Prefrontal contributions to relational encoding in amnestic mild cognitive impairment

Abstract

Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI). Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI) have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads), both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease.

Keywords: Aging; Functional MRI; Mild cognitive impairment; Relational memory.

Fig. 1

Experimental paradigm. (A) Examples of to-be-encoded triads from each condition. All triads consisted of a category word presented on top of exemplar words where either none were related to the category word (zero-link), one was related to the category word (one-link), or two were related to the category word (two-link). (B) Control trials were presented as an active baseline and a response was collected in the same way as they were for to-be-encoded triads. (C) Post scanning, participants were given a forced-choice recognition test between a previously seen triad and a new triad. New triads were created by altering one exemplar in the triad. Adapted from Addis and McAndrews (2006).

Fig. 2

(A) Regions that showed common negative modulations between the healthy controls (HC) and participants with amnestic mild cognitive impairment (aMCI) including the right parahippocampal gyrus and left superior parietal lobule. (B) Activity in the inferior frontal gyrus was modulated by the degree of generation during encoding for aMCI participants only.