Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of disabilities resulting from cognitive and neurological deficits, as well as psychological disorders. Only recently, preclinical research on electrical stimulation methods as a potential treatment of TBI sequelae has gained more traction. However, the underlying mechanisms of the anticipated improvements induced by these methods are still not fully understood. It remains unclear in which stage after TBI they are best applied to optimize the therapeutic outcome, preferably with persisting effects. Studies with animal models address these questions and investigate beneficial long- and short-term changes mediated by these novel modalities. METHODS: In this review, we present the state-of-the-art in preclinical research on electrical stimulation methods used to treat TBI sequelae. We analyze publications on the most commonly used electrical stimulation methods, namely transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS) and vagus nerve stimulation (VNS), that aim to treat disabilities caused by TBI. We discuss applied stimulation parameters, such as the amplitude, frequency, and length of stimulation, as well as stimulation time frames, specifically the onset of stimulation, how often stimulation sessions were repeated and the total length of the treatment. These parameters are then analyzed in the context of injury severity, the disability under investigation and the stimulated location, and the resulting therapeutic effects are compared. We provide a comprehensive and critical review and discuss directions for future research. RESULTS AND CONCLUSION: We find that the parameters used in studies on each of these stimulation methods vary widely, making it difficult to draw direct comparisons between stimulation protocols and therapeutic outcome. Persisting beneficial effects and adverse consequences of electrical simulation are rarely investigated, leaving many questions about their suitability for clinical applications. Nevertheless, we conclude that the stimulation methods discussed here show promising results that could be further supported by additional research in this field.