Search

The cortical development of our brains is in a hierarchical manner and promotes the emergence of large-scale functional hierarchy. However, under interindividual heterogenicity, how the spatiotemporal features of brain networks reflect brain development and mental health remains unclear. Here we collect both resting-state electroencephalography and functional magnetic resonance imaging data from the Child Mind Institute Biobank to demonstrate that during brain growth, the global dynamic patterns of brain states become more active and the dominant networks shift from sensory to higher-level networks; the individual functional network patterns become more similar to that of adults and their spatial coupling tends to be invariable. Furthermore, the properties of multimodality brain networks are sufficiently robust to identify healthy brain age and mental disorders at specific ages. Therefore, multimodality brain networks provide new insights into the functional development of the brain and a more reliable and reasonable approach for age prediction and individual diagnosis., (© 2024. The Author(s).)

Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear., Objective: We aimed to explore oscillatory activities within the STN-GPi circuit and their correlation with the severity of dystonia and efficacy achieved by DBS treatment., Methods: Local field potentials were recorded simultaneously from the STN and GPi from 13 dystonia patients. Spectral power analysis was conducted for selected frequency bands from both nuclei, while power correlation and the weighted phase lag index were used to evaluate power and phase couplings between these two nuclei, respectively. These features were incorporated into generalized linear models to assess their associations with dystonia severity and DBS efficacy., Results: The results revealed that pallidal theta power, subthalamic beta power and subthalamic-pallidal theta phase coupling and beta power coupling all correlated with clinical severity. The model incorporating all selected features predicts empirical clinical scores and DBS-induced improvements, whereas the model relying solely on pallidal theta power failed to demonstrate significant correlations., Conclusions: Beyond pallidal theta power, subthalamic beta power, STN-GPi couplings in theta and beta bands, play a crucial role in understanding the pathophysiological mechanism of dystonia and developing optimal strategies for DBS., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To explore the impact of different intraoperative intraocular pressure (IOP) settings on the safety and prognosis in phacoemulsification., Methods: Age related cataract patients who met the inclusion criteria and underwent phacoemulsification by using active sentry handpiece and active fluidics system. According to different intraoperative IOP settings during surgery, they were randomly divided into two groups: the 20mmHg group and the 60mmHg group. The best corrected visual acuity (BCVA), cumulative dissipated energy (CDE), total U/S time, active surge mitigation (ASM), estimated fluid usage (EFU) as well as the changes in corneal thickness (CT), corneal epithelial layer thickness (CELT) and endothelial cell density (ECD) were collected. The post-operative follow-up was only 1 day., Results: A total of 110 cases (110 eyes) were included in the study. There were 55 eyes in each group. There was no statistically significant difference in postoperative BCVA (p = 0.839). The CDE, total U/S time and EFU during surgery were (5.22 ± 3.31), (30.60 ± 15.06), (45.07 ± 12.68) and (4.70 ± 2.83), (27.39 ± 13.75), (42.38 ± 11.93) in the 20mmHg group and 60mmHg group (p = 0.381, 0.246, 0.254). The ASM during surgery in the 20mmHg group and 60mmHg group were (0.95 ± 2.77) and (7.24 ± 6.34), respectively. The 20mmHg group showed a significant decrease in ASM (p < 0.001). There was no statistically significant difference in the changes in CT, CELT and ECD before and after surgery between the two groups (p = 0.913, 0.825, 0.624). Both groups did not experience any intraoperative complications, such as posterior capsule rupture., Conclusion: A lower IOP setting of 20 mmHg can significantly reduce the occurrence of intraoperative surges during phacoemulsification. And there was no increase in rate of complications., Trial Registration: The trial registration number is ChiCTR2100050240. The registered date is August 24th, 2021., (© 2024. The Author(s).)

Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The characterization of neural signatures within the somatosensory pathway is essential for elucidating the pathogenic mechanisms of central post-stroke pain (CPSP) and developing more effective treatments such as deep brain stimulation (DBS). We explored the characteristics of thalamic neural oscillations in response to varying pain levels under multi-day local field potential (LFP) recordings and examined the influences of continuous DBS on these thalamic activities. We recorded LFPs from the left ventral posterolateral thalamus (VPL) of a patient with CPSP in the resting state under both off- and on-stimulation conditions. We observed significant differences in the power spectral density (PSD) of different pain levels in the delta, theta and gamma frequency bands of the left VPL; 75Hz DBS significantly increased the PSD of delta and decreased the PSD of low-beta, while 130Hz DBS significantly reduced the PSD of theta and low-beta. Thalamic stimulation modulated the neural oscillations related to pain, and the changes in neural activities in response to stimulation could serve as quantitative indicators for pain relief., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Closed-loop neuromodulation with intelligence methods has shown great potentials in providing novel neuro-technology for treating neurological and psychiatric diseases. Development of brain-machine interactive neuromodulation strategies could lead to breakthroughs in precision and personalized electronic medicine. The neuromodulation research tool integrating artificial intelligent computing and performing neural sensing and stimulation in real-time could accelerate the development of closed-loop neuromodulation strategies and translational research into clinical application. In this study, we developed a brain-machine interactive neuromodulation research tool (BMINT), which has capabilities of neurophysiological signals sensing, computing with mainstream machine learning algorithms and delivering electrical stimulation pulse by pulse in real-time. The BMINT research tool achieved system time delay under 3 ms, and computing capabilities in feasible computation cost, efficient deployment of machine learning algorithms and acceleration process. Intelligent computing framework embedded in the BMINT enable real-time closed-loop neuromodulation developed with mainstream AI ecosystem resources. The BMINT could provide timely contribution to accelerate the translational research of intelligent neuromodulation by integrating neural sensing, edge AI computing and stimulation with AI ecosystems., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective. Beta triggered closed-loop deep brain stimulation (DBS) shows great potential for improving the efficacy while reducing side effect for Parkinson's disease. However, there remain great challenges due to the dynamics and stochasticity of neural activities. In this study, we aimed to tune the amplitude of beta oscillations with different time scales taking into account influence of inherent variations in the basal ganglia-thalamus-cortical circuit. Approach . A dynamic basal ganglia-thalamus-cortical mean-field model was established to emulate the medication rhythm. Then, a dynamic target model was designed to embody the multi-timescale dynamic of beta power with milliseconds, seconds and minutes. Moreover, we proposed a closed-loop DBS strategy based on a proportional-integral-differential (PID) controller with the dynamic control target. In addition, the bounds of stimulation amplitude increments and different parameters of the dynamic target were considered to meet the clinical constraints. The performance of the proposed closed-loop strategy, including beta power modulation accuracy, mean stimulation amplitude, and stimulation variation were calculated to determine the PID parameters and evaluate neuromodulation performance in the computational dynamic mean-field model. Main results . The Results show that the dynamic basal ganglia-thalamus-cortical mean-field model simulated the medication rhythm with the fasted and the slowest rate. The dynamic control target reflected the temporal variation in beta power from milliseconds to minutes. With the proposed closed-loop strategy, the beta power tracked the dynamic target with a smoother stimulation sequence compared with closed-loop DBS with the constant target. Furthermore, the beta power could be modulated to track the control target under different long-term targets, modulation strengths, and bounds of the stimulation increment. Significance . This work provides a new method of closed-loop DBS for multi-timescale beta power modulation with clinical constraints., (© 2024 IOP Publishing Ltd.)

