Home-based monitoring of persons with advanced Parkinson's disease using smartwatch-smartphone technology.

Movement deterioration is the hallmark of Parkinson's disease (PD), characterized by levodopa-induced motor-fluctuations (i.e., symptoms' variability related to the medication cycle) in advanced stages. However, motor symptoms are typically too sporadically and/or subjectively assessed, ultimately preventing the effective monitoring of their progression, and thus leading to suboptimal treatment/therapeutic choices. Smartwatches (SW) enable a quantitative-oriented approach to motor-symptoms evaluation, namely home-based monitoring (HBM) using an embedded inertial measurement unit. Studies validated such approach against in-clinic evaluations. In this work, we aimed at delineating personalized motor-fluctuations' profiles, thus capturing individual differences. 21 advanced PD patients with motor fluctuations were monitored for 2 weeks using a SW and a smartphone-dedicated app (Intel Pharma Analytics Platform). The SW continuously collected passive data (tremor, dyskinesia, level of activity using dedicated algorithms) and active data, i.e., time-up-and-go, finger tapping, hand tremor and hand rotation carried out daily, once in OFF and once in ON levodopa periods. We observed overall high compliance with the protocol. Furthermore, we observed striking differences among the individual patterns of symptoms' levodopa-related variations across the HBM, allowing to divide our participants among four data-driven, motor-fluctuations' profiles. This highlights the potential of HBM using SW technology for revolutionizing clinical practices.

Using virtual reality-based neurocognitive testing and eye tracking to study naturalistic cognitive-motor performance.

Natural human behavior arises from continuous interactions between the cognitive and motor domains. However, assessments of cognitive abilities are typically conducted using pen and paper tests, i.e., in isolation from "real life" cognitive-motor behavior and in artificial contexts. In the current study, we aimed to assess cognitive-motor task performance in a more naturalistic setting while recording multiple motor and eye tracking signals. Specifically, we aimed to (i) delineate the contribution of cognitive and motor components to overall task performance and (ii) probe for a link between cognitive-motor performance and pupil size. To that end, we used a virtual reality (VR) adaptation of a well-established neurocognitive test for executive functions, the 'Color Trails Test' (CTT). The VR-CTT involves performing 3D reaching movements to follow a trail of numbered targets. To tease apart the cognitive and motor components of task performance, we included two additional conditions: a condition where participants only used their eyes to perform the CTT task (using an eye tracking device), incurring reduced motor demands, and a condition where participants manually tracked visually-cued targets without numbers on them, incurring reduced cognitive demands. Our results from a group of 30 older adults (>65) showed that reducing cognitive demands shortened completion times more extensively than reducing motor demands. Conditions with higher cognitive demands had longer target search time, as well as decreased movement execution velocity and head-hand coordination. We found larger pupil sizes in the more cognitively demanding conditions, and an inverse correlation between pupil size and completion times across individuals in all task conditions. Lastly, we found a possible link between VR-CTT performance measures and clinical signatures of participants (fallers versus non-fallers). In summary, performance and pupil parameters were mainly dependent on task cognitive load, while maintaining systematic interindividual differences. We suggest that this paradigm opens the possibility for more detailed profiling of individual cognitive-motor performance capabilities in older adults and other at-risk populations.

Developing multiple shortened forms of virtual reality-based color trails test.

The Color Trails Test (CTT) is a pencil-and-paper (P&P) neuropsychological test. The CTT is divided into two parts that assess sustained visual attention (Trails A) and divided attention (Trails B). The CTT can also be performed in a virtual reality setting (VR-CTT) introducing a wider spatial range of targets. In cases of multiple assessments, repeating the same CTT configuration can bias the results due to fatigue and learning effects. The aim of this study is to create five different short versions of the VR-CTT. The different forms were created by rotating or flipping the original targets spatial layout on one of the axes and by ending it at ball #13. Healthy young participants (N = 15) performed the shortened VR-CTT forms (in a counterbalanced order), the P&P CTT and the original VR-CTT. We found no difference between the completion times of the five forms (p > 0.2), and a significant difference between Trails A and B across all forms (p < 0.04). Additionally, there was no evidence of a learning effect between trials (p > 0.4). Moreover, the shortened VR-CTT forms showed correlations with the P&P CTT (p < 0.05) and with the original VR-CTT (p < 0.06). These findings suggest that all five forms have an equal level of difficulty and that the different forms managed to mitigate the learning effects reported for repeated testing of the same spatial layout. This opens the possibility of applying the shortened VR-CTT forms for research settings and sets the basis for developing it into a clinical diagnostics tool.

Bilateral leg stepping coherence as a predictor of freezing of gait in patients with Parkinson's Disease walking with wearable sensors.

Freezing of Gait (FOG) is among the most debilitating symptoms of Parkinson's Disease (PD), characterized by a sudden inability to generate effective stepping. In preparation for the development of a real-time FOG prediction and intervention device, this work presents a novel FOG prediction algorithm based on detection of altered interlimb coordination of the legs, as measured using two inertial movement sensors and analyzed using a wavelet coherence algorithm. METHODS: Fourteen participants with PD (in OFF state) were asked to walk in challenging conditions (e.g. with turning, dual-task walking, etc.) while wearing inertial motion sensors (waist, 2 shanks) and being videotaped. Occasionally, participants were asked to voluntarily stop (VOL). FOG and VOL events were identified by trained researchers based on videos. Wavelet analysis was performed on shank sagittal velocity signals and a synchronization loss threshold (SLT) was defined and compared between FOG and VOL. A proof-of-concept analysis was performed for a subset of the data to obtain preliminary classification characteristics of the novel measure. RESULTS: 128 FOG and 42 VOL episodes were analyzed. SLT occurred earlier for FOG (MED=1.81 sec prior to stop, IQR=1.57) than for VOL events (MED=0.22 sec, IQR=0.76) (Z=-4.3, p<0.001, ES=1.15). These time differences were not related with measures of disease severity. Preliminary results demonstrate sensitivity of 98%, specificity of 42% (mostly due to 'turns' detection) and balanced accuracy of 70% for SLT-based prediction, with good differentiation between FOG and VOL. CONCLUSIONS: Wavelet analysis provides a relatively simple, promising approach for prediction of FOG in people with PD.