The nested hierarchy of overt, mouthed, and imagined speech activity evident in intracranial recordings.

Recent studies have demonstrated that it is possible to decode and synthesize various aspects of acoustic speech directly from intracranial measurements of electrophysiological brain activity. In order to continue progressing toward the development of a practical speech neuroprosthesis for the individuals with speech impairments, better understanding and modeling of imagined speech processes are required. The present study uses intracranial brain recordings from participants that performed a speaking task with trials consisting of overt, mouthed, and imagined speech modes, representing various degrees of decreasing behavioral output. Speech activity detection models are constructed using spatial, spectral, and temporal brain activity features, and the features and model performances are characterized and compared across the three degrees of behavioral output. The results indicate the existence of a hierarchy in which the relevant channels for the lower behavioral output modes form nested subsets of the relevant channels from the higher behavioral output modes. This provides important insights for the elusive goal of developing more effective imagined speech decoding models with respect to the better-established overt speech decoding counterparts.

Designing daily-life research combining experience sampling method with parallel data.

BACKGROUND: Ambulatory monitoring is gaining popularity in mental and somatic health care to capture an individual's wellbeing or treatment course in daily-life. Experience sampling method collects subjective time-series data of patients' experiences, behavior, and context. At the same time, digital devices allow for less intrusive collection of more objective time-series data with higher sampling frequencies and for prolonged sampling periods. We refer to these data as parallel data. Combining these two data types holds the promise to revolutionize health care. However, existing ambulatory monitoring guidelines are too specific to each data type, and lack overall directions on how to effectively combine them. METHODS: Literature and expert opinions were integrated to formulate relevant guiding principles. RESULTS: Experience sampling and parallel data must be approached as one holistic time series right from the start, at the study design stage. The fluctuation pattern and volatility of the different variables of interest must be well understood to ensure that these data are compatible. Data have to be collected and operationalized in a manner that the minimal common denominator is able to answer the research question with regard to temporal and disease severity resolution. Furthermore, recommendations are provided for device selection, data management, and analysis. Open science practices are also highlighted throughout. Finally, we provide a practical checklist with the delineated considerations and an open-source example demonstrating how to apply it. CONCLUSIONS: The provided considerations aim to structure and support researchers as they undertake the new challenges presented by this exciting multidisciplinary research field.

Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson's disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. METHODS: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. RESULTS: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. CONCLUSION: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.

Rapid Dynamic Naturalistic Monitoring of Bradykinesia in Parkinson's Disease Using a Wrist-Worn Accelerometer.

Motor fluctuations in Parkinson's disease are characterized by unpredictability in the timing and duration of dopaminergic therapeutic benefits on symptoms, including bradykinesia and rigidity. These fluctuations significantly impair the quality of life of many Parkinson's patients. However, current clinical evaluation tools are not designed for the continuous, naturalistic (real-world) symptom monitoring needed to optimize clinical therapy to treat fluctuations. Although commercially available wearable motor monitoring, used over multiple days, can augment neurological decision making, the feasibility of rapid and dynamic detection of motor fluctuations is unclear. So far, applied wearable monitoring algorithms are trained on group data. In this study, we investigated the influence of individual model training on short timescale classification of naturalistic bradykinesia fluctuations in Parkinson's patients using a single-wrist accelerometer. As part of the Parkinson@Home study protocol, 20 Parkinson patients were recorded with bilateral wrist accelerometers for a one hour OFF medication session and a one hour ON medication session during unconstrained activities in their own homes. Kinematic metrics were extracted from the accelerometer data from the bodyside with the largest unilateral bradykinesia fluctuations across medication states. The kinematic accelerometer features were compared over the 1 h duration of recording, and medication-state classification analyses were performed on 1 min segments of data. Then, we analyzed the influence of individual versus group model training, data window length, and total number of training patients included in group model training, on classification. Statistically significant areas under the curves (AUCs) for medication induced bradykinesia fluctuation classification were seen in 85% of the Parkinson patients at the single minute timescale using the group models. Individually trained models performed at the same level as the group trained models (mean AUC both 0.70, standard deviation respectively 0.18 and 0.10) despite the small individual training dataset. AUCs of the group models improved as the length of the feature windows was increased to 300 s, and with additional training patient datasets. We were able to show that medication-induced fluctuations in bradykinesia can be classified using wrist-worn accelerometry at the time scale of a single minute. Rapid, naturalistic Parkinson motor monitoring has the clinical potential to evaluate dynamic symptomatic and therapeutic fluctuations and help tailor treatments on a fast timescale.

