Effects of 20 Hz Repetitive Transcranial Magnetic Stimulation on Disorders of Consciousness: A Resting-State Electroencephalography Study

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC). To date, there has been little research into the use of rTMS in DOC and the therapeutic effects have been variously documented. This study aimed to examine the effects of 20 Hz rTMS on the electroencephalography (EEG) reactivity and clinical response in patients with DOC and to explore the neuromodulatory effects of high-frequency rTMS. In this randomized, sham-controlled, crossover study, real or sham 20 Hz rTMS was applied to the left primary motor cortex (M1) of patients with DOC for 5 consecutive days. Evaluations were blindly performed at the baseline (T0), immediately after the end of the 5 days of treatment (T1) and 1 week after the treatment (T2) using the JFK coma recovery scale-revised (CRS-R) and resting-state EEG. Only one patient, with a history of 2 months of traumatic brain injury, showed long-lasting (T1, T2) behavioral and neurophysiological modifications after the real rTMS stimulation. The 5 remaining patients presented brain reactivity localized at several electrodes, and the EEG modification was not significant. rTMS stimulation may improve awareness and arousal of DOC. Additionally, EEG represents a potential biomarker for the therapeutic efficacy of rTMS. This trial is registered with (NCT03385278).

Computational Methods for Resting-State EEG of Patients With Disorders of Consciousness

“…Other current EEG-related techniques in DOC are Event-Related Potential (ERP) (Signorino et al, 1995; Faugeras et al, 2011; Morlet and Fischer, 2014), Transcranial Magnetic Stimulation (TMS)-EEG (Casali et al, 2013) and EEG with transcranial direct current stimulation (tDCS) (Bai et al, 2017b). Furthermore, resting-state EEG, flanked by appropriate quantitative methods (i.e., QEEG), provides objective clinical assessment thus avoiding subjective errors (Stefan et al, 2018) in the clinical practice for diagnosis (Sitt et al, 2014), prognosis (Chennu et al, 2017), and treatment evaluation (Bai et al, 2017b, 2018; Estraneo et al, 2017; He et al, 2018).…”

Therapeutic interventions in patients with prolonged disorders of consciousness

“…The last small sample crossover RCT evaluated the effects of 5 sessions of M1 20 Hz rTMS, lasting ~10 minutes, in 3 UWS, 2 MCS and 1 EMCS patients (1-28 months post-injury). 48 At the group level, no treatment effect was found, but at the single subject level, one UWS patient recovered localization to painful stimulation and maintained this behavior at 1-week follow-up. This clinical improvement was paralleled with an increase in alpha and beta power.…”

“…However, at the group level, no behavioral enhancements were noticed in any of the RCTs when applied over M1. 45,46,48 Future RCTs should target the DLPFC, similarly to tDCS, as two uncontrolled observational rTMS studies show some positive effects. 50,51 Demographic and clinical characteristics of responders should also be investigated in larger RCTs or meta-analyses.…”

Emotional consciousness preserved in patients with disorders of consciousness?

“…Of these 15 patients, seven met the diagnostic criteria for UWS; the remaining eight were diagnosed with minimally conscious state (MCS). All subjects met the following study inclusion criteria: (1) no centrally acting drugs, (2) no neuromuscular function blockers and no sedation within the 24 h prior to the study, (3) periods of spontaneous eye opening, and (4) with non-traumatic brain injury [ 10 – 12 ]. Demographic and clinical characteristics of the enrolled patients are shown in Table 1 .…”