Resting-state EEG microstates as electrophysiological biomarkers in post-stroke disorder of consciousness

 Probably important for your doctor to know about this. 

I'd suggest you call up the hospital president and ask if they have a research analyst whose only job is to monitor and implement stroke research. If they don't have one, YOU DON'T HAVE A FUNCTIONING STROKE HOSPITAL! RUN AWAY!

Resting-state EEG microstates as electrophysiological biomarkers in post-stroke disorder of consciousness

Fang Yu¹ Yanzhe Gao² Fenglian Li^1* Xueying Zhang^1* Fengyun Hu^3* Wenhui Jia³ Xiaohui Li¹

• ¹College of Electronic Information and Optical Engineering, Taiyuan University of Technology, Taiyuan, China
• ²College of Life Sciences, Nankai University, Tianjin, China
• ³The Fifth Clinical Medical College of Shanxi Medical University, Department of Neurology, Shanxi Provincial People’s Hospital, Taiyuan, China

Introduction: Ischemic stroke patients commonly experience disorder of consciousness (DOC), leading to poorer discharge outcomes and higher mortality risks. Therefore, the identification of applicable electrophysiological biomarkers is crucial for the rapid diagnosis and evaluation of post-stroke disorder of consciousness (PS-DOC), while providing supportive evidence for cerebral neurology.

Methods: In our study, we conduct microstate analysis on resting-state electroencephalography (EEG) of 28 post-stroke patients with awake consciousness and 28 patients with PS-DOC, calculating the temporal features of microstates. Furthermore, we extract the Lempel-Ziv complexity of microstate sequences and the delta/alpha power ratio of EEG on spectral. Statistical analysis is performed to examine the distinctions in features between the two groups, followed by inputting the distinctive features into a support vector machine for the classification of PS-DOC.

Results: Both groups obtain four optimal topographies of EEG microstates, but notable distinctions are observed in microstate C. Within the PS-DOC group, there is a significant increase in the mean duration and coverage of microstates B and C, whereas microstate D displays a contrasting trend. Additionally, noteworthy variations are found in the delta/alpha ratio and Lempel-Ziv complexity between the two groups. The integration of the delta/alpha ratio with microstates’ temporal and Lempel-Ziv complexity features demonstrates the highest performance in the classifier (Accuracy = 91.07%).

Discussion: Our results suggest that EEG microstates can provide insights into the abnormal brain network dynamics in DOC patients post-stroke. Integrating the temporal and Lempel-Ziv complexity microstate features with spectral features offers a deeper understanding of the neuro mechanisms underlying brain damage in patients with DOC, holding promise as effective electrophysiological biomarkers for diagnosing PS-DOC.

1. Introduction

Stroke is widely acknowledged as the second leading cause of death and a prominent contributor to disability globally (Feigin et al., 2017, 2021), which results in severe behavioral impairments and widespread structural and functional network disruptions (Alkhachroum et al., 2022). Post-stroke, patients commonly experience symptoms such as disorder of consciousness (DOC) or coma, which contribute to increasing in-hospital mortality and unfavorable outcomes upon discharge for stroke patients (Li et al., 2016). Therefore, it is crucial to diagnose post-stroke disorder of consciousness (PS-DOC) promptly and accurately, while gaining a comprehensive understanding of the neural mechanisms underlying brain injury. Traditionally, clinical rating scales like the Glasgow Coma Scale (GCS) and Coma Recovery Scale Revision (CRS-R) have been used to assess patients with DOC. Although clinical behavioral assessment remains the gold standard (Hermann et al., 2020), these scoring systems exhibit high inter-rater and inter-examiner variability and lack objective evidence of central nervous system damage following brain injury (Claassen et al., 2016; Giacino et al., 2018; Song et al., 2018).