The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. However, the characteristics of neural circuits reconstructed by electrical signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. We demonstrate that a stimulus frequency of 10-20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury., (© 2024. The Author(s).)

Closed-loop deep brain stimulation (DBS) shows great potential for precise neuromodulation of various neurological disorders, particularly Parkinson's disease (PD). However, substantial challenges remain in clinical translation due to the complex programming procedure of closed-loop DBS parameters. In this study, we proposed an online optimized amplitude adaptive strategy based on the particle swarm optimization (PSO) and proportional-integral-differential (PID) controller for modulation of the beta oscillation in a PD mean field model over long-term dynamic conditions. The strategy aimed to calculate the stimulation amplitude adapting to the fluctuations caused by circadian rhythm, medication rhythm, and stochasticity in the basal ganglia-thalamus-cortical circuit. The PID gains were optimized online using PSO, based on modulation accuracy, mean stimulation amplitude, and stimulation variation. The results showed that the proposed strategy optimized the stimulation amplitude and achieved beta power modulation under the influence of circadian rhythm, medication rhythm, and stochasticity of beta oscillations. This work offers a novel approach for precise neuromodulation with the potential for clinical translation.

Objective: Our previous study found that ErbB4 gene expression was changed after oxygen-glucose deprivation/reperfusion (OGD/R). However, the exact role and mechanism of ErbB4 in brain ischemia are largely unknown. In this study, we explored the protective effects of ErbB4 and its possible mechanism after OGD/R., Methods: Cerebral ischemia/reperfusion (I/R) injury model was established in vitro and in vivo. Cell viability, apoptosis, and ROS production were measured by MTT, TUNEL, and fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA). Infarct size was evaluated by TTC. We performed bioinformatics analyses to screen for novel key genes involved in ErbB4 changes. RNA-Seq was used to transcriptome analysis. RNA and protein expression were detected by quantitative RT‒PCR and western bloting., Results: The expression of 80-kDa ErbB4 decreased after cerebral I/R injury in vitro and in vivo. Co-expression network analysis revealed that ErbB4 expression was correlated with the changes in Adrb1, Adrb2, Ldlr, and Dab2. Quantitative RT‒PCR revealed that the mRNA expression levels of Adrb1, Adrb2, and Dab2 were upregulated, and that of Ldlr was decreased after OGD/R. Activation of ErbB4 expression by neuregulin 1 (NRG1) significantly promoted cell survival, attenuated hippocampal apoptosis, and decreased ROS production after OGD/R. Furthermore, the elimination of ErbB4 using a specific siRNA reversed these beneficial effects., Conclusion: Our data revealed the neuroprotective effects of ErbB4 against OGD/R injury, and the action could be related to changes in the ErbB4 membrane-associated fragment and the expression of Adrb1, Adrb2, Ldlr, and Dab2., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This article presents a multichannel EEG/BIOZ acquisition application specific integrated circuit (ASIC) with 4 EEG channels and a BIOZ channel, a switch resistor low-pass filter (SR-LPF). Each EEG channel includes a frontend, and a 4-channel multiplexed analog-to-digital converter (ADC), while the BIOZ channel features a pseudo sine current generator and a pair of readout paths with multiplexed SR-LPF and ADC. The ASIC is designed for size and power minimization, utilizing a 3-step ADC with a novel signal-dependent low power strategy. The proposed ADC operates at a sampling rate of 1600 S/s with a resolution of 15.2 bits, occupying only 0.093 mm 2 . With the help of the proposed signal-dependent low-power strategy, the ADC's power dissipation drops from 32.2 μW to 26.4 μW, resulting in an 18% efficiency improvement without performance degradation. Moreover, the EEG channels deliver excellent noise performance with a NEF of 7.56 and 27.8 nV/√Hz at the expense of 0.16 mm 2 per channel. In BIOZ measurement, a 5-bit programmable current source is used to generate pseudo sine injection current ranging from 0 to 22 μApp, and the detection sensitivity reaches 2.4 mΩ/√Hz. Finally, the presented multichannel EEG/BIOZ acquisition ASIC has a compact active area of 1.5 mm 2 in an 180nm CMOS technology.

