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Abstract: Periodic rain tests have been carried out for simulating atmospheric corrosion of aeronautical aluminium alloys. A digital image preprocessing and analysis method based on wavelet transformation was used to study the corrosion morphology of aluminium alloys samples, through which an image feature parameter δ was extracted and discussed. The influences of orthogonal experiment parameters on acceleration were analyzed according to image feature parameter δ with analysis of variance (ANOVA) method, and the optimal parameters for accelerated corrosion test were also obtained. The result was shown to be consistent with that from weight loss method. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

• The study provides a coding approach of multiple temporally varying oscillations. • Motor symptoms are associated with the neural states coded with multi-oscillations. • Dynamic neural states cloud be biomarkers for closed-loop deep brain stimulation. 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). 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. 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. This study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD. 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. [ABSTRACT FROM AUTHOR]

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 (H2O2) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H2O2-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H2O2-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 H2O2-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 H2O2-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives The nucleus accumbens (NAc) is known to regulate the motivation and underlie addictive behaviors, and the anterior limb of the internal capsule (ALIC) is involved in several psychiatric disorders. Our study aimed to explore the functions of NAc and ALIC electrophysiologically. Methods The local field potentials (LFPs) of the NAc and ALIC were recorded from 7 heroin addicts treated with deep brain stimulation. Correlation analysis was made between LFP powers in various frequency bands and the subjects’ neuropsychological test scores; coherence was calculated for the LFPs in NAc and ALIC. Results Both the NAc and ALIC exhibited prominent theta and alpha frequency band activity in the LFP power spectra. Additionally, a distinct beta band peak was detected in the power spectra of ALIC LFPs, which may represent the activity of striatal bridge cells. There was a significant negative correlation between the power of the theta frequency band of ALIC LFPs and visual analogue scale (VAS) scores indicative of cravings (Spearman’s ρ  = −0.758, P  = 0.002), and a significant positive correlation was found between the power of the alpha frequency band of NAc LFPs and subjects’ scores on the Hamilton depression inventory ( ρ  = 0.727, P  = 0.005). LFPs of the NAc and ALIC exhibited higher coherence values in the theta and alpha frequency bands. Conclusions The results suggest that theta power in the ALIC/dorsal striatum and alpha power in the NAc may be associated with drug cravings and depressive symptoms, respectively, in heroin addicts. For these subjects, the neural activities in the dorsal and ventral striatum were mainly coordinated within the low-frequency band. Significance The study illustrates the neurophysiologic characteristics of heroin addiction and its comorbidities, providing a potential theoretical basis for optimizing deep brain stimulation (DBS) therapy. [ABSTRACT FROM AUTHOR]

Objective This study aims to use the activities recorded directly from the deep brain stimulation (DBS) electrode to address the focality and distinct nature of the local field potential (LFP) activities of different frequency. Methods Pre-operative and intra-operative magnetic resonance imaging (MRI) were acquired from patients with Parkinson’s disease (PD) who underwent DBS in the subthalamic nucleus and intra-operative LFP recording at rest and during cued movements. Images were reconstructed and 3-D visualized using Lead-DBS® toolbox to determine the coordinates of contact. The resting spectral power and movement-related power modulation of LFP oscillations were estimated. Results Both subthalamic LFP activity recorded at rest and its modulation by movement had focal maxima in the alpha, beta and gamma bands. The spatial distribution of alpha band activity and its modulation was significantly different to that in the beta band. Moreover, there were significant differences in the scale and timing of movement related modulation across the frequency bands. Conclusion Subthalamic LFP activities within specific frequency bands can be distinguished by spatial topography and pattern of movement related modulation. Significance Assessment of the frequency, focality and pattern of movement related modulation of subthalamic LFPs reveals a heterogeneity of neural population activity in this region. This could potentially be leveraged to finesse intra-operative targeting and post-operative contact selection. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • The balance between oscillations significantly differed between the high and low dystonic muscular contraction conditions. • The balance between low and high beta oscillations was correlated with the dystonic severity. • The balance between oscillations may reflect the pathological mechanisms of dystonic symptoms. [ABSTRACT FROM AUTHOR]

