Estimulação epidural de corrente contínua de baixa intensidade sobre o córtex pré-frontal medial esquerdo : novo método de modulação da memória operacional em ratos

Abstract

The prefrontal cortex (PFC) is the most complex and highly developed region of the neocortical regions of the human brain and is considered the cortex of association of the frontal lobe. It can be considered as a “key cortical substrate of the highest-level mental processes”, managing all the necessary processes for short- or long-term goals and to regulate immediate behavior and to plan behavior in the future by exerting a “top-down” control over which information is relevant and has to be utilized while excluding non-relevant information for the a specific task at hand. Therefore, it is implicated in working memory processing. Many studies have been carried out in order to modulate the CPF excitability using techniques of low-intensity direct current stimulation in order to treat several diseases and to improve cognitive functions. Neuroimaging techniques and brain mapping have revealed positive data and have shown that direct current stimulation can modulate the human brain functions inducing persisting, but reversible, changes in cortical excitability. The objective of this study was to develop a new method of brain stimulation by direct current stimulation that offers a focal stimulation and less loss of current using an epidural stimulation protocol. Male Wistar rats (n = 23, 250 - 300 g) well trained in the radial maze procedure and with electrode implanted over the medial PFC (mPFC) (B: 2.5 mm A, +/- 1 mm L), received epidural direct current stimulation (eDCS) (400 µA) applied for 11 minutes before the delayed tasks sessions in the 8-arms radial maze. The animals performed delayed tasks of 1, 4 and 10 hous (long-term memory). Animals receiving eDCS showed statistically significant decrease in the number of errors compared to sham animals in the post-delays performances after 1 hour (eDCS 1.22 ± 0.22 vs Sham 2.78 ± 0.49, n = 18, p = 0.01), 4 hours (eDCS 0.89 ± 0.26 vs Sham 3.56 ± 0.29, n = 18, p < 0.0001) and 10 hours (eDCS 2.00 ± 0.26 vs Sham 3.71 ± 0.15, n = 16, p < 0.0001). These results showed that eDCS applied over left mPFC improved the performance of long-termed delayed tasks in the 8-arm radial maze, and suggests that eDCS over mPFC facilitates the long term spatial working memory processing.