Purpose: The aim of this study was to investigate the protective effect of long non-coding lnc-PXMP4-2-4 on myocardial cell damage caused by acute myocardial infarction (AMI)., Methods: Peripheral blood mononuclear cells (PBMC) were collected from 24 patients with AMI on the day of admission, the first day after percutaneous coronary intervention (PCI) and the third day after surgery, and 24 patients with clinical control group. Real-time quantitative PCR(QRT-PCR) was used to detect the expression of related genes. Then in human cardiomyocytes (AC16), Cell Counting Kit-8 (CCK-8) was used to determine cell viability, lactate dehydrogenase release assay (LDH) was used to determine the release of lactate dehydrogenase, PCR was used to detect the expression of genes, cell death was detected by flow cytometry, and the expression of related proteins was measured by Western blot. The effect of lnc-PXMP4-2-4 was further studied by silencing and overexpressing lnc-PXMP4-2-4., Results: Compared with clinical control group, the expression of lnc-PXMP4-2-4 in PBMC of AMI patients was significantly higher than it. Compared with pre-operation, the expression of lnc-PXMP4-2-4 was significantly up-regulated on day 1 after PCI, and recovered to pre-operation level on day 3 after surgery. In AC16 cells, lnc-PXMP4-2-4 inhibited the proliferation of AC16, promoted the release of LDH and increased cell death, aggravated the cardiomyocyte injury caused by H 2 O 2 , and inhibited the expression of JAK2 and STAT3 mRNA and protein. The up-regulation of lnc-PXMP-4-2-4 had the opposite effect. In addition, the inhibition of the signal pathway by JAK2/STAT3 pathway inhibitor AG490 partially weakened the enhanced viability of AC16 cells, decreased LDH release and apoptosis induced by lnc-PXMP4-2-4 overexpression, increased Bcl-2 expression and down-regulated Bax expression., Conclusion: Therefore, we conclude that lnc-PXMP4-2-4 protects cardiomyocytes from injury by activating the JAK2/STAT3 signaling pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background and Objective: The balance between neural oscillations provides valuable insights into the organisation of neural oscillations related to brain states, which may play important roles in dystonia. We aim to investigate the relationship of the balance in the globus pallidus internus (GPi) with the dystonic severity under different muscular contraction conditions., Methods: Twenty-one patients with dystonia were recruited. All of them underwent bilateral GPi implantation, and local field potentials (LFPs) from the GPi were recorded via simultaneous surface electromyography. The power spectral ratio between neural oscillations was computed as the measure of neural balance. This ratio was calculated under high and low dystonic muscular contraction conditions, and its correlation with the dystonic severity was assessed using clinical scores., Results: The power spectral of the pallidal LFPs peaked in the theta and alpha bands. Within participant comparison showed that the power spectral of the theta oscillations significantly increased during high muscle contraction compared with that during low contraction. The power spectral ratios between the theta and alpha, theta and low beta, and theta and high gamma oscillations were significantly higher during high contraction than during low contraction. The total score and motor score were associated with the power spectral ratio between the low and high beta oscillations, which was correlated with the dystonic severity both during high and low contractions. The power spectral ratios between the low beta and low gamma and between the low beta and high gamma oscillations showed a significantly positive correlation with the total score during both high and low contractions; a correlation with the motor scale score was found only during high contraction. Meanwhile, the power spectral ratio between the theta and alpha oscillations during low contraction showed a significantly negative correlation with the total score. The power spectral ratios between the alpha and high beta, alpha and low gamma, and alpha and high gamma oscillations were significantly correlated with the dystonic severity only during low contraction., Conclusion: The balance between neural oscillations, as quantified by the power ratio between specific frequency bands, differed between the high and low muscular contraction conditions and was correlated with the dystonic severity. The balance between the low and high beta oscillations was correlated with the dystonic severity during both conditions, making this parameter a new possible biomarker for closed-loop deep brain stimulation in patients with dystonia., Competing Interests: Declaration of Competing Interest Nothing to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute myocardial infarction has increasingly become a global health problem and is a primary cause of cardiovascular disease-related death. Although long noncoding RNAs have been reported to play an important role in various cardiovascular diseases, their protective effects on cardiomyocytes against reactive oxygen species-induced oxidative injury have nonetheless been poorly studied. The present study aims to explore the effect of a novel long noncoding RNA, NONHSAT098487.2, on cardiomyocyte injury induced by H 2 O 2 . The expression of NONHSAT098487.2 and pathway-related genes was evaluated by quantitative real-time polymerase chain reaction. Cell viability, release of lactate dehydrogenase, and apoptosis levels were detected by cell counting kit-8, lactate dehydrogenase release assay, and flow cytometry analysis, respectively. The protein levels were estimated by western blotting. The results showed that NONHSAT098487.2 was expressed at a high level in peripheral blood mononuclear cells from acute myocardial infarction patients, which showed a positive correlation with the HS-TnT and CK-MB levels of patients. Furthermore, it is also upregulated in human AC16 cardiomyocytes treated with H 2 O 2 or exposed to hypoxia/reoxygenation conditions. Knockdown of NONHSAT098487.2 restrained the Notch signalling pathway and aggravated H 2 O 2 -induced cardiomyocyte oxidative stress injury. In contrast, overexpression of NONHSAT098487.2 activated the Notch signalling pathway and suppressed H 2 O 2 -induced oxidative stress injury. However, the Notch inhibitor DAPT weakened the protective effects of NONHSAT098487.2. Therefore, the novel lncRNA NONHSAT098487.2 may play a role in protecting cardiomyocytes from oxidative stress injury by regulating the Notch pathway., Competing Interests: The authors declare no conflict of interest.The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

Purposes: The purpose of this meta-analysis is to systematically compare the safety, efficacy, and predictability of small incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK)., Methods: This study covered the data searched from the PubMed, the EMBASE and the Cochrane Library. The Cochrane Handbook was also referred to as evaluating the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software., Results: A total of 11 randomized controlled trails (RCTs) were included. The proportion of eyes with refraction within ±0.5D was higher in LASIK group compared with SMILE group (RR, 0.91; 95% CI, 0.83 to 0.99; p = .04). The spherical aberration (SA) was smaller in SMILE group compared with LASIK group (RR, -0.12; 95% CI, -0.23 to -0.01; p = .04). There were no significant differences between two groups with regard to final mean refractive spherical equivalent (SE) (MD, -0.04; 95% CI, -0.12 to 0.03; p = .22), proportion of eyes losing one or more lines of corrected distance visual acuity (CDVA) (RR, 1.14; 95% CI, 0.58 to 2.27; p = .70), proportion of eyes with uncorrected distance visual acuity (UCVA) of 20/20 or better (RR, 0.99; 95% CI, 0.94 to 1.05; p = .71), postoperative mean logMAR UCVA (MD, 0.01; 95% CI, -0.00 to 0.03; p = .13), postoperative refraction within ±1.0D (RR, 1.00; 95% CI, 0.98 to 1.02; p = .60), postoperative astigmatism within ±0.25, 0.5 and 1.0D (RR, 0.80, 0.99, 1.00; 95% CI, 0.35 to 1.83, 0.94 to 1.05, 0.98 to 1.02; p = .60, 0.86, 0.87), postoperative higher order aberrations (HOAs) (RR, 0.00; 95% CI, -0.16 to 0.16; p = .99)., Conclusion: For predictability, LASIK was superior to SMILE. There were comparably safety and efficacy for the correction of myopia and myopic astigmatism in SMILE and LASIK. SA was smaller after SMILE than after LASIK.

