Poorer Theory of Mind in Amnestic Mild Cognitive Impairment Is Associated with Decreased Functional Connectivity in the Default Mode Network

Abstract

Background: Older adults living with amnestic mild cognitive impairment (aMCI) not only demonstrate impairments in Theory of Mind (ToM), relative to adults with non-amnestic MCI (naMCI), but are also at a higher risk of developing dementia. Objective: Our primary objective was to ascertain whether default mode network (DMN) functional connectivity was differentially associated with ToM abilities between MCI subgroups. Methods: Using functional magnetic resonance imaging, we investigated alterations in resting-state functional connectivity within the brain’s DMN in a sample of 43 older adults with aMCI (n = 19) and naMCI (n = 24), previously reported to demonstrate poorer ToM abilities. Results: Compared to naMCI, the aMCI subgroup revealed a significant association between poorer ToM performance and reduced functional connectivity between the bilateral temporal pole (TempP) and the left lateral temporal cortex (LTC) (LTC_L-TempP_L: b = –0.06, t(33) = –3.53, p = 0.02; LTC_L-TempP_R: b = –0.07,t(33) = –3.20, p = 0.03); between the right TempP and the dorsal medial prefrontal cortex (dMPFC) (b = –0.04, t(33) = –3.02, p = 0.03) and between the left and right TempP (b = –0.05, t(33) = –3.26, p = 0.03). In the naMCI subgroup, the opposite relationship was present between the bilateral TempP and the left LTC (Combined correlation: r = –0.47, p = 0.02), however, not between the right TempP and the dMPFC (r = –0.14, p = 0.51) or the left and right TempP (r = –0.31, p = 0.14). Conclusion: Our findings suggest that alterations in functional connectivity within the DMN involving temporal and frontal lobe regions are associated with ToM deficits in aMCI.

Theory of mind in patients with mild cognitive impairment: A systematic review

“…First, Michaelian et al ( 2021 ), on a sample of 43 adults with MCI (aMCI, n = 19; naMCI, n = 24) used RMET (Baron-Cohen et al, 2001 ) to assess TOM and functional magnetic resonance imaging to investigate the alterations in resting-state functional connectivity within the default mode network (DMN). The authors discovered that the aMCI group revealed a significant association between poorer TOM performance and reduced functional connectivity between the bilateral temporal pole (TempP) and the left lateral temporal cortex.…”

“…Those results depend on the variety of tests used by the authors to investigate multiple domains of social cognition; in particular, out of 20 articles 19 different tests were used (see Table 2 ). This aspect is an advantage but, on the other hand, it is a limitation because it culminated in ambiguous results; for example, some studies reported lower TOM performance while investigating only the cognitive domain of TOM (Baglio et al, 2012 ; Maki et al, 2013 ; Moreau et al, 2015 ), yet there are studies that showed the same results using only affective tasks (Poletti and Bonuccelli, 2013 ; Yildirim et al, 2020 ; Eramudugolla et al, 2021 ; Michaelian et al, 2021 ; Orso et al, 2022 ). This heterogeneity in the adoption of the tests does not allow for overlapping results.…”

Shared and specific dynamics of brain activity and connectivity in amnestic and nonamnestic mild cognitive impairment

“…Additionally, functional MRI studies suggested that aMCI and naMCI patients exhibited differences in activity and connectivity: (1) aMCI patients exhibited a decreased amplitude of low‐frequency fluctuations (ALFF) in the superior temporal gyrus, insula, precentral gyrus, lingual gyrus, and superior frontal gyrus compared with naMCI groups and controls; 13,14 (2) aMCI patients but not naMCI patients exhibited decreased regional homogeneity (ReHo) in the anterior cingulate gyrus compared with controls; 14 (3) compared with controls, aMCI patients and naMCI patients exhibited a different pattern of functional connectivity (FC) between the hippocampus and posterior cingulate cortex 15 and FC within the default mode network; 16 and (4) aMCI patients and naMCI patients exhibited different patterns of activation in temporal‐parietal regions during memory recognition compared with controls 17 . Moreover, aMCI and naMCI patients exhibited opposite associations between Theory of mind performance and FC between the bilateral temporal pole and the left lateral temporal cortex 18 …”

“…17 Moreover, aMCI and naMCI patients exhibited opposite associations between Theory of mind performance and FC between the bilateral temporal pole and the left lateral temporal cortex. 18 All the mentioned studies mainly focus on the static aspect of functional abnormalities, which assume that brain activity and connectivity are static over a whole resting-state functional MRI scan. However, evidence from both task-based fMRI studies and animal electrophysiology demonstrates that functional activity and connectivity may exhibit dynamic changes within time scales of seconds to minutes.…”

“… 17 Moreover, aMCI and naMCI patients exhibited opposite associations between Theory of mind performance and FC between the bilateral temporal pole and the left lateral temporal cortex. 18 …”