UTFacultiesETEventsPhD Defence Alexander Kuck

PhD Defence Alexander Kuck

Trans-spinal direct current stimulation for the modulation of the lumbar spinal motor networks

Alexander Kuck is a PhD Student in the research group Biomechatronics and Rehabilitation Technology, his supervisors are Professor Herman van der Kooij from the Faculty Engineering Technology (ET) and Professor Dick Stegeman (Vrije Universiteit Amsterdam) 

Trans-spinal Direct Current Stimulation (tsDCS) is a noninvasive neuromodulatory tool for the modulation of the spinal neurocircuitry. Initial studies have shown that tsDCS is able to induce a significant and lasting change in spinal-reflex- and corticospinal information processing. It is therefore hypothesized that tsDCS may be a useful tool in the rehabilitation of spinal cord dysfunctions or injuries. However, to efficiently utilize tsDCS as a tool in neurorehabilitation, more knowledge is necessary about its mechanisms of action, as well as how tsDCS needs to be applied to ensure the desired outcome. This dissertation therefore focuses on the use of tsDCS for the modulation of the lumbar spinal motor circuitry, aiming at a possible application in spinal cord injury rehabilitation. This is investigated using theoretical as well as experimental techniques.

To increase the theoretical understanding of tsDCS, chapter 2 focusses on simulating the electric field (EF) generated during tsDCS and its interaction with the targeted neural structures. This includes visualization and analysis of the generated EF as well as the identification of neural structures, likely to be most targeted by the intervention. Furthermore, a comparison with existing human tsDCS studies as well as the possible effects of electrode misplacement during application are discussed. Methodologically, the EF is calculated via the Finite Element Method and subsequently combined with a multicompartmental model of an alpha-motoneuron and its main incoming axon connections. The resulting neural membrane polarization is used to identify the primary neural target of tsDCS. Additional analyses investigated the expected acute network responses via an existing lumbar spinal network model, which are then compared to in-vivo measurements from literature. The primary results, give an insight into the distribution and strength of the generated EF in the spinal cord for several electrode configurations. Furthermore, axon terminals were identified as the primary cellular target of tsDCS. The simulated acute network effects were in opposite direction when related to the electrophysiological long-term changes observed in human tsDCS studies.

After having established a theoretical basis of some of the underlying mechanisms of action, the following two chapters deal with experimentally assessing the effects of tsDCS for different protocol variations. The main motivation of these studies, was the optimization of tsDCS for a more targeted use in a clinical setting.

Chapter 3 deals with experimentally assessing the effects of tsDCS applied with different EF directions, as well as the repeatability of results previously obtained by others. The central question hereby was to assess whether the tsDCS outcome is dependent on EF direction. This question was addressed in a randomized, double-blind placebo controlled study, whereby 10 healthy subjects received lumbar spinal tsDCS in three different electrode configurations, plus a placebo stimulation. The H-reflex recruitment curve was utilized as a probe for the induced neural changes. The primary outcome confirms, that the effects of tsDCS are dependent on EF direction. Furthermore, results previously reported by others could not be replicated. This highlights current challenges, with regards to repeatability, in the field of neuromodulation research.

Chapter 4 compares the effects of tsDCS during active movement and rest, to investigate during which of the two conditions the application of tsDCS leads to larger modulatory effects. The underlying hypothesis is, that the modulatory effect of tsDCS can be significantly increased when paired with ongoing neural activity. As in the previous study, this question was investigated in a randomized, double-blind placebo controlled study, which included 10 healthy subjects. In four different experiments, subjects received real- or placebo tsDCS during either lying and walking. The resulting neural changes were measured using the H-reflex. The results confirm, that the outcome of tsDCS is dependent on neural activity during stimulation. Thereby, tsDCS in combination with walking had a significantly larger modulatory effect compared to placebo stimulation during walking. No modulatory effect was detected for tsDCS during rest.

Lastly, chapter 5 investigates important safety aspects, when tsDCS is applied in the presence of metallic spinal implants. The presence of metallic implants in the body is still a safety concern, in connection with electrical stimulation procedures. Since spinal implants are expected to be present in at least part of the targeted population with spinal cord injury, it is necessary to explore the safety and application specific consequences of tsDCS with the presence of a spinal metallic implant. This was investigated by simulating the tsDCS induced electric field and current density in the presence of a metallic spinal implant. Calculations were performed via Finite Element Analysis.  The results show that implant presence was able to substantially affect peak current density, compared to the no-implant condition. Nonetheless, the highest calculated current density levels were a factor six lower than the most conservative estimate of what is thought to lead to tissue damaging effects. Additionally, implant presence did not considerably affect the average electric field inside the spinal cord. The findings do therefore not indicate potentially unsafe current density levels, or significant alterations to stimulation intensity inside the spinal cord, caused by a spinal implant during tsDCS.