Abstract

The proposal to use brain connectivity as a biomarker for dementia phenotyping can be potentiated by conducting large-scale multicentric studies using high-density electroencephalography (hd-EEG). Nevertheless, several barriers preclude the development of a systematic "ConnEEGtome" in dementia research. Here we review critical sources of variability in EEG connectivity studies, and provide general guidelines for multicentric protocol harmonization. We describe how results can be impacted by the choice for data acquisition, and signal processing workflows. The implementation of a particular processing pipeline is conditional upon assumptions made by researchers about the nature of EEG. Due to these assumptions, EEG connectivity metrics are typically applicable to restricted scenarios, e.g., to a particular neurocognitive disorder. "Ground truths" for the choice of processing workflow and connectivity analysis are impractical. Consequently, efforts should be directed to harmonizing experimental procedures, data acquisition, and the first steps of the preprocessing pipeline. Conducting multiple analyses of the same data and a proper integration of the results need to be considered in additional processing steps. Furthermore, instead of using a single connectivity measure, using a composite metric combining different connectivity measures brings a powerful strategy to scale up the replicability of multicentric EEG connectivity studies. These composite metrics can boost the predictive strength of diagnostic tools for dementia. Moreover, the implementation of multi-feature machine learning classification systems that include EEG-based connectivity analyses may help to exploit the potential of multicentric studies combining clinical-cognitive, molecular, genetics, and neuroimaging data towards a multi-dimensional characterization of the dementia.