Physiological challenges for intracortical electrodes

The clinical use of chronic electrode implants for measurement or stimulation of neuronal activity has increased over the past decade with the advent of deep brain stimulation and the use of brain-computer interfaces. However, despite the wide-spread application of electrode implants, their chronic use is still limited by technical difficulties. Many of the reported issues, ranging from short-circuits to loss of signal due to increased electrical impedance, may be traced back to the reaction of the cortical tissue to the implanted devices: the foreign body response (FBR). This response consists of several phases that ultimately result in neuronal loss and the formation of a dense glial sheath that encapsulates the implant. Empirical evidence suggests that reducing the FBR has a positive effect on the electrical properties of implants, which can potentially expand their clinical use by improving their chronic usability. The primary focus of this work is to review the consequences of the FBR and recent developments that can be considered to control and limit its development. We will discuss how the choice of device material and electrode-architecture influences the tissue reaction, as well as modifications that allow for less stiff implants, increase electrode conductivity, or improve the implant-tissue integration. Several promising biological solutions include the local release of anti-inflammatory compounds to weaken the initial inflammatory phase of the FBR, as well as methods to diminish the negative effects of the glial sheath on neuronal regrowth.