Currently, the utilization of electrophysiological methods, specifically electroencephalography (EEG), to measure neurological function in patients has been demonstrated as an effective method for rapidly assisting in the diagnosis of DOC (Bai et al., 2021b; Ballanti et al., 2022; Duszyk-Bogorodzka et al., 2022). Extensive research utilizing EEG-based spectral analysis, source imaging analysis, and graph theory analysis has improved neurophysiological assessments in the fields of stroke and DOC rehabilitation and diagnosis (Finnigan et al., 2016; Bai et al., 2021a; Zhuang et al., 2022; Bouchereau et al., 2023; Colombo et al., 2023). Regarding spectral patterns, previous studies have documented a notable reduction in alpha power after brain injury, including stroke (Edlow et al., 2021). Consequently, stroke leads to a marked elevation in the delta/alpha ratio (DAR), which quantifies the ratio of delta band power to alpha band power (Finnigan and van Putten, 2013). Likewise, distinguishing between patients with DOC and healthy controls often relies on the analysis of delta and alpha frequency bands, where increased delta rhythms and diminished alpha rhythms serve as prominent indicators of reduced consciousness levels (Rossi Sebastiano et al., 2015). Specifically, DOC patients demonstrate higher delta power than healthy controls (Sitt et al., 2014), while an augmentation in alpha power is observed during the recovery of consciousness in these individuals (Stefan et al., 2018). These studies seem to suggest that we can observe the relationship between the spectral feature DAR and reduced consciousness in patients with PS-DOC.

Although traditional spectral analysis of resting-state EEG integrates brain activity over several seconds in different frequency bands, this method fails to capture the spatial and temporal characteristics of resting-state brain networks occurring at shorter time scales (e.g., tens of milliseconds; Li et al., 2022). In contrast, multi-channel fusion of EEG microstate analysis can capture the spatiotemporal dynamics of activity in different brain regions at a sub-second time scale (Bréchet et al., 2019). Microstates represent specific topological patterns of electrical potentials and are typically classified into four distinct classes (Michel and Koenig, 2018), and the microstates persist for a transient period of approximately 60–120 ms in a quasi-stable state before rapidly transitioning to another microstate category (Lehmann et al., 1987). The swift transitions between microstates reflect rapid changes in brain dynamics, revealing the interconnectedness between cognitive function, information processing, and neural regulation in the brain (Khanna et al., 2014; Von Wegner et al., 2018; Liu et al., 2020). Furthermore, different microstate classes exhibit strong associations with specific resting-state networks (RSNs) in the brain, including the auditory network, visual network, salience network, and attention network, among others (Britz et al., 2010; Michel and Koenig, 2018). Increasing evidence suggests that abnormal alterations in temporal characteristics (such as mean duration, coverage, and occurrence) of microstates are observed in various neuropsychiatric disorders, including post-traumatic stress disorder (Terpou et al., 2022), schizophrenia (Rieger et al., 2016; Lin et al., 2022), Alzheimer’s disease (Tait et al., 2020), Parkinson’s disease (Pal et al., 2021), and depression (Zhao et al., 2022). However, microstate analysis research related to DOC primarily focuses on patients with diverse etiologies, including brain trauma, intracranial bleeding, hypoxic–ischemic, and other conditions (Guo et al., 2022; Toplutaş et al., 2023; Zhang et al., 2023). In contrast, there is limited research on microstate analysis in DOC patients with a single etiology, such as ischemic stroke, and our understanding of the temporal dynamics and spatiotemporal interaction effects in their brains remains insufficient.

Moreover, substantial evidence suggests that microstate time sequences display dynamic and nonlinear characteristics, including non-Markovian transition behaviors, where the transition to the next microstate class is independent of the current microstate class (Gschwind et al., 2015; Von Wegner et al., 2017). Increasing studies have introduced nonlinear measures applied to microstate sequences. In particular, Tait et al. pioneered the utilization of the Lempel-Ziv complexity (LZC) algorithm to investigate microstate transition patterns (Tait et al., 2020), revealing a reduction in microstate LZC among individuals with Alzheimer’s disease in comparison to their healthy counterparts. Subsequently, Zhang et al. explored the alterations in the LZC of microstate sequences in patients with brain diseases (Zhang et al., 2021), and Zhao et al. discovered an increase in the LZC of microstates in adolescents with depression (Zhao et al., 2022). Nonlinear analysis of EEG microstate sequences quantifies the persistent characteristics of brain electrical activity, revealing complex dynamic changes at very small time scales (Von Wegner et al., 2023). We suggest that the microstate LZC in PS-DOC patients may also exhibit some degree of abnormality, providing new insights into the neuro anomalies associated with DOC.

