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

Article type: Research Article

Authors: Michaelian, Johannes C.^{a; b; c; d} | Duffy, Shantel L.^{b; d; e} | Mowszowski, Loren^{a; b; c; d} | Guastella, Adam J.^f | McCade, Donna^b | McKinnon, Andrew C.^{a; b; c; d; 1} | Naismith, Sharon L.^{a; b; c; d; 1; *}

Affiliations: [a] School of Psychology, University of Sydney, Sydney, Australia | [b] Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Sydney, Australia | [c] Brain and Mind Centre, University of Sydney, Sydney, Australia | [d] Charles Perkins Centre, University of Sydney, Sydney, Australia | [e] School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia | [f] Brain and Mind Centre, Children’s Hospital Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

Correspondence: [*] Correspondence to: Professor Sharon Naismith, Healthy Brain Ageing Program, Brain and Mind Centre, The University of Sydney, 94 Mallett Street, Camperdown NSW 2050, Australia. Tel.: +612 9351 0781; Fax: +612 9351 0551; E-mail: [email protected].

Note: [1] Joint last authors

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.

Keywords: Amnestic mild cognitive impairment, default mode network, functional connectivity, functional magnetic resonance imaging, theory of mind

DOI: 10.3233/JAD-201284

Journal: Journal of Alzheimer's Disease, vol. 81, no. 3, pp. 1079-1091, 2021