Methylated CpG binding protein 2 (MeCP2) plays an important role in the development and normal function of the neural system. Abnormally high expression of MECP2 leads to a subtype of autism called MECP2 duplication syndrome and MECP2 is considered one of the key pathogenic genes for autism spectrum disorders. However, the effect of MECP2 overexpression on neural activity is still not fully understood. Thus, transgenic (TG) animals that abnormally overexpress MeCP2 are important disease models in research on neurological function and autism. To create an animal model with a stronger and more stable autism phenotype, this study established a human MECP2 TG rat model and evaluated its movement ability, anxiety, and social behavior through behavioral tests. The results showed that MECP2 TG rats had an abnormally increased anxiety phenotype and social deficits in terms of abnormal social approach and social novelty preference, but no movement disorder. These autism-like behavioral phenotypes suggest that human MECP2 TG rats are suitable models for studying autism as they show more severe social deficit phenotypes and without interference from movement disorders affecting other phenotypes, which is an issue for mouse models with MECP2 duplication. In addition, this study performed preliminary exploration of the influence of the human MECP2 transgene on neural oscillation stability of the medial prefrontal cortex (mPFC), which is an important brain region for social interactions. Oscillation stability in MECP2 TG rats showed abnormal responses to social conditions. Overall, the results of this study provide a new research tool for understanding the mechanism of social impairment and treatment of autism. The results also provide evidence for the influence of MECP2 duplication on mPFC neural activity., Competing Interests: Declaration of competing interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although previous studies have reported correlations between alpha oscillations and the "retention" subprocess of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain oscillations. Conventional transcranial alternating current stimulation (tACS) is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention subprocess). Here, we developed an online phase-corrected tACS system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits the modulation of brain oscillations at the target stimulation frequency within a short stimulation period and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to participants during the retention subprocess of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. These findings strongly support a causal link between alpha oscillations and WM retention and illustrate the broad application prospects of phase-corrected tACS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following H 2 O 2 injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke.

Rhythmic neural activities are critical to the efficiency of regulatory procedures in brain functions. However, brain functions usually decline in aging as accompanied by frequency shift and temporal dedifferentiation of neural activities. Considering the strong oscillations and long-lasting after-effects induced by rhythmic brain stimulations, we suggest that non-invasive rhythmic brain stimulation technique may help restore the natural frequencies of neural activities in aging to that in younger and healthy brains. Although with tremendous work to do, this technique offers great opportunities for the restoration of normal brain functions in aging, or even in those suffering from neurodegenerative diseases and neuropsychiatric disorders., 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 © 2022 Qiao, Wang and Wang.)

Objective: To investigate the effects of quantitative nursing and psychological interventions on stress response, mental health, and prognosis in endometrial cancer patients having laparoscopic surgery., Methods: The random number table approach was used to identify and split 98 patients with endometrial cancer undergoing laparoscopic surgery at our hospital's Obstetrics and Gynecology Hospital ( n = 49) into observation and control groups ( n = 49) from May 2020 to February 2022. Both groups received standard care in the operating room, while those in the observation group received quantitative and psychological interventions in the operating room. Both groups were compared for perioperative markers, stress indicators, coping strategies, and pain levels., Results: In terms of age, TNM stage, or pathology, there was no statistically significant difference between the two groups ( P > 0.05). Both the observation and control groups experienced statistically significant ( P < 0.05) reductions in the perioperative markers of operation time, intraoperative blood loss, and overall hospital stay. Both groups' SAS and SDS scores were lower than they had been prior to surgery, but the observation group had lower scores than the control group, and these differences were statistically significant ( P < 0.05). Postsurgery, the observation group's cortisol and adrenaline levels were lower than those of the control group, and both groups' levels were higher than before surgery, with statistical significance ( P < 0.05) in both groups. Neither coping style nor pain level differed significantly between the two groups before surgery ( P > 0.05). Postoperatively, while yield item scores were lower and faces scores were higher than the control group, the observation group's avoidance item score was lower than the control group. All with statistical significance. There were substantial differences in NRS SCORE between observers and controls., Conclusion: After laparoscopic surgery to remove endometrial cancer, patients may benefit from the combination of quantitative nursing and psychological intervention in the operating room to alleviate postoperative anxiety and sadness and reduce stress reaction., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xiaojing Chen et al.)

Purposes: The purpose of this meta-analysis is to systematically compare the IOP-lowering effect of different microstents combined with phacoemulsification versus phacoemulsification for patients with OAG and cataract., Methods: This work was done through the data searched from PubMed, EMBASE, and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software., Results: A total of 8 randomized controlled trials (RCTs) were included. Compared with phacoemulsification alone, microstent implantation with phacoemulsification resulted in significant reduction in the postoperative IOP (MD = -1.66, 95%CI: [-2.25 to -1.06]). Patients with medication free and patients with beyond 20% IOP reduction were significantly increased in the microstent implantation with phacoemulsification group compared with phacoemulsification alone group (RR = 1.54, 95%CI: [1.34 to 1.77]; RR = 1.34, 95%CI: [1.24 to 1.45])., Conclusion: Both microstent implantation with concurrent phacoemulsification and phacoemulsification alone result in a significant reduction in IOP. In terms of both reductions, microstent implantation with phacoemulsification significantly outperforms phacoemulsification alone.

Purpose: We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH)., Method: We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups - 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC)., Results: The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739-0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694-0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762-0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774-0.794]., Conclusion: ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases., (© 2022. The Author(s).)

Background: The vigilance fluctuation and decrement of sustained attention have large detrimental consequences to most tasks in daily life, especially among the elderly. Non-invasive brain stimulations (e.g., transcranial direct current stimulation, tDCS) have been widely applied to improve sustained attention, however, with mixed results., Objective: An infraslow frequency oscillatory tDCS approach was designed to improve sustained attention., Methods: The infraslow frequency oscillatory tDCS (O-tDCS) over the left dorsolateral prefrontal cortex at 0.05 Hz was designed and compared with conventional tDCS (C-tDCS) to test whether this new protocol improves sustained attention more effectively. The sustained attention was evaluated by reaction time and accuracy., Results: Compared with the C-tDCS and sham, the O-tDCS significantly enhanced sustained attention by increasing response accuracy, reducing response time, and its variability. These effects were predicted by the evoked oscillation of response time at the stimulation frequency., Conclusion: Similar to previous studies, the modulation effect of C-tDCS on sustained attention is weak and unstable. In contrast, the O-tDCS effectively and systematically enhances sustained attention by optimizing vigilance fluctuation. The modulation effect of O-tDCS is probably driven by neural oscillations at the infraslow frequency range., 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 © 2022 Qiao, Li, Wang, Wang, Li, Lu and Wang.)

