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Background: Disorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes., Methods: This retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure., Results: Our findings revealed that in patients with better outcome, there are significant less patient with electrode shift ( p  = 0.019). Further, a linear correlation was found between the length of electrode shift and patients' outcome (Rho = 0.583, p  = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode ( p  = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS ( p  = 0.033)., Conclusion: These results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients' outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Yang, Xu, Niu, Wu, Huang, Chai, Cao, Wang, Wong, He, Yang and Zhao.)

Background: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions., Objective: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients., Methods: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science)., Results: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian-parafascicular complex (CM-pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 μs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow-up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates., Conclusion: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition., (© 2024 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

A brain-computer interface (BCI) serves as a direct communication channel between brain activity and external devices, typically a computer or robotic limb. Advances in technology have led to the increasing use of intracranial electrical recording or stimulation in the treatment of conditions such as epilepsy, depression, and movement disorders. This indicates that BCIs can offer clinical neurological rehabilitation for patients with disabilities and functional impairments. They also provide a means to restore consciousness and functionality for patients with sequelae from major brain diseases. Whether invasive or non-invasive, the collected cortical or deep signals can be decoded and translated for communication. This review aims to provide an overview of the advantages of endovascular BCIs compared with conventional BCIs, along with insights into the specific anatomical regions under study. Given the rapid progress, we also provide updates on ongoing clinical trials and the prospects for current research involving endovascular electrodes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Neurological and psychiatric diseases can lead to motor, language, emotional disorder, and cognitive, hearing or visual impairment By decoding the intention of the brain in real time, the Brain-computer interface (BCI) can first assist in the diagnosis of diseases, and can also compensate for its damaged function by directly interacting with the environment; In addition, provide output signals in various forms, such as actual motion, tactile or visual feedback, to assist in rehabilitation training; Further intervention in brain disorders is achieved by close-looped neural modulation. In this article, we envision the future BCI digital prescription system for patients with different functional disorders and discuss the key contents in the prescription the brain signals, coding and decoding protocols and interaction paradigms, and assistive technology. Then, we discuss the details that need to be specially included in the digital prescription for different intervention technologies. The third part summarizes previous examples of intervention, focusing on how to select appropriate interaction paradigms for patients with different functional impairments. For the last part, we discussed the indicators and influencing factors in evaluating the therapeutic effect of BCI as intervention., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Speech perception depends on the dynamic interplay of bottom-up and top-down information along a hierarchically organized cortical network. Here, we test, for the first time in the human brain, whether neural processing of attended speech is dynamically modulated by task demand using a context-free discrimination paradigm. Electroencephalographic signals were recorded during 3 parallel experiments that differed only in the phonological feature of discrimination (word, vowel, and lexical tone, respectively). The event-related potentials (ERPs) revealed the task modulation of speech processing at approximately 200 ms (P2) after stimulus onset, probably influencing what phonological information to retain in memory. For the phonological comparison of sequential words, task modulation occurred later at approximately 300 ms (N3 and P3), reflecting the engagement of task-specific cognitive processes. The ERP results were consistent with the changes in delta-theta neural oscillations, suggesting the involvement of cortical tracking of speech envelopes. The study thus provides neurophysiological evidence for goal-oriented modulation of attended speech and calls for speech perception models incorporating limited memory capacity and goal-oriented optimization mechanisms., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The accurate evaluation of operators' mental workload in human-machine systems plays an important role in ensuring the correct execution of tasks and the safety of operators. However, the performance of cross-task mental workload evaluation based on physiological metrics remains unsatisfactory. To explore the changes in dynamic functional connectivity properties with varying mental workload in different tasks, four mental workload tasks with different types of information were designed and a newly proposed dynamic brain network analysis method based on EEG microstate was applied in this paper. Six microstate topographies labeled as Microstate A-F were obtained to describe the task-state EEG dynamics, which was highly consistent with previous studies. Dynamic brain network analysis revealed that 15 nodes and 68 pairs of connectivity from the Frontal-Parietal region were sensitive to mental workload in all four tasks, indicating that these nodal metrics had potential to effectively evaluate mental workload in the cross-task scenario. The characteristic path length of Microstate D brain network in both Theta and Alpha bands decreased whereas the global efficiency increased significantly when the mental workload became higher, suggesting that the cognitive control network of brain tended to have higher function integration property under high mental workload state. Furthermore, by using a SVM classifier, an averaged classification accuracy of 95.8% for within-task and 80.3% for cross-task mental workload discrimination were achieved. Results implies that it is feasible to evaluate the cross-task mental workload using the dynamic functional connectivity metrics under specific microstate, which provided a new insight for understanding the neural mechanism of mental workload with different types of information.

