Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial.

RATIONALE: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. AIM AND HYPOTHESIS: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. DESIGN: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. PARTICIPANTS: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. INTERVENTION: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. COMPARISON: Matching placebo plus standardized rehabilitation. OUTCOMES: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. CONCLUSION: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

A Transferable Lidar-Based Method to Conduct Contactless Assessments of Gait Parameters in Diverse Home-like Environments.

Gait abnormalities in older adults are linked to increased risks of falls, institutionalization, and mortality, necessitating accurate and frequent gait assessments beyond traditional clinical settings. Current methods, such as pressure-sensitive walkways, often lack the continuous natural environment monitoring needed to understand an individual's gait fully during their daily activities. To address this gap, we present a Lidar-based method capable of unobtrusively and continuously tracking human leg movements in diverse home-like environments, aiming to match the accuracy of a clinical reference measurement system. We developed a calibration-free step extraction algorithm based on mathematical morphology to realize Lidar-based gait analysis. Clinical gait parameters of 45 healthy individuals were measured using Lidar and reference systems (a pressure-sensitive walkway and a video recording system). Each participant participated in three predefined ambulation experiments by walking over the walkway. We observed linear relationships with strong positive correlations (R2>0.9) between the values of the gait parameters (step and stride length, step and stride time, cadence, and velocity) measured with the Lidar sensors and the pressure-sensitive walkway reference system. Moreover, the lower and upper 95% confidence intervals of all gait parameters were tight. The proposed algorithm can accurately derive gait parameters from Lidar data captured in home-like environments, with a performance not significantly less accurate than clinical reference systems.

Effects of immersive virtual reality on sensory overload in a random sample of critically ill patients.

Background: Sensory overload and sensory deprivation have both been associated with negative health outcomes in critically ill patients. While there is a lack of any clear treatment or prevention strategies, immersive virtual reality is a promising tool for addressing such problems, but which has not been repetitively tested in random samples. Therefore, this study aimed to determine how critically ill patients react to repeated sessions of immersive virtual reality. Methods: This exploratory study was conducted in the mixed medical-surgical intermediate care unit of the University Hospital of Bern (Inselspital). Participants (N = 45; 20 women, 25 men; age = 57.73 ± 15.92 years) received two immersive virtual reality sessions via a head-mounted display and noise-canceling headphones within 24 h during their stay in the unit. Each session lasted 30-min and showed a 360-degree nature landscape. Physiological data were collected as part of the participants' standard care, while environmental awareness, cybersickness, and general acceptance were assessed using a questionnaire designed by our team (1 = not at all, 10 = extremely). Results: During both virtual reality sessions, there was a significant negative linear relationship found between the heart rate and stimulation duration [first session: r(43) = -0.78, p < 0.001; second session: r(38) = -0.81, p < 0.001] and between the blood pressure and stimulation duration [first session: r(39) = -0.78, p < 0.001; second session: r(30) = -0.78, p < 0.001]. The participants had a high comfort score [median (interquartile range {IQR}) = 8 (7, 10); mean = 8.06 ± 2.31], did not report being unwell [median (IQR) = 1 (1, 1); mean = 1.11 ± 0.62], and were not aware of their real-world surroundings [median (IQR) = 1 (1, 5); mean = 2.99 ± 3.22]. Conclusion: The subjectively reported decrease in environmental awareness as well as the decrease in the heart rate and blood pressure over time highlights the ability of immersive virtual reality to help critically ill patients overcome sensory overload and sensory deprivation. Immersive virtual reality can successfully and repetitively be provided to a randomly selected sample of critically ill patients over a prolonged duration.

Creating Custom Immersive 360-Degree Videos for Use in Clinical and Nonclinical Settings: Tutorial.

The use of virtual reality (VR) stimulation in clinical settings has increased in recent years. In particular, there has been increasing interest in the use of VR stimulation for a variety of purposes, including medical training, pain therapy, and relaxation. Unfortunately, there is still a limited amount of real-world 360-degree content that is both available and suitable for these applications. Therefore, this tutorial paper describes a pipeline for the creation of custom VR content. It covers the planning and designing of content; the selection of appropriate equipment; the creation and processing of footage; and the deployment, visualization, and evaluation of the VR experience. This paper aims to provide a set of guidelines, based on first-hand experience, that readers can use to help create their own 360-degree videos. By discussing and elaborating upon the challenges associated with making 360-degree content, this tutorial can help researchers and health care professionals anticipate and avoid common pitfalls during their own content creation process.