Background: Chlorhexidine and povidone-iodine are the most common disinfectants used in preoperative skin preparation. However, there is no consistent conclusion regarding the prevention of surgical site infection (SSI) and bacterial culture data., Objective: To assess the efficacy of chlorhexidine and povidone-iodine in the prevention of postoperative SSI and relevant bacterial data., Design: Systematic Review and Meta-Analysis SETTINGS: N/A PARTICIPANTS: N/A METHOD: Literature relevant to "skin antisepsis" and "surgical site infections" was retrieved from PUBMED, Web of Science, EMBASE, CINHAL and CNKI. The incidence of SSI was the primary outcome, while the secondary outcome was bacterial data from the infected incision. All data were analyzed with Revman 5.3 and Stata Statistical Software., Results: A total of 36 studies were identified in this study, which included 16,872 participants. This study revealed that chlorhexidine is superior to povidone-iodine in the prevention of postoperative SSI (risk ratio [RR], 0.73; 95% confidence interval [CI], 0.61-0.87; p = 0.019, I 2  = 39%). Further meta-regression analysis revealed that the effect of chlorhexidine was directly associated with the type of incision, but failed to differentiate between the subgroups divided according to the type of incision. With respect to bacteria colonization, the most common bacteria for chlorhexidine arm were propionibacterium's, while the most common bacteria for the iodine arm were staphylococci species., Conclusion: In comparison to povidone-iodine, chlorhexidine showed better results in preventing postoperative SSI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates)., Methods: The systematic review was performed in PubMed/Medline, EMBASE, PsycINFO, Web of Sciences, and OpenGrey. Two authors performed independent literature screening and data extraction. The primary outcomes were the standardized mean difference (SMD) for continuous depression scores after treatment and odds ratio (OR) dropout rate; secondary outcomes included ORs for response and remission rates. Random effects models with 95% confidence intervals were employed in all outcomes. The overall effect of tDCS was investigated by meta-analysis. Sources of heterogeneity were explored via subgroup analyses, meta-regression, sensitivity analyses, and assessment of publication bias., Results: Twelve randomised, sham-controlled trials (active group: N = 251, sham group: N = 204) were included. Overall, the integrated depression score of the active group after treatment was significantly lower than that of the sham group (g = - 0.442, p = 0.017), and further analysis showed that only tDCS + medication achieved a significant lower score (g = - 0.855, p < 0.001). Moreover, this combination achieved a significantly higher response rate than sham intervention (OR = 2.7, p = 0.006), while the response rate remained unchanged for the other three therapies. Dropout and remission rates were similar in the active and sham groups for each therapy and also for the overall intervention. The meta-regression results showed that current intensity is the only predictor for the response rate. None of publication bias was identified., Conclusion: The effect size of tDCS treatment was obviously larger in depression score compared with sham stimulation. The tDCS combined selective serotonin re-uptake inhibitors is the optimized therapy that is effective on depression score and response rate. tDCS monotherapy and combined psychotherapy have no significant effects. The most important parameter for optimization in future trials is treatment strategy., (© 2021. The Author(s).)

Objective. Closed-loop deep brain stimulation (DBS) with neural feedback has shown great potential in improving the therapeutic effect and reducing side effects. However, the amplitude of stimulation artifacts is much larger than the local field potentials, which remains a bottleneck in developing a closed-loop stimulation strategy with varied parameters. Approach. We proposed an irregular sampling method for the real-time removal of stimulation artifacts. The artifact peaks were detected by applying a threshold to the raw recordings, and the samples within the contaminated period of the stimulation pulses were excluded and replaced with the interpolation of the samples prior to and after the stimulation artifact duration. This method was evaluated with both simulation signals and in vivo closed-loop DBS applications in Parkinsonian animal models. Main results . The irregular sampling method was able to remove the stimulation artifacts effectively with the simulation signals. The relative errors between the power spectral density of the recovered and true signals within a wide frequency band (2-150 Hz) were 2.14%, 3.93%, 7.22%, 7.97% and 6.25% for stimulation at 20 Hz, 60 Hz, 130 Hz, 180 Hz, and stimulation with variable low and high frequencies, respectively. This stimulation artifact removal method was verified in real-time closed-loop DBS applications in vivo , and the artifacts were effectively removed during stimulation with frequency continuously changing from 130 Hz to 1 Hz and stimulation adaptive to beta oscillations. Significance. The proposed method provides an approach for real-time removal in closed-loop DBS applications, which is effective in stimulation with low frequency, high frequency, and variable frequency. This method can facilitate the development of more advanced closed-loop DBS strategies., (© 2021 IOP Publishing Ltd.)

Prolonged periods of cognitive workload will cause mental fatigue, but objective, quantitative, and sensitive measurements that reflect long-term, stress-induced mental fatigue have yet to be elucidated. This study aims to apply a potential marker of Rényi entropy to investigate the mental fatigue changes in a long-term, high-level stress condition and compare three different instruments for assessment of mental fatigue: EEG, the oddball task, and self-scoring. We recruited nine individuals who participated in a 5-day intellectually challenging competition. The participants were assessed for mental fatigue each day of the competition using prefrontal cortex electroencephalogram (EEG). Reaction time in an oddball task and self-rated scoring were used comparatively to evaluate the performance of the EEG. Repeated measures ANOVA was utilized to analyze the differences among score, reaction time, and wavelet Rényi entropy. The results demonstrated that both wavelet Rényi entropy extracted from EEG and self-rated scoring revealed significant increases in mental fatigue during the 5 days of competition ( P < 0.001). The reaction time of the oddball task did not show significant changes during the five-day competition ( P = 0.066). Moreover, the wavelet Rényi entropy analysis of EEG showed greater sensitivity than the self-rated scoring and reaction time of the oddball task for measuring mental fatigue changes. In conclusion, this study shows that mental fatigue accumulates during long-term, high-level stress situations. The study also indicates that EEG wavelet Rényi entropy is an efficient metric to reflect the change of mental fatigue under a long-term stress condition and that EEG is a better method to assess long-term mental fatigue., 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 © 2021 Zhang, Wang, Geng, Li and Wang.)