To explore the effectiveness of using Electro- encephalogram (EEG) spectral power and multiscale sample entropy for accessing mental workload in different tasks, working memory tasks with different information types (verbal, object and spatial) and various mental loads were designed based on the N-Back paradigm. Subjective scores, accuracy and response time were used to verify the rationality of the tasks. EEGs from 18 normal adults were acquired when tasks were being performed, an independent component analysis (ICA) based artifact removal method were applied to get clean data. Linear (relative power in Theta and Alpha band, etc.) and nonlinear (multiscale sample entropy) features of EEGs were then extracted. Indices that can effectively reflect mental workload levels were selected by using multivariate analysis of variance statistical approach. Results showed that with the increment of task load, power of frontal Theta, Theta/Alpha ratio and sample entropies at scale more than 10 in parietal regions increased significantly first and decreased slightly then, while the power of central-parietal Alpha decreased significantly first and increased slightly then. Considering the difference between task types, no difference in power of frontal Theta, central-parietal Alpha and sample entropies at scales more than 10 of parietal regions were found between verbal and object tasks, as well as between two spatial tasks. No difference of frontal Theta/Alpha ratio was found in all the four tasks. The results can provide evidence for the mental workload evaluation in tasks with different information types.

More and more hybrid brain-computer interfaces (BCI) supplement traditional single-modality BCI in practical applications. Combinations based on steady-state visual evoked potential (SSVEP) and electromyography (EMG) are the widely used hybrid BCIs. The EMG of jaw clench is commonly used together with SSVEP. This article explored the interference with SSVEP from occipital electrodes by the jaw clench-related EMG so that SSVEP with specific frequency can be identified even during occlusal movements. The experiment was divided into three sets base on the jaw clench patterns (no clenches, chew, and long clench). In each set, the subjects used the same visual stimuli, which were realized by the three flashing targets at different frequencies (6.2Hz, 9.8Hz, and 14.6Hz). After collecting the SSVEP at 4 sites in the occipital region, the SSVEP response spectrum of each stimulus was observed under the three jaw clench patterns. Then, the SSVEP signal was identified by the canonical correlation analysis method for accuracy statistics. Spectrum responses showed that the interference of the jaw clench EMG on SSVEP could be avoided when the stimulation frequency is lower than 20Hz. SSVEP could be identified based on the frequency domain characteristics of these signals. During steady-state visual stimulation with jaw clenches, the recognition rate of SSVEP was still high (no clenches: 100.0%, chew: 94.7%, and long clench: 100.0%). Through reasonable frequency selecting and signal processing, the influence of the jaw clench movement on the SSVEP could be reduced and a high recognition accuracy could be achieved, even the jaw clench actions and the SSVEP stimulation occur simultaneously.

