tDCS to the left DLPFC improves cognitive control but not action cancellation in patients with ADHD: a behavioral and electrophysiological study

Abstract ADHD is a neurodevelopmental disorder associated with significant morbidity and mortality that affects 5% of children, adolescents and adults worldwide. Pharmacological and behavioral therapies exist, but critical symptoms such as dysexecutive deficits remain unaffected. In this randomized, placebo-controlled, double-blind, cross-over study we assess the cognitive and physiological effects of tDCS in adult ADHD patients in order to understand (1) the role of DLPFC laterality in ADHD dysexecutive deficits, (2) the physiological dynamics sustaining the modulation of executive function by tDCS, and (3) the impact of state-dependent dynamics of tDCS effect. The participants consisted of a random sample of 40 adult patients with a primary diagnosis of ADHD. Each patient performed three experimental sessions in which they received 30 minutes of 2mA tDCS stimulation targeting the left DLPFC (anodal F3, cathodal Fp2), the right DLPFC (anodal F4, cathodal Fp1) and Sham. Before and after each session, half of the patients completed the Flanker task (EFT) and the other half performed the Stop Signal Task (SST), while we assessed cognitive (reaction time, accuracy) and neurophysiological measures (EEG Event-Related-Potentials). Results show that anodal tDCS to the left DLPFC modulated cognitive (reaction time) and physiological measures (P300 amplitude) in the Flanker task in a state-dependent manner, but there were no significant effects in the Stop Signal Reaction Time of the SST. We interpret these results as an improvement in interference cognitive control (captured by the EFT) but not in action cancellation (assessed by the SST), supporting the hypothesis of the existence of different impulsivity constructs with overlapping but distinct anatomical substrates and therapeutic strategies. We conclude that anodal tDCS over the left DLPFC using a simple bipolar montage has pro-cognitive effects in dysexecutive patients with ADHD associated with the modulation of physiological signatures of cognitive control (i.e. treatment target), supporting specific hypotheses and strategies for neuromodulation treatment development under an experimental therapeutics framework aiming to link target engagement (cognitive and physiological) with clinical benefit. In addition, we also provide empirical evidence supporting the value of the P200, N200 and P300 as cross-sectional biomarkers of cognitive performance across tasks. Last, we provide mechanistic support for the state-dependent nature of the effects of tDCS, highlighting the importance of controlling the neural states before and during stimulation as a relevant therapeutic strategy.