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How cortical oscillations are involved in the coordination of functionally coupled muscles and how this is modulated by different movement contexts (static vs dynamic) remains unclear. Here, this is investigated by recording high-density electroencephalography (EEG) and electromyography (EMG) from different forearm muscles while healthy participants (n = 20) performed movement tasks (static and dynamic posture holding, and reaching) with their dominant hand. When dynamic perturbation was applied, beta band (15-35 Hz) activities in the motor cortex contralateral to the performing hand reduced during the holding phase, comparative to when there was no perturbation. During static posture holding, transient periods of increased cortical beta oscillations (beta bursts) were associated with greater corticomuscular coherence and increased phase synchrony between muscles (intermuscular coherence) in the beta frequency band compared to the no-burst period. This effect was not present when resisting dynamic perturbation. The results suggest that cortical beta bursts assist synchronisation of different muscles during static posture holding in healthy motor control, contributing to the maintenance and stabilisation of functional muscle groups. Theoretically, increased cortical beta oscillations could lead to exaggerated synchronisation in different muscles making the initialisation of movements more difficult, as observed in Parkinson's disease., 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 © 2024. Published by Elsevier Inc.)

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.)

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

Brain-computer interfaces (BCIs) provide a communication interface between the brain and external devices and have the potential to restore communication and control in patients with neurological injury or disease. For the invasive BCIs, most studies recruited participants from hospitals requiring invasive device implantation. Three widely used clinical invasive devices that have the potential for BCIs applications include surface electrodes used in electrocorticography (ECoG) and depth electrodes used in Stereo-electroencephalography (SEEG) and deep brain stimulation (DBS). This review focused on BCIs research using surface (ECoG) and depth electrodes (including SEEG, and DBS electrodes) for movement decoding on human subjects. Unlike previous reviews, the findings presented here are from the perspective of the decoding target or task. In detail, five tasks will be considered, consisting of the kinematic decoding, kinetic decoding,identification of body parts, dexterous hand decoding, and motion intention decoding. The typical studies are surveyed and analyzed. The reviewed literature demonstrated a distributed motor-related network that spanned multiple brain regions. Comparison between surface and depth studies demonstrated that richer information can be obtained using surface electrodes. With regard to the decoding algorithms, deep learning exhibited superior performance using raw signals than traditional machine learning algorithms. Despite the promising achievement made by the open-loop BCIs, closed-loop BCIs with sensory feedback are still in their early stage, and the chronic implantation of both ECoG surface and depth electrodes has not been thoroughly evaluated.

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side effects. However, several questions remain unanswered. First, there is a normal physiological reduction of STN beta band power just prior to and during voluntary movement. ADBS systems will therefore reduce or cease stimulation during movement in people with Parkinson's disease and could therefore compromise motor performance compared to CDBS. Second, beta power was smoothed and estimated over a time period of 400 ms in most previous ADBS studies, but a shorter smoothing period could have the advantage of being more sensitive to changes in beta power, which could enhance motor performance. In this study, we addressed these two questions by evaluating the effectiveness of STN beta-triggered ADBS using a standard 400 ms and a shorter 200 ms smoothing window during reaching movements. Results from 13 people with Parkinson's disease showed that reducing the smoothing window for quantifying beta did lead to shortened beta burst durations by increasing the number of beta bursts shorter than 200 ms and more frequent switching on/off of the stimulator but had no behavioural effects. Both ADBS and CDBS improved motor performance to an equivalent extent compared to no DBS. Secondary analysis revealed that there were independent effects of a decrease in beta power and an increase in gamma power in predicting faster movement speed, while a decrease in beta event related desynchronization (ERD) predicted quicker movement initiation. CDBS suppressed both beta and gamma more than ADBS, whereas beta ERD was reduced to a similar level during CDBS and ADBS compared with no DBS, which together explained the achieved similar performance improvement in reaching movements during CDBS and ADBS. In addition, ADBS significantly improved tremor compared with no DBS but was not as effective as CDBS. These results suggest that STN beta-triggered ADBS is effective in improving motor performance during reaching movements in people with Parkinson's disease, and that shortening of the smoothing window does not result in any additional behavioural benefit. When developing ADBS systems for Parkinson's disease, it might not be necessary to track very fast beta dynamics; combining beta, gamma, and information from motor decoding might be more beneficial with additional biomarkers needed for optimal treatment of tremor., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Beyond the established effects of subthalamic nucleus deep brain stimulation (STN-DBS) in reducing motor symptoms in Parkinson's disease, recent evidence has highlighted the effect on non-motor symptoms. However, the impact of STN-DBS on disseminated networks remains unclear. This study aimed to perform a quantitative evaluation of network-specific modulation induced by STN-DBS using Leading Eigenvector Dynamics Analysis (LEiDA). We calculated the occupancy of resting-state networks (RSNs) in functional MRI data from 10 patients with Parkinson's disease implanted with STN-DBS and statistically compared between ON and OFF conditions. STN-DBS was found to specifically modulate the occupancy of networks overlapping with limbic RSNs. STN-DBS significantly increased the occupancy of an orbitofrontal limbic subsystem with respect to both DBS OFF ( p = 0.0057) and 49 age-matched healthy controls ( p = 0.0033). Occupancy of a diffuse limbic RSN was increased with STN-DBS OFF when compared with healthy controls ( p = 0.021), but not when STN-DBS was ON, which indicates rebalancing of this network. These results highlight the modulatory effect of STN-DBS on components of the limbic system, particularly within the orbitofrontal cortex, a structure associated with reward processing. These results reinforce the value of quantitative biomarkers of RSN activity in evaluating the disseminated impact of brain stimulation techniques and the personalization of therapeutic strategies., (© 2023 Massachusetts Institute of Technology.)

