Where did I put that? Patients with amnestic mild cognitive impairment demonstrate widespread reductions in activity during the encoding of ecologically relevant object-location associations

Abstract

Remembering the location of objects in the environment is both important in everyday life and difficult for patients with amnestic mild cognitive impairment (aMCI), a clinical precursor to Alzheimer’s disease. To test the hypothesis that memory impairment for object location in aMCI reflects hippocampal dysfunction, we used an event-related functional magnetic resonance imaging paradigm to compare patients with aMCI and healthy elderly controls (HEC) as they encoded 90 ecologically-relevant object-location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1-hour delay. The groups were well matched on demographics and brain volumetrics. Behaviorally, HEC remembered significantly more OLAs than did aMCI patients. Activity differences were assessed by contrasting activation for successfully encoded novel stimuli vs. repeated stimuli. The HEC demonstrated activity within object-related (ventral visual stream), spatial location-related (dorsal visual stream), and feature binding-related cortical regions (hippocampus and other memory-related regions) as well as in frontal cortex and associated subcortical structures. Activity in most of these regions correlated with memory test performance. Although the aMCI patients demonstrated a similar activation pattern, the HEC showed significantly greater activity within each of these regions. Memory test performance in aMCI patients, in contrast to the HEC, was correlated with activity in regions involved in sensorimotor processing. We conclude that aMCI patients demonstrate widespread cerebral dysfunction, not limited to the hippocampus, and rely on encoding-related mechanisms that differ substantially from healthy individuals.

Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults

“…However, we [14] and others [15] have reported widespread hypoactivation in patients with MCI, suggesting network-level dysfunction. Further, correlational analyses between activation magnitude and behavioral performance have revealed marked shifts in the brain regions associated with new memories in MCI patients relative to controls [14, 16]. Such findings led us to hypothesize that MCI patients rely on more basic cognitive processes (e.g., focusing on physical properties of stimuli) while learning new information, at the expense of more effective “top-down” strategies that are at least partially dependent on the PFC [14].…”

“…In contrast to the normal patterns of learning and memory described above, patients with MCI experience characteristic memory deficits that are typically attributed to medial temporal lobe (e.g., hippocampal) dysfunction [12, 13]. However, we [14] and others [15] have reported widespread hypoactivation in patients with MCI, suggesting network-level dysfunction. Further, correlational analyses between activation magnitude and behavioral performance have revealed marked shifts in the brain regions associated with new memories in MCI patients relative to controls [14, 16].…”

“…Further, correlational analyses between activation magnitude and behavioral performance have revealed marked shifts in the brain regions associated with new memories in MCI patients relative to controls [14, 16]. Such findings led us to hypothesize that MCI patients rely on more basic cognitive processes (e.g., focusing on physical properties of stimuli) while learning new information, at the expense of more effective “top-down” strategies that are at least partially dependent on the PFC [14]. This interpretation is consonant with both behavioral [17–19] and neuroimaging [20] findings of impaired top-down control in patients with MCI.…”

Mild Cognitive Impairment Is Not “Mild” at All in Altered Activation of Episodic Memory Brain Networks: Evidence from ALE Meta-Analysis

“…Browndyke et al (2013), however, included four of them except one (Clément and Belleville, 2010). With respect to the lower activation foci in aMCI in the MTL structure, six studies (Trivedi et al, 2008; Mandzia et al, 2009; Hampstead et al, 2011; Hanseeuw et al, 2011; Jin et al, 2012; van der Meulen et al, 2012) were analyzed in the present study providing nine foci. Browndyke et al (2013), however, included only three studies (Johnson et al, 2006, 2008; Trivedi et al, 2008) with five foci.…”

“…Due to the ALE analysis technique, the present study cannot fully prove which explanaiton is more reasonable. From the tasks perspective (intentional encoding) used in the studies which provided the foci (i.e., Machulda et al, 2009; Hampstead et al, 2011), the first hypothesis is more plausible.…”