Characterization of sound pressure levels and sound sources in the intensive care unit: a 1 week observational study.

Background: Exposure to elevated sound pressure levels within the intensive care unit is known to negatively affect patient and staff health. In the past, interventions to address this problem have been unsuccessful as there is no conclusive evidence on the severity of each sound source and their role on the overall sound pressure levels. Therefore, the goal of the study was to perform a continuous 1 week recording to characterize the sound pressure levels and identify negative sound sources in this setting. Methods: In this prospective, systematic, and quantitative observational study, the sound pressure levels and sound sources were continuously recorded in a mixed medical-surgical intensive care unit over 1 week. Measurements were conducted using four sound level meters and a human observer present in the room noting all sound sources arising from two beds. Results: The mean 8 h sound pressure level was significantly higher during the day (52.01 ± 1.75 dBA) and evening (50.92 ± 1.66 dBA) shifts than during the night shift (47.57 ± 2.23; F(2, 19) = 11.80, p < 0.001). No significant difference was found in the maximum and minimum mean 8 h sound pressure levels between the work shifts. However, there was a significant difference between the two beds in the based on location during the day (F(3, 28) = 3.91, p = 0.0189) and evening (F(3, 24) = 5.66, p = 0.00445) shifts. Cleaning of the patient area, admission and discharge activities, and renal interventions (e.g., dialysis) contributed the most to the overall sound pressure levels, with staff talking occurring most frequently. Conclusion: Our study was able to identify that continuous maintenance of the patient area, patient admission and discharge, and renal interventions were responsible for the greatest contribution to the sound pressure levels. Moreover, while staff talking was not found to significantly contribute to the sound pressure levels, it was found to be the most frequently occurring activity which may indirectly influence patient wellbeing. Overall, identifying these sound sources can have a meaningful impact on patients and staff by identifying targets for future interventions, thus leading to a healthier environment.

An item sorting heuristic to derive equivalent parallel test versions from multivariate items.

Parallel test versions require a comparable degree of difficulty and must capture the same characteristics using different items. This can become challenging when dealing with multivariate items, which are for example very common in language or image data. Here, we propose a heuristic to identify and select similar multivariate items for the generation of equivalent parallel test versions. This heuristic includes: 1. inspection of correlations between variables; 2. identification of outlying items; 3. application of a dimension-reduction method, such as for example principal component analysis (PCA); 4. generation of a biplot, in case of PCA of the first two principal components (PC), and grouping the displayed items; 5. assigning of the items to parallel test versions; and 6. checking the resulting test versions for multivariate equivalence, parallelism, reliability, and internal consistency. To illustrate the proposed heuristic, we applied it exemplarily on the items of a picture naming task. From a pool of 116 items, four parallel test versions were derived, each containing 20 items. We found that our heuristic can help to generate parallel test versions that meet requirements of the classical test theory, while simultaneously taking several variables into account.

Joint impact on attention, alertness and inhibition of lesions at a frontal white matter crossroad.

