Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

Abstract

Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline.

Keywords: DTI; aging neuroscience; fMRI; hippocampus; magnetic resonance spectroscopy; memory; preclinical MRI.

FIGURE 1

Schematic illustration of (A) the BOLD signal, which is positively correlated with memory, such that impaired memory is associated with reduced BOLD activity in the hippocampus. (B) Discharge activity of hippocampal cells in response to environmental stimuli is not related to age or memory. Rather, cognitive impairment is associated with reduced ability to modify discharge activity. (C) Synaptic transmission and synaptic plasticity in the hippocampal slice is reduced with age, particularly in memory-impaired animals.