A Pilot Study on Data-Driven Adaptive Deep Brain Stimulation in Chronically Implanted Essential Tremor Patients.

Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) and essential-tremor (ET). In adaptive DBS (aDBS) systems, online tuning of stimulation parameters as a function of neural signals may improve treatment efficacy and reduce side-effects. State-of-the-art aDBS systems use symptom surrogates derived from neural signals-so-called neural markers (NMs)-defined on the patient-group level, and control strategies assuming stationarity of symptoms and NMs. We aim at improving these aDBS systems with (1) a data-driven approach for identifying patient- and session-specific NMs and (2) a control strategy coping with short-term non-stationary dynamics. The two building blocks are implemented as follows: (1) The data-driven NMs are based on a machine learning model estimating tremor intensity from electrocorticographic signals. (2) The control strategy accounts for local variability of tremor statistics. Our study with three chronically implanted ET patients amounted to five online sessions. Tremor quantified from accelerometer data shows that symptom suppression is at least equivalent to that of a continuous DBS strategy in 3 out-of 4 online tests, while considerably reducing net stimulation (at least 24%). In the remaining online test, symptom suppression was not significantly different from either the continuous strategy or the no treatment condition. We introduce a novel aDBS system for ET. It is the first aDBS system based on (1) a machine learning model to identify session-specific NMs, and (2) a control strategy coping with short-term non-stationary dynamics. We show the suitability of our aDBS approach for ET, which opens the door to its further study in a larger patient population.

Identifying controllable cortical neural markers with machine learning for adaptive deep brain stimulation in Parkinson's disease.

The identification of oscillatory neural markers of Parkinson's disease (PD) can contribute not only to the understanding of functional mechanisms of the disorder, but may also serve in adaptive deep brain stimulation (DBS) systems. These systems seek online adaptation of stimulation parameters in closed-loop as a function of neural markers, aiming at improving treatment's efficacy and reducing side effects. Typically, the identification of PD neural markers is based on group-level studies. Due to the heterogeneity of symptoms across patients, however, such group-level neural markers, like the beta band power of the subthalamic nucleus, are not present in every patient or not informative about every patient's motor state. Instead, individual neural markers may be preferable for providing a personalized solution for the adaptation of stimulation parameters. Fortunately, data-driven bottom-up approaches based on machine learning may be utilized. These approaches have been developed and applied successfully in the field of brain-computer interfaces with the goal of providing individuals with means of communication and control. In our contribution, we present results obtained with a novel supervised data-driven identification of neural markers of hand motor performance based on a supervised machine learning model. Data of 16 experimental sessions obtained from seven PD patients undergoing DBS therapy show that the supervised patient-specific neural markers provide improved decoding accuracy of hand motor performance, compared to group-level neural markers reported in the literature. We observed that the individual markers are sensitive to DBS therapy and thus, may represent controllable variables in an adaptive DBS system.

An Easy-to-Use and Fast Assessment of Patient-Specific DBS-Induced Changes in Hand Motor Control in Parkinson's Disease.

For Parkinson's disease (PD), efficient and fast monitoring of fine motor function is fundamental for capturing transient phenomena induced by deep brain stimulation (DBS), thus, enabling a fast and accurate tuning of stimulation parameters. Tuning of DBS parameters is important for obtaining a patient-specific optimal clinical effect and to regularly compensate for disease progress. We propose a fine motor function assessment framework for capturing transient DBS-induced changes. The main goals are to obtain a fast, repeatable, objective, robust, and DBS-sensitive motor-score, in addition to a high-dimensional characterization of motor components by means of an interpretable data-driven model. To achieve this, we combine a hand motor-task, termed the copy-draw test, with a linear model for analyzing features extracted from the proposed task. The approach was tested with four patients totaling eight sessions analyzed. Our approach delivers a motor-score that is sensitive to DBS-induced changes in motor function. It can be applied repeatedly within seconds. The interpretability of the underlying machine learning model provides a direct overview of the feature relevance. This analysis allows to detect and characterize single movement components that are sensitive to DBS. The proposed assessment framework is an useful tool to push forward the data-driven identification of PD-relevant neural markers. Consequent to this end, the source code of the paradigm is made publicly available.