In everyday life, information from different cognitive domains-such as visuospatial attention, alertness and inhibition-needs to be integrated between different brain regions. Early models suggested that completely segregated brain networks control these three cognitive domains. However, more recent accounts, mainly based on neuroimaging data in healthy participants, indicate that different tasks lead to specific patterns of activation within the same, higher-order and 'multiple-demand' network. If so, then a lesion to critical substrates of this common network should determine a concomitant impairment in all three cognitive domains. The aim of the present study was to critically investigate this hypothesis, i.e. to identify focal stroke lesions within the network that can concomitantly affect visuospatial attention, alertness and inhibition. We studied an unselected sample of 60 first-ever right-hemispheric, subacute stroke patients using a data-driven, bottom-up approach. Patients performed 12 standardized neuropsychological and oculomotor tests, four per cognitive domain. A principal component analysis revealed a strong relationship between all three cognitive domains: 10 of 12 tests loaded on a first, common component. Analysis of the neuroanatomical lesion correlates using different approaches (i.e. voxel-based and tractwise lesion-symptom mapping, disconnectome maps) provided convergent evidence on the association between severe impairment of this common component and lesions at the intersection of superior longitudinal fasciculus II and III, frontal aslant tract and, to a lesser extent, the putamen and inferior fronto-occipital fasciculus. Moreover, patients with a lesion involving this region were significantly more impaired in daily living cognition, which provides an ecological validation of our results. A probabilistic functional atlas of the multiple-demand network was performed to confirm the potential relationship between patients' lesion substrates and observed cognitive impairments as a function of the multiple-demand network connectivity disruption. These findings show, for the first time, that a lesion to a specific white matter crossroad can determine a concurrent breakdown in all three considered cognitive domains. Our results support the multiple-demand network model, proposing that different cognitive operations depend on specific collaborators and their interaction, within the same underlying neural network. Our findings also extend this hypothesis by showing (i) the contribution of superior longitudinal fasciculus and frontal aslant tract to the multiple-demand network; and (ii) a critical neuroanatomical intersection, crossed by a vast amount of long-range white matter tracts, many of which interconnect cortical areas of the multiple-demand network. The vulnerability of this crossroad to stroke has specific cognitive and clinical consequences; this has the potential to influence future rehabilitative approaches.

Naturalistic visualization of reaching movements using head-mounted displays improves movement quality compared to conventional computer screens and proves high usability.

BACKGROUND: The relearning of movements after brain injury can be optimized by providing intensive, meaningful, and motivating training using virtual reality (VR). However, most current solutions use two-dimensional (2D) screens, where patients interact via symbolic representations of their limbs (e.g., a cursor). These 2D screens lack depth cues, potentially deteriorating movement quality and increasing cognitive load. Head-mounted displays (HMDs) have great potential to provide naturalistic movement visualization by incorporating improved depth cues, reduce visuospatial transformations by rendering movements in the space where they are performed, and preserve eye-hand coordination by showing an avatar-with immersive VR (IVR)-or the user's real body-with augmented reality (AR). However, elderly populations might not find these novel technologies usable, hampering potential motor and cognitive benefits. METHODS: We compared movement quality, cognitive load, motivation, and system usability in twenty elderly participants (>59 years old) while performing a dual motor-cognitive task with different visualization technologies: IVR HMD, AR HMD, and a 2D screen. We evaluated participants' self-reported cognitive load, motivation, and usability using questionnaires. We also conducted a pilot study with five brain-injured patients comparing the visualization technologies while using an assistive device. RESULTS: Elderly participants performed straighter, shorter duration, and smoother movements when the task was visualized with the HMDs than screen. The IVR HMD led to shorter duration movements than AR. Movement onsets were shorter with IVR than AR, and shorter for both HMDs than the screen, potentially indicating facilitated reaction times due to reduced cognitive load. No differences were found in the questionnaires regarding cognitive load, motivation, or usability between technologies in elderly participants. Both HMDs proved high usability in our small sample of patients. CONCLUSIONS: HMDs are a promising technology to be incorporated into neurorehabilitation, as their more naturalistic movement visualization improves movement quality compared to conventional screens. HMDs demonstrate high usability, without decreasing participants' motivation, and might potentially lower cognitive load. Our preliminary clinical results suggest that brain-injured patients may especially benefit from more immersive technologies. However, larger patient samples are needed to draw stronger conclusions.*.

Resting-State Functional Networks Correlate with Motor Performance in a Complex Visuomotor Task: An EEG Microstate Pilot Study on Healthy Individuals.