In patients with Parkinson's disease (PD), suppression of beta and increase in gamma oscillations in the subthalamic nucleus (STN) have been associated with both levodopa treatment and motor functions. Recent results suggest that modulation of the temporal dynamics of theses oscillations (bursting activity) might contain more information about pathological states and behaviour than their average power. Here we directly compared the information provided by power and burst analyses about the drug-related changes in STN activities and their impact on motor performance within PD patients. STN local field potential (LFP) signals were recorded from externalized patients performing self-paced movements ON and OFF levodopa. When normalised across medication states, both power and burst analyses showed an increase in low-beta oscillations in the dopamine-depleted state during rest. When normalised within-medication state, both analyses revealed that levodopa increased movement-related modulation in the alpha and low-gamma bands, with higher gamma activity around movement predicting faster reaches. Finally, burst analyses helped to reveal opposite drug-related changes in low- and high-beta frequency bands, and identified additional within-patient relationships between high-beta bursting and movement performance. Our findings suggest that although power and burst analyses share a lot in common they also provide complementary information on how STN-LFP activity is associated with motor performance, and how levodopa treatment may modify these relationships in a way that helps explain drug-related changes in motor performance. Different ways of normalisation in the power analysis can reveal different information. Similarly, the burst analysis is sensitive to how the threshold is defined - either for separate medication conditions separately, or across pooled conditions. In addition, the burst interpretation has far-reaching implications about the nature of neural oscillations - whether the oscillations happen as isolated burst-events or are they sustained phenomena with dynamic amplitude variations? This can be different for different frequency bands, and different for different medication states even for the same frequency band., (© 2023. The Author(s).)

Processing incoming neural oscillatory signals in real-time and decoding from them relevant behavioral or pathological states is often required for adaptive Deep Brain Stimulation (aDBS) and other brain-computer interface (BCI) applications. Most current approaches rely on first extracting a set of predefined features, such as the power in canonical frequency bands or various time-domain features, and then training machine learning systems that use those predefined features as inputs and infer what the underlying brain state is at each given time point. However, whether this algorithmic approach is best suited to extract all available information contained within the neural waveforms remains an open question. Here, we aim to explore different algorithmic approaches in terms of their potential to yield improvements in decoding performance based on neural activity such as measured through local field potentials (LFPs) recordings or electroencephalography (EEG). In particular, we aim to explore the potential of end-to-end convolutional neural networks, and compare this approach with other machine learning methods that are based on extracting predefined feature sets. To this end, we implement and train a number of machine learning models, based either on manually constructed features or, in the case of deep learning-based models, on features directly learnt from the data. We benchmark these models on the task of identifying neural states using simulated data, which incorporates waveform features previously linked to physiological and pathological functions. We then assess the performance of these models in decoding movements based on local field potentials recorded from the motor thalamus of patients with essential tremor. Our findings, derived from both simulated and real patient data, suggest that end-to-end deep learning-based methods may surpass feature-based approaches, particularly when the relevant patterns within the waveform data are either unknown, difficult to quantify, or when there may be, from the point of view of the predefined feature extraction pipeline, unidentified features that could contribute to decoding performance. The methodologies proposed in this study might hold potential for application in adaptive deep brain stimulation (aDBS) and other brain-computer interface systems., 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 © 2023 Rodriguez, He and Tan.)

