Theoretical Basis for Closed-Loop Stimulation as a Therapeutic Approach to Brain Injury

Abstract

Neuroprosthetic devices generally can be categorized as open-loop neuromodulation systems, which directly or indirectly excite neural tissue, or brain–computer interfaces, which derive control signals from the brain to operate external devices. Increasingly, neuroscientists, computer scientists, and engineers are beginning to envision and develop closed-loop systems that stimulate neuronal populations contingent upon a particular neuronal signal derived from another population of neurons. In the near future, investigations into the feasibility and efficacy of closed-loop systems for treating neurological conditions will likely emerge. Such conditions will include epilepsy, Parkinson’s disease, and potentially stroke, traumatic brain injury, and spinal cord injury. Thus, it is now critical to understand how such systems interact with the neural circuitry and how communication may be altered. The present theoretical model focuses on the potential ability for closed-loop systems to regulate synaptic potentiation in long-distance pathways in the nervous system, particularly corticocortical pathways between different functional areas. Because the demonstration of long-term potentiation and long-term depression in animal preparations has utilized stimulation timing protocols that are not typically feasible using noninvasive techniques, the present theoretical model focuses on the use of recording microelectrodes implanted within the cerebral cortex and that are able to discriminate individual action potentials. Likewise, the proposed model assumes that stimulating microelectrodes are also implanted intracortically, allowing focal stimulation of a small volume of cortical tissue. Despite the challenges of invasive procedures using implantable technology, such closed-loop systems have the potential to provide new treatment avenues in a host of neurological conditions.