Towards hippocampal navigation for brain-computer interfaces.

Automatic wheelchairs directly controlled by brain activity could provide autonomy to severely paralyzed individuals. Current approaches mostly rely on non-invasive measures of brain activity and translate individual commands into wheelchair movements. For example, an imagined movement of the right hand would steer the wheelchair to the right. No research has investigated decoding higher-order cognitive processes to accomplish wheelchair control. We envision an invasive neural prosthetic that could provide input for wheelchair control by decoding navigational intent from hippocampal signals. Navigation has been extensively investigated in hippocampal recordings, but not for the development of neural prostheses. Here we show that it is possible to train a decoder to classify virtual-movement speeds from hippocampal signals recorded during a virtual-navigation task. These results represent the first step toward exploring the feasibility of an invasive hippocampal BCI for wheelchair control.

Decoding executed and imagined grasping movements from distributed non-motor brain areas using a Riemannian decoder.

Using brain activity directly as input for assistive tool control can circumventmuscular dysfunction and increase functional independence for physically impaired people. The motor cortex is commonly targeted for recordings, while growing evidence shows that there exists decodable movement-related neural activity outside of the motor cortex. Several decoding studies demonstrated significant decoding from distributed areas separately. Here, we combine information from all recorded non-motor brain areas and decode executed and imagined movements using a Riemannian decoder. We recorded neural activity from 8 epilepsy patients implanted with stereotactic-electroencephalographic electrodes (sEEG), while they performed an executed and imagined grasping tasks. Before decoding, we excluded all contacts in or adjacent to the central sulcus. The decoder extracts a low-dimensional representation of varying number of components, and classified move/no-move using a minimum-distance-to-geometric-mean Riemannian classifier. We show that executed and imagined movements can be decoded from distributed non-motor brain areas using a Riemannian decoder, reaching an area under the receiver operator characteristic of 0.83 ± 0.11. Furthermore, we highlight the distributedness of the movement-related neural activity, as no single brain area is the main driver of performance. Our decoding results demonstrate a first application of a Riemannian decoder on sEEG data and show that it is able to decode from distributed brain-wide recordings outside of the motor cortex. This brief report highlights the perspective to explore motor-related neural activity beyond the motor cortex, as many areas contain decodable information.

Dataset of Speech Production in intracranial.Electroencephalography.

Speech production is an intricate process involving a large number of muscles and cognitive processes. The neural processes underlying speech production are not completely understood. As speech is a uniquely human ability, it can not be investigated in animal models. High-fidelity human data can only be obtained in clinical settings and is therefore not easily available to all researchers. Here, we provide a dataset of 10 participants reading out individual words while we measured intracranial EEG from a total of 1103 electrodes. The data, with its high temporal resolution and coverage of a large variety of cortical and sub-cortical brain regions, can help in understanding the speech production process better. Simultaneously, the data can be used to test speech decoding and synthesis approaches from neural data to develop speech Brain-Computer Interfaces and speech neuroprostheses.

Workshops of the Eighth International Brain-Computer Interface Meeting: BCIs: The Next Frontier.

The Eighth International Brain-Computer Interface (BCI) Meeting was held June 7-9th, 2021 in a virtual format. The conference continued the BCI Meeting series' interactive nature with 21 workshops covering topics in BCI (also called brain-machine interface) research. As in the past, workshops covered the breadth of topics in BCI. Some workshops provided detailed examinations of specific methods, hardware, or processes. Others focused on specific BCI applications or user groups. Several workshops continued consensus building efforts designed to create BCI standards and increase the ease of comparisons between studies and the potential for meta-analysis and large multi-site clinical trials. Ethical and translational considerations were both the primary topic for some workshops or an important secondary consideration for others. The range of BCI applications continues to expand, with more workshops focusing on approaches that can extend beyond the needs of those with physical impairments. This paper summarizes each workshop, provides background information and references for further study, presents an overview of the discussion topics, and describes the conclusion, challenges, or initiatives that resulted from the interactions and discussion at the workshop.

Continuously Decoding Grasping Movements using Stereotactic Depth Electrodes.