Developing motor and cognitive skills is needed to achieve expert (motor) performance or functional recovery from a neurological condition, e.g., after stroke. While extensive practice plays an essential role in the acquisition of good motor performance, it is still unknown whether certain person-specific traits may predetermine the rate of motor learning. In particular, learners' functional brain organisation might play an important role in appropriately performing motor tasks. In this paper, we aimed to study how two critical cognitive brain networks-the Attention Network (AN) and the Default Mode Network (DMN)-affect the posterior motor performance in a complex visuomotor task: virtual surfing. We hypothesised that the preactivation of the AN would affect how participants divert their attention towards external stimuli, resulting in robust motor performance. Conversely, the excessive involvement of the DMN-linked to internally diverted attention and mind-wandering-would be detrimental for posterior motor performance. We extracted seven widely accepted microstates-representing participants mind states at rest-out of the Electroencephalography (EEG) resting-state recordings of 36 healthy volunteers, prior to execution of the virtual surfing task. By correlating neural biomarkers (microstates) and motor behavioural metrics, we confirmed that the preactivation of the posterior DMN was correlated with poor posterior performance in the motor task. However, we only found a non-significant association between AN preactivation and the posterior motor performance. In this EEG study, we propose the preactivation of the posterior DMN-imaged using EEG microstates-as a neural trait related to poor posterior motor performance. Our findings suggest that the role of the executive control system is to preserve an homeostasis between the AN and the DMN. Therefore, neurofeedback-based downregulation of DMN preactivation could help optimise motor training.

Investigating the role of auditory and visual sensory inputs for inducing relaxation during virtual reality stimulation.

Stress is a part of everyday life which can be counteracted by evoking the relaxation response via nature scenes presented using immersive virtual reality (VR). The aim of this study was to determine which sensory aspect of immersive VR intervention is responsible for the greatest relaxation response. We compared four conditions: auditory and visual combined (audiovisual), auditory only, visual only, and no artificial sensory input. Physiological changes in heart rate, respiration rate, and blood pressure were recorded, while participants reported their preferred condition and awareness of people, noise, and light in the real-world. Over the duration of the stimulation, participants had the lowest heart rate during the audiovisual and visual only conditions. They had the steadiest decrease in respiration rate and the lowest blood pressure during the audiovisual condition, compared to the other conditions, indicating the greatest relaxation. Moreover, ratings of awareness indicated that participants reported being less aware of their surroundings (i.e., people, noise, light, real environment) during the audiovisual condition versus the other conditions (p < 0.001), with a preference for audiovisual inputs. Overall, the use of audiovisual VR stimulation is more effective at inducing a relaxation response compared to no artificial sensory inputs, or the independent inputs.

Design of a Haptic Palmar Device with Thumb Flexion and Circumduction Movements for Sensorimotor Stroke Rehabilitation.

To address the clinical need for high-intensity, repetitive sensorimotor hand training after stroke, we developed in a first step a novel haptic device for practicing finger movements. Because the thumb plays a fundamental role in the loss of autonomy and prehensile functions after stroke, we present here the development of a thumb module that complements our previous design. The novelties of our device are that it reduces the complexity to a minimum from a user perspective while still allowing anatomical thumb flexion/extension and circumduction movements with a highly functional range of motion. Moreover, it enables sensorimotor training thanks to its backlash-free and backdrivable actuation that allows for high-quality haptic rendering. Our device was co-created together with clinicians to incorporate clinical and anatomical requirements, and therefore, maximize its clinical relevance.

A systems approach towards remote health-monitoring in older adults: Introducing a zero-interaction digital exhaust.

Using connected sensing devices to remotely monitor health is a promising way to help transition healthcare from a rather reactive to a more precision medicine oriented proactive approach, which could be particularly relevant in the face of rapid population ageing and the challenges it poses to healthcare systems. Sensor derived digital measures of health, such as digital biomarkers or digital clinical outcome assessments, may be used to monitor health status or the risk of adverse events like falls. Current research around such digital measures has largely focused on exploring the use of few individual measures obtained through mobile devices. However, especially for long-term applications in older adults, this choice of technology may not be ideal and could further add to the digital divide. Moreover, large-scale systems biology approaches, like genomics, have already proven beneficial in precision medicine, making it plausible that the same could also hold for remote-health monitoring. In this context, we introduce and describe a zero-interaction digital exhaust: a set of 1268 digital measures that cover large parts of a person's activity, behavior and physiology. Making this approach more inclusive of older adults, we base this set entirely on contactless, zero-interaction sensing technologies. Applying the resulting digital exhaust to real-world data, we then demonstrate the possibility to create multiple ageing relevant digital clinical outcome assessments. Paired with modern machine learning, we find these assessments to be surprisingly powerful and often on-par with mobile approaches. Lastly, we highlight the possibility to discover novel digital biomarkers based on this large-scale approach.