Introduction: Decoding brain states from subcortical local field potentials (LFPs) indicative of activities such as voluntary movement, tremor, or sleep stages, holds significant potential in treating neurodegenerative disorders and offers new paradigms in brain-computer interface (BCI). Identified states can serve as control signals in coupled human-machine systems, e.g., to regulate deep brain stimulation (DBS) therapy or control prosthetic limbs. However, the behavior, performance, and efficiency of LFP decoders depend on an array of design and calibration settings encapsulated into a single set of hyper-parameters. Although methods exist to tune hyper-parameters automatically, decoders are typically found through exhaustive trial-and-error, manual search, and intuitive experience., Methods: This study introduces a Bayesian optimization (BO) approach to hyper-parameter tuning, applicable through feature extraction, channel selection, classification, and stage transition stages of the entire decoding pipeline. The optimization method is compared with five real-time feature extraction methods paired with four classifiers to decode voluntary movement asynchronously based on LFPs recorded with DBS electrodes implanted in the subthalamic nucleus of Parkinson's disease patients., Results: Detection performance, measured as the geometric mean between classifier specificity and sensitivity, is automatically optimized. BO demonstrates improved decoding performance from initial parameter setting across all methods. The best decoders achieve a maximum performance of 0.74 ± 0.06 (mean ± SD across all participants) sensitivity-specificity geometric mean. In addition, parameter relevance is determined using the BO surrogate models., Discussion: Hyper-parameters tend to be sub-optimally fixed across different users rather than individually adjusted or even specifically set for a decoding task. The relevance of each parameter to the optimization problem and comparisons between algorithms can also be difficult to track with the evolution of the decoding problem. We believe that the proposed decoding pipeline and BO approach is a promising solution to such challenges surrounding hyper-parameter tuning and that the study's findings can inform future design iterations of neural decoders for adaptive DBS and BCI., 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 © 2023 Martineau, He, Vaidyanathan and Tan.)

Background: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation., Objective: We aimed to explore if enhanced theta power was also present in STN and if stimulation-induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia., Methods: We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus., Results: We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely-tuned gamma oscillations, and an increase in aperiodic exponents in STN-LFPs. Both power suppression and ERNA localize to STN. Based on this, single-pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases., Conclusions: Our results show that STN stimulation-induced spectral changes are a nondisease-specific response to high-frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Evoked resonant neural activity (ERNA) is induced by subthalamic deep brain stimulation (DBS) and was recently suggested as a marker of lead placement and contact selection in Parkinson's disease. Yet, its underlying mechanisms and how it is modulated by stimulation parameters are unclear. Here, we recorded local field potentials from 27 Parkinson's disease patients, while leads were externalised to scrutinise the ERNA. First, we show that ERNA in the time series waveform and spectrogram likely represent the same activity, which was contested before. Second, our results show that the ERNA has fast and slow dynamics during stimulation, consistent with the synaptic failure hypothesis. Third, we show that ERNA parameters are modulated by different DBS frequencies, intensities, medication states and stimulation modes (continuous DBS vs. adaptive DBS). These results suggest the ERNA might prove useful as a predictor of the best DBS frequency and lowest effective intensity in addition to contact selection. Changes with levodopa and DBS mode suggest that the ERNA may indicate the state of the cortico-basal ganglia circuit making it a putative biomarker to track clinical state in adaptive DBS., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Brain computer interfaces (BCIs) have been demonstrated to have the potential to enhance motor recovery after stroke. However, some stroke patients with severe paralysis have difficulty achieving the BCI performance required for participating in BCI-based rehabilitative interventions, limiting their clinical benefits. To address this issue, we presented a BCI intervention approach that can adapt to patients' BCI performance and reported that adaptive BCI-based functional electrical stimulation (FES) treatment induced clinically significant, long-term improvements in upper extremity motor function after stroke more effectively than FES treatment without BCI intervention. These improvements were accompanied by a more optimized brain functional reorganization. Further comparative analysis revealed that stroke patients with low BCI performance (LBP) had no significant difference from patients with high BCI performance in rehabilitation efficacy improvement. Our findings suggested that the current intervention may be an effective way for LBP patients to engage in BCI-based rehabilitation treatment and may promote lasting motor recovery, thus contributing to expanding the applicability of BCI-based rehabilitation treatments to pave the way for more effective rehabilitation treatments.

Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson's disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson's disease, and that together these different states predict motor impairment with high fidelity. Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz. Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients' hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone. We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of the midbrain and pons, playing an important role in modulating posture and locomotion. Deep brain stimulation of the PPN has been proposed as an emerging treatment for patients with Parkinson's disease (PD) or multiple system atrophy (MSA) who have gait-related atypical parkinsonian syndromes. In this study, we investigated PPN activities during gait to better understand its functional role in locomotion. Specifically, we investigated whether PPN activity is rhythmically modulated by gait cycles during locomotion. PPN local field potential (LFP) activities were recorded from PD or MSA patients with gait difficulties during stepping in place or free walking. Simultaneous measurements from force plates or accelerometers were used to determine the phase within each gait cycle at each time point. Our results showed that activities in the alpha and beta frequency bands in the PPN LFPs were rhythmically modulated by the gait phase within gait cycles, with a higher modulation index when the stepping rhythm was more regular. Meanwhile, the PPN-cortical coherence was most prominent in the alpha band. Both gait phase-related modulation in the alpha/beta power and the PPN-cortical coherence in the alpha frequency band were spatially specific to the PPN and did not extend to surrounding regions. These results suggest that alternating PPN modulation may support gait control. Whether enhancing alternating PPN modulation by stimulating in an alternating fashion could positively affect gait control remains to be tested. SIGNIFICANCE STATEMENT The therapeutic efficacy of pedunculopontine nucleus (PPN) deep brain stimulation (DBS) and the extent to which it can improve quality of life are still inconclusive. Understanding how PPN activity is modulated by stepping or walking may offer insight into how to improve the efficacy of PPN DBS in ameliorating gait difficulties. Our study shows that PPN alpha and beta activity was modulated by the gait phase, and that this was most pronounced when the stepping rhythm was regular. It remains to be tested whether enhancing alternating PPN modulation by stimulating in an alternating fashion could positively affect gait control., (Copyright © 2021 He et al.)