Brain-Computer Interfaces (BCIs) that decode a patient's movement intention to control a prosthetic device could restore some independence to paralyzed patients. An important step on the road towards naturalistic prosthetic control is to decode movement continuously with low-latency. BCIs based on intracortical micro-arrays provide continuous control of robotic arms, but require a minor craniotomy. Surface recordings of neural activity using EEG have made great advances over the last years, but suffer from high noise levels and large intra-session variance. Here, we investigate the use of minimally invasive recordings using stereotactically implanted EEG (sEEG). These electrodes provide a sparse sampling across many brain regions. So far, promising decoding results have been presented using data measured from the subthalamic nucleus or trial-to-trial based methods using depth electrodes. In this work, we demonstrate that grasping movements can continuously be decoded using sEEG electrodes, as well. Beta and high-gamma activity was extracted from eight participants performing a grasping task. We demonstrate above chance level decoding of movement vs rest and left vs right, from both frequency bands with accuracies up to 0.94 AUC. The vastly different electrode locations between participants lead to large variability. In the future, we hope that sEEG recordings will provide additional information for the decoding process in neuroprostheses.

Speech Synthesis from Stereotactic EEG using an Electrode Shaft Dependent Multi-Input Convolutional Neural Network Approach.

Neurological disorders can lead to significant impairments in speech communication and, in severe cases, cause the complete loss of the ability to speak. Brain-Computer Interfaces have shown promise as an alternative communication modality by directly transforming neural activity of speech processes into a textual or audible representations. Previous studies investigating such speech neuroprostheses relied on electrocorticography (ECoG) or microelectrode arrays that acquire neural signals from superficial areas on the cortex. While both measurement methods have demonstrated successful speech decoding, they do not capture activity from deeper brain structures and this activity has therefore not been harnessed for speech-related BCIs. In this study, we bridge this gap by adapting a previously presented decoding pipeline for speech synthesis based on ECoG signals to implanted depth electrodes (sEEG). For this purpose, we propose a multi-input convolutional neural network that extracts speech-related activity separately for each electrode shaft and estimates spectral coefficients to reconstruct an audible waveform. We evaluate our approach on open-loop data from 5 patients who conducted a recitation task of Dutch utterances. We achieve correlations of up to 0.80 between original and reconstructed speech spectrograms, which are significantly above chance level for all patients (p < 0.001). Our results indicate that sEEG can yield similar speech decoding performance to prior ECoG studies and is a promising modality for speech BCIs.

Real-time synthesis of imagined speech processes from minimally invasive recordings of neural activity.

Speech neuroprosthetics aim to provide a natural communication channel to individuals who are unable to speak due to physical or neurological impairments. Real-time synthesis of acoustic speech directly from measured neural activity could enable natural conversations and notably improve quality of life, particularly for individuals who have severely limited means of communication. Recent advances in decoding approaches have led to high quality reconstructions of acoustic speech from invasively measured neural activity. However, most prior research utilizes data collected during open-loop experiments of articulated speech, which might not directly translate to imagined speech processes. Here, we present an approach that synthesizes audible speech in real-time for both imagined and whispered speech conditions. Using a participant implanted with stereotactic depth electrodes, we were able to reliably generate audible speech in real-time. The decoding models rely predominately on frontal activity suggesting that speech processes have similar representations when vocalized, whispered, or imagined. While reconstructed audio is not yet intelligible, our real-time synthesis approach represents an essential step towards investigating how patients will learn to operate a closed-loop speech neuroprosthesis based on imagined speech.

Predicting mortality of individual patients with COVID-19: a multicentre Dutch cohort.

OBJECTIVE: Develop and validate models that predict mortality of patients diagnosed with COVID-19 admitted to the hospital. DESIGN: Retrospective cohort study. SETTING: A multicentre cohort across 10 Dutch hospitals including patients from 27 February to 8 June 2020. PARTICIPANTS: SARS-CoV-2 positive patients (age ≥18) admitted to the hospital. MAIN OUTCOME MEASURES: 21-day all-cause mortality evaluated by the area under the receiver operator curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. The predictive value of age was explored by comparison with age-based rules used in practice and by excluding age from the analysis. RESULTS: 2273 patients were included, of whom 516 had died or discharged to palliative care within 21 days after admission. Five feature sets, including premorbid, clinical presentation and laboratory and radiology values, were derived from 80 features. Additionally, an Analysis of Variance (ANOVA)-based data-driven feature selection selected the 10 features with the highest F values: age, number of home medications, urea nitrogen, lactate dehydrogenase, albumin, oxygen saturation (%), oxygen saturation is measured on room air, oxygen saturation is measured on oxygen therapy, blood gas pH and history of chronic cardiac disease. A linear logistic regression and non-linear tree-based gradient boosting algorithm fitted the data with an AUC of 0.81 (95% CI 0.77 to 0.85) and 0.82 (0.79 to 0.85), respectively, using the 10 selected features. Both models outperformed age-based decision rules used in practice (AUC of 0.69, 0.65 to 0.74 for age >70). Furthermore, performance remained stable when excluding age as predictor (AUC of 0.78, 0.75 to 0.81). CONCLUSION: Both models showed good performance and had better test characteristics than age-based decision rules, using 10 admission features readily available in Dutch hospitals. The models hold promise to aid decision-making during a hospital bed shortage.

