High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic mild cognitive impairment
By Michael A. Yassa, Shauna M. Stark, A. Bakker, Marilyn S. Albert, M. Gallagher, Craig E. L. Stark. NeuroImage, 2010
490 citations recorded by the source corpus.
Functional magnetic resonance imaging (fMRI) studies have observed hyperactivity in the hippocampal region in individuals with Mild Cognitive Impairment (MCI). However, the actual source of such hyperactivity is not well understood. Studies of aged rats observed similar hyperactive signals in the CA3 region of the hippocampus that correlated with spatial memory deficits and, in particular, with their ability to represent novel environments as being distinct from familiar ones (pattern separation). In this study, we tested the hypothesis that patients with amnestic MCI (aMCI) have deficits in pattern separation, along with hyperactive fMRI BOLD activity in the CA3 region of the hippocampus. We used high-resolution fMRI during a continuous recognition task designed to emphasize pattern separation. We conducted hippocampal subfield-level region of interest analyses to test for dysfunctional activity in aMCI patients. We found that patients showed impaired performance on trials that taxed their pattern separation abilities. We also observed hyperactive BOLD signals in the CA3/dentate and hypoactive signals in the entorhinal cortex during the separation condition. In a high-resolution morphometric analysis of hippocampal subfields, aMCI patients also had smaller CA3/dentate and CA1 volumes (no difference in the subiculum). The CA3/dentate region bilaterally also exhibited the largest shape deformations in aMCI patients, suggesting that this locus is affected early in the course of the disease. These findings suggest that structural and functional changes in the CA3/dentate region of the hippocampus contribute to the deficits in episodic memory that are observed in patients with aMCI. The functional hyperactivity may be evidence for a dysfunctional encoding mechanism, consistent with the predictions of computational models of hippocampal learning.
Subfields: Cognitive Neuroscience, Physiology
View Paper: https://www.semanticscholar.org/paper/14f580f5dec6fca9380f8fef2fa700961b1c637d
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Citations in the corpus
- Automated Volumetry and Regional Thickness Analysis of Hippocampal Subfields and Medial Temporal Cortical Structures in Mild Cognitive Impairment (2014, unknown): “…2011; Kerchner et al., 2010; Kirov et al., 2013; La Joie et al., 2013; Malykhin et al., 2010; Mueller et al., 2007a; Mueller and Weiner, 2009; Olsen et al., 2013; Pluta et al., 2012; Van Leemput et al., 2009; Wisse et al., 2012; Winterburn et al., 2013; Yassa et al., 2010; Zeineh et al., 2003].”
- A pathophysiological framework of hippocampal dysfunction in ageing and disease (2011, background): “Indeed, impairment in pattern separation tasks has been suggested in subjects who might be in the early stages of Alzheimer's disease, in which the entorhinal cortex is affecte”
- A Reproducible Evaluation of ANTs Similarity Metric Performance in Brain Image Registration (2010, background): “ANTs users employ this technology in a variety of application domains, including but not limited to, fMRI analysis (Yassa et al., 2010), morphometry (Hanson et al., 2010), anatomical labeling of both human and mouse anatomy as well as in computer vision.”
- Pattern separation: a common function for new neurons in hippocampus and olfactory bulb (2011, unknown): “In addition, impaired pattern separation has also been reported during aging and in individuals with mild cognitive impairment (Toner et al., 2009; Yassa et al., 2010a, 2010b).”