Effect of acoustic stimuli in patients with

Introduction

Disorders of consciousness (DOC), such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), are commonly caused by severe brain by Laureys, UWS is the new term for a vegetative state characterized by “wakeful unawareness” (Laureys et al., 2010). Patients in UWS show spontaneous eye opening,breathing, and occasionally meaningless limb movement,but with no evidence of awareness. Meanwhile, patients that demonstrate reproducible but fluctuating behavioral evidence of awareness of self or their environment are considered to be in MCS (Machado, 2002).

In the last decade, great efforts have been focused on identifying efficient awakening methods for DOC. Sensory stimula-tion (especially acoustic stimuli) is an experimental awakening approach that exhibits superiority over non-invasive methods and has low risk. It is based on the idea that sensory stimulation may potentially affect neural networks, accelerate brain plasticity, and avoid sensory deprivation (Herdener et al., 2010; Luo et al., 2012; Zhu et al., 2014). The “arousal and mood hypothesis”explains the enhancing effect of music and a subjects’ own name (SON). As emotionally salient content, music and SON have proven to elicit enhanced spontaneous brain responses in distributed brain networks. Moreover, they activate limbic and paralimbic structures, as well as the reward circuit (Janata,2009; Castro et al., 2015; Schnakers et al., 2016; Tacikowski and Ehrsson, 2016). Similarly, the moderate brain arousal model postulates that white noise regulates dopamine transmission and facilitates signal transmission in the brain (Soderlund et al., 2016). Dopamine is related to attention, cognition, and motivated behavior (Sikstr?m and S?derlund, 2007). There are current studies on the effectiveness of auditory stimulation for DOC, but the results vary because of the various assessment indicators, heterogeneous patient groups, and multifarious sound characteristics of the stimulation materials used in different studies. Hence, in this study, we compared stimulation awakening effects in the same subjects, who were stimulated with three acoustic stimuli: music, SON, and white noise.

The Coma Recovery Scale-Revised (CRS-R) is a widely used behavioral assessment scale for DOC (American Congress of Rehabilitation Medicine et al., 2010; Gerrard et al., 2014).However, high test-retest and interrater variability can in fluence the accuracy of clinical assessment (L?vstad et al., 2010).Quantitative electroencephalography (QEEG) as a non-invasive and objective assessment method may qualify as an alternative. The power spectrum is divided into four bandwidths(δ, θ, α, β). Among these, increased δ and θ activity usually reflects encephalopathy and/or structural lesions, which are interpreted as poor outcome predictors for DOC (Fingelkurts et al., 2011). Additionally, α and β power is associated with chance of recovery (Babiloni et al., 2009). A previous study found that δ+θ/α+β value was a sensitive index for brain function in DOC. Further, CRS-R score is strongly associated with spectral EEG at rest (Lechinger et al., 2013). However, there is insuf ficient evidence on validity of clinical prognosis, and few studies have explored the diagnostic and prognostic use of QEEG with stimulation settings. Functional neuroimaging demonstrates that DOC prognosis can be predicted by analysis of specific brain areas (Leon-Carrion et al., 2012). In contrast to QEEG studies on precise temporal resolution, analysis of distinct lobes is scarce, and only a few studies have investigated the predictive value of QEEG in susceptible regions.

Thus, in this study, we examined brain activation to music, SON, and white noise (as determined by QEEG in both the resting state and to acoustic stimulation) to investigate the predictive value of QEEG in various brain regions of DOC patients.

Participants and Methods

Participants

In this case-control study, 14 patients (11 men and 3 women) were recruited from the Neuro-Rehabilitation Unit of Hangzhou Hospital of Zhejiang Armed Police Corps of China. Inclusion criteria were: (1) age ＞ 18 years; (2) diagnosis of UWS and MCS based on CRS-R (American Congress of Rehabilitation Medicine et al., 2010; Gerrard et al., 2014); (3)at least one side showing no auditory injury, as evaluated by Brainstem Auditory Evoked Potentials (Fellinger et al., 2011);(4) no history of neurological or psychiatric disease and with stable vital parameters; and (5) the guardian had provided informed consent and signed the consent form. Exclusion criteria were: (1) significant neurological history; and (2)had received centrally acting drugs, neuromuscular function blockers, or sedating drugs 24 hours prior to study (Fellinger et al., 2011). CRS-R was conducted by medical staff before the experiment, and each patient’s outcome was assessed using the Glasgow Outcome Scale (GOS). A GOS value of ＜ 3 was considered a bad recovery, while a GOS value of ≥ 3 was considered a good recovery (Schnakers et al., 2008).

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