Brain fog in neuropathic postural tachycardia syndrome may be associated with autonomic hyperarousal and improves after water drinking.

Background: Brain fog is a common and highly disturbing symptom for patients with neuropathic postural tachycardia syndrome (POTS). Cognitive deficits have been measured exclusively in the upright body position and mainly comprised impairments of higher cognitive functions. The cause of brain fog is still unclear today. This study aimed to investigate whether increased autonomic activation might be an underlying mechanism for the occurrence of brain fog in neuropathic POTS. We therefore investigated cognitive function in patients with neuropathic POTS and a healthy control group depending on body position and in relation to catecholamine release as a sensitive indicator of acute stress. The second aim was to test the effect of water intake on cardiovascular regulation, orthostatic symptoms, cognitive function and catecholamine release. Methods: Thirteen patients with neuropathic POTS and 15 healthy control subjects were included. All participants completed a total of four rounds of cognitive testing: two before and two after the intake of 500 ml still water, each first in the supine position and then during head-up tilt. At the end of each cognitive test, a blood sample was collected for determination of plasma catecholamines. After each head-up tilt phase participants were asked to rate their current symptoms on a visual analogue scale. Results: Working memory performance in the upright body position was impaired in patients, which was associated with self-reported symptom severity. Patients had elevated plasma norepinephrine independent of body position and water intake that increased excessively in the upright body position. The excessive increase of plasma norepinephrine was related to heart rate and symptom severity. Water intake in patients decreased norepinephrine concentrations and heart rate, and improved symptoms as well as cognitive performance. Conclusion: Brain fog and symptom severity in neuropathic POTS are paralleled by an excessive norepinephrine secretion. Bolus water drinking down-regulates norepinephrine secretion and improves general symptom severity including brain fog.

Effects of Virtual Reality-Based Multimodal Audio-Tactile Cueing in Patients With Spatial Attention Deficits: Pilot Usability Study.

BACKGROUND: Virtual reality (VR) devices are increasingly being used in medicine and other areas for a broad spectrum of applications. One of the possible applications of VR involves the creation of an environment manipulated in a way that helps patients with disturbances in the spatial allocation of visual attention (so-called hemispatial neglect). One approach to ameliorate neglect is to apply cross-modal cues (ie, cues in sensory modalities other than the visual one, eg, auditory and tactile) to guide visual attention toward the neglected space. So far, no study has investigated the effects of audio-tactile cues in VR on the spatial deployment of visual attention in neglect patients. OBJECTIVE: This pilot study aimed to investigate the feasibility and usability of multimodal (audio-tactile) cueing, as implemented in a 3D VR setting, in patients with neglect, and obtain preliminary results concerning the effects of different types of cues on visual attention allocation compared with noncued conditions. METHODS: Patients were placed in a virtual environment using a head-mounted display (HMD). The inlay of the HMD was equipped to deliver tactile feedback to the forehead. The task was to find and flag appearing birds. The birds could appear at 4 different presentation angles (lateral and paracentral on the left and right sides), and with (auditory, tactile, or audio-tactile cue) or without (no cue) a spatially meaningful cue. The task usability and feasibility, and 2 simple in-task measures (performance and early orientation) were assessed in 12 right-hemispheric stroke patients with neglect (5 with and 7 without additional somatosensory impairment). RESULTS: The new VR setup showed high usability (mean score 10.2, SD 1.85; maximum score 12) and no relevant side effects (mean score 0.833, SD 0.834; maximum score 21). A repeated measures ANOVA on task performance data, with presentation angle, cue type, and group as factors, revealed a significant main effect of cue type (F30,3=9.863; P<.001) and a significant 3-way interaction (F90,9=2.057; P=.04). Post-hoc analyses revealed that among patients without somatosensory impairment, any cue led to better performance compared with no cue, for targets on the left side, and audio-tactile cues did not seem to have additive effects. Among patients with somatosensory impairment, performance was better with both auditory and audio-tactile cueing than with no cue, at every presentation angle; conversely, tactile cueing alone had no significant effect at any presentation angle. Analysis of early orientation data showed that any type of cue triggered better orientation in both groups for lateral presentation angles, possibly reflecting an early alerting effect. CONCLUSIONS: Overall, audio-tactile cueing seems to be a promising method to guide patient attention. For instance, in the future, it could be used as an add-on method that supports attentional orientation during established therapeutic approaches.