The Potential of Stereotactic-EEG for Brain-Computer Interfaces: Current Progress and Future Directions.

Stereotactic electroencephalogaphy (sEEG) utilizes localized, penetrating depth electrodes to measure electrophysiological brain activity. It is most commonly used in the identification of epileptogenic zones in cases of refractory epilepsy. The implanted electrodes generally provide a sparse sampling of a unique set of brain regions including deeper brain structures such as hippocampus, amygdala and insula that cannot be captured by superficial measurement modalities such as electrocorticography (ECoG). Despite the overlapping clinical application and recent progress in decoding of ECoG for Brain-Computer Interfaces (BCIs), sEEG has thus far received comparatively little attention for BCI decoding. Additionally, the success of the related deep-brain stimulation (DBS) implants bodes well for the potential for chronic sEEG applications. This article provides an overview of sEEG technology, BCI-related research, and prospective future directions of sEEG for long-term BCI applications.

Mobile Health Daily Life Monitoring for Parkinson Disease: Development and Validation of Ecological Momentary Assessments.

BACKGROUND: Parkinson disease monitoring is currently transitioning from periodic clinical assessments to continuous daily life monitoring in free-living conditions. Traditional Parkinson disease monitoring methods lack intraday fluctuation detection. Electronic diaries (eDiaries) hold the potential to collect subjective experiences on the severity and burden of motor and nonmotor symptoms in free-living conditions. OBJECTIVE: This study aimed to develop a Parkinson disease-specific eDiary based on ecological momentary assessments (EMAs) and to explore its validation. METHODS: An observational cohort of 20 patients with Parkinson disease used the smartphone-based EMA eDiary for 14 consecutive days without adjusting free-living routines. The eDiary app presented an identical questionnaire consisting of questions regarding affect, context, motor and nonmotor symptoms, and motor performance 7 times daily at semirandomized moments. In addition, patients were asked to complete a morning and an evening questionnaire. RESULTS: Mean affect correlated moderate-to-strong and moderate with motor performance (R=0.38 to 0.75; P<.001) and motor symptom (R=0.34 to 0.50; P<.001) items, respectively. The motor performance showed a weak-to-moderate negative correlation with motor symptoms (R=-0.31 to -0.48; P<.001). Mean group answers given for on-medication conditions vs wearing-off-medication conditions differed significantly (P<.05); however, not enough questionnaires were completed for the wearing-off-medication condition to reproduce these findings on individual levels. CONCLUSIONS: We presented a Parkinson disease-specific EMA eDiary. Correlations between given answers support the internal validity of the eDiary and underline EMA's potential in free-living Parkinson disease monitoring. Careful patient selection and EMA design adjustment to this targeted population and their fluctuations are necessary to generate robust proof of EMA validation in future work. Combining clinical Parkinson disease knowledge with practical EMA experience is inevitable to design and perform studies, which will lead to the successful integration of eDiaries in free-living Parkinson disease monitoring.

Machine learning prediction of motor response after deep brain stimulation in Parkinson's disease-proof of principle in a retrospective cohort.