Background: High-frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor., Objective: We proposed to close the loop of thalamic stimulation by detecting tremor-provoking movement states using local field potentials recorded from the same electrodes implanted for stimulation, so that the stimulation is only delivered when necessary., Methods: Eight patients with essential tremor participated in this study. Patient-specific support vector machine classifiers were first trained using data recorded while the patient performed tremor-provoking movements. Then, the trained models were applied in real-time to detect these movements and triggered the delivery of stimulation., Results: Using the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor-evoking movements were present. In comparison, the stimulation was switched on for 12.71 ± 7.06% of the time when the patients were at rest and tremor-free. Compared with continuous stimulation, a similar amount of tremor suppression was achieved while only delivering 36.62 ± 13.49% of the energy used in continuous stimulation., Conclusions: The results suggest that responsive thalamic stimulation for essential tremor based on tremor-provoking movement detection can be achieved without any requirement for external sensors or additional electrocorticography strips. Further research is required to investigate whether the decoding model is stable across time and generalizable to the variety of activities patients may engage with in everyday life. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Previous studies have explored neurofeedback training for Parkinsonian patients to suppress beta oscillations in the subthalamic nucleus (STN). However, its impacts on movements and Parkinsonian tremor are unclear. We developed a neurofeedback paradigm targeting STN beta bursts and investigated whether neurofeedback training could improve motor initiation in Parkinson's disease compared to passive observation. Our task additionally allowed us to test which endogenous changes in oscillatory STN activities are associated with trial-to-trial motor performance. Neurofeedback training reduced beta synchrony and increased gamma activity within the STN, and reduced beta band coupling between the STN and motor cortex. These changes were accompanied by reduced reaction times in subsequently cued movements. However, in Parkinsonian patients with pre-existing symptoms of tremor, successful volitional beta suppression was associated with an amplification of tremor which correlated with theta band activity in STN local field potentials, suggesting an additional cross-frequency interaction between STN beta and theta activities., Competing Interests: SH, AM, ES, FT, GT, PF, AP, HH, YL, EP, HT No competing interests declared, KA has received educational grants from Medtronic and Abbott, PB is a consultant for Medtronic., (© 2020, He et al.)

Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of 10 Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of DBS strategies to ameliorate gait impairments. SIGNIFICANCE STATEMENT We tested whether the subthalamic nucleus (STN) in humans is causally involved in controlling stepping movements. To this end, we studied patients with Parkinson's disease who have undergone therapeutic deep brain stimulation (DBS), as in these individuals we can stimulate the STNs in a controlled manner. We developed an alternating pattern of stimulation that mimics the pattern of activity modulation recorded in this nucleus during stepping. The alternating DBS (altDBS) could entrain patients' stepping rhythm, suggesting a causal role of the STN in dynamic gait control. This type of stimulation may potentially form the basis for improved DBS strategies for gait., (Copyright © 2020 Fischer, He et al.)

Objective: A challenging task for an electroencephalography (EEG)-based asynchronous brain-computer interface (BCI) is to effectively distinguish between the idle state and the control state while maintaining a short response time and a high accuracy when commands are issued in the control state. This study proposes a novel hybrid asynchronous BCI system based on a combination of steady-state visual evoked potentials (SSVEPs) in the EEG signal and blink-related electrooculography (EOG) signals., Methods: Twelve buttons corresponding to 12 characters are included in the graphical user interface (GUI). These buttons flicker at different fixed frequencies and phases to evoke SSVEPs and are simultaneously highlighted by changing their sizes. The user can select a character by focusing on its frequency-phase stimulus and simultaneously blinking his/her eyes in accordance with its highlighting as his/her EEG and EOG signals are recorded. A multifrequency band-based canonical correlation analysis (CCA) method is applied to the EEG data to detect the evoked SSVEPs, whereas the EOG data are analyzed to identify the user's blinks. Finally, the target character is identified based on the SSVEP and blink detection results., Results: Ten healthy subjects participated in our experiments and achieved an average information transfer rate (ITR) of 105.52 bits/min, an average accuracy of 95.42%, an average response time of 1.34 s and an average false-positive rate (FPR) of 0.8%., Conclusion: The proposed BCI generates multiple commands with a high ITR and low FPR., Significance: The hybrid asynchronous BCI has great potential for practical applications in communication and control.

