Modulation of slow and fast oscillations by direct current stimulation in the cerebral cortex in vitro

Abstract

AbstractNon-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), play a growing role in the treatment of neurological disorders. However, the mechanisms by which electric fields modulate cortical network activity are only partially understood. To explore the spatiotemporal modulation of cortical activity by electric fields (DC fields), we exposed neocortical slices to constant fields of varying intensity and direction and we measured their effect on the low (<1 Hz) and high frequencies (beta 15-30 Hz and gamma 30-90 Hz) of spontaneously generated cortical oscillations. Slow oscillations consist of Up (active) and Down (silent) states. We found that DC fields ranging from -6 to +6 V/m induced an exponential increase in the frequency of slow oscillations through the regulation of the excitability and duration of Down states, while hardly affecting Up states duration. A computational model based on the mean-field theory of attractor dynamics provided a mechanistic and quantitative description of the network dynamics underlying such precise modulation of slow oscillatory frequency. The modulation of high frequencies by DC fields was less consistent, the high frequency power varying with the intensity of the fields only in a fraction of slices. Interestingly, negative DC fields of increasing intensities progressively and effectively reversed the increase in high frequency power induced by kainate application. Our findings have implications for the understanding of cortical oscillations and the mechanisms by which they are modulated by DC fields and may contribute to the future development of tools with an accurate spatiotemporal control of cortical activity.Significance statementActing on the brain through electrical stimulation in order to correct dysfunctions or to induce functional recovery is a relatively common technique nowadays used in the clinical realm. In spite of the existence of previous studies on the effect of electric fields on neuronal and network physiology, questions regarding the mechanisms underlying exogenous electrical modulation of cortical dynamics still remain open. We demonstrate that continuous electric fields between -6 and +6 V/m induce a precise modulation of slow and fast cortical rhythms. Based on both experimental evidence and theoretical analysis, we describe some of the mechanistic underpinnings at play and provide useful information for the development of tools with better spatiotemporal control of cortical activity.