Imagined paralysis reduces motor cortex excitability.

Mental imagery is a powerful capability that engages similar neurophysiological processes that underlie real sensory and motor experiences. Previous studies show that motor cortical excitability can increase during mental imagery of actions. In this study, we focused on possible inhibitory effects of mental imagery on motor functions. We assessed whether imagined arm paralysis modulates motor cortical excitability in healthy participants, as measured by motor evoked potentials (MEPs) of the hand induced by near-threshold transcranial magnetic stimulation (TMS) over the primary motor cortex hand area. We found lower MEP amplitudes during imagined arm paralysis when compared to imagined leg paralysis or baseline stimulation without paralysis imagery. These results show that purely imagined bodily constraints can selectively inhibit basic motor corticospinal functions. The results are discussed in the context of motoric embodiment/disembodiment.

Eigenbehaviour as an Indicator of Cognitive Abilities.

With growing use of machine learning algorithms and big data in health applications, digital measures, such as digital biomarkers, have become highly relevant in digital health. In this paper, we focus on one important use case, the long-term continuous monitoring of cognitive ability in older adults. Cognitive ability is a factor both for long-term monitoring of people living alone as well as a relevant outcome in clinical studies. In this work, we propose a new potential digital biomarker for cognitive abilities based on location eigenbehaviour obtained from contactless ambient sensors. Indoor location information obtained from passive infrared sensors is used to build a location matrix covering several weeks of measurement. Based on the eigenvectors of this matrix, the reconstruction error is calculated for various numbers of used eigenvectors. The reconstruction error in turn is used to predict cognitive ability scores collected at baseline, using linear regression. Additionally, classification of normal versus pathological cognition level is performed using a support-vector machine. Prediction performance is strong for high levels of cognitive ability but grows weaker for low levels of cognitive ability. Classification into normal and older adults with mild cognitive impairment, using age and the reconstruction error, shows high discriminative performance with an ROC AUC of 0.94. This is an improvement of 0.08 as compared with a classification with age only. Due to the unobtrusive method of measurement, this potential digital biomarker of cognitive ability can be obtained entirely unobtrusively-it does not impose any patient burden. In conclusion, the usage of the reconstruction error is a strong potential digital biomarker for binary classification and, to a lesser extent, for more detailed prediction of inter-individual differences in cognition.

A Sensor-Driven Visit Detection System in Older Adults' Homes: Towards Digital Late-Life Depression Marker Extraction.

Modern sensor technology is increasingly used in older adults to not only provide additional safety but also to monitor health status, often by means of sensor derived digital measures or biomarkers. Social isolation is a known risk factor for late-life depression, and a potential component of social-isolation is the lack of home visits. Therefore, home visits may serve as a digital measure for social isolation and late-life depression. Late-life depression is a common mental and emotional disorder in the growing population of older adults. The disorder, if untreated, can significantly decrease quality of life and, amongst other effects, leads to increased mortality. Late-life depression often goes undiagnosed due to associated stigma and the incorrect assumption that it is a normal part of ageing. In this work, we propose a visit detection system that generalizes well to previously unseen apartments - which may differ largely in layout, sensor placement, and size from apartments found in the semi-annotated training dataset. We find that by using a self-training-based domain adaptation strategy, a robust system to extract home visit information can be built (ROC AUC = 0.773). We further show that the resulting visit information correlates well with the common geriatric depression scale screening tool ( ρ = -0.87, p = 0.001), providing further support for the idea of utilizing the extracted information as a potential digital measure or even as a digital biomarker to monitor the risk of late-life depression.

Face Perception and Pareidolia Production in Patients With Parkinson's Disease.

