Metric comparison of connectome-based lesion-symptom mapping in post-stroke aphasia

Connectome-based lesion-symptom mapping relates behavioural impairments to disruption of structural brain connectivity. Connectome-based lesion-symptom mapping can be based on different approaches (diffusion MRI versus lesion mask), network scales (whole brain versus regions of interest) and measure types (tract-based, parcel-based, or network-based metrics). We evaluated the similarity of different connectome-based lesion-symptom mapping processing choices and identified factors that influence the results using multiverse analysis-the strategy of conducting and displaying the results of all reasonable processing choices. Metrics derived from lesion masks and diffusion-weighted images were tested for association with Boston Naming Test and Token Test performance in a sample of 50 participants with aphasia following left hemispheric stroke. 'Direct' measures were derived from diffusion-weighted images. 'Indirect' measures were derived by overlaying lesion masks on a white matter atlas. Parcel-based connectomes were constructed for the whole brain and regions of interest (14 language-relevant parcels). Numerous tract-based and network-based metrics were calculated. There was a high discrepancy across processing approaches (diffusion-weighted images versus lesion masks), network scales (whole brain versus regions of interest) and metric types. Results indicate weak correlations and different connectome-based lesion-symptom mapping results across the processing choices. Substantial methodological work is needed to validate the various decision points that arise when conducting connectome-based lesion-symptom mapping analyses. Multiverse analysis is a useful strategy for evaluating the similarity across different processing choices in connectome-based lesion-symptom mapping.