Cathodal transcranial direct current stimulation on the prefrontal cortex applied after reactivation attenuates fear memories and prevent reinstatement after extinction

Abstract

BackgroundIn the last decade, pharmacological strategies targeting reconsolidation after memory retrieval have shown promising efforts to attenuate persistent memories and overcome fear recovery. However, most reconsolidation inhibiting agents have not been approved for human testing. While non-invasive neuromodulation can be considered an alternative approach to pharmacological treatments, there is a lack of evidence about the efficacy of these technologies when modifying memory traces via reactivation/reconsolidation mechanism. ObjectiveIn this study, we evaluate the effect of cathodal (c-tDCS) and anodal (a-DCS) transcranial direct current stimulation applied after memory reactivation and extinction in rats. MethodsMale Wistar rats were randomly assigned into three groups: one sham group, one anodal tDCS group, and one cathodal tDCS group (500 μA, 20 min). Reconsolidation and extinction of fear memories were evaluated using a contextual fear conditioning. ResultsOur results showed that c-tDCS and a-tDCS after memory reactivation can attenuate mild fear memories. However, only c-tDCS stimulation prevented both fear expression under strong fear learning and fear recovery after a reinstatement protocol without modification of learning rate or extinction retrieval. Nevertheless, the remote memories were resistant to modification through this type of neuromodulation. Our results are discussed considering the interaction between intrinsic excitability promoted by learning and memory retrieval and the electric field applied during tDCS. ConclusionThese results point out some of the boundary conditions influencing the efficacy of tDCS in fear attenuation and open new ways for the development of noninvasive interventions aimed to control fear-related disorders via reconsolidation.