Neural, Behavioural, and Clinical Effects of tDCS in PDOC; Feasibility Study

Patients with prolonged disorders of consciousness (PDOC) have very limited therapeutic options, and they often show little to no progress over time. Here, the investigators will assess whether transcranial direct current stimulation can improve patients' responsiveness. The investigators will use a protocol designed to target specific brain networks that have been shown to play a key role in explaining the lack of voluntary responses in PDOC. The study will focus on characterising the mechanisms of action of tDCS and the bases for potential individual differences in responsiveness to the stimulation across participants. This feasibility study is the first step towards developing personalised tDCS interventions to restore external responsiveness in PDOC patients. Its 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.

• Transcranial direct current stimulation (Other), also known as tDCS: tDCS alters neural excitability in a polarity-specific manner via a weak direct electric current delivered through electrodes placed on the scalp. There are 3 types of stimulation: anodal, cathodal, and sham. In anodal tDCS, the positive electrode is placed over the target brain area to increase neuronal excitability. In cathodal tDCS, the negative electrode is placed over the target brain area to decrease neuronal excitability. Sham tDCS emulates the physical sensations of active (anodal/cathodal) tDCS but current is only delivered for a short period of time and is not enough to cause any neuromodulations

Primary outcomes

• Retention at end of active phase [through completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream]: percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure)
• Retention at 3 months [3 months after start of participation]: percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure). This Outcome applies to the bedside stream only
• Retention at 6 months [6 months after start of participation]: percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure). This Outcome applies to the bedside stream only
• Completion [through completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream]: percentage of tDCS, MRI, and electrophysiology assessments completed per polarity

Secondary outcomes

• Structural MRI [day 1 and day 5 of tDCS each polarity]: This will include assessments of the gross macrostructure, and microstructure of brain tissue grey matter, white matter, and cerebrospinal fluid
• Functional MRI in response to task instructions [day 1 and day 5 of tDCS each polarity]: This will include assessments of the BOLD (blood oxygen level-dependent) response to characterise brain activity and connectivity during command following
• EEG power in the alpha band in response to task instructions [days 1 and 4 of each polarity in the MRI stream and day 1 of each polarity in the bedside stream]: Envelope of bandpass filtered EEG data between 8-12 Hertz
• EEG power in the beta band in response to task instructions [days 1 and 4 of each polarity in the MRI stream and day 1 of each polarity in the bedside stream]: Envelope of bandpass filtered EEG data between 13-30 Hertz
• EMG (electromyography) amplitude changes [days 1-4 and day 2 of each polarity in the MRI and bedside streams respectively]: Changes in the amplitude of the rectified EMG signal (high-pass filtered > 50Hz) in response to instructions to move
• Coma recovery scale -revised [regularly through active phase of study (baseline and outcome assessments), on average 4 weeks for bedside stream and 8 weeks for MRI stream]: clinical diagnostic scale for disorders of consciousness. Total score ranges from 0 to 23, where higher scores mean a higher level of functioning and awareness
• Glasgow Outcome Scale-extended [at 3 and 6 months after start of participation]: Scale for functional outcome after brain injury. Total score ranges from 1 to 8, where higher values correspond to better outcome

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Aged 18 years or older
* Receiving care at a recruitment site, with a consensus clinical diagnosis of PDOC from any aetiology (i.e. traumatic or non-traumatic injury).
* Stable and with no need of mechanical support (i.e. respirator, etc.)

Exclusion Criteria:

* Scalp skin sores or any skin damage at the electrode sites
* Metallic implants in the face or skull
* Craniectomy or cranioplasty
* No evidence of auditory startle in clinical observations, or absent brainstem auditory evoked potentials in recent clinical history (if data available)
* MRI incompatible: metal plates incompatible with MRI scanners, pacemaker, inability to lay flat for prolonged periods of time, aneurysm clips, neurostimulators, brain/subdural electrodes, etc. (MRI stream ONLY)