The aforementioned analysis indicates that the current understanding of EEG microstates in PS-DOC remains limited. To this end, the innovations and contributions of our study are summarized as follows.

Firstly, to the best of our knowledge, this paper is the first work to investigate the differences in EEG microstates between PS-DOC patients and post-stroke awake (PS-AW) conscious state patients. Comparison results show that there exist differences in microstate topographies between the two groups and especially exhibit significant alterations in temporal features among them.

Secondly, we analyze the Lempel-Ziv complexity of the microstate time sequences and find that, there exhibits higher repetitiveness and slower transition trends in the microstates of PS-DOC patients than that of PS-AW patients. Additionally, to supplement the spectral information in resting-state EEG, we calculate the DAR of spectral features in both groups. We find that DAR is significantly higher in PS-DOC patients.

Finally, we explore the potential of the aforementioned extracted features that are sensitive to intergroup variability in the classification of DOC. In particular, we fuse these features and feed the combined sets into an SVM classifier to identify the DOC among stroke patients. The outcome demonstrates that our work could accurately identify 92.86% of DOC patients.

In summary, our study contributes to a better understanding of resting-state EEG microstate features in patients with DOC post-stroke, helps us to identify potentially valid electrophysiological biomarkers, and provides important insights and neurological evidence into the causative mechanisms of decreased levels of consciousness post-stroke.

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Effect of acupuncture for disorders of consciousness in patients with stroke: A systematic review and meta-analysis

You have got to be kidding:

Impossible to have effects except as a placebo. Energy meridians have never been proven to exist.
No mechanism of action is possible. 

But you're also using appeal to antiquity  which is not scientific

But if you believe, have at it, recognizing these possible side effects;

• acupuncture side effects (1)

 The latest here:

 

Effect of acupuncture for disorders of consciousness in patients with stroke: A systematic review and meta-analysis

Zhibin Huang^1†, Yuning Chen^1†, Qilan Xiao^2,3, Weichuan Kuang^1,4, Kun Liu^1,4, Ye Jiang^1,4, Xi Wen^1,4, Weiting Qin⁵, Yue Liu^1,4* and Tong Liu^1,4*

• ¹Department of Acupuncture and Rehabilitation, The Fifth College of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
• ²Department of Rehabilitation, Equivalent Master's Degree Applicants of Guangzhou University of Chinese Medicine, Guangzhou, China
• ³Department of Rehabilitation, The Sixth Affiliated Hospital of Jinan University, Dongguan, China
• ⁴Department of Acupuncture and Rehabilitation, Guangdong Second Hospital of Traditional Chinese Medicine, Guangzhou, China
• ⁵Department of Urinary Surgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China

Background: Disorder of consciousness (DOC) is frequent in patients with stroke, which is the second most common cause of death and a leading cause of disability. Acupuncture has been used as a curative method for DOC treatment in China. Nevertheless, no critical systematic review of acupuncture's effect on DOC has been published. This review aims to evaluate the present evidence regarding the efficacy of acupuncture for DOC after stroke.

Methods: Seven databases were searched from their inception to November 1, 2021, containing three English databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) and four Chinese databases (CNKI, CBM, VIP, and Wanfang Database). The primary outcomes comprise the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) before and after treatment. Secondary outcomes involve resuscitation rate, resuscitation time, and adverse events. Data synthesis was calculated by RevMan (V.5.4.1) software. According to the Cochrane Handbook, methodological quality was assessed with the risk of bias tool 2.0 (RoB2).