Post-hoc Labeling of Arbitrary M/EEG Recordings for Data-Efficient Evaluation of Neural Decoding Methods.

Many cognitive, sensory and motor processes have correlates in oscillatory neural source activity, which is embedded as a subspace in the recorded brain signals. Decoding such processes from noisy magnetoencephalogram/electroencephalogram (M/EEG) signals usually requires data-driven analysis methods. The objective evaluation of such decoding algorithms on experimental raw signals, however, is a challenge: the amount of available M/EEG data typically is limited, labels can be unreliable, and raw signals often are contaminated with artifacts. To overcome some of these problems, simulation frameworks have been introduced which support the development of data-driven decoding algorithms and their benchmarking. For generating artificial brain signals, however, most of the existing frameworks make strong and partially unrealistic assumptions about brain activity. This limits the generalization of results observed in the simulation to real-world scenarios. In the present contribution, we show how to overcome several shortcomings of existing simulation frameworks. We propose a versatile alternative, which allows for an objective evaluation and benchmarking of novel decoding algorithms using real neural signals. It allows to generate comparatively large datasets with labels being deterministically recoverable from the arbitrary M/EEG recordings. A novel idea to generate these labels is central to this framework: we determine a subspace of the true M/EEG recordings and utilize it to derive novel labels. These labels contain realistic information about the oscillatory activity of some underlying neural sources. For two categories of subspace-defining methods, we showcase how such labels can be obtained-either by an exclusively data-driven approach (independent component analysis-ICA), or by a method exploiting additional anatomical constraints (minimum norm estimates-MNE). We term our framework post-hoc labeling of M/EEG recordings. To support the adoption of the framework by practitioners, we have exemplified its use by benchmarking three standard decoding methods-i.e., common spatial patterns (CSP), source power-comodulation (SPoC), and convolutional neural networks (ConvNets)-wrt. Varied dataset sizes, label noise, and label variability. Source code and data are made available to the reader for facilitating the application of our post-hoc labeling framework.

A simulated environment for early development stages of reinforcement learning algorithms for closed-loop deep brain stimulation.

In recent years, closed-loop adaptive deep brain stimulation (aDBS) for Parkinson's disease (PD) has gained focus in the research community, due to promising proof-of-concept studies showing its suitability for improving DBS therapy and ameliorating related side effects.The main challenges faced in the aDBS control problem is the presence of non-stationary/non-linear dynamics and the heterogeneity of PD's phenotype, making the exploration of data-driven dynamics-aware control algorithms a promising research direction. However, due to the severe safety constraints related to working with patients, aDBS is a sensitive research field that requires surrogate development platforms with growing complexity, as novel control algorithms are validated.With our current contribution, we propose the characterization and categorization of non-stationary dynamics found in the aDBS problem. We show how knowledge about these dynamics can be embedded in a surrogate simulation environment, which has been designed to support early development stages of aDBS control strategies, specifically those based on reinforcement learning (RL) algorithms. Finally, we present a comparison of representative RL methods designed to cope with the type of non-stationary dynamics found in aDBS.To allow reproducibility and encourage adoption of our approach, the source code of the developed methods and simulation environment are made available online.

Characterizing Regularization Techniques for Spatial Filter Optimization in Oscillatory EEG Regression Problems : Guidelines Derived from Simulation and Real-World Data.

We report on novel supervised algorithms for single-trial brain state decoding. Their reliability and robustness are essential to efficiently perform neurotechnological applications in closed-loop. When brain activity is assessed by multichannel recordings, spatial filters computed by the source power comodulation (SPoC) algorithm allow identifying oscillatory subspaces. They regress to a known continuous trial-wise variable reflecting, e.g. stimulus characteristics, cognitive processing or behavior. In small dataset scenarios, this supervised method tends to overfit to its training data as the involved recordings via electroencephalogram (EEG), magnetoencephalogram or local field potentials generally provide a low signal-to-noise ratio. To improve upon this, we propose and characterize three types of regularization techniques for SPoC: approaches using Tikhonov regularization (which requires model selection via cross-validation), combinations of Tikhonov regularization and covariance matrix normalization as well as strategies exploiting analytical covariance matrix shrinkage. All proposed techniques were evaluated both in a novel simulation framework and on real-world data. Based on the simulation findings, we saw our expectations fulfilled, that SPoC regularization generally reveals the largest benefit for small training sets and under severe label noise conditions. Relevant for practitioners, we derived operating ranges of regularization hyperparameters for cross-validation based approaches and offer open source code. Evaluating all methods additionally on real-world data, we observed an improved regression performance mainly for datasets from subjects with initially poor performance. With this proof-of-concept paper, we provided a generalizable regularization framework for SPoC which may serve as a starting point for implementing advanced techniques in the future.

