Deep brain stimulation (DBS) is an invasive treatment option for patients with Parkinson's disease. Recently, adaptive DBS (aDBS) systems have been developed, which adjust stimulation timing and amplitude in real-time. However, it is unknown how changes in parameters, movement states and the controllability of subthalamic beta activity affect aDBS performance. To characterize how parameter choice, movement state and controllability interactively affect the electrophysiological and behavioral response to single threshold aDBS. We recorded subthalamic local field potentials in 12 patients with Parkinson's disease receiving single threshold aDBS in the acute post-operative state. We investigated changes in two aDBS parameters: the onset time and the smoothing of real-time beta power. Electrophysiological patterns and motor performance were assessed while patients were at rest and during a simple motor task. We further studied the impact of controllability on aDBS performance by comparing patients with and without beta power modulation during continuous stimulation. Our findings reveal that changes in the onset time control the extent of beta power suppression achievable with single threshold adaptive stimulation during rest. Behavioral data indicate that only specific parameter combinations yield a beneficial effect of single threshold aDBS. During movement, action induced beta power suppression reduces the responsivity of the closed loop algorithm. We further demonstrate that controllability of beta power is a prerequisite for effective parameter dependent modulation of subthalamic beta activity. Our results highlight the interaction between single threshold aDBS parameter selection, movement state and controllability in driving subthalamic beta activity and motor performance. By this means, we identify directions for the further development of closed-loop DBS algorithms.

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.

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.

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.

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.

Accurate real-life monitoring of motor and non-motor symptoms is a challenge in Parkinson’s disease (PD). The unobtrusive capturing of symptoms and their naturalistic fluctuations within or between days can improve evaluation and titration of therapy. First-generation commercial PD motion sensors are promising to augment clinical decision-making in general neurological consultation, but concerns remain regarding their short-term validity, and long-term real-life usability. In addition, tools monitoring real-life subjective experiences of motor and non-motor symptoms are lacking. The dataset presented in this paper constitutes a combination of objective kinematic data and subjective experiential data, recorded parallel to each other in a naturalistic, long-term real-life setting. The objective data consists of accelerometer and gyroscope data, and the subjective data consists of data from ecological momentary assessments. Twenty PD patients were monitored without daily life restrictions for fourteen consecutive days. The two types of data can be used to address hypotheses on naturalistic motor and/or non-motor symptomatology in PD.