High frequency Deep Brain Stimulation (DBS) targeting the motor thalamus is an effective therapy for essential tremor (ET). However, since tremor mainly affects periods of voluntary movements and sustained postures in ET, conventional continuous stimulation may deliver unnecessary current to the brain. Here we tried to decode movement states based on local field potentials (LFPs) recorded from motor thalamus and zona incerta in real-time to trigger the switching on and off of DBS in three patients with ET. Patient-specific models were first identified using thalamic LFPs recorded while the patient performed movements that tended to trigger tremor in everyday life. During the real-time test, LFPs were continuously recorded to decode movements and tremor, and the detection triggered stimulation. Results show that voluntary movements can be detected with a mean sensitivity ranging from 76.8% to 88.6% and a false positive rate ranging from 16.0% to 23.1% Postural tremor was detected with similar accuracy. The closed-loop DBS triggered by tremor detection suppressed intention tremor by 90.5% with a false positive rate of 20.3%.Clinical Relevance- This is the first study on closed-loop DBS triggered by real-time movement and tremor decoding based solely on thalamic LFPs. The results suggest that responsive DBS based on movement and tremor detection can be achieved without any requirement for external sensors or additional electrocorticography strips.

Neural oscillating patterns, or time-frequency features, predicting voluntary motor intention, can be extracted from the local field potentials (LFPs) recorded from the sub-thalamic nucleus (STN) or thalamus of human patients implanted with deep brain stimulation (DBS) electrodes for the treatment of movement disorders. This paper investigates the optimization of signal conditioning processes using deep learning to augment time-frequency feature extraction from LFP signals, with the aim of improving the performance of real-time decoding of voluntary motor states. A brain-computer interface (BCI) pipeline capable of continuously classifying discrete pinch grip states from LFPs was designed in Pytorch, a deep learning framework. The pipeline was implemented offline on LFPs recorded from 5 different patients bilaterally implanted with DBS electrodes. Optimizing channel combination in different frequency bands and frequency domain feature extraction demonstrated improved classification accuracy of pinch grip detection and laterality of the pinch (either pinch of the left hand or pinch of the right hand). Overall, the optimized BCI pipeline achieved a maximal average classification accuracy of 79.67±10.02% when detecting all pinches and 67.06±10.14% when considering the laterality of the pinch.

Continuous high frequency Deep Brain Stimulation (DBS) is a standard therapy for several neurological disorders. Closed-loop DBS is expected to further improve treatment by providing adaptive, on-demand therapy. Local field potentials (LFPs) recorded from the stimulation electrodes are the most often used feedback signal in closed-loop DBS. However, closed-loop DBS based on LFPs requires simultaneous recording and stimulating, which remains a challenge due to persistent stimulation artefacts that distort underlying LFP biomarkers. Here we first investigate the nature of the stimulation-induced artefacts and review several techniques that have been proposed to deal with them. Then we propose a new method to synchronize the sampling clock with the stimulation pulse so that the stimulation artefacts are never sampled, while at the same time the Nyquist-Shannon theorem is satisfied for uninterrupted LFP recording. Test results show that this method achieves true uninterrupted artefact-free LFP recording over a wide frequency band and for a wide range of stimulation frequencies.Clinical relevance-The method proposed here provides continuous and artefact-free recording of LFPs close to the stimulation target, and thereby facilitates the implementation of more advanced closed-loop DBS using LFPs as feedback.

Abnormally increased β bursts in cortical-basal ganglia-thalamic circuits are associated with rigidity and bradykinesia in patients with Parkinson's disease. Increased β bursts detected in the motor cortex have also been associated with longer reaction times (RTs) in healthy participants. Here we further hypothesize that suppressing β bursts through neurofeedback training can improve motor performance in healthy subjects. We conducted a double-blind sham-controlled study on 20 human volunteers (10 females) using a sequential neurofeedback-behavior task with the neurofeedback reflecting the occurrence of β bursts over sensorimotor cortex quantified in real time. The results show that neurofeedback training helps healthy participants learn to volitionally suppress β bursts in the sensorimotor cortex, with training being accompanied by reduced RT in subsequent cued movements. These changes were only significant in the real feedback group but not in the sham group, confirming the effect of neurofeedback training over simple motor imagery. In addition, RTs correlated with the rate and accumulated duration of β bursts in the contralateral motor cortex before the go-cue, but not with averaged β power. The reduced RTs induced by neurofeedback training positively correlated with reduced β bursts across all tested hemispheres. These results strengthen the link between the occurrence of β bursts in the sensorimotor cortex before the go-cue and slowed movement initiation in healthy motor control. The results also highlight the potential benefit of neurofeedback training in facilitating voluntary suppression of β bursts to speed up movement initiation. SIGNIFICANCE STATEMENT This double-blind sham-controlled study suggested that neurofeedback training can facilitate volitional suppression of β bursts in sensorimotor cortex in healthy motor control better than sham feedback. The training was accompanied by reduced reaction time (RT) in subsequent cued movements, and the reduced RT positively correlated with the level of reduction in cortical β bursts before the go-cue, but not with average β power. These results provide further evidence of a causal link between sensorimotor β bursts and movement initiation and suggest that neurofeedback training could potentially be used to train participants to speed up movement initiation., (Copyright © 2020 He et al.)

