Abstract Background Transcranial direct current stimulation (tDCS) has been used to enhance motor and language rehabilitation following a stroke. However, improving the effectiveness of clinical tDCS protocols depends on understanding how lesions may influence tDCS-induced current flow through the brain. Objective We systematically investigated the effect of brain lesions on the magnitude of electric fields (e-mag) induced by tDCS, and how to overcome lesion-induced inter-individual variability in e-mag. Methods We simulated the effect of 630 different lesions - by varying lesion location, distance from the target region of interest (ROI), size and conductivity - on tDCS-induced e-mag in the brains of two participants. Current flow modelling was conducted for two tDCS montages commonly used in clinical applications, which target either primary motor cortex (M1) or Broca’s area (BA44), respectively. We further explored how the inherent variability in e-mag that is introduced by inter-lesion differences can be overcome by individualising tDCS protocols. Results The effect on absolute e-mag was highly dependent on lesion size, conductance and the distance from the target ROI. Larger lesions, with high conductivity, closer to the ROI caused e-mag changes of more than 30%. The sign of this change was determined by the location of the lesion. Specifically, lesions located in-line with the predominant direction of current flow increased e-mag in the ROI, whereas lesions located in the opposite direction caused a decrease. Lesions had a large impact on the optimal electrode configuration if attempting to maximise for the total e-mag in the ROI, but little impact if only the component of e-mag flowing radially inward to the cortex was maximised. Knowing the effect of a given lesion on e-mag also allows for individualising tDCS intensity to reduce variability. Conclusions These results demonstrate that tDCS-induced electric fields are profoundly influenced by lesion characteristics, and further exacerbate the known variability in e-mag across individuals. Additionally, the dependence of these results on the assigned conductance of the lesion underlines the need for improved estimates of lesion conductivity for current flow models. Our results highlight the need for individualised dose control of tDCS in the lesioned brain to overcome the substantial inter-individual variability in electric fields delivered to a cortical target region. Highlights - Lesions can alter tDCS-induced electric field magnitude (e-mag) in a target by 30% - Lesions can cause increases or decreases to e-mag - Direction of change depends on the position of the lesion relative to current flow - Lesion conductivity - the true value for which is unknown - also impacts change - E-mag variability can be reduced by individualising montage and stimulation intensity

The impact of brain lesions on tDCS-induced electric field magnitude