Abstract
Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.
Highlights
After an acute phase of coma, severe acute brain injuries can lead to lasting disorders of consciousness (DoC)
Measures of the effects consecutive to a single transcranial direct current stimulation session. (B) Individual patients’ Coma Recovery Scale-Revised (CRS-R) scores before and after tDCS are represented for responders (R+, in black) and non-responders (R−, in gray), together with the number of patients and their state. (C) The proportion of each state of consciousness, before and after tDCS showed an increase in the higher states of consciousness (exit minimally conscious state (EMCS) and minimally conscious state ‘plus’ (MCS+)), at the expense of lower states of consciousness (vegetative state/unresponsive wakefulness syndrome (VS/UWS) and MCS ‘minus’ (MCS-))
Between October 2015 and September 2018, among 69 eligible DoC patients, 66 patients were treated prospectively with a single 20 minutes tDCS session with the anode placed over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital cortex, using the www.nature.com/scientificreports same parameters as previously reported in DoC patients[22]
Summary
After an acute phase of coma, severe acute brain injuries can lead to lasting disorders of consciousness (DoC). In DoC patients, the effects of tDCS on brain activity have only been investigated in a few small sample studies using sparse and diverse EEG metrics, roughly showing an increase in fronto-parietal coherence in high frequencies[29,30], decrease in lower frequencies[26] and increase in cortical excitability following tDCS28,40. This diversity of metrics and the lack of clear underlying hypotheses regarding the electrophysiology of consciousness make it hard to interpret the effect of tDCS on consciousness. We investigated the possible mechanism of action of tDCS by correlating the electrophysiological response to the applied electric fields estimated from individual patients’ head and brain MRI anatomy
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