In Parkinson's disease (PD) patients, visual misperceptions are a major problem within the non-motor symptoms. Pareidolia, i.e., the tendency to perceive a specific, meaningful image in an ambiguous visual pattern, is a phenomenon that occurs also in healthy subjects. Literature suggests that the perception of face pareidolia may be increased in patients with neurodegenerative diseases. We aimed to examine, within the same experiment, face perception and the production of face pareidolia in PD patients and healthy controls (HC). Thirty participants (15 PD patients and 15 HC) were presented with 47 naturalistic photographs in which faces were embedded or not. The likelihood to perceive the embedded faces was modified by manipulating their transparency. Participants were asked to decide for each photograph whether a face was embedded or not. We found that PD patients were significantly less likely to recognize embedded faces than controls. However, PD patients also perceived faces significantly more often in locations where none were actually present than controls. Linear regression analyses showed that gender, age, hallucinations, and Multiple-Choice Vocabulary Intelligence Test (MWT) score were significant predictors of face pareidolia production in PD patients. Montreal Cognitive Assessment (MoCA) was a significant predictor for pareidolia production in PD patients in trials in which a face was embedded in another region [F (1, 13) = 24.4, p = <0.001]. We conclude that our new embedded faces paradigm is a useful tool to distinguish face perception performance between HC and PD patients. Furthermore, we speculate that our results observed in PD patients rely on disturbed interactions between the Dorsal (DAN) and Ventral Attention Networks (VAN). In photographs in which a face is present, the VAN may detect this as a behaviourally relevant stimulus. However, due to the deficient communication with the DAN in PD patients, the DAN would not direct attention to the correct location, identifying a face at a location where actually none is present.

Behavioral Differences Across Theta Burst Stimulation Protocols. A Study on the Sense of Agency in Healthy Humans.

BACKGROUND: Theta burst stimulation (TBS) is a non-invasive brain stimulation method. Various stimulation protocols have been proposed, for instance, stimulation at 50 Hz with pattern at 5 Hz, or at 30 Hz with pattern at 6 Hz. To identify better stimulation parameters for behavioral applications, we investigated the effects of 50-Hz continuous TBS (cTBS) on the sense of agency (SoA), and compared them with a previously published study with 30-Hz cTBS. METHODS: Based on power analysis from a previous sample using two applications of 30-Hz cTBS, we recruited 20 healthy subjects in a single-blind, Vertex-controlled, randomized, crossover trial. Participants were stimulated with one application of 50-Hz cTBS over the right posterior parietal cortex (rPPC), a key area for agency processing, and the vertex, in a random order. A behavioral task targeting the SoA was done before and after stimulation. After controlling for baseline differences across samples, we studied the effect of stimulation in the two protocols separately. RESULTS: Compared to the previously published 30-Hz protocol, 50-Hz cTBS over the rPPC did not reveal significant changes in the SoA, similar to sham Vertex stimulation. CONCLUSION: One application of 50-Hz cTBS was not sufficient to elicit behavioral effects, compared to two applications of 30-Hz cTBS, as previously described. This may be due to a mechanism of synaptic plasticity, consolidated through consecutive stimulation cycles. Our results are relevant for future studies aiming at modulating activity of the rPPC in cognitive domains other than agency, and in patients affected by abnormal agency, who could benefit from treatment options based on TBS.

Spatial asymmetries ("pseudoneglect") in free visual exploration-modulation of age and relationship to line bisection.

When humans visually explore an image, they typically tend to start exploring its left side. This phenomenon, so-called pseudoneglect, is well known, but its time-course has only sparsely been studied. Furthermore, it is unclear whether age influences pseudoneglect, and the relationship between visuo-spatial attentional asymmetries in a free visual exploration task and a classical line bisection task has not been established. To address these questions, 60 healthy participants, aged between 22 and 86, were assessed by means of a free visual exploration task with a series of naturalistic, colour photographs of everyday scenes, while their gaze was recorded by means of a contact-free eye-tracking system. Furthermore, a classical line bisection task was administered, and information concerning handedness and subjective alertness during the experiment was obtained. The results revealed a time-sensitive window during visual exploration, between 260 and 960 ms, in which age was a significant predictor of the leftward bias in gaze position, i.e., of pseudoneglect. Moreover, pseudoneglect as assessed by the line bisection task correlated with the average gaze position throughout a time-window of 300-1490 ms during the visual exploration task. These results suggest that age influences visual exploration and pseudoneglect in a time-sensitive fashion, and that the degree of pseudoneglect in the line bisection task correlates with the average gaze position during visual exploration in a time-sensitive manner.