Investigating the semantic control network and its structural decline in mild cognitive impairment and mild dementia

Abstract

Although the episodic and semantic memory systems have long been studied separately, recent literature revealed shared neural substrates, including the medial temporal lobe (MTL). One important aspect of semantic memory is semantic control, which tailors automatic spreading activation during concept retrieval between highly related concepts to suit the current context.
One way to explore the role of the MTL in the semantic memory system is through individuals with mild cognitive impairment and mild dementia, who show episodic memory deficits due to MTL atrophy (Korf et al., 2004). Some individuals show additional language impairment and executive dysfunction, but it is unknown what role semantic control plays in the observed deficits.
Most evidence on the brain network for semantic control comes from stroke-induced lesions to perisylvian language areas or healthy participants undergoing stimulation of these areas, which has led to a cortico-centric neuroanatomical model comprising two central hubs located in the left inferior frontal gyrus (LIFG) and the posterior middle temporal cortex (Whitney et al., 2010). However, little is known about the role of the MTL and the white-matter circuitry subjacent to these hubs in semantic control. Importantly, ventral white-matter pathways have been shown to contribute to semantic processing (e.g., Sierpowska et al., 2019).
The present study proposes to examine a possible extension to the cortical semantic control network, by investigating the role of the MTL in individuals with pre-dementia.
Semantic control was investigated with a word-picture verification task. Participants indicated whether a word matched a subsequently presented picture as quickly and accurately as possible. Congruent (“pilot” – picture: pilot) and incongruent word-picture pairs were presented, the latter being semantically related (“pilot” – picture: airplane) or unrelated (“knife” – picture: airplane). Semantic control was operationalized as the reaction time and error percentage difference between the related and unrelated condition. MTL atrophy was rated by two independent raters on T1-weighted images ranging from 0 (no atrophy) to 4 (severe hippocampal volume loss).
Reaction times (RTs) were analyzed using linear mixed modelling and error rates using generalized linear mixed modelling. Results of patients (n = 7; aged 60 – 87) and matched controls (n = 18) confirm longer reaction times in related relative to unrelated trials (p < 0.001), attesting to the increased need for control, with patients making disproportionately more errors in the related condition (p = 0.02). Despite MTL atrophy related to healthy aging, no pathological atrophy was found for controls (ranging from 0–2 versus the pre-dementia group 0–4). Further investigation of the high error percentage in the pre-dementia group revealed two individuals with severe MTL atrophy (score of 4) scoring 6.7 and 8.0 standard deviations above the mean error percentage of controls in related trials requiring enhanced control.
These results tentatively indicate a contribution of semantic control to the deficits observed in pre-dementia patients and place the MTL as a potential node in the semantic control network. Additionally, the outcome of ongoing analyses of the diffusion-weighted data focusing on the ventral white-matter pathways will further supply neuroanatomical specificity to these findings.