Pure agraphia represents a rare neuropsychological syndrome in which writing is selectively impaired while other language modalities remain intact, providing a unique window into the specialized cognitive and neural mechanisms that support written language production. Drawing on the dual-route cognitive model that posits separable lexical and sublexical spelling mechanisms (Patterson, Acquired disorders of spelling, 1988; Rapp and Caramazza, J Exp Psychol: Human Perception and Performance 23:1130-152, 1997; Rapp et al., Cogn Neuropsychology 19:1-29, 2002), whereas network models emphasize distributed interactions, this case offers a multilevel analysis of the deficits observed in pure agraphia due to a focal lesion in Exner's area in the left frontal lobe (Chen et al., Sci Rep 9:55129, 2019; Hickok and Poeppel, Nat Rev Neurosci 8:393-402, 2007; Stevens et al., J Neurosci 37:5288-297, 2017; Vigneau et al. NeuroImage 30:1414-432,2006). Exner's area—located in the posterior portion of the left middle frontal gyrus, immediately anterior to the hand region of the primary motor cortex and anterior and inferior to the left Frontal Eye Field— has been implicated in the interface between linguistic and motor aspects of writing. The patient was a 47-year-old right-handed male with 14 years of formal education and no prior history of language or writing deficits. Four weeks before admission, his wife reported progressive deterioration in writing, characterized by incorrect word selection and spelling errors. Mild drooling from the right corner of the mouth and food retention on the right side of the tongue subsequently appeared. CT and MRI revealed a left frontotemporal mass lesion with partial haemorrhagic transformation confined to Exner’s area in the frontal lobe. Comprehensive neuropsychological and neurolinguistic assessment, including the Aachen Aphasia Test and the Lexicon Model Oriented battery, revealed intact oral language, reading, repetition, copying, and general cognition, in striking contrast to a profound writing impairment. The patient exhibited selective difficulties with irregular words, loanwords, and pseudowords, with writing accuracy declining to 40

INTRODUCTION:Post-stroke depression (PSD) frequently occurs after acute stroke and negatively affects rehabilitation. Dopamine has beneficial effects on motivation and emotional stability. In stroke patients, low dopamine levels are linked to PSD. This study investigated whether levodopa treatment during in-hospital rehabilitation impacts PSD compared to placebo. PATIENTS AND METHODS:ESTREL-Depression was a pre-planned analysis of the multicenter, randomized, double-blind, placebo-controlled ESTREL trial. Participants with an acute ischemic or hemorrhagic stroke were randomly assigned to receive either levodopa/carbidopa (100/25 mg) or placebo three times daily for 39 days. All ESTREL participants with (1) information about the presence or absence of depression at three months and (2) who took at least 80% of the study medication were eligible for the study. Participants with a history of depression were excluded. For the primary outcome, the presence of PSD was defined as having a T-score of ≥55 in the Patient-Reported Outcomes Measurement Information System short-form depression-4a 3 months after randomization. Binary logistic regression was performed to assess the effect of levodopa on PSD. RESULTS:The study included 407 ESTREL participants (median age 72, 60% male), 209 receiving levodopa, and 198 receiving placebo. At 3 months, the frequency and odds of PSD did not differ between the levodopa group (26%) and the placebo group (28%) (OR = 0.93, 95% CI, 0.60-1.43). CONCLUSION:In the ESTREL-Depression study, treatment with levodopa had no impact on the occurrence of PSD. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov: NCT03735901 (https://clinicaltrials.gov/study/NCT03735901).

INTRODUCTION:Levodopa did not enhance early motor recovery at 3 months after stroke in the Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) trial. However, whether levodopa modifies the time course of recovery, leading to a delayed benefit remains unclear. Here, we examined levodopa's effects on the trajectories of motor recovery up to 6 months after stroke. PATIENTS AND METHODS:The ESTREL trial, a double-blind, randomised controlled clinical trial, compared a 39-day regimen of levodopa/carbidopa (100 mg/25 mg, 3×/day) to placebo alongside standardised task-oriented training. We longitudinally analysed Fugl-Meyer Motor Assessment (FMA) total scores (primary outcome), mRS and NIHSS (secondary outcomes) at baseline (0-7 days post stroke), 5 weeks, 3 and 6 months using linear mixed-effects models including timepoint, treatment allocation and their interaction. RESULTS:In total, 576 of 610 (94%) participants (median age 73 years; 40% female) were analysed. FMA scores improved over time in both groups (P < .001), with no overall levodopa effect across visits (estimate 0.65 points, 95% CI, -3.3 to 4.6; P = .75). There was no indication that levodopa modified the recovery trajectory (χ2 = 0.52, df = 3, P = .91), and estimated levodopa-placebo differences in FMA changes across visit intervals were small, ranging from -0.7 to +0.8 points, with confidence intervals crossing zero. Secondary outcomes showed similar longitudinal improvement, without evidence of a treatment effect. CONCLUSION:In this post hoc analysis of ESTREL participants with repeated FMA assessments, motor impairment improved from the first days after stroke up to 6 months. Levodopa added to task-oriented inpatient rehabilitation did not improve motor recovery or alter its trajectory over this period. CLINICAL TRIAL REGISTRATION:NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1.

