Combined neuromodulatory approaches in the central nervous system for treatment of spinal cord injury

Purpose of review To report progress in neuromodulation following spinal cord injury (SCI) using combined brain and spinal neuromodulation. Neuromodulation refers to alterations in neuronal activity for therapeutic purposes. Beneficial effects are established in disease states such as Parkinson's Disease (PD), chronic pain, epilepsy, and SCI. The repertoire of neuromodulation and bioelectric medicine is rapidly expanding. After SCI, cohort studies have reported the benefits of epidural stimulation (ES) combined with training. Recently, we have explored combining ES with deep brain stimulation (DBS) to increase activation of descending motor systems to address limitations of ES in severe SCI. In this review, we describe the types of applied neuromodulation that could be combined in SCI to amplify efficacy to enable movement. These include ES, mesencephalic locomotor region (MLR) - DBS, noninvasive transcutaneous stimulation, transcranial magnetic stimulation, paired-pulse paradigms, and neuromodulatory drugs. We examine immediate and longer-term effects and what is known about: (1) induced neuroplastic changes, (2) potential safety concerns; (3) relevant outcome measures; (4) optimization of stimulation; (5) therapeutic limitations and prospects to overcome these. Recent findings DBS of the mesencephalic locomotor region is emerging as a potential clinical target to amplify supraspinal command circuits for locomotion. Summary Combinations of neuromodulatory methods may have additive value for restoration of function after spinal cord injury.