Brain stimulation as a therapeutic tool for Cerebral Palsy: a multimodal study

Thesis

Cerebral palsy (CP) is a heterogeneous condition, defined by shared clinical features: motor impairment due to an insult to the developing brain. As the most common cause of motor disability in childhood, clinically relevant and time-efficient interventions to improve motor function in CP are urgently needed. Transcranial direct current stimulation (tDCS) has been proposed as a therapeutic tool to augment neuroplasticity and improve function. However, tDCS study outcomes are discordant, with significant inter-individual variation. This thesis investigates the utility of this technique in CP, and explores potential contributing factors to variability.

Chapter 2 is an opportunistic study conducted during the COVID-19 lockdown. It demonstrated the negative effect of interrupting rehabilitation on motor function in CP and highlighted the need for improved rehabilitation techniques.

Chapter 3 details a pilot clinical trial of motor training and tDCS, versus training alone. While both groups showed improvement in motor function, there was no additional group-level effect of anodal primary motor cortex tDCS on outcome. Further chapters assessed pre-intervention neuroimaging data to explain variation in response to the trial intervention, with the aim of identifying possible biomarkers of rehabilitation potential with tDCS.

Chapter 4 applies a novel automated individualised probabilistic tractography technique to quantify corticospinal tract (CST) integrity. This technique is feasible and robust to structural lesions in the study population. At baseline, CST integrity correlated to hand function but not lower limb function or eventual rehabilitation outcome.

Finally, Chapter 5 interrogates the effect of electric field strength as a potential explanation for tDCS variability. Substantial variation in electric field focality and strength was demonstrated across participants. This may contribute to interindividual variability but did not predict individual motor outcome.

This work demonstrates the positive potential of motor training in improving function in CP. There may be a role for advanced neuroimaging and computational models to introspect rehabilitation outcomes in complex heterogenous conditions such as CP in future studies to better model the effect of tDCS across the clinical and pathologic spectrum of CP.

Authors: Gavine, B

• DOI: 10.5287/ora-xvrejbebm
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: corticospinal tract; electric field modelling; clinical trial; neuroimaging; diffusion imaging; cerebral palsy; transcranial direct current stimulation; probabilistic tractography; non invasive brain stimulation
• Subjects: neuroimaging; Neurodevelopmental treatment; Pediatric neurology--Research; neuroscience