Objective To investigate the link between neuronal activity recorded from the sensory thalamus and periventricular gray/periaqueductal gray (PVAG) and pain relief by deep brain stimulation (DBS). Methods Local field potentials (LFPs) were recorded from the sensory thalamus and PVAG post-operatively from ten patients with neuropathic pain. The LFPs were quantified using spectral and time–frequency analysis, the relationship between the LFPs and pain relief was quantified with nonlinear correlation analysis. Results The theta oscillations of both sensory thalamus and PVAG correlated inversely with pain relief. The high beta oscillations in the sensory thalamus and the alpha oscillations in the PVAG correlated positively with pain relief. Moreover, the ratio of high-power duration to low-power duration of theta band activity in the sensory thalamus and PVAG correlated inversely with pain relief. The duration ratio at the high beta band in the sensory thalamus correlated positively with pain relief. Conclusions Our results reveal distinct neuronal oscillations at the theta, alpha, and beta frequencies correlating with pain relief by DBS. Significance The study provides quantitative measures for predicting the outcomes of neuropathic pain relief by DBS as well as potential biomarkers for developing adaptive stimulation strategies. [ABSTRACT FROM AUTHOR]

Highlights: [•] Development of architecture for decoding of volitional bioacoustic activity. [•] Application to tongue-movement ear pressure (TMEP) signals. [•] Real-time evaluation of architecture including interference rejection capabilities. [•] Utility of interface for complementing neuroprosthetic control strategies. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to improve the accuracy and robustness of a real-time assistive human machine interface system by classifying between the controlled movements related tongue-movement ear pressure (TMEP) signals and the interfering signals. The controlled movement TMEP signals were collected during left, right, up, down, flicking and pushing tongue motions. The TMEP signals were processed and classified using detection, segmentation, feature extraction and classification. The segmented signals were decomposed into the time-scale domain using a wavelet packet transform. The variance of the wavelet packet coefficients and its ratio between low-to-high scales were defined as features and the intended tongue movement commands and interfering signals were classified using both a Bayesian and support vector machine (SVM) classifiers for comparison. The average classification accuracy for discriminating between the controlled movements and the interfering signals achieved 97.8% (Bayesian) and 98.5% (SVM). The classifiers were robust remaining at a similar performance level when generalised interferences from all subjects were used. It was shown that the Bayesian classifier performed better than the SVM in a real-time environment. The approach of combining the Bayesian classifier and the wavelet packet transform provides a robust and efficient method for a real-time assistive human machine interface based on tongue-movement ear pressure signals. [Copyright &y& Elsevier]

Objective: Kawasaki disease (KD) is characterized by systemic vasculitis of an unknown cause. A previous study has indicated that a polymorphism of the inositol 1,4,5-trisphosphate 3-kinase C ( ITPKC) gene is involved in the susceptibility to KD. ORAI (also known as CRACM1) is one of the components of store-operated calcium channels involved in regulating immune and inflammatory reactions. This study was conducted to investigate if polymorphisms in ORAI1/CRACM1, a gene downstream from ITPKC, are associated with KD susceptibility and clinical outcomes. Materials and Methods: A total of 1,056 subjects (341 KD patients and 715 controls) were investigated to identify five tagging single nucleotide polymorphisms (tSNPs) in ORAI1/CRACM1 (rs12313273, rs6486795, rs7135617, rs12320939, and rs712853) by using the TaqMan Allelic Discrimination assay. Results: No significant associations between genotype and allele frequency of the five ORAI1/CRACM1 tSNPs were observed in the KD patients and controls. In KD patients, no significant associations between ORAI1/CRACM1 polymorphisms and coronary artery lesion (CAL) formation or intravenous immunoglobulin (IVIG) treatment response were observed. The results from haplotype analysis were insignificant. Conclusions: This study showed for the first time that ORAI1/CRACM1 polymorphisms are not associated with KD susceptibility, CAL formation, or IVIG treatment response in the Taiwanese population. [ABSTRACT FROM AUTHOR]

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).)

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).)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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: 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.)

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.

