Dynamical states of the cerebral cortex and electric neuromodulation

Abstract

[eng] The cerebral cortex exhibits a wide range of physiological spatiotemporal activity patterns, spanning from synchronized oscillations during slow wave sleep to desynchronized firing during wakefulness. Normal brain function depends on the maintenance of these physiological oscillations, which relies on a dynamical balance of neuronal excitability and neural synchronicity. Failure to maintain this equilibrium is associated to a multitude of pathological conditions. In such case, a potential treatment strategy involves the use of non-invasive electrical stimulation, since it allows a modulation of cortical excitability (direct current (DC) fields) and synchronicity (alternating current (AC) fields). However, to achieve the desired neuromodulatory effect, it is crucial to understand the precise mechanisms through which weak currents impact neuronal oscillations and determine the optimal parameters of stimulation. The main goals of this Thesis were to provide a deeper insight into brain dynamics emerging in the local cortical network at different levels of excitability and synchronicity and explore the mechanisrns underlying their modulation by exogenous EFs. To achieve this goal, we (1) characterized

the spontaneous activity emerging from human cortical slices; (2) investigated the emergence of a meta-rhythm with alternating periods of synchronous and asynchronous activity (microarousals) in vitro; (3) described the generation of hypersynchronous and hyperexcitable epileptiform activity by GABAA blockade; (4) researched the effects of DC field orientation of cortical modulation; (5) explored the potential of DC fields in the modulation of epileptiform activity; (6) characterized the enhancement and attenuation of cortical oscillations by AC fields and (7) proposed a more robust protocol for achieving the desired cortical dynamic in response to an exogenous AC field. By enhancing the comprehension of electric field modulation of cortical dynamics, our results might potentially help the development of effective electric neuromodulation protocols, diminishing the high variability observed in the clinical applications of transcranial electric stimulation.