Association between tDCS computational modeling and clinical outcomes in depression: data from the ELECT-TDCS trial

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention investigated for the treatment of depression. Clinical results have been heterogeneous, partly due to the variability of electric field (EF) strength in the brain owing to interindividual differences in head anatomy. Therefore, we investigated whether EF strength was correlated with behavioral changes in 16 depressed patients using simulated electric fields in real patient data from a controlled clinical trial. We hypothesized that EF strength in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), brain regions implicated in depression pathophysiology, would be associated with changes in depression, mood and anxiety scores. SimNIBS were used to simulate individual electric fields based on the MRI structural T1-weighted brain scans of depressed subjects. Linear regression models showed, at the end of the acute treatment phase, that simulated EF strength was inversely associated with negative affect in the bilateral ACC (left: β = - 160.463, CI [- 291.541, - 29.385], p = 0.021; right: β = - 189.194, CI [- 289.479, - 88.910], p = 0.001) and DLPFC (left: β = - 93.210, CI [- 154.960, - 31.461], p = 0.006; right: β = - 82.564, CI [- 142.867, - 22.262], p = 0.011) and with depression scores in the left ACC (β = - 156.91, CI [- 298.51, - 15.30], p = 0.033). No association between positive affect or anxiety scores, and simulated EF strength in the investigated brain regions was found. To conclude, our findings show preliminary evidence that EF strength simulations might be associated with further behavioral changes in depressed patients, unveiling a potential mechanism of action for tDCS. Further studies should investigate whether individualization of EF strength in key brain regions impact clinical response.