Disulfiram (DSF) is a well-known drug for alcohol abuse. In recent decades, DSF has been demonstrated to exhibit anti-tumor activity; DSF chelated with copper shows enhanced anti-tumor effect. Our goal was to explore the effect of DSF/Cu complex on the growth and metastasis of gastric cancer (GC) in vitro and in vivo . DSF/Cu complex suppressed the proliferation, migration of MKN-45 and BGC-823 GC cells. Furthermore, DSF/Cu treatment reduced the tumor volume in GC mouse models with a tumor suppression rate of 48.24%. Additionally, DSF/Cu induced apoptosis in vitro in MKN-45 and BGC-823 GC cells in a dose- and time-dependent manner as well as in vivo in the xenograft tumor mouse model. Furthermore, DSF/Cu induced autophagy and autophagic flux in MKN-45 and BGC-823 cells, increased the expression of autophagy-related Beclin-1 and LC3 proteins in vivo . Additionally, DSF/Cu suppressed aerobic glycolysis and oxidative phosphorylation by reducing oxygen consumption rate and extracellular acidification rate, respectively, in MKN-45 and BGC-823 cells. Treatment with DSF/Cu induced oxidative stress and DNA damage response by elevating the reactive oxygen species levels; increasing the expression of P53, P21, and γ-H2AX proteins; and inhibiting Wnt/β-catenin signaling in vitro and in vivo . Thus, DSF/Cu suppressed the growth and metastasis of GC cells via modulating the stress response and Wnt/β-catenin signaling. Hence, DSF may be used as a potential therapeutic agent for the treatment of GC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wang, Chai, Wan, Zhang, Zhou, Xiang, Paul and Li.)

Background and Objective: In flicker-based steady-state visual evoked potentials (SSVEP) brain-computer interface (BCI), the system performance decreases due to prolonged repeated visual stimulation. To reduce the performance decrease due to visual fatigue, the zoom motion based steady-state motion visual evoked potentials (SSMVEPs) paradigm had been proposed. In this study, the stimulation parameters of the paradigm are optimised to mitigate the decrease in detection accuracy for SSMVEP due to visual fatigue., Methods: Eight zoom motion-based SSMVEP paradigms with different stimulation parameters were compared. The graph size, luminance, colour, and shape, as well as the frequency range and interval of the stimulation and refresh rate of the screen was changed to determine the optimal paradigm with high recognition accuracy and reduced fatigue effects. The signal-to-noise ratio (SNR) of SSMVEP was also calculated for four fatigue levels. Moreover, the power spectral density of electroencephalograph (EEG) alpha and theta bands during ongoing activity was calculated for the stimulation experiment to evaluate fatigue at the start and end of the stimulation task., Results: All stimulation SSMVEP paradigms exhibited high accuracies. Changes in luminance, colour, and shape did not impact the recognition accuracy, nor did a higher stimulation frequency or lower frequency interval of each stimulation block. However, the paradigm with smaller stimulus achieved the highest average target selection accuracy of 97.2%, compared to 94.9% for the standard paradigm. Furthermore, it exhibited almost zero reduction in recognition accuracy due to fatigue. From fatigue level 1 to level 4, the smaller zoom motion-based SSMVEP exhibited a lower decrease in the SNR of SSMVEP and a lower alpha/theta ratio decrease during ongoing stimulation activity compared to the standard paradigm., Conclusions: For a zoom motion-based SSMVEP paradigm, changing multiple stimulation parameters can lead to the same high performance as the standard paradigm. Moreover, using a smaller stimulus can reduce the accuracy decrease caused by fatigue because the SNR decrease in the evoked SSMVEP state was negligible and the alpha/theta index decrease during ongoing activity was lower than that for the standard paradigm., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Background: In steady state visual evoked potential (SSVEP)-based brain-computer interfaces, prolonged repeated flicker stimulation would reduce the system performance. To reduce the visual discomfort and fatigue, while ensuring recognition accuracy, and information transmission rate (ITR), a novel motion paradigm based on the steady-state motion visual evoked potentials (SSMVEPs) is proposed. Methods: The novel SSMVEP paradigm of the radial zoom motion was realized using the sinusoidal form to modulate the size of the stimuli. The radial zoom motion-based SSMVEP paradigm was compared with the flicker-based SSVEP paradigm and the SSMVEP paradigm based on Newton's ring motion. The canonical correlation analysis was used to identify the frequency of the eight targets, the recognition accuracy of different paradigms with different stimulation frequencies, and the ITR under different stimulation durations were calculated. The subjective comfort scores and fatigue scores, and decrease in the accuracy due to fatigue was evaluated. Results: The average recognition accuracy of the novel radial zoom motion-based SSMVEP paradigm was 93.4%, and its ITR reached 42.5 bit/min, which was greater than the average recognition accuracy of the SSMVEP paradigm based on Newton's ring motion. The comfort score of the novel paradigm was greater than both the flicker-based SSVEP paradigm and SSMVEP paradigm based on Newton's ring motion. The decrease in the recognition accuracy due to fatigue was less than that of the SSSMVEP paradigm based on Newton's ring motion. Conclusion: The SSMVEP paradigm based on radial zoom motion has high recognition accuracy and ITR with low visual discomfort and fatigue scores. The method has potential advantages in overcoming the performance decline caused by fatigue.