This paper presents a new asynchronous hybrid brain-computer interface (BCI) system that integrates a speller, a web browser, an e-mail client, and a file explorer using electroencephalographic (EEG) and electrooculography (EOG) signals. More specifically, an EOG-based button selection method, which requires the user to blink his/her eyes synchronously with the target button's flashes during button selection, is first presented. Next, we propose a mouse control method by combining EEG and EOG signals, in which the left-/right-hand motor imagery (MI)-related EEG is used to control the horizontal movement of the mouse and the blink-related EOG is used to control the vertical movement of the mouse and to select/reject a target. These two methods are further combined to develop the integrated hybrid BCI system. With the hybrid BCI, users can input text, access the internet, communicate with others via e-mail, and manage files in their computer using only EEG and EOG without any body movements. Ten healthy subjects participated in a comprehensive online experiment, and superior performance was achieved compared with our previously developed P300- and MI-based BCI and some other asynchronous BCIs, therefore demonstrating the system's effectiveness.

Most existing brain-computer Interfaces (BCIs) are designed to control a single assistive device, such as a wheelchair, a robotic arm or a prosthetic limb. However, many daily tasks require combined functions which can only be realized by integrating multiple robotic devices. Such integration raises the requirement of the control accuracy and is more challenging to achieve a reliable control compared with the single device case. In this study, we propose a novel hybrid BCI with high accuracy based on electroencephalogram (EEG) and electrooculogram (EOG) to control an integrated wheelchair robotic arm system. The user turns the wheelchair left/right by performing left/right hand motor imagery (MI), and generates other commands for the wheelchair and the robotic arm by performing eye blinks and eyebrow raising movements. Twenty-two subjects participated in a MI training session and five of them completed a mobile self-drinking experiment, which was designed purposely with high accuracy requirements. The results demonstrated that the proposed hBCI could provide satisfied control accuracy for a system that consists of multiple robotic devices, and showed the potential of BCI-controlled systems to be applied in complex daily tasks., (Copyright © 2019 Huang, Zhang, Yu, He and Li.)

Background: Delayed onset of lactation is a key factor in the low rate of exclusive breast-feeding in 6 months after caesarean section. The mechanism of delayed onset of lactation is not clear. Milk production depends largely on mitochondrial adenosine triphosphate synthesis, and the neutrophil-lymphocyte ratio is closely related to mitochondrial deoxyribonucleic acid copy number and adenosine triphosphate production. Presently, it is unclear whether a difference in the neutrophil-lymphocyte ratio exists between those undergoing vaginal delivery and those undergoing caesarean delivery and, if so, whether the difference correlates to the time of onset of lactation., Objectives: To identify whether the neutrophil-lymphocyte ratio at 24 hours after delivery is different between mothers delivering by caesarean section and those giving birth vaginally and whether the neutrophil-lymphocyte ratio is related to the delayed onset of lactation., Design: The study adopted a prospective cohort study design., Settings: Maternity units of an Obstetrics & Gynecology Hospital., Participants: 327 mother-infant pairs who met inclusion/exclusion criteria and were followed up to the time of onset of lactation., Methods: Mother-infant pairs were allocated to the vaginal birth group or the caesarean section group according to birth method. The neutrophil-lymphocyte ratio was calculated as the absolute value of neutrophils divided by the absolute value of lymphocytes based on full blood counts. Before delivery, full blood counts were obtained from medical records. After delivery, blood samples were drawn 24 hours postpartum, and blood cells were classified and counted. The onset of lactation was confirmed by the maternal perception of breast fullness. The neutrophil-lymphocyte ratio and its relationship with lactation onset were analyzed by multivariable regression., Results: The neutrophil-lymphocyte ratios of both groups were elevated after delivery. Based on the covariance analysis, after adjusting for baseline full blood counts before delivery, the neutrophil-lymphocyte ratio in the caesarean group was higher than the ratio in the vaginal group after delivery (p = .000). In addition, after adjustment for confounding factors, multivariable regression analyses showed that an increased neutrophil-lymphocyte ratio was correlated with delayed onset of lactation (95% confidence interval 0.285-1.646)., Conclusions: The neutrophil-lymphocyte ratio in the caesarean section group was higher than that in the vaginal delivery group and was related to a delayed onset of lactation. Given the decreased mitochondrial copy number in the elevated neutrophil-lymphocyte ratio and therefore the associated reduction in adenosine triphosphate synthesis, these findings may elucidate the mechanism for delayed onset of lactation in caesarean section births., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.)