INTRODUCTION: Despite careful patient selection for subthalamic nucleus deep brain stimulation (STN DBS), some Parkinson's disease patients show limited improvement of motor disability. Innovative predictive analysing methods hold potential to develop a tool for clinicians that reliably predicts individual postoperative motor response, by only regarding clinical preoperative variables. The main aim of preoperative prediction would be to improve preoperative patient counselling, expectation management, and postoperative patient satisfaction. METHODS: We developed a machine learning logistic regression prediction model which generates probabilities for experiencing weak motor response one year after surgery. The model analyses preoperative variables and is trained on 89 patients using a five-fold cross-validation. Imaging and neurophysiology data are left out intentionally to ensure usability in the preoperative clinical practice. Weak responders (n = 30) were defined as patients who fail to show clinically relevant improvement on Unified Parkinson Disease Rating Scale II, III or IV. RESULTS: The model predicts weak responders with an average area under the curve of the receiver operating characteristic of 0.79 (standard deviation: 0.08), a true positive rate of 0.80 and a false positive rate of 0.24, and a diagnostic accuracy of 78%. The reported influences of individual preoperative variables are useful for clinical interpretation of the model, but cannot been interpreted separately regardless of the other variables in the model. CONCLUSION: The model's diagnostic accuracy confirms the utility of machine learning based motor response prediction based on clinical preoperative variables. After reproduction and validation in a larger and prospective cohort, this prediction model holds potential to support clinicians during preoperative patient counseling.

EEG Movement Artifact Suppression in Interactive Virtual Reality.

The integration of electroencephalogram (EEG) sensors into virtual reality (VR) headsets can provide the capability of tracking the user's cognitive state and eventually be used to increase the sense of immersion. Recent developments in wireless, room-scale VR tracking allow users to move freely in the physical and virtual spaces. Such motion can create significant movement artifacts in EEG sensors mounted to the VR headset. This study explores the removal of EEG movement artifacts caused by repetitive, stereotyped movements during an interactive VR task.

Evaluation of Parkinson's Disease at Home: Predicting Tremor from Wearable Sensors.

The continuous monitoring of Parkinsons's disease (PD) symptoms would allow to automatically adjust medication or deep brain stimulation parameters to a patient's momentary condition. Wearable sensors have been proposed to monitor PD symptoms and have been validated in a number of lab and hospital settings. However, taking these sensors into the daily life of patients introduces a number of difficulties, most notably the absence of an observable ground truth of what the user is currently doing. In this pilot study, we investigate PD symptoms by combining wearable sensors on both wrist and the chest with a questionnaire based evaluation of PD symptoms, in the form of experience sampling method. For a tremor dominant patient, we show that experienced tremor severity can be predicted from the sensor data with correlations of up to r = 0.43. We evaluated different window lengths to calculate the features in and see better results for longer window lengths. Our results show that continuous monitoring of PD symptoms in daily life is feasible using wearable sensors.

Decoding Mental Workload in Virtual Environments: A fNIRS Study using an Immersive n-back Task.

Virtual Reality (VR) has emerged as a novel paradigm for immersive applications in training, entertainment, rehabilitation, and other domains. In this paper, we investigate the automatic classification of mental workload from brain activity measured through functional near-infrared spectroscopy (fNIRS) in VR. We present results from a study which implements the established n-back task in an immersive visual scene, including physical interaction. Our results show that user workload can be detected from fNIRS signals in immersive VR tasks both person-dependently and -adaptively.

Estimating Cognitive Workload in an Interactive Virtual Reality Environment Using EEG.

With the recent surge of affordable, high-performance virtual reality (VR) headsets, there is unlimited potential for applications ranging from education, to training, to entertainment, to fitness and beyond. As these interfaces continue to evolve, passive user-state monitoring can play a key role in expanding the immersive VR experience, and tracking activity for user well-being. By recording physiological signals such as the electroencephalogram (EEG) during use of a VR device, the user's interactions in the virtual environment could be adapted in real-time based on the user's cognitive state. Current VR headsets provide a logical, convenient, and unobtrusive framework for mounting EEG sensors. The present study evaluates the feasibility of passively monitoring cognitive workload via EEG while performing a classical n-back task in an interactive VR environment. Data were collected from 15 participants and the spatio-spectral EEG features were analyzed with respect to task performance. The results indicate that scalp measurements of electrical activity can effectively discriminate three workload levels, even after suppression of a co-varying high-frequency activity.

Towards Restoration of Articulatory Movements: Functional Electrical Stimulation of Orofacial Muscles.

Millions of individuals suffer from impairments that significantly disrupt or completely eliminate their ability to speak. An ideal intervention would restore one's natural ability to physically produce speech. Recent progress has been made in decoding speech-related brain activity to generate synthesized speech. Our vision is to extend these recent advances toward the goal of restoring physical speech production using decoded speech-related brain activity to modulate the electrical stimulation of the orofacial musculature involved in speech. In this pilot study we take a step toward this vision by investigating the feasibility of stimulating orofacial muscles during vocalization in order to alter acoustic production. The results of our study provide necessary foundation for eventual orofacial stimulation controlled directly from decoded speech-related brain activity.