Objective: This study aims to discriminate the dynamic synchronization states from the subthalamic local field potentials and investigate their correlations with the motor symptoms in Parkinson's Disease (PD)., Methods: The resting-state local field potentials of 10 patients with PD were recorded from the subthalamic nucleus. The dynamic neural states of multiple oscillations were discriminated and analyzed. The Spearman correlation was used to investigate the correlations between occurrence rate or duration of dynamic neural states and the severity of motor symptoms., Results: The proportion of long low-beta and theta synchronized state was significantly correlated with the general motor symptom and tremor, respectively. The duration of combined low/high-beta state was significantly correlated with rigidity, and the duration of combined alpha/high-beta state was significantly correlated with bradykinesia., Conclusions: This study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD., Significance: This study may advance the understanding of the neurophysiological mechanisms of the motor symptoms and provide potential biomarkers for closed-loop deep brain stimulation in PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

This study aimed to preliminarily illustrate the cerebral hemodynamic correlates of transcutaneous auricular vagal nerve stimulation (taVNS) in consciousness restoration. Arterial spin labeling (ASL) was adopted with functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) changes before and after taVNS in 10 qualified patients with disorders of consciousness (DOC). Before taVNS, five patients responded to auditory stimuli (RtAS), and five did not respond to auditory stimuli (nRtAS). The RtAS DOC patients obtained favorable prognoses after the 4-week taVNS treatment, whereas the nRtAS ones did not. Simultaneously, taVNS increased CBF of multiple brain regions in the RtAS DOC patients, but hardly in the nRtAS ones. In conclusion, the preserved auditory function might be the prior key factor of the taVNS responders in DOC patients, and taVNS might alleviate RtAS DOC by activating the salience network, the limbic system, and the interoceptive system., 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 © 2021 Yu, Yang, Gan, Guo, Fang, Wang, Tang, Bai, He and Rong.)

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H 2 O 2 ) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H 2 O 2 -induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H 2 O 2 -induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation, and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H 2 O 2 -induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H 2 O 2 -induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.

Emerging evidence shows that the coronavirus disease 2019 (COVID-19) pandemic is negatively affecting mental health around the globe. Interventions to alleviate the psychological impact of the pandemic are urgently needed. Whether mindfulness practice may protect against the harmful emotional effects of a pandemic crisis remains hitherto unknown. We investigated the influence of mindfulness training on mental health during the COVID-19 outbreak in China. We hypothesized that mindfulness practitioners might manifest less pandemic-related distress, depression, anxiety, and stress than non-practitioners and that more frequent practice would be associated with an improvement in mental health during the pandemic. Therefore, we assessed pandemic-related distress and symptoms of depression, anxiety, and stress, as well as the frequency of meditation practice at the peak of new infections (Feb 4-5; N = 673) and three weeks later (Feb 29-30; N = 521) in mindfulness practitioners via online questionnaires. Self-reported symptoms were also collected from non-practitioners at peak time only (N = 1550). We found lower scores of pandemic-related distress in mindfulness practitioners compared to non-practitioners. In general, older participants showed fewer symptoms of depression and anxiety. In younger practitioners, pandemic-related distress decreased from peak to follow-up. Importantly, increased mindfulness training during the preceding two weeks was associated with lower scores of depression and anxiety at both assessments. Likewise, practice frequency predicted individual improvement in scores of depression, anxiety, and stress at follow-up. Our results indicate that mindfulness meditation might be a viable low-cost intervention to mitigate the psychological impact of the COVID-19 crisis and future pandemics.

Deep brain stimulation (DBS) is one of the most important clinical therapies for neurological disorders. DBS also has great potential to become a great tool for clinical neuroscience research. Recently, the National Engineering Laboratory for Neuromodulation at Tsinghua University held an international Deep Brain Stimulation Initiative workshop to discuss the cutting-edge technological achievements and clinical applications of DBS. We specifically addressed new clinical approaches and challenges in DBS for movement disorders (Parkinson's disease and dystonia), clinical application toward neurorehabilitation for stroke, and the progress and challenges toward DBS for neuropsychiatric disorders. This review highlighted key developments in (1) neuroimaging, with advancements in 3-Tesla magnetic resonance imaging DBS compatibility for exploration of brain network mechanisms; (2) novel DBS recording capabilities for uncovering disease pathophysiology; and (3) overcoming global healthcare burdens with online-based DBS programming technology for connecting patient communities. The successful event marks a milestone for global collaborative opportunities in clinical development of neuromodulation to treat major neurological disorders., 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 © 2021 Sui, Tian, Ko, Wang, Jia, Horn, De Ridder, Choi, Bari, Wang, Hamani, Baker, Machado, Aziz, Fonoff, Kühn, Bergman, Sanger, Liu, Haber and Li.)

Neuroscience has long sought to develop methods that can "edit" or even "erase" memories, with the aim to provide treatments for memory-related neurological and psychiatric diseases such as anxiety and addiction. Current efforts are heavily focused on modifying cognitive behavioral therapy protocols or pharmacological treatments, but the efficacy and safety of these methods have been called into question by several studies. Advances in modern technology and the rapid emergence of techniques that can directly stimulate/alter neuronal activity, such as neuromodulation, have great potential in achieving the goal of memory modification for treating dementia such as Alzheimer's disease. However, more research and validation studies are required before these memory editing technologies can be applied clinically. In this mini-review, we compare and highlight the advantages and disadvantages of cognitive behavioral therapy, pharmacological methods, and neuromodulation techniques. We believe that neuromodulation techniques will play a key role in overcoming the challenges of translating memory-manipulating techniques to clinical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The periventricular/periaqueductal gray (PAG/PVG) is critical for pain perception and is associated with the emotional feelings caused by pain. However, the electrophysiological characteristics of the PAG/PVG have been little investigated in humans with chronic pain. The present study analyzed the oscillatory characteristics of local field potentials (LFPs) in the PAG/PVG of eighteen neuropathic pain patients. Power spectrum analysis and neural state analysis were applied to the PAG/PVG LFPs. Neural state analysis is based on a dynamic neural state identification approach and discriminates the LFPs into different neural states, including a single neural state based on one oscillation and a combinational neural state based on two paired oscillations. The durations and occurrence rates were used to quantify the dynamic features of the neural state. The results show that the combined neural state forms three local networks based on neural oscillations that are responsible for the perceptive, sensory, and affective components of pain. The first network is formed by the interaction of the delta oscillation with other oscillations and is responsible for the coding of pain perception. The second network is responsible for the coding of sensory pain information, uses high gamma as the main node, and is widely connected with other neural oscillations. The third network is responsible for the coding of affective pain information, and beta oscillations play an important role in it. This study suggested that the combination of two neural oscillations in the PAG/PVG is essential for encoding perceptive, sensory, and affective measures of pain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The quantitative characterization of movement disorders and their related neurophysiological signals is important for the management of Parkinson's disease (PD). The aim of this study is to develop a novel wearable system enabling the simultaneous measurement of both motion and other neurophysiological signals in PD patients. We designed a wearable system that consists of five motion sensors and three electrophysiology sensors to measure the motion signals of the body, electroencephalogram, electrocardiogram, and electromyography, respectively. The data captured by the sensors are transferred wirelessly in real time, and the outcomes are analyzed and uploaded to the cloud-based server automatically. We completed pilot studies to (1) test its validity by comparing outcomes to the commercialized systems, and (2) evaluate the deep brain stimulation (DBS) treatment effects in seven PD patients. Our results showed: (1) the motion and neurophysiological signals measured by this wearable system were strongly correlated with those measured by the commercialized systems ( r > 0.94, p < 0.001); and (2) by completing the clinical supination and pronation frequency test, the frequency of motion as measured by this system increased when DBS was turned on. The results demonstrated that this multi-sensor wearable system can be utilized to quantitatively characterize and monitor motion and neurophysiological PD.

