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

Abstract

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.

The Rehabilitation Potential of Neurostimulation for Mild Traumatic Brain Injury in Animal and Human Studies

“…Our goal in reviewing TBI response to neurostimulation was to highlight limitations attributable to heterogeneous approaches and to raise the possibility of a more efficient, efficacious path. Similarly, previous reports have noted a wide variety of stimulation parameters have hindered the ability to draw comparisons between protocols and outcomes [1]. To accelerate the research and federal consensus on the mechanisms and proper research parameters for each condition, more interdisciplinary research that is mechanistically focused is needed.…”

“…The research will be further advanced by a systematic hypothesis-driven approach to experimental design regarding stimulation parameters. This review emphasizes the difficulty in synthesis and comparisons between protocols when there is little consistency in paradigms [1]. This issue can be remediated by integration across fields and with emphasis on mechanisms-even in the face of a heterogeneous condition like mTBI.…”

Optimized high-definition tDCS in patients with skull defects and skull plates

“…Seok Lew, Olivet Nazarene University, United States Maria-Carla Piastra, University of Twente, Netherlands Guillen et al 10.3389/fnhum.2023.1239105 Frontiers in Human Neuroscience 02 frontiersin.org Ziesel et al, 2023). High-definition (HD) tDCS leverages several small disc electrodes (~6 mm radius) to achieve better focality compared to conventional pad electrodes (Datta et al, 2009).…”

“…As an emerging neuromodulation technique, transcranial direct current stimulation (tDCS) has been shown to have therapeutic effects for a wide range of neurological disorders such as major depression ( Bikson et al, 2008 ), epilepsy ( Fregni et al, 2006b ; Auvichayapat et al, 2013 ), Parkinson’s disease ( Fregni et al, 2006a ), chronic pain ( Fregni et al, 2007 ), and stroke ( Meinzer et al, 2016 ). It is shown that tDCS has the potential to promote motor recovery and improve cognitive functions after traumatic brain injury (TBI) ( Kim et al, 2019 ; Schwertfeger et al, 2023 ; Ziesel et al, 2023 ). High-definition (HD) tDCS leverages several small disc electrodes (~6 mm radius) to achieve better focality compared to conventional pad electrodes ( Datta et al, 2009 ).…”

“…To the best of our knowledge, there is still no data reported in the literature that shows if we can efficiently stimulate brain regions below the skull defects or skull plates by optimizing the electrode montages. This is important for patients with TBI as they usually have defects in their skull (also known as the decompressive craniectomy), and tDCS has shown benefits to recovery after TBI ( Kim et al, 2019 ; Schwertfeger et al, 2023 ; Ziesel et al, 2023 ). In this study, we aim to computationally investigate how skull defects or plates affect the current flow induced by optimized HD-tDCS.…”