Exploring the neural, behavioural, and clinical effects of transcranial direct current stimulation in patients with a Prolonged Disorder of Consciousness; protocol for a double-blind randomised crossover feasibility study

Background: Therapeutic options for patients with prolonged disorders of consciousness (PDOC) are very limited, and patients often show little to no progress over time. It is widely recognized that some PDOC patients retain a higher level of cognition that may be apparent on the basis of their external responses, and simply are unable to produce purposeful motor behaviours. This dissociation has been linked to specific impairments in the motor network that lead to a reduction in thalamo-cortical coupling. Here, we will assess whether transcranial direct current stimulation (tDCS) can modulate thalamo-cortical coupling and improve patients’ responsiveness. We will focus on characterising the mechanisms of action of tDCS and the bases for potential individual differences in responsiveness to the stimulation across participants.Methods: This is a multi-centre double-blind randomised crossover feasibility study. It is divided into two streams: (a) MRI stream: 5 PDOC patients will complete 5 anodal, cathodal, and sham stimulation sessions (paired with passive mobilisation of the thumb) in separate weeks. We will measure brain activity and connectivity with functional magnetic resonance imaging and electroencephalography (EEG). We will look at brain structures to assess differences associated with responsiveness. (b) Bedside stream: 10 patients will complete one session of anodal or cathodal stimulation and one session of sham. We will measure brain activity and connectivity with EEG and we will conduct follow up assessments at 3 and 6 months. In both streams we will also look at changes in the clinical profile of patients with the Coma Recovery Scale Revised and in command following behaviour with electromyography and motion tracking. We will assess feasibility on measures of eligibility, recruitment, retention, and completion of tests.Discussion: This feasibility study is the first step towards developing personalised tDCS interventions to restore external responsiveness in PDOC patients. Our results will inform the design of a future trial fully powered for characterising neural, behavioural, and clinical effects of tDCS in PDOC as well as the mechanisms underlying individual differences in responsiveness.