Task-based fMRI brain activation in mild cognitive impairment and Alzheimer's disease: an ALE meta-analysis

Two decades of task-based fMRI studies have revealed atypical task-related activation and hypoactivation patterns in Alzheimer's disease (AD) and mild cognitive impairment (MCI), implicating the impaired cognitive processing observed in these neurocognitive disorders. The current coordinate-based meta-analysis provides an updated picture of the pathophysiological neurocognitive mechanisms implicated in MCI and AD, which better controls for false positive findings. To pool and summarise these findings, we conducted activation likelihood estimation (ALE) meta-analyses on 90 eligible studies (N_total = 2824) with cluster-level family-wise error correction to compare AD/MCI and healthy controls (HC) on fMRI activity during cognitive tasks across four different domains. ALE assesses whether there is a spatial convergence of activation among experiments. We then conducted meta-analytic functional decoding on the ALE meta-analysis results to infer the functional relevance of the significant clusters. Significant activation clusters, mostly overlapping with the dorsal attention and frontoparietal networks, were observed in MCI and HC when comparing them across memory tasks and all tasks, regardless of cognitive domain. Functional decoding analyses suggest these clusters are linked to spatial and phonological processing. Significant activation converged in the superior temporal gyrus in AD and overlapped with the somatomotor network. Functional decoding indicates it is related to auditory functions. Our findings illustrated the spatial convergence of aberrant task-related activation and hypoactivation in AD and MCI, highlighting the atypical neurocognitive processing across a broad range of tasks.