Objective: In this study, we combine a wheelchair and an intelligent robotic arm based on an electrooculogram (EOG) signal to help patients with spinal cord injuries (SCIs) accomplish a self-drinking task. The main challenge is to accurately control the wheelchair to ensure that the randomly located object is within a limited reachable space of the robotic arm (length: 0.8 m; width: 0.4 m; height: 0.6 m), which requires decimeter-level precision, and is still undemonstrated for EOG-based systems as well as EEG-based systems., Approach: A novel high-precision EOG-based human machine interface (HMI) is proposed which can effectively translate two kinds of eye movements (i.e. blinking and eyebrow raising) into various commands. For the wheelchair, positional precision can reach decimeter-level and the minimal steering angle is [Formula: see text]. For the intelligent robotic arm, shared control is implemented based on an EOG-based HMI, two cameras and the arm's own intelligence., Main Results: After brief training, five healthy subjects and five paralyzed patients with severe SCIs successfully completed three experiments. For the healthy subjects/patients with SCIs, the system achieved an average accuracy of 99.3%/97.3%, an average response time of 1.91 s/2.02 s per command and an average stop-response time of 1.30 s/1.36 s with a 0 false operation rate., Significance: The EOG-based HMI can provide sufficient precision control to integrate a wheelchair and a robotic arm into a system which can help patients with SCIs to accomplish a self-drinking task. (ChiCTR1800019764).

Increased oscillatory activities in the beta frequency band (13-30 Hz) in the subthalamic nucleus (STN), and in particular prolonged episodes of increased synchrony in this frequency band, have been associated with motor symptoms such as bradykinesia and rigidity in Parkinson's disease (PD). Numerous studies have investigated sensorimotor cortical beta oscillations either as a control signal for Brain Computer Interfaces (BCI) or as target signal for neurofeedback training (NFB). However, it still remains unknown whether patients with PD can gain control of the pathological oscillations recorded from a subcortical site - the STN - with neurofeedback training. We tried to address this question in the current study. Specifically, we designed a simple basketball game, in which the position of a basketball changes based on the occurrence of events of temporally increased beta power quantified in real-time. Participants practised in the game to control the position of the basketball, which requires modulation of the beta oscillations recorded from STN local field potentials (LFPs). Our results suggest that it is possible to use neurofeedback training for PD patients to downregulate pathological beta oscillations in STN LFPs, and that this can lead to a reduction of beta oscillations in the cortical-STN motor network.

Objective: This paper presents an asyn-chronous electrooculography (EOG)-based human-machine interface (HMI) for smart home environmental control with the purpose of providing daily assistance for severe spinal cord injury (SCI) patients., Methods: The proposed HMI allows users to interact with a smart home environment through eye blinking. Specifically, several buttons, each corresponding to a control command, randomly flash on a graphical user interface. Each flash of the buttons functions as a visual cue for the user to blink. To issue a control command, the user can blink synchronously with the flashes of the corresponding button. Through detecting blinks based on the recorded EOG signal, the target button and its corresponding control command are determined. Seven SCI patients participated in an online experiment, during which the patients were required to control a smart home environment including household electrical appliances, an intelligent wheelchair, as well as a nursing bed via the proposed HMI., Results: The average false operation ratio in the control state was 4.1%, whereas during the idle state, no false operations occurred., Conclusion: All SCI patients were able to control the smart home environment using the proposed EOG-based HMI with satisfactory performance in terms of the false operation ratio in both the control and the idle states., Significance: The proposed HMI offers a simple and effective approach for patients with severe SCIs to control a smart home environment. Therefore, it is promising to assist severe SCI patients in their daily lives.

Objective: Nonmanual human-machine interfaces (HMIs) have been studied for wheelchair control with the aim of helping severely paralyzed individuals regain some mobility. The challenge is to rapidly, accurately, and sufficiently produce control commands, such as left and right turns, forward and backward motions, acceleration, deceleration, and stopping. In this paper, a novel electrooculogram (EOG) based HMI is proposed for wheelchair control., Methods: A total of 13 flashing buttons, each of which corresponds to a command, are presented in the graphical user interface. These buttons flash on a one-by-one manner in a predefined sequence. The user can select a button by blinking in sync with its flashes. The algorithm detects the eye blinks from a channel of vertical EOG data and determines the user's target button based on the synchronization between the detected blinks and the button's flashes., Results: For healthy subjects/patients with spinal cord injuries, the proposed HMI achieved an average accuracy of 96.7% / 91.7% and a response time of 3.53 s/3.67 s with 0 false positive rates (FPRs)., Conclusion: Using one channel of vertical EOG signals associated with eye blinks, the proposed HMI can accurately provide sufficient commands with a satisfactory response time., Significance: The proposed HMI provides a novel nonmanual approach for severely paralyzed individuals to control a wheelchair. Compared with a newly established EOG-based HMI, the proposed HMI can generate more commands with higher accuracy, lower FPR, and fewer electrodes.