Pre-Trial EEG-Based Single-Trial Motor Performance Prediction to Enhance Neuroergonomics for a Hand Force Task.

We propose a framework for building electrophysiological predictors of single-trial motor performance variations, exemplified for SVIPT, a sequential isometric force control task suitable for hand motor rehabilitation after stroke. Electroencephalogram (EEG) data of 20 subjects with mean age of 53 years was recorded prior to and during 400 trials of SVIPT. They were executed within a single session with the non-dominant left hand, while receiving continuous visual feedback of the produced force trajectories. The behavioral data showed strong trial-by-trial performance variations for five clinically relevant metrics, which accounted for reaction time as well as for the smoothness and precision of the produced force trajectory. 18 out of 20 tested subjects remained after preprocessing and entered offline analysis. Source Power Comodulation (SPoC) was applied on EEG data of a short time interval prior to the start of each SVIPT trial. For 11 subjects, SPoC revealed robust oscillatory EEG subspace components, whose bandpower activity are predictive for the performance of the upcoming trial. Since SPoC may overfit to non-informative subspaces, we propose to apply three selection criteria accounting for the meaningfulness of the features. Across all subjects, the obtained components were spread along the frequency spectrum and showed a variety of spatial activity patterns. Those containing the highest level of predictive information resided in and close to the alpha band. Their spatial patterns resemble topologies reported for visual attention processes as well as those of imagined or executed hand motor tasks. In summary, we identified subject-specific single predictors that explain up to 36% of the performance fluctuations and may serve for enhancing neuroergonomics of motor rehabilitation scenarios.

Solving the EEG inverse problem based on space-time-frequency structured sparsity constraints.

We introduce STOUT (spatio-temporal unifying tomography), a novel method for the source analysis of electroencephalograpic (EEG) recordings, which is based on a physiologically-motivated source representation. Our method assumes that only a small number of brain sources are active throughout a measurement, where each of the sources exhibits focal (smooth but localized) characteristics in space, time and frequency. This structure is enforced through an expansion of the source current density into appropriate spatio-temporal basis functions in combination with sparsity constraints. This approach combines the main strengths of two existing methods, namely Sparse Basis Field Expansions (Haufe et al., 2011) and Time-Frequency Mixed-Norm Estimates (Gramfort et al., 2013). By adjusting the ratio between two regularization terms, STOUT is capable of trading temporal for spatial reconstruction accuracy and vice versa, depending on the requirements of specific analyses and the provided data. Due to allowing for non-stationary source activations, STOUT is particularly suited for the localization of event-related potentials (ERP) and other evoked brain activity. We demonstrate its performance on simulated ERP data for varying signal-to-noise ratios and numbers of active sources. Our analysis of the generators of visual and auditory evoked N200 potentials reveals that the most active sources originate in the temporal and occipital lobes, in line with the literature on sensory processing.

Probing meaningfulness of oscillatory EEG components with bootstrapping, label noise and reduced training sets.

As oscillatory components of the Electroencephalogram (EEG) and other electrophysiological signals may co-modulate in power with a target variable of interest (e.g. reaction time), data-driven supervised methods have been developed to automatically identify such components based on labeled example trials. Under conditions of challenging signal-to-noise ratio, high-dimensional data and small training sets, however, these methods may overfit to meaningless solutions. Examples are spatial filtering methods like Common Spatial Patterns (CSP) and Source Power Comodulation (SPoC). It is difficult for the practitioner to tell apart meaningful from arbitrary, random components. We propose three approaches to probe the robustness of extracted oscillatory components and show their application to both, simulated and EEG data recorded during a visually cued hand motor reaction time task.