Multi-session tDCS paired with passive mobilisation of the thumb modulates thalamo-cortical coupling during command following in the healthy brain.

Therapeutic options to restore responsiveness in patients with prolonged disorder of consciousness (PDOC) are limited. We have recently shown that a single session of tDCS over M1 delivered at rest can reduce thalamic self-inhibition during motor command following. Here, we build upon this by exploring whether pairing tDCS with a concurrent passive mobilisation protocol can further influence thalamo-M1 dynamics and whether these changes are enhanced after multiple stimulation sessions. Specifically, we used Dynamic Causal Modelling (DCM) of functional magnetic resonance imaging (fMRI) data from 22 healthy participants to assess changes in effective connectivity within the motor network during active thumb movements after 1 or 5 sessions of tDCS paired with passive mobilisations of the thumb. We found that a single anodal tDCS session decreased self-inhibition in M1, with five sessions further enhancing this effect. In addition, anodal tDCS increased thalamo-M1 excitation as compared to cathodal stimulation, with the effects maintained after 5 sessions. Together, our results suggest that pairing anodal tDCS with passive mobilisation across multiple sessions may facilitate thalamo-cortical dynamics that are relevant for behavioural responsiveness in PDOC. More broadly, they offer a mechanistic window into the neural underpinnings of the cumulative effects of multi-session tDCS.

tDCS modulates effective connectivity during motor command following; a potential therapeutic target for disorders of consciousness.

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a potential therapeutic route for unresponsive patients with prolonged disorders of consciousness (PDOC). However, research to date has had mixed results. Here, we propose a new direction by directly addressing the mechanisms underlying lack of responsiveness in PDOC, and using these to define our targets and the success of our intervention in the healthy brain first. We report 2 experiments that assess whether tDCS to the primary motor cortex (M1-tDCS; Experiment 1) and the cerebellum (cb-tDCS; Experiment 2) administered at rest modulate thalamo-cortical coupling in a subsequent command following task typically used to clinically assess awareness. Both experiments use sham- and polarity-controlled, randomised, double-blind, crossover designs. In Experiment 1, 22 participants received anodal, cathodal, and sham M1-tDCS sessions while in the MRI scanner. A further 22 participants received the same protocol with cb-tDCS in Experiment 2. We used Dynamic Causal Modelling of fMRI to characterise the effects of tDCS on brain activity and dynamics during simple thumb movements in response to command. We found that M1-tDCS increased thalamic excitation and that Cathodal cb-tDCS increased excitatory coupling from thalamus to M1. All these changes were polarity specific. Combined, our experiments demonstrate that tDCS can successfully modulate long range thalamo-cortical dynamics during command following via targeting of cortical regions. This suggests that M1- and cb-tDCS may allow PDOC patients to overcome the motor deficits at the root of their reduced responsiveness, improving their rehabilitation options and quality of life as a result.

Therapeutic Use of Transcranial Direct Current Stimulation in the Rehabilitation of Prolonged Disorders of Consciousness.

Patients with Prolonged Disorders of Consciousness (PDOC) have catastrophic disabilities and very complex needs for care. Therapeutic options are very limited, and patients often show little functional improvement over time. Neuroimaging studies have demonstrated that a significant number of PDOC patients retain a high level of cognitive functioning, and in some cases even awareness, and are simply unable to show this with their external behavior - a condition known as cognitive-motor dissociation (CMD). Despite vast implications for diagnosis, the discovery of covert cognition in PDOC patients is not typically associated with a more favorable prognosis, and the majority of patients will remain in a permanent state of low responsiveness. Recently, transcranial direct current stimulation (tDCS) has attracted attention as a potential therapeutic tool in PDOC. Research to date suggests that tDCS can lead to clinical improvements in patients with a minimally conscious state (MCS), especially when administered over multiple sessions. While promising, the outcomes of these studies have been highly inconsistent, partially due to small sample sizes, heterogeneous methodologies (in terms of both tDCS parameters and outcome measures), and limitations related to electrode placement and heterogeneity of brain damage inherent to PDOC. In addition, we argue that neuroimaging and electrophysiological assessments may serve as more sensitive biomarkers to identify changes after tDCS that are not yet apparent behaviorally. Finally, given the evidence that concurrent brain stimulation and physical therapy can enhance motor rehabilitation, we argue that future studies should focus on the integration of tDCS with conventional rehabilitation programmes from the subacute phase of care onwards, to ascertain whether any synergies exist.