INTRODUCTION:Post-stroke fatigue (PSF) is common and impacts stroke rehabilitation. Dopaminergic treatment may have beneficial effects on PSF. This study investigated whether levodopa, compared with placebo, was associated with a lower frequency or severity of PSF during in-hospital rehabilitation. PATIENTS AND METHODS:Enhancement of Stroke Rehabilitation with Levodopa (ESTREL)-Fatigue was an exploratory analysis of secondary outcome data obtained in the multicentre, randomised, placebo-controlled ESTREL trial. Participants with acute stroke received levodopa 100 mg/carbidopa 25 mg or placebo 3 times daily for 39 days to enhance motor recovery. Participants who (i) reported fatigue at 5 weeks and who (ii) took at least 80% of the study medication were included in ESTREL-Fatigue. No adjustments for confounding were made. The primary endpoint was the presence of PSF at 5 weeks, defined as a T-score of ≥ 55 on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short-form-4a. As secondary endpoints, T-score cutoffs of ≥ 60 (moderate fatigue) and ≥ 70 (severe fatigue) were used. Binary logistic regression was used to compare PSF at 5 weeks between treatment groups. Results are presented as odds ratios (ORs) with 95% CI. RESULTS:A total of 456 of 505 (90.3%) participants were included (levodopa/placebo 235/221, median age 73 years, 41% female). Post-stroke fatigue at 5 weeks was present in 63/235 (26.8%) levodopa-treated participants and in 65/221 (29.4%) placebo-treated participants (OR: 0.88; 95% CI, 0.58-1.32; risk ratio 0.91; risk difference - 2.6%). For cutoffs of ≥ 60 and ≥ 70, ORs were 0.78 (95% CI, 0.43-1.41) and 0.8 (95% CI, 0.25-2.44), respectively. A sensitivity analysis as per intention-to-treat with all 610 randomised ESTREL participants also showed no significant difference in fatigue presence between levodopa and placebo groups (OR: 0.95; 95% CI, 0.65-1.39) and a sensitivity analysis using a mixed-effects logistic regression showed no evidence of centre-related clustering. CONCLUSION:In ESTREL-Fatigue, levodopa, compared to placebo, was not associated with less PSF during in-hospital rehabilitation.

Robotic devices, in combination with virtual reality games, have the potential to increase therapy dosage while enhancing patient's motivation. Yet, current robotic interventions suffer from poor usability, over-reliance on the availability of trained therapists, and the inability to provide meaningful somatosensory information despite its importance for relearning skillful movements. To address this gap, we co-created two novel haptic rehabilitation robots for in-clinic and in-home rehabilitation capable of high-fidelity haptic rendering during functional reach and grasp training in motivating virtual games together with rehabilitation experts. We evaluated the usability of our solutions with therapists and patients following a mixed-methods approach, gathering quantitative and qualitative data from questionnaires and semi-structured interviews. The results showed good usability and high enjoyment, with the fidelity of virtual object interactions highly praised. Some mechanical design improvements, mainly with regard to comfort, were also identified. Our devices offer naturalistic sensations during training, paving the way for more holistic sensorimotor neurorehabilitation.

The thalamus plays a key role in motor and sensory processes of the brain. Though thalamic stroke is among the less frequent, even a minimal lesion can result in a serious impairment and long-lasting disability. After thalamic stroke, cases of dysexecutive syndrome and so-called diencephalic amnesia have been observed, yet the precise characterisation or categorisation of such amnestic syndrome is not available. Pure amnesia can be the one and only indication of a thalamic lesion. We present a unique case of a patient after left anterolateral thalamic stroke suffering from isolated severe amnesia and disorientation. We conducted extensive neuropsychological testing of the patient’s memory and discovered contrasting results in different aspects of memory. A 75-year-old woman was admitted for neurological rehabilitation two weeks after being diagnosed with acute left anterolateral thalamic ischemic stroke. The initial symptoms with which she presented in the emergency room were acute confusion, disorientation and memory impairment; apart from that, the patient did not have any other neurologic signs. As observed on the MRI, the lesion was restricted mostly to the left anterior nucleus without affecting the mammillothalamic tract. The neuropsychological testing revealed anterograde episodic memory loss with preserved visual recognition and auditive short term memory; inability to freely recall semantic information, spatial and time disorientation, apathy and significantly reduced intrinsic and phasic attention, and immediate and delayed prose recall deficiency. The knowledge that memory impairment and disorientation can be the only symptoms of the stroke is a crucial piece of information, which is needed to be able to make a decision about proper treatment. Abstention from immediate intervention often leads to irreparable memory deficit for the rest of the patient’s life. The results of neuropsychological testing show the essential role of AN in creating episodic memory, in the working memory network and indicate its role as a critical interface between short-term and long-term memory. A theory explaining such a profound impairment of working and anterograde episodic memory has not yet been formulated.