Background: With the growing number of the aged population, the number of Parkinson's disease (PD) affected people is also mounting. Unfortunately, due to insufficient resources and awareness in underdeveloped countries, proper and timely PD detection is highly challenged. Besides, all PD patients' symptoms are neither the same nor they all become pronounced at the same stage of the illness. Therefore, this work aims to combine more than one symptom (rest tremor and voice degradation) by collecting data remotely using smartphones and detect PD with the help of a cloud-based machine learning system for telemonitoring the PD patients in the developing countries., Method: This proposed system receives rest tremor and vowel phonation data acquired by smartphones with built-in accelerometer and voice recorder sensors. The data are primarily collected from diagnosed PD patients and healthy people for building and optimizing machine learning models that exhibit higher performance. After that, data from newly suspected PD patients are collected, and the trained algorithms are evaluated to detect PD. Based on the majority-vote from those algorithms, PD-detected patients are connected with a nearby neurologist for consultation. Upon receiving patients' feedback after being diagnosed by the neurologist, the system may update the model by retraining using the latest data. Also, the system requests the detected patients periodically to upload new data to track their disease progress., Result: The highest accuracy in PD detection using offline data was [Formula: see text] from voice data and [Formula: see text] from tremor data when used separately. In both cases, k-nearest neighbors (kNN) gave the highest accuracy over support vector machine (SVM) and naive Bayes (NB). The application of maximum relevance minimum redundancy (MRMR) feature selection method showed that by selecting different feature sets based on the patient's gender, we could improve the detection accuracy. This study's novelty is the application of ensemble averaging on the combined decisions generated from the analysis of voice and tremor data. The average accuracy of PD detection becomes [Formula: see text] when ensemble averaging was performed on majority-vote from kNN, SVM, and NB., Conclusion: The proposed system can detect PD using a cloud-based system for computation, data preserving, and regular monitoring of voice and tremor samples captured by smartphones. Thus, this system can be a solution for healthcare authorities to ensure the older population's accessibility to a better medical diagnosis system in the developing countries, especially in the pandemic situation like COVID-19, when in-person monitoring is minimal.

Objective: To identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression., Methods: In this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated ( p < 0.01) with clinical scores (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Parts I-III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes., Results: Two neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years., Conclusion: Robust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised., Methods: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings., Results: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz)., Conclusions: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Gait impairments including shuffling gait and hesitation are common in people with Parkinson's disease (PD), and have been linked to increased fall risk and freezing of gait. Nowadays the gait metrics mostly focus on the spatiotemporal characteristics of gait, but less is known of the angular characteristics of the gait, which may provide helpful information pertaining to the functional status and effects of the treatment in PD., Objective: This study aimed to quantify the angles of steps during walking, and explore if this novel step angle metric is associated with the severity of PD and the effects of the treatment including the acute levodopa challenge test (ALCT) and deep brain stimulation (DBS)., Methods: A total of 18 participants with PD completed the walking test before and after the ALCT, and 25 participants with PD completed the test with the DBS on and off. The walking test was implemented under two conditions: walking normally at a preferred speed (single task) and walking while performing a cognitive serial subtraction task (dual task). A total of 17 age-matched participants without PD also completed this walking test. The angular velocity was measured using wearable sensors on each ankle, and three gait angular metrics were obtained, that is mean step angle, initial step angle, and last step angle. The conventional gait metrics (ie, step time and step number) were also calculated., Results: The results showed that compared to the control, the following three step angle metrics were significantly smaller in those with PD: mean step angle (F 1,48 =69.75, P<.001, partial eta-square=0.59), initial step angle (F 1,48 =15.56, P<.001, partial eta-square=0.25), and last step angle (F 1,48 =61.99, P<.001, partial eta-square=0.56). Within the PD cohort, both the ALCT and DBS induced greater mean step angles (ACLT: F 1,38 =5.77, P=.02, partial eta-square=0.13; DBS: F 1,52 =8.53, P=.005, partial eta-square=0.14) and last step angles (ACLT: F 1,38 =10, P=.003, partial eta-square=0.21; DBS: F 1,52 =4.96, P=.003, partial eta-square=0.09), but no significant changes were observed in step time and number after the treatments. Additionally, these step angles were correlated with the Unified Parkinson's Disease Rating Scale, Part III score: mean step angle (single task: r=-0.60, P<.001; dual task: r=-0.52, P<.001), initial step angle (single task: r=-0.35, P=.006; dual task: r=-0.35, P=.01), and last step angle (single task: r=-0.43, P=.001; dual task: r=-0.41, P=.002)., Conclusions: This pilot study demonstrated that the gait angular characteristics, as quantified by the step angles, were sensitive to the disease severity of PD and, more importantly, can capture the effects of treatments on the gait, while the traditional metrics cannot. This indicates that these metrics may serve as novel markers to help the assessment of gait in those with PD as well as the rehabilitation of this vulnerable cohort., (©Jingying Wang, Dawei Gong, Huichun Luo, Wenbin Zhang, Lei Zhang, Han Zhang, Junhong Zhou, Shouyan Wang. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 20.03.2020.)

