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BackgroundSmartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem. ObjectiveThis analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS). MethodsThe proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated. ResultsA total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely. ConclusionsReported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials.

Significant advancements have been achieved in delineating the progress of the Global PROMS (PROMS) Initiative. The PROMS Initiative, a collaborative endeavor by the European Charcot Foundation and the Multiple Sclerosis International Federation, strives to amplify the influence of patient input on MS care and establish a cohesive perspective on Patient-Reported Outcomes (PROs) for diverse stakeholders. This initiative has established an expansive, participatory governance framework launching four dedicated working groups that have made substantive contributions to research, clinical management, eHealth, and healthcare system reform. The initiative prioritizes the global integration of patient (For the purposes of the Global PROMS Initiative, the term “patient” refers to the people with the disease (aka People with Multiple Sclerosis – pwMS): any individual with lived experience of the disease. People affected by the disease/Multiple Sclerosis: any individual or group that is affected by the disease: E.g., family members, caregivers will be also engaged as the other stakeholders in the initiative). insights into the management of MS care. It merges subjective PROs with objective clinical metrics, thereby addressing the complex variability of disease presentation and progression. Following the completion of its second phase, the initiative aims to help increasing the uptake of eHealth tools and passive PROs within research and clinical settings, affirming its unwavering dedication to the progressive refinement of MS care. Looking forward, the initiative is poised to continue enhancing global surveys, rethinking to the relevant statistical approaches in clinical trials, and cultivating a unified stance among ‘industry’, regulatory bodies and health policy making regarding the application of PROs in MS healthcare strategies.

Abstract Objective To compare the efficacy of Dextrain Manipulandum™ training of dexterity components such as force control and independent finger movements, to dose-matched conventional therapy (CT) post-stroke. Methods A prospective, single-blind, pilot randomized clinical trial was conducted. Chronic-phase post-stroke patients with mild-to-moderate dexterity impairment (Box and Block Test (BBT) > 1) received 12 sessions of Dextrain or CT. Blinded measures were obtained before and after training and at 3-months follow-up. Primary outcome was BBT-change (after–before training). Secondary outcomes included changes in motor impairments, activity limitations and dexterity components. Corticospinal excitability and short intracortical inhibition (SICI) were measured using transcranial magnetic stimulation. Results BBT-change after training did not differ between the Dextrain (N = 21) vs CT group (N = 21) (median [IQR] = 5[2–7] vs 4[2–7], respectively; P = 0.36). Gains in BBT were maintained at the 3-month post-training follow-up, with a non-significant trend for enhanced BBT-change in the Dextrain group (median [IQR] = 3[− 1–7.0], P = 0.06). Several secondary outcomes showed significantly larger changes in the Dextrain group: finger tracking precision (mean ± SD = 0.3 ± 0.3N vs − 0.1 ± 0.33N; P

BackgroundWe performed a pilot study on whether tablet-based measures of manual dexterity can provide behavioral markers for detection of first-episode psychosis (FEP), and whether cortical excitability/inhibition was altered in FEP.MethodsBehavioral and neurophysiological testing was undertaken in persons diagnosed with FEP (N = 20), schizophrenia (SCZ, N = 20), autism spectrum disorder (ASD, N = 20), and in healthy control subjects (N = 20). Five tablet tasks assessed different motor and cognitive functions: Finger Recognition for effector (finger) selection and mental rotation, Rhythm Tapping for temporal control, Sequence Tapping for control/memorization of motor sequences, Multi Finger Tapping for finger individuation, and Line Tracking for visuomotor control. Discrimination of FEP (from other groups) based on tablet-based measures was compared to discrimination through clinical neurological soft signs (NSS). Cortical excitability/inhibition, and cerebellar brain inhibition were assessed with transcranial magnetic stimulation.ResultsCompared to controls, FEP patients showed slower reaction times and higher errors in Finger Recognition, and more variability in Rhythm Tapping. Variability in Rhythm Tapping showed highest specificity for the identification of FEP patients compared to all other groups (FEP vs. ASD/SCZ/Controls; 75% sensitivity, 90% specificity, AUC = 0.83) compared to clinical NSS (95% sensitivity, 22% specificity, AUC = 0.49). Random Forest analysis confirmed FEP discrimination vs. other groups based on dexterity variables (100% sensitivity, 85% specificity, balanced accuracy = 92%). The FEP group had reduced short-latency intra-cortical inhibition (but similar excitability) compared to controls, SCZ, and ASD. Cerebellar inhibition showed a non-significant tendency to be weaker in FEP.ConclusionFEP patients show a distinctive pattern of dexterity impairments and weaker cortical inhibition. Easy-to-use tablet-based measures of manual dexterity capture neurological deficits in FEP and are promising markers for detection of FEP in clinical practice.