Random noise stimulation (tRNS) applied to the dorsolateral prefrontal cortex (DLPFC) enhances fluency and originality in verbal divergent thinking tasks. However, the underlying neural mechanisms of this behavioral change remain unclear. Given that the DLPFC is a key node of the executive control network (ECN) and that creativity is a two-stage process in which the ECN is primarily involved in the final idea selection stage, application of tRNS to this region shall not only result in an increase of originality and flexibility but also in a modulation of EEG activity. To test these assumptions, we collected 256-channel EEG of 40 participants before and after tRNS/sham applied to the DLPFC, during which participants performed two verbal creativity tasks. To assess stimulation-induced connectivity changes and to capture large-scale cortical communication, a source space alpha (8-12 Hz) imaginary coherence was calculated. We found that the tRNS-induced improvements in originality and flexibility were associated with bilateral DLPFC alpha coherence changes. From a large-scale networks perspective, these results suggest that tRNS-induced ECN activity is associated with increased originality and flexibility, potentially by enhancing selectivity in the idea evaluation phase. This study, for the first time, indicates a link between neurophysiological activity and tRNS-induced changes in verbal creativity.

Levodopa enhances dopaminergic signaling and may stimulate neuroplasticity, which could potentially enhance motor recovery after stroke. Levodopa is used in stroke rehabilitation despite mixed evidence for its effectiveness. To determine whether levodopa compared with placebo, administered in addition to standardized rehabilitation based on active task-oriented training, is associated with enhanced motor recovery in patients with acute stroke. A double-blind, placebo-controlled randomized clinical trial at 13 stroke units and centers and 11 collaborating rehabilitation centers in Switzerland. Between June 14, 2019 (first patient, first visit), and August 27, 2024 (last patient, last visit), 610 patients with acute ischemic or hemorrhagic stroke with clinically meaningful hemiparesis (ie, a total score of ≥3 points on the following National Institutes of Health Stroke Scale items: motor arm, motor leg, or limb ataxia) were randomized 1:1 to receive levodopa or placebo. Statistical analyses were conducted from November 2024 to August 2025. Patients received levodopa/carbidopa (100 mg/25 mg; n = 307) or placebo (n = 303) 3 times daily for 39 days, alongside standardized rehabilitation therapy based on active task-oriented training. The primary outcome was the adjusted mean between-group difference in the Fugl-Meyer Assessment (FMA) total score (range, 0-100 points; fewer points indicate worse motor function; 6-point difference considered patient-relevant) at 3 months. Among the 610 participants (median [IQR] age, 73 [64-82] years; 252 [41.3%] female; median baseline FMA total score, 34 [14-54]), 28 participants died by 3 months, leaving 582 (95.4%) participants eligible for the primary analysis. At 3 months, the median (IQR) FMA total score was 68 (42-85) points in the levodopa group and 64 (44-83) points in the placebo group. The mean difference in the FMA total score between the levodopa and placebo groups was −0.90 points (95% CI, −3.78 to 1.98; P = .54). There were 126 serious adverse events in the levodopa group and 129 in the placebo group; the most common was infection (levodopa, n = 55; placebo, n = 44). In this randomized clinical trial, among patients receiving inpatient rehabilitation for acute stroke, levodopa added to standardized rehabilitation did not significantly improve motor function at 3 months compared with placebo plus standardized rehabilitation. These results do not support the use of levodopa as an adjunct to rehabilitation therapy for enhancing motor recovery after acute stroke. ClinicalTrials.gov Identifier: NCT03735901