Understanding the functional dynamics of neural oscillations in the sensory thalamus is essential for elucidating the perception and modulation of neuropathic pain. Local field potentials were recorded from the sensory thalamus of twelve neuropathic pain patients. Single and combinational neural states were defined by the activity state of a single or paired oscillations. Relationships between the duration or occurrence rate of neural state and pre-operative pain level or pain relief induced by deep brain stimulation were evaluated. Results showed that the occurrence rate of the single neural state of low-beta oscillation was significantly correlated with pain relief. The duration and occurrence rate of combinational neural states of the paired low-beta with delta, theta, alpha, high-beta or low-gamma oscillations were more significantly correlated with pain relief than the single neural states. Moreover, these significant combinational neural states formed a local oscillatory network with low-beta oscillation as a key node. The results also showed correlations between measures of combinational neural states and subjective pain level as well. The duration of combinational neural states of paired alpha with delta or theta oscillations and the occurrence rate of neural states of the paired delta with low-beta or low-gamma oscillations were significantly correlated with pre-operative pain level. In conclusion, this study revealed that the integration of oscillations and the functional dynamics of neural states were differentially involved in modulation and perception of neuropathic pain. The functional dynamics could be biomarkers for developing neural state-dependent deep brain stimulation for neuropathic pain., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Purpose: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance., Methods: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt., Results: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean - 8.3% versus - 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005)., Conclusion: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.

Aim: Autophagy was activated after cerebral ischemia reperfusion (I/R) injury. However, the molecular mechanisms underlying regulation of autophagy in cerebral I/R injury were not completely understood. Studies reported that Forked-box class O (FoxO) transcription factors involved in autophagy and might be the regulator of autophagy in multiple cells. In this study, we investigated the effects of FoxO3 on regulating autophagy after cerebral I/R injury. Materials and methods: Rats were subjected to MCAO for 2 h and reperfusion for different times, western blot was used to examine the expression of p-FoxO3, FoxO3 and the autophagic marker LC3 and Beclin-1 in penumbral region. Then rats were injected with WT-FoxO3 or TM-FoxO3 adenovirus by lateral cerebral ventricle to increase the function of FoxO3, western blot was used to examine the expression of LC3 and Beclin-1 in penumbral region. TTC and HE staining were used to evaluate the effects of increased FoxO3 activation on I/R induced brain damage. Results: Our studies showed that I/R injury resulted in induction of autophagy in penumbral brain tissue with concomitant dephosphorylation of FoxO3, consistent with increased activity of nuclear FoxO3 transcription factor. Increased FoxO3 activation led to autophagy significantly increased and had a protective effects on I/R injury. Conclusion: These data revealed an important role of FoxO3 in regulating autophagy in brain, and provided a new approach for further prevention and treatment of cerebral ischemia.

Background: High frequency Deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET., Objective: We aim to decode both voluntary movements and the presence of postural tremor from the Local field potentials (LFPs) recorded from the electrode implanted in motor thalamus for stimulation, in order to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes., Methods: LFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements were simultaneously recorded in seven ET patients during temporary lead externalisation 3-5 days after the first surgery for DBS when they performed different voluntary upper limb movements. Nine different patients were recorded during the surgery, when they were asked to lift their arms to trigger postural tremor. A machine learning based binary classifier was used to detect voluntary movements and postural tremor based on features extracted from thalamic LFPs., Results: Cross-validation demonstrated that both voluntary movements and postural tremor can be decoded with an average sensitivity of 0.8 and false detection rate of 0.2. Oscillatory activities in the beta frequency bands (13-23 Hz) and the theta frequency bands (4-7 Hz) contributed most to the decoding of movements and postural tremor, respectively, though incorporating features in different frequency bands using a machine learning approach increased the accuracy of decoding., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Automatic recognition of electroencephalogram (EEG) signals plays a major role in epilepsy diagnosis and assessment. However, the recognition accuracy of conventional methods is usually not satisfactory because of the inconsistent distribution of training and testing data in practical applications. To overcome this problem, we used cross-domain mean joint approximation embedding (CMJAE) transductive transfer learning method to realize the knowledge transfer from the training data to the testing data by measuring the distribution difference between them. We combined the subspace learning and joint distribution to adapt the marginal and conditional distribution discrepancy. Our method was able to effectively learn a model for the testing data from training data with different distribution at a low computational complexity cost. On a public dataset, an ad-hoc cross-validation scheme of the proposed method exhibited that the average recognition accuracy, sensitivity, specificity of different states was 97.5%, 94.3%, 92.7% respectively, much better than conventional machine learning or deep learning methods, which may serve as a promising strategy for epileptic states recognition algorithms.

Enhancers and super-enhancers exert indispensable roles in maintaining cell identity through spatiotemporally regulating gene transcription. Meanwhile, active enhancers and super-enhancers also produce transcripts termed enhancer RNAs (eRNAs) from their DNA elements. Although enhancers have been identified for more than 30 years, widespread transcription from enhancers are just discovered by genome-wide sequencing and considered as the key to understand longstanding questions in gene transcription. RNA-transcribed enhancers are marked by histone modifications such as H3K4m1/2 and H3K27Ac, and enriched with transcription regulatory factors such as LDTFs, P300, CBP, BRD4 and MED1. Those regulatory factors might constitute a Mega-Trans-like complex to potently activate enhancers. Compared to mRNAs, eRNAs are quite unstable and play roles at local. Functionally, it has been shown that eRNAs promote formation of enhancer-promoter loops. Several studies also demonstrated that eRNAs help the binding of RNA polymerase II (RNAPII) or transition of paused RNAPII by de-association of the negative elongation factor (NELF) complex. Nevertheless, these proposed mechanisms are not universally accepted and still under controversy. Here, we comprehensively summarize the reported findings and make perspectives for future exploration. We also believe that super-enhancer derived RNAs (seRNAs) might be informative to understand the nature of super-enhancers.

It is a significant but ignored issue to quantify the influence of Deep Brain Stimulation (DBS) surgery in patients with Parkinson's disease during the whole perioperative period. In this paper, wearable sensors were utilized to record patients' motor changes in the time before surgery, after surgery with stimulation off and stimulation on. The results showed that the DBS surgery is effective and safe in the perioperative period.