Motor dysfunction is the main clinical symptom and diagnosis basis of patients with Parkinson's disease (PD). A total of 30 subjects were recruited in this study, including 15 PD patients (PD group) and 15 healthy subjects (control group). Then 5 wearable inertial sensor nodes were worn on the bilateral upper limbs, lower limbs and waist of subjects. When completing the 6 paradigm tasks, the acceleration and angular velocity signals from different parts of the body were acquired and analyzed to obtain 20 quantitative parameters which contain information about the amplitude, frequency, and fatigue degree of movements to assess the motor function. The clinical data of the two groups were statistically analyzed and compared, and then Back Propagation (BP) Neural Network was used to classify the two groups and predict the clinical score. The final results showed that most of the parameters had significant difference between the two groups, ten times of 5-fold cross validation showed that the classification accuracy of the BP Neural Network for the two groups was 90%, and the predictive accuracy of Hoehn-Yahr (H-Y) staging and unified PD rating scale (UPDRS) Ⅲ score of the patients were 72.80% and 68.64%, respectively. This study shows the feasibility of quantitative assessment of motor function in PD patients using wearable sensors, and the quantitative parameters obtained in this paper may have reference value for future related research.

Quantitative assessment of the symptoms of Parkinson’s disease is the key for precise diagnosis and treatment and essential for long term management over years.The challenges of quantitative assessment on Parkinson’s disease are rich information,ultra-low load,long term and large range monitoring in free-moving condition.In this paper,we developed wearable devices with multiple sensors to monitor and quantify the movement symptoms of Parkinson’s disease.Five wearable sensors were used to record motion signals from bilateral forearms,legs and waist.A local area network based on low power Wi-Fi technology was built for long distance wireless data transmission.A software was developed for signal recording and analyzing.The size of each sensor was 39mm×33mm×16mm and the weight was 18 g.The sensors were rechargeable and able to run 12 hours.The wireless transmission radius is about 45 m.The wearable devices were tested in patients and normal subjects.The devices were reliable and accurate for movement monitoring in hospital.

The effect of deep brain stimulation(DBS)surgery treatment for Parkinson’s disease is determined by the accuracy of the electrodes placement and localization.The subthalamic nuclei(STN)as the implant target is small and has no clear boundary on the images.In addition,the intra-operative magnetic resonance images(MRI)have such a low resolution that the artifacts of the electrodes impact the observation.The three-dimensional(3D)visualization of STN and other nuclei nearby is able to provide the surgeons with direct and accurate localizing information.In this study,pre-and intra-operative MRIs of the Parkinson’s disease patients were used to realize the 3Dvisualization.After making a co-registration between the high-resolution pre-operative MRIs and the low-resolution intraoperative MRIs,we normalized the MRIs into a standard atlas space.We used a special threshold mask to search the lead trajectories in each axial slice.After checking the location of the electrode contacts with the coronal MRIs of the patients,we reconstructed the whole lead trajectories.Then the STN and other nuclei nearby in the standard atlas space were visualized with the grey images of the standard atlas,accomplishing the lead reconstruction and nerve nuclei visualization near STN of all patients.This study provides intuitive and quantitative information to identify the accuracy of the DBS electrode implantation,which could help decide the post-operative programming setting.

In this study,an implantable optrode was developed for optogenetics stimulation of neural population in nuclei or multi-sites in neural circuits.The optrode was composed of base layer,micro-light emitting diode(LED)and coating layer.The base layer was a 150μm thick polyimide substrate on which copper wires and contacts were fabricated by flexible printed circuit board processes.The micro-LED was soldered on the contacts using SnBi.ParyleneC was deposited over the optrode as the coating layer using a vacuum vapor deposition system.The optical output power was tested by optical power meter and the insulating property was tested using saline in the experiment.The stimulation function of the optrode was demonstrated through animal experiment.The width of the optrode was500μm and the maximum thickness of the optrode was 310μm at the LED position.The thickness of the parylene coating layer was about 1μm.The maximum optical output power of optrode was 9.31 mW and the effective illumination area was a 3.03mm2 spherical cap at 650μm deep in brain tissue.The optrode was still functional after 14 days in physiological saline.Conventional copper electrodes were used to verify the efficacy of the optrode for stimulation and robust spiking activities of the expressing Channelrhodopsin-2neurons in the entire cortex of a mouce were recorded.Obvious behavior change happened when light stimulation was applied to the expressing Channelrhodopsin-2neurons in the secondary motor cortex of the mice.The optrode has the characteristics of large effective illumination range,flexible in implantation and long-term implantable,which provide neural population in nuclei research a new tool.