Electrooculography (EOG) signals, which can be used to infer the intentions of a user based on eye movements, are widely used in human-computer interface (HCI) systems. Most existing EOG-based HCI systems incorporate a limited number of commands because they generally associate different commands with a few different types of eye movements, such as looking up, down, left, or right. This paper presents a novel single-channel EOG-based HCI that allows users to spell asynchronously by only blinking. Forty buttons corresponding to 40 characters displayed to the user via a graphical user interface are intensified in a random order. To select a button, the user must blink his/her eyes in synchrony as the target button is flashed. Two data processing procedures, specifically support vector machine (SVM) classification and waveform detection, are combined to detect eye blinks. During detection, we simultaneously feed the feature vectors extracted from the ongoing EOG signal into the SVM classification and waveform detection modules. Decisions are made based on the results of the SVM classification and waveform detection. Three online experiments were conducted with eight healthy subjects. We achieved an average accuracy of 94.4% and a response time of 4.14 s for selecting a character in synchronous mode, as well as an average accuracy of 93.43% and a false positive rate of 0.03/min in the idle state in asynchronous mode. The experimental results, therefore, demonstrated the effectiveness of this single-channel EOG-based speller.

This study proposes an event-related potential (ERP) BCI-based environmental control system that integrates household electrical appliances, a nursing bed, and an intelligent wheelchair to provide daily assistance to paralyzed patients with severe spinal cord injuries (SCIs)., Methods: An asynchronous mode is used to switch the environmental control system on or off or to select a device (e.g., a TV) for achieving selfpaced control. In the asynchronous mode, we introduce several pseudo-keys and a verification mechanism to effectively reduce the false operation rate. By contrast, when the user selects a function of the device (e.g., a TV channel), a synchronous mode is used to improve the accuracy and speed of BCI detection. Two experiments involving six SCI patients were conducted separately in a nursing bed and a wheelchair, and the patients were instructed to control the nursing bed, the wheelchair, and household electrical appliances (an electric light, an air conditioner, and a TV)., Results: The average false rate of BCI commands in the control state was 10.4%, whereas the average false operation ratio was 4.9% (a false BCI command might not necessarily result in a false operation according to our system design). During the idle state, there was an average of 0.97 false positives per minute, which did not result in any false operations., Conclusion: All SCI patients could use the proposed ERP BCIbased environmental control system satisfactorily., Significance: The proposed ERP-based environmental control system could be used to assist patients with severe SCIs in their daily lives.

The key issue of electroencephalography (EEG)-based brain switches is to detect the control and idle states in an asynchronous manner. Most existing methods rely on a threshold. However, it is often time consuming to select a satisfactory threshold, and the chosen threshold might be inappropriate over a long period of time due to the variability of the EEG signals. This paper presents a new P300-based threshold-free brain switch. Specifically, one target button and three pseudo buttons, which are intensified in a random order to produce P300 potential, are set in the graphical user interface. The user can issue a switch command by focusing on the target button. Two support vector machine (SVM) classifiers, namely, SVM1 and SVM2, are used in the detection algorithm. During detection, we first obtained four SVM scores, corresponding to the four flashing buttons, by applying SVM1 to the ongoing EEG. If the SVM score corresponding to the target button was negative or not at the maximum, then an idle state was determined. Moreover, if the target button had a maximum and positive score, then we fed the four SVM scores as features into SVM2 to further discriminate the control and idle states. As an application, this brain switch was used to produce a start/stop command for an intelligent wheelchair, of which the left, right, forward, backward functions were carried out by an autonomous navigation system. Several experiments were conducted with eight healthy subjects and five patients with spinal cord injuries (SCIs). The experimental results not only demonstrated the effectiveness of our approach but also illustrated the potential application for patients with SCIs.

Background: Patient safety culture is an important measure in assessing the quality of health care. There is a growing recognition of the need to establish a culture of hospital focused on patient safety. This study explores the attitudes and perceptions of patient safety culture for health care workers in China by using a Hospital Survey on Patient Safety Culture (HSPSC) questionnaire and comparing it with the psychometric properties of an adapted translation of the HSPSC in Chinese hospitals with that of the US., Method: We used the modified HSPSC questionnaire to measure 10 dimensions of patient safety culture from 32 hospitals in 15 cities all across China. The questionnaire included 1160 Chinese health-care workers who consisted of predominately internal physicians and nurses. We used SPSS 17.0 and Microsoft Excel 2007 to conduct the statistical analysis on survey data including descriptive statistics and validity and reliability of survey. All data was input and checked by two investigators independently., Result: A total of 1500 questionnaires were distributed of which 1160 were responded validly (response rate 77%). The positive response rate for each item ranged from 36% to 89%. The positive response rate on 5 dimensions (Teamwork Within Units, Organization Learning-Continuous Improvement, Communication Openness, Non-punitive Response and Teamwork Across Units) was higher than that of AHRQ data (P < 0.05). There was a statistical difference on the perception of patient safety culture in groups of different work units, positions and qualification levels. The internal consistency of the total survey was comparatively satisfied (Cronbach's α = 0.84)., Conclusion: The results show that amongst the health care workers surveyed in China there was a positive attitude towards the patient safety culture within their organizations. The differences between China and the US in patient safety culture suggests that cultural uniqueness should be taken into consideration whenever safety culture measurement tools are applied in different culture settings.