Sensorimotor network rewiring in mild cognitive impairment and Alzheimer's disease

Abstract

This study aimed at elucidating whether (a) brain areas associated with motor function show a change in functional magnetic resonance imaging (fMRI) signal in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), (b) such change is linear over the course of the disease, and (c) fMRI changes in aMCI and AD are driven by hippocampal atrophy, or, conversely, reflect a nonspecific neuronal network rewiring generically associated to brain tissue damage. FMRI during the performance of a simple motor task with the dominant right-hand, and structural MRI (i.e., dual-echo, 3D T1-weighted, and diffusion tensor [DT] MRI sequences) were acquired from 10 AD patients, 15 aMCI patients, and 11 healthy controls. During the simple-motor task, aMCI patients had decreased recruitment of the left (L) inferior frontal gyrus compared to controls, while they showed increased recruitment of L postcentral gyrus and head of L caudate nucleus, and decreased activation of the cingulum compared with AD patients. Effective connectivity was altered between primary sensorimotor cortices (SMC) in aMCI patients vs. controls, and between L SMC, head of L caudate nucleus, and cingulum in AD vs. aMCI patients. Altered fMRI activations and connections were correlated with the hippocampal atrophy in aMCI and with the overall GM microstructural damage in AD. Motor-associated functional cortical changes in aMCI and AD mirror fMRI changes of the cognitive network, suggesting the occurrence of a widespread brain rewiring with increasing structural damage rather than a specific response of cognitive network.

Figure 1

Cortical activations on a rendered brain from healthy controls (A), patients with amnestic mild cognitive impairment (aMCI) (B), and patients with Alzheimer's disease (AD) (C) during the performance of a simple motor task with the right hand (within‐group analysis; one‐sample t test). Activated foci are shown with a significance threshold set at P < 0.001, uncorrected for multiple comparisons (color‐coded t values). See text for further details.

Figure 2

Comparison between healthy controls and patients with amnestic mild cognitive impairment (aMCI) during the performance of a simple motor task with the right hand (random effect analysis, ANOVA, P < 0.05, after small volume correction). Compared with patients with aMCI, healthy controls showed an increased recruitment of the left inferior frontal gyrus (IFG) (A). The activation is shown on a high‐resolution T1‐weighted image in the standard SPM space. In B, signal plots detected in the three groups of subjects of the study (healthy controls, aMCI and Alzheimer's disease [AD] patients) in the previous region are shown.

Figure 3

Comparison between patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) during the performance of a simple motor task with the right hand (random effect analysis, ANOVA, P < 0.05, after small volume correction). Compared with AD, aMCI patients had an increased recruitment of the left postcentral gyrus (A) and the head of the left caudate nucleus (C). Compared with aMCI, AD patients had an increased recruitment of the cingulum (E). Foci of activations are shown on a high‐resolution T1‐weighted image in the standard SPM space. In B, D, and F, signal plots detected in the three groups of subjects of the study (healthy controls, aMCI and AD patients) in the previous regions are shown.

Figure 4

Results of the between‐group analysis of connectivity: histograms of path coefficients (mean values) which were significantly different at the between‐group comparisons are shown in light grey for healthy controls, dark grey for amnestic mild cognitive impairment (aMCI) patients, and black for Alzheimer's disease (AD) patients.