Parkinson’s disease (PD) encompasses motor (e.g., bradykinesia) and non-motor (e.g., apathy) symptoms. We aimed to use reflexive and voluntary saccades as a proxy for bradykinesia and apathy. Seventeen PD patients and thirteen controls (matched for age and educational level) were recruited. We assessed apathy using the Dimensional Apathy Scale (DAS) and bradykinesia using MDS-UPDRS III. Subjects were asked to fixate successively two green points (cues, 40° apart) alternating at 1 Hz. After 20 s, all stimuli disappeared, and participants were required to continue fixating on the previous locations of the cues at the same frequency for another 20 s. We measured the Maximal Amplitude (MA) (saccade amplitude from side to side) and its period. Linear mixed models assessed the effect of the group (patient/control), cue, DAS, and bradykinesia score. Overall, the DAS was similarly correlated to the period (p = 0.0157) and the MA (p = 0.0002) in the absence of a cue. However, this correlation was significant only in the patient subgroup for the MA (p = 0.0005). In the absence of cue, bradykinesia was similarly correlated to the period (p = .0001) and the MA (p = 0.0004). However, the period was better correlated to bradykinesia than the DAS. While the saccade period best correlates with bradykinesia, maximal amplitude in the absence of cue better reflects the severity of apathy. Our paradigm may be a promising objective biomarker for assessing bradykinesia and apathy in PD.

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.

BACKGROUND AND PURPOSE:Patients with postural tachycardia syndrome report position-dependent visual symptoms. Despite their impact on daily life, these symptoms have remained largely unexplored in research. The aim of this study was to investigate the nature of visual symptoms in postural tachycardia syndrome and possible underlying pathophysiological mechanisms. METHODS:Fifteen patients with postural tachycardia syndrome and 15 healthy controls were included in the study. Through a comprehensive array of measurements, including haemodynamics, subjective symptom assessments, eye movement tracking and pupil diameter analysis, participants were assessed during free image exploration in both supine and 60° head-up tilt positions. RESULTS:During head-up tilt, patients showed a decreased number and duration of fixations, as well as a decreased number, peak velocity and amplitude of saccades compared to the supine position and the control group. This reduction in visual exploration occurred primarily in the peripheral field of view and coincided with the occurrence of subjective visual symptoms. No significant differences in the saccade main sequence were observed between the two groups in either body position. CONCLUSIONS:Patients with postural tachycardia syndrome have a reduced exploration of the peripheral field of view when in an upright body position, potentially leading to tunnel vision. Since the normality of the saccade main sequence in patients combined with the focus on the centre of the field of view and the lower saccade amplitudes points to an intact brainstem function, the decrease in peripheral visual exploration may be attributed to a position-dependent dysfunction of the frontal eye field.

Topographical disorientation refers to the selective inability to orient oneself in familiar surroundings. However, to date its neural correlates remain poorly understood. Here we use quantitative lesion analysis and a lesion network mapping approach in order to investigate seven patients with topographical disorientation. Our findings link not only the posterior parahippocampal gyrus (PHG) and retrosplenial cortex but also the lingual gyrus, the precuneus and the fusiform gyrus to topographical disorientation. We propose that topographical disorientation is due to the inability to integrate familiar landmarks within a framework of allocentric and egocentric orientation, supported by a neural network including the posterior PHG, the retrosplenial and the lingual cortex.

INTRODUCTION:There is currently a lack of easy-to-use and effective robotic devices for upper-limb rehabilitation after stroke. Importantly, most current systems lack the provision of somatosensory information that is congruent with the virtual training task. This paper introduces a novel haptic robotic system designed for upper-limb rehabilitation, focusing on enhancing sensorimotor rehabilitation through comprehensive haptic rendering. METHODS:We developed a novel haptic rehabilitation device with a unique combination of degrees of freedom that allows the virtual training of functional reach and grasp tasks, where we use a physics engine-based haptic rendering method to render whole-hand interactions between the patients' hands and virtual tangible objects. To evaluate the feasibility of our system, we performed a clinical mixed-method usability study with seven patients and seven therapists working in neurorehabilitation. We employed standardized questionnaires to gather quantitative data and performed semi-structured interviews with all participants to gain qualitative insights into the perceived usability and usefulness of our technological solution. RESULTS:The device demonstrated ease of use and adaptability to various hand sizes without extensive setup. Therapists and patients reported high satisfaction levels, with the system facilitating engaging and meaningful rehabilitation exercises. Participants provided notably positive feedback, particularly emphasizing the system's available degrees of freedom and its haptic rendering capabilities. Therapists expressed confidence in the transferability of sensorimotor skills learned with our system to activities of daily living, although further investigation is needed to confirm this. CONCLUSION:The novel haptic robotic system effectively supports upper-limb rehabilitation post-stroke, offering high-fidelity haptic feedback and engaging training tasks. Its clinical usability, combined with positive feedback from both therapists and patients, underscores its potential to enhance robotic neurorehabilitation.

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.

BackgroundSensory 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.MethodsThis 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).ResultsDuring 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].ConclusionThe 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.

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.

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.

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.

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.

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.