Table 1.

Open questions on dose-response.

- Has the scale of research on tDCS efficacy outstripped understanding of dose response?

- To what extent could non-monotonic dose response, which is dependent on individual anatomy and subject to interactions with brain state (e.g. task engagement), lead to false-negatives?

The limited work on tDCS dose response had typically applied a straightforward model to measure a response with increased tDCS intensity (e.g. from 1 to 2 mA).

- To what extent is this approach subject to assumptions about the spatial extent of current flow?

- Could not accounting for inter-individual anatomical variability in such cases lead to false-negatives?

- Could inter-individual variations in the intensity of current delivered to the brain combined with a non-monotonic response of the brain lead to false-negatives?

- How can the assumptions, implicit in conventional dose-testing studies, be made more explicit?

- In dose response studies, can computational models be used to retrospectively predict brain current intensity across individuals for a fixed applied current ?

- Can the above retrospectively and prospective use of computational models reduce variability and/or increase effect size in tDCS efficacy trials?