Results: Seventeen studies containing 1,208 patients were eventually included in our review. Overall, most trials were rated as high or had some concerns regarding the risk of bias. GCS was reported in 16 trials, and a meta-analysis showed that GCS improvement in the acupuncture group was greater than in the non-acupuncture group (MD 1.45, 95% CI 0.94–1.97, P < 0.0001). One trial reported that GOS improvement in the acupuncture plus medication group was greater than in the medication group (MD 0.58, 95% CI 0.11–1.05, P = 0.01). Another study reported that acupuncture plus medication was statistically more effective in shortening resuscitation time than medication alone (MD−0.89, 95% CI −1.53 to −0.25, P = 0.006). Four trials reported that the resuscitation rate in the acupuncture group was higher than without acupuncture intervention (RR 1.68, 95% CI 1.30–2.18, I² 0%, P = 0.39). Adverse events were reported in two studies, with one case in the acupuncture group suffering from subcutaneous hematoma.

Conclusion: Acupuncture may improve consciousness level, increase the resuscitation rate, and shorten resuscitation time for post-stroke patients with DOC. Adverse events from acupuncture were rare, tolerable, and recoverable. However, the results should be interpreted cautiously, and more rigorous RCTs with better methodology are warranted.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=289802, identifier 289802.

Introduction

Stroke, a common acute cerebrovascular accident, can be clinically divided into two types according to pathogenesis: ischemic stroke and hemorrhagic stroke—the former accounts for about 62.4% and the latter, 37.6% (1). High incidence, morbidity, mortality, and recurrence rate constitute the significant characteristics of stroke. From a global perspective, stroke, in particular, has imposed a ponderous burden on developing countries (2). In 2017, the total number of stroke deaths worldwide was 6.16 million, while China accounts for about one-third of the total, with 2.1 million (3). Besides, the overall lifetime risk of stroke in China is 39.9%, the highest in the world, which means that about two out of five people may suffer from a stroke during their lifetime. In 2017, the per capita hospitalization expenses for patients with ischemic and hemorrhagic strokes in China were 9,607 and 18,525 Chinese yuan (CNY), an increase of 60 and 118%, respectively, compared with 2007 (4). Therefore, more attention should be paid to strokes.

Several complications could be involved in stroke, such as consciousness disorder, depression, dysphagia, cognitive impairment, and so on (5). The sequelae of a stroke may lead to a lengthy recovery period, high medical expenses, and a poor prognosis for post-stroke patients (6). Among various sequelae, a disorder of consciousness (DOC) occurs frequently. According to an evidence-based practice guideline for stroke, nearly one out of every three stroke patients suffers from DOC to varying degrees (7). Moreover, it was also shown that 40% of patients with DOC have difficulty regaining normal consciousness (8). In a clinical randomized controlled study involving 6,336 people, the results indicated that the hospital mortality rate of stroke patients with DOC was higher than those without (35.9 vs. 2.6%) (9).

Currently, stroke treatment is based primarily on surgery and drug thrombolytic therapy (10, 11). In terms of stroke sequelae, it has been pointed out that multidisciplinary cooperative rehabilitation units could achieve superior outcomes (12). As a relatively well-recognized traditional therapy, acupuncture has broadly been used in post-stroke rehabilitation in China (13). Studies have indicated that acupuncture treatment for stroke can adjust the stability of the human body environment through the influence of the nerve-endocrine-immune network (14). Specific to stroke, acupuncture affects the neurovascular unit through multiple levels to promote cerebral blood perfusion in the focal area of stroke patients and improve the function of damaged brain cells (15, 16). Furthermore, with respect to the therapeutic method regarding post-stroke patients with impaired consciousness, acupuncture has been carried out in correspondent clinical study (17).

However, no systematic review assessing the effect of acupuncture for DOC has been carried out until now. Consequently, we performed this review to explore whether acupuncture was an efficacious therapy for DOC.

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