Objective: To propose a square's ring motion stimulation based on steady-state motion visual evoked potential, and compare it with the commonly used visual stimulation modes (Newton's ring motion, square flicker and circular flicker)., Methods: EEG signals were collected while 9 experimental subjects gazing at four stimulation and pattern analyzed by Canonical Correlation Analysis (CCA). Stimulation were evaluated by recognition accuracy and subjective scores., Results: The classification accuracies of SSVEP elicited by the square's ring motion(82.8%±14.1%) and Newton's ring(83.3%±11.5%) have no significant difference between them, which are lower than that of the square flicker(98.3%±4.1%) and the circular flicker(99.2%±1.8%). The shape of the figure has no significant influence on the classification accuracy either in motion mode or flicker mode. The comfort of the square's ring motion is higher than the other three stimulation according to subjective scores., Conclusions: The square's ring motion can elicit EEG and reduce the discomfort caused by flicker modes. The square's ring motion can be used as a visual stimulation in SSMVEP-based BCI system.

Investigation of the interaction between cardiovascular variables and respiration provides a quantitative and noninvasive approach to assess the autonomic control of cardiovascular function. The aim of this paper is to investigate the changes of cardiopulmonary coupling (CPC), blood pressure (BP) and pulse transit time (PTT) during a stepwise-paced breathing (SPB) procedure (spontaneous breathing followed by paced breathing at 14, 12.5, 11, 9.5, 8 and 7 breaths per minute, 3 min each) and gain insights into the characteristics of slow breathing exercises. RR interval, respiration, BP and PTT are collected during the SPB procedure (48 healthy subjects, 27 ± 6 years). CPC is assessed through investigating both the phase and amplitude dynamics between the respiration-induced components from RR interval and respiration by the approach of ensemble empirical mode decomposition. It was found that even though the phase synchronization and amplitude oscillation of CPC were both enhanced by the SPB procedure, phase coupling does not increase monotonically along with the amplitude oscillation during the whole procedure. Meanwhile, BP was reduced significantly by the SPB procedure (SBP: from 122.0 ± 13.4 to 114.2 ± 14.9 mmHg, p < 0.001, DBP: from 82.2 ± 8.6 to 77.0 ± 9.8 mmHg, p < 0.001, PTT: from 172.8 ± 20.1 to 176.8 ± 19.2 ms, p < 0.001). Our results demonstrate that the SPB procedure can reduce BP and lengthen PTT significantly. Compared with amplitude dynamics, phase dynamics is a different marker for CPC analysis in reflecting cardiorespiratory coherence during slow breathing exercise. Our study provides a methodology to practice slow breathing exercise, including the setting of target breathing rate, change of CPC and the importance of regular breathing. The applications and usability of the study results have also been discussed.

Rhythmic respiratory movement in a deep and slow pattern can be beneficial to cardiovascular system, this paper investigates the effect of step-wise paced breathing procedure on blood oxygen saturation (SpO2). Experiment objects were divided into two groups, the normobaric hypoxia (simulated altitude of 4 500 meters hypoxia environment, 8 persons), normoxia and normobaric group (laboratory environment, 49 persons). The respiratory movements were performed by a high-to-low progressive change in two groups respectively. During the experiment, each object's blood oxygen saturation and heart rate were recorded. Results showed that progressive guided breathing could significantly increase the subjects' blood oxygen saturation level from 90% to 95% under the hypoxic condition. Even under the normobaric and normoxic condition, progressive guided breathing with stable blood oxygen saturation level can also enhance the blood oxygen saturation level. In both groups, mean heart rate declined in the progressive guided breathing. The research showed that the step-wise paced breathing technique could regulate the blood oxygen saturation and effectively improve the level of blood oxygen saturation by adjusting the respiratory motion in the low oxygen environment.

