Lee, Jenny; (2023) Individualised non-invasive brain stimulation for post-stroke motor rehabilitation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Physical therapy improves upper limb rehabilitation after stroke, however access to high-dose training is often limited. Innovation is greatly needed to increase efficiency and accessibility of post-stroke rehabilitation. Transcranial direct current stimulation (tDCS) is a candidate tool to support neuroplasticity for rehabilitation. Exciting developments and potentially clinically relevant applications of tDCS are however subject to high outcome variability across studies, suggesting a need for further improvement of the technique. The work presented in this thesis aims to identify and minimise sources of tDCS outcome variability when applied in stroke. Advances in current flow modelling (CFM) software now allow greater control over where, and in what manner exogenous fields encounter neuronal populations of interest, and improved mechanistic understanding of tDCS-induced excitability changes allows researchers to consider the potential neurophysiological impact of DC fields. However, increased control of tDCS application has not yet translated to improved outcomes. While modulation of motor evoked potential (MEP) amplitude by tDCS has been reported, the magnitude of the effect has steadily decreased since the turn of the century (Horvath et al., 2015), and optimal study conditions remain unknown. Here, a candidate computationally individualised tDCS protocol is described, including in-depth discussion of its methodological rationale and potential barriers to optimisation. This protocol was not found to significantly alter cortical excitability, probed using transcranial magnetic stimulation (TMS), in stroke survivors and neurotypical participants. Meanwhile, reduced intra-cortical inhibition is here reported in sub-acute stroke survivors compared to neurotypical participants, and persistently increased variability in TMS-assessed excitability is reported in survivors up to 12 months post-stroke. The known state-dependent properties of tDCS suggest that individualised application may be required to further optimise the intervention in the heterogenous stroke population. Finally, a large computational study demonstrates the significant impact of stroke lesions on simulated tDCS electric field (E-field) delivered to the hand representation of the primary motor cortex, compared to neurotypical controls. This suggests that stroke-induced changes to brain anatomy may significantly impact E-field properties at a cortical target, which has recently been shown to correlate with neurophysiological outcomes. Taken together, heterogeneity in cortical anatomy and function in stroke survivors may contribute to variable tDCS outcomes and explain why computational approaches have not yet translated into larger effect sizes. Consequently, an individualised approach to protocol design is recommended to innovate tDCS application in stroke.

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