Occitanie grant 2016-2018

Neural substrates of language production in typical aging and Alzheimer's disease

Effect of healthy aging on language functional connectivity

Although language is quite preserved from aging, it remains unclear whether age-related differences lead to a deterioration or reorganisation in language functional networks, or to different dynamics with other domains (e.g., the multiple-demand system). In a first study, we examined language network, using resting-state functional magnetic resonance imaging in typical aging in relation to language performance. Twenty-three (23) younger adults and 24 healthy older adults were recruited. Volumetric gray matter differences between the 2 groups were assessed using voxel-based morphometry. Then, seed-based analyses, integrated local correlations in core regions of the language network, and within- and between-network connectivity were performed. We expected less extended connectivity maps, local coherence diminution, and higher connectivity with the multiple-demand system in older adults. On the contrary, analyses showed language network differences in healthy aging (i.e., increased connectivity with areas inside and outside language network), but no deterioration, despite widespread atrophy in older adults. Integrated local correlation revealed alterations that were unnoticeable with other analyses. Although gray matter loss was not correlated with language performance, connectivity differences were positively correlated with fluency performance in the older group. These results differ from the literature concerning other cognitive networks in aging in that they show extra internetwork connections without a decrease in intranetwork language connections. This reorganisation could explain older adults' good language performance and could be interpreted in accordance with the scaffolding theory of aging and cognition.

Figure 1. Increased connectivity with areas inside and outside language network in healthy aging (here, during seed-based analyses). These changes were positively correlated with fluency performance in the older group

Effect of early Alzheimer's disease on language functional connectivity

Unlike healthy aging, language production deficits occur early in the course of Alzheimer’s disease (AD); however, only a few studies have focused on language network’s functional connectivity in mild cognitive impairment (MCI) due to AD. A second study aimed to uncover the extent of language alteration at the MCI stage, at a behavioural and neural level, using univariate and multivariate analyses of structural MRI and resting-state fMRI. Twenty-four MCI due to AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI, and resting-state fMRI. We performed seed-based analyses, using the left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analysed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; within the executive control networks, as well as the pattern of functional connectivity within the language network and within the executive control networks. MCI due to AD participants had language impairment during clinical language tasks and connected-speech production. Regarding functional connectivity, univariate analyses were not able to discriminate participants, while multi- variate pattern analyses could significantly predict participants’ group. Language network’s functional connectivity could discriminate MCI due to AD participants better than executive control networks. Most notably, they revealed an increased connectivity at the MCI stage positively correlated with language performance (e.g. fluency tasks), but not correlated with disfluency production during connected-speech production.

Figure 2. Contribution of each feature when classifying the pattern of functional connectivity within the language network in healthy older adults and AD participants. The dashed lines represent the threshold for significance (p<0.05) obtained through permutations. Significant features are indicated in bold red on the y-axis. Increased connectivity was positively correlated with language performance (standardized tasks) in the AD group but not with discourse measures and disfluency production.

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