Heart rate variability (HRV) analysis technology based on an autoregressive (AR) model is widely used in the assessment of autonomic nervous system function. The order of AR models has important influence on the accuracy of HRV analysis. This article presents a method to determine the optimum order of AR models. After acquiring the ECG signal of 46 healthy adults in their natural breathing state and extracting the beat-to-beat intervals (RRI) in the ECG, we used two criteria, i. e. final prediction error (FPE) criterion to estimate the optimum model order for AR models, and prediction error whiteness test to decide the reliability of the model. We compared the frequency domain parameters including total power, power in high frequency (HF), power in low frequency (LF), LF power in normalized units and ratio of LF/HF of our HRV analysis to the results of Kubios-HRV. The results showed that the correlation coefficients of the five parameters between our methods and Kubios-HRV were greater than 0.95, and the Bland-Altman plot of the parameters was in the consistent band. The results indicate that the optimization algorithm of HRV analysis based on AR models proposed in this paper can obtain accurate results, and the results of this algorithm has good coherence with those of the Kubios-HRV software in HRV analysis.

In comparison with the measurement of heart rate variability from ECG and from photoplethysmographic signal from 46 healthy adults in their spontaneous breathing state. The beat-to-beat intervals in ECG and pulse-to-pulse intervals in photoplethysmographic signal are extracted, and then the parameters of heart rate variability are calculated. Three kinds of algorithms are chosen to get the pulse-to-pulse intervals, which are the intervals of maximum of second derivative, the maximum of PPG signal and the tangent intersection. The results show that the correlation coefficients of the HRV parameters in the two calculation methods are highly correlated. The Bland-Altman scattered plots show the relative bias results from the algorithm of the maximum of PPG signal are smallest and singular points that deviate from the consistent limits are the least compared with the other two algorithms.

To investigate the effect of stepwise paced breathing (PB) on pulse transit time (PTT), we collected physiological signals of electrocardiogram (ECG), respiration and arterial pulse wave during a procedure of stepwise PB, which consists of 6 different breathing rates changing in a protocol of 14.0-12.5-11.0-9.5-8.0-7.0 breath per minute (BPM), with each breathing rate lasting 3 minutes. Twenty two healthy adults involved in this experiment and the change of PTT was analyzed during the stepwise PB procedure. In our study, the PTT was measured by calculating the time interval from the R-spike of the ECG to the peaks of the second derivative of the arterial pulse wave. Ensemble empirical mode decomposition (EEMD) was applied to PTT to decompose the signal into different intrinsic mode function, and respiratory oscillation and trend component (baseline) in PTT were further extracted. It was found that the respiratory oscillations in the PTT increased with decreasing of the PB rate, and many of the subjects (14 out of 22) showed the phenomena of PTT baseline increasing during the stepwise PB procedure. The results indicated that the stepwise PB procedure induced a high level of cardiovascular oscillation and produced an accumulative effect of PTT baseline increase. As PTT is capable of predicting changes in BP over a short period of time, increase of PTT baseline indicates the decrease of blood pressure. The experiments showed that the stepwise PB procedure could reduce blood pressure for most subjects. For future work, it is necessary to develop certain indices differentiating the effectiveness of the stepwise PB procedure on the PTT baseline change, and to test the effectiveness of this stepwise PB procedure on blood pressure reduction for patients with essential hypertension.

This paper introduces a free and publicly open ICU database: multi-parameter intelligent monitoring in intensive care II: MIMIC-II, which has been built up and maintained by the laboratory of computational physiology at the Massachusetts Institute Technology, Beth Israel Deaconess Medical Center and Philips Healthcare over the past decade. This paper briefly introduces its infrastructure, implementation and applications in clinical studies. Clinical study pertaining to circadian variation in heart rate and blood pressure during sepsis is shown as a typical example of research performed with MIMIC-II. In this study, it was found there was significant difference in circadian variation in both heart rate and blood pressure between survival and non-survival groups in septic patients. This study tackled several important techniques necessary for the investigation of the circadian rhythm.