Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients?

Abstract

Purpose: Disorders of consciousness (DOC) diagnosis relies on the presence or absence of purposeful motor responsiveness, which characterizes the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS), respectively. Functional neuroimaging studies have raised the question of possible residual conscious awareness also in clinically-defined UWS patients. The aim of our study was to identify electrophysiological parameters, by means of a transcranial magnetic stimulation approach, which might potentially express the presence of residual networks sustaining fragmentary behavioral patterns, even when no conscious behavior can be observed. Methods: We enrolled 25 severe DOC patients, following post-anoxic or traumatic brain injury and 20 healthy individuals (HC) as control group. Baseline electrophysiological evaluation evidenced, in comparison to HC, a partial preservation of cortical effective connectivity and excitability in clinically defined MCS, whereas these components were absent in clinically defined UWS. Then, we applied an anodal transcranial direct current stimulation (a-tDCS) protocol over the orbitofrontal cortex. Result: a-tDCS was able to boost cortical connectivity and excitability in all HC, MCS, and to unmask such excitability/ connectivity in some UWS patients. Conclusion: a-tDCS could be useful in identifying residual connectivity markers in clinically-defined UWS, who may lack of purposeful behavior as a result of a motor-output failure.

TDCS modulates cortical excitability in patients with disorders of consciousness

“…A long duration tDCS protocol applied to MCS and VS patients showed that all patients with MCS had clinical improvement immediately after tDCS, but no patient in VS showed immediate improvement (Angelakis et al 2014). Another study demonstrated that tDCS can boost cortical connectivity and excitability in MCS and VS patients (Naro et al 2015a). …”

Metaplasticity: A Promising Tool to Disentangle Chronic Disorders of Consciousness Differential Diagnosis

“…One could concern that the relatively small sample size limits the significance of multiple comparisons made (as the required sample size increases linearly with the logarithm of the number of comparisons made). However, the required sample size for detecting a between-group difference between TDCS after-effects using the typical conventions of 80% power, a two-tailed alpha of 0.05, and a putative metaplasticity effect size of approximately 0.40 (in keeping with the available literature data on TDCS in patients with DoC), [98][99][100][101][102][103][104][105] should be of at least 35 subjects, 106,107 which is satisfied by our sample. Further, the differences between the patients with DoC were statistically significant, as also shown by the effect size data indicating a big effect of TDCS on SICI, above all.…”

“…Given the small number of available studies dealing with TDCS in patients with DoC, [100][101][102][103][104][105] we can only try to quantify the relevance of our method in comparison with the other state-of-the-art methods. Our data indicate that metaplasticity is valuable in differentiating patients with DoC.…”

Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology

“…The rationale of using NIBS to highlight neural patterns potentially subtending awareness relies on the fact that awareness recovery requires that neuroplasticity mechanisms reach a determined threshold for awareness to emerge [131]. This issue was well evidenced by several experimental approaches, including the assessment of EEG oscillatory microstate occurrence (fast alpha and theta/delta), and brain operational architectonics (size, instability, speed of growth, and life span of neuronal assemblies; number and strength of connections; and strength of the DMN synchrony) [132][133][134][135][136][137][138][139][140][141]. Indeed, NIBS can furnish the required, still missing amount of neuroplasticity allowing awareness to emerge, even transiently [37,[76][77][78].…”