More focal, less heterogeneous? Multi-level meta-analysis of cathodal high-definition transcranial direct current stimulation effects on language and cognition.

High-definition transcranial direct current stimulation (HD-tDCS) is a relatively focal, novel non-invasive brain stimulation method with the potential to investigate the causal contributions of specific cortical brain regions to language and cognition. Studies with HD-tDCS typically employ a 4 × 1 electrode design with a single central target electrode surrounded by four return electrodes, among which return current intensity is evenly distributed. With cathodal HD-tDCS, neural excitability in the target region is assumed to be reduced, which offers interesting perspectives for neuropsychological research and interventions. This multi-level meta-analysis compiles published studies using cathodal HD-tDCS in 4 × 1 configuration to modulate cognition and behavior. Regarding HD-tDCS, 77 effect sizes were gathered from 11 eligible reports. We extended this database with 52 effect sizes from 11 comparable reports using conventional tDCS with cathodal polarity. We observed no significant overall effect and no moderation by within-study and between-study variables in HD. In the extended analysis, results suggested a non-linear moderation of cathodal tDCS effects by intensity, driven by negative effect sizes at 1.5 mA. However, studies varied tremendously in task parameters, outcomes, and even technical parameters. Interestingly, within-study heterogeneity exceeded between-study heterogeneity in the present sample, and moderators hardly reduced the residual heterogeneity. Across domains and configurations, both positive and negative effect sizes are possible. We discuss the findings in relation to conventional cathodal tDCS and the framework of polarity specificity. Fundamental aspects of cathodal HD-tDCS are still to be addressed in future research.