal cortical regions, left medial frontal cortex and right amygdala (p < 0.01, uncorr.). PLS analysis revealed positive associations of delayed primacy recall with FC between regions of the DMN, including the left and right hippocampus, as well as middle cingulate cortex and thalamus (p < 0.04). In conclusion, in the light of decreased hippocampus function in aMCI, inter-hemispheric hippocampus FC and hippocampal FC with brain regions predominantly included in the DMN may contribute to residual primacy recall in aMCI.
Highlights
Impaired consolidation of verbal information into long-term episodic memory is the dominant symptom in Alzheimer’s disease (AD) (Carlesimo and Oscar-Berman, 1992; PenaCasanova et al, 2012; Weintraub et al, 2012)
Given previous findings on the central role of hippocampus activation in primacy recall in healthy adults and the fact that the hippocampus is impaired in amnestic mild cognitive impairment (aMCI) (e.g., Apostolova et al, 2010), we aimed to test whether functional connectivity of the hippocampus to other cortical areas typically involved in memory is associated with residual primacy recall in aMCI
The brain regions involved in episodic memory are numerous, as shown by task-functional magnetic resonance imaging (fMRI) studies in HC (Cabeza, 2004; Dickerson et al, 2007; Axmacher et al, 2009; Spaniol et al, 2009; for a meta-analyis, see Kim, 2011)
Summary
Impaired consolidation of verbal information into long-term episodic memory is the dominant symptom in Alzheimer’s disease (AD) (Carlesimo and Oscar-Berman, 1992; PenaCasanova et al, 2012; Weintraub et al, 2012). In amnestic mild cognitive impairment (aMCI), which is associated with increased risk of AD dementia (Petersen et al, 1999; Albert et al, 2011), memory consolidation is impaired and the primacy effect is reduced (Howieson et al, 2011; Cunha et al, 2012; Moser et al, 2014). Primacy recall performance relies on the functionality of the hippocampal system and neocortical regions, as shown for young healthy subjects in functional magnetic resonance imaging (fMRI) studies using memory tasks (Strange et al, 2002; Talmi et al, 2005; Axmacher et al, 2009) and for elderly healthy subjects in volumetric MRI studies (Bruno et al, 2015). The present study aimed to investigate whether resting state fMRI FC between the hippocampus and cortical brain regions, especially the DMN, is associated with primacy recall performance in aMCI
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