Objective: Quantification of lower limb spasticity after stroke and the differentiation of neural from passive muscle resistance remain key clinical challenges. The aim of this study was to validate the novel NeuroFlexor foot module, to assess the intrarater reliability of measurements and to identify normative cut-off values. Methods: Fifteen patients with chronic stroke with clinical history of spasticity and 18 healthy subjects were examined with the NeuroFlexor foot module at controlled velocities. Elastic, viscous and neural components of passive dorsiflexion resistance were quantified (in Newton, N). The neural component, reflecting stretch reflex mediated resistance, was validated against electromyography activity. A test-retest design with a 2-way random effects model permitted study of intra-rater reliability. Finally, data from 73 healthy subjects were used to establish cutoff values according to mean + 3 standard deviations and receiver operating characteristic curve analysis. Results: The neural component was higher in stroke patients, increased with stretch velocity and correlated with electromyography amplitude. Reliability was high for the neural component (intraclass correlation coefficient model 2.1 (ICC2,1) ≥ 0.903) and good for the elastic component (ICC2,1 ≥ 0.898). Cutoff values were identified, and all patients with neural component above the limit presented pathological electromyography amplitude (area under the curve (AUC) = 1.00, sensitivity = 100%, specificity = 100%). Conclusion: The NeuroFlexor may offer a clinically feasible and non-invasive way to objectively quantify lower limb spasticity. LAY ABSTRACT Spasticity is a sensorimotor impairment, which often occurs after stroke as well as after other injuries to the central nervous system. Spasticity is characterized by increased resistance to passive stretch of weak muscles due to increased reflex activity. Spasticity is currently measured clinically while the examiner passively stretches a muscle. However, the clinical method cannot differentiate resistance due to increased reflex activity from resistance due to muscle stiffness, which can develop over time in weakened muscles. The aim of this study was to evaluate the novel NeuroFlexor foot module, which was developed to quantify and distinguish nerve and muscle components of resistance during passive stretching of the lower limb muscles. By quantifying these factors, one can obtain more reliable information than the clinical examination allows. NeuroFlexor measurements in 15 patients in the chronic stage after stroke and 18 healthy individuals allowed the validity of the method to be evaluated by assessing the relationship with velocity of stretch and by simultaneously examining the reflex activity using surface electromyography. The reliability of NeuroFlexor measurements was studied by comparing repeated measurements. Finally, the study established normal NeuroFlexor values from 73 healthy individuals. The results suggest that the NeuroFlexor foot module may be a valid, reliable and easy-to-use objective method to quantify lower limb spasticity.

Abstract Background We developed five tablet-based tasks (applications) to measure multiple components of manual dexterity. Aim: to test reliability and validity of tablet-based dexterity measures in healthy participants. Methods Tasks included: (1) Finger recognition to assess mental rotation capacity. The subject taps with the finger indicated on a virtual hand in three orientations (reaction time, correct trials). (2) Rhythm tapping to evaluate timing of finger movements performed with, and subsequently without, an auditory cue (inter-stimulus interval). (3) Multi-finger tapping to assess independent finger movements (reaction time, correct trials, unwanted finger movements). (4) Sequence tapping to assess production and memorization of visually cued finger sequences (successful taps). (5) Line-tracking to assess movement speed and accuracy while tracking an unpredictably moving line on the screen with the fingertip (duration, error). To study inter-rater reliability, 34 healthy subjects (mean age 35 years) performed the tablet tasks twice with two raters. Relative reliability (Intra-class correlation, ICC) and absolute reliability (Standard error of measurement, SEM) were established. Task validity was evaluated in 54 healthy subjects (mean age 49 years, range: 20–78 years) by correlating tablet measures with age, clinical dexterity assessments (time taken to pick-up objects in Box and Block Test, BBT and Moberg Pick Up Test, MPUT) and with measures obtained using a finger force-sensor device. Results Most timing measures showed excellent reliability. Poor to excellent reliability was found for correct trials across tasks, and reliability was poor for unwanted movements. Inter-session learning occurred in some measures. Age correlated with slower and more variable reaction times in finger recognition, less correct trials in multi-finger tapping, and slower line-tracking. Reaction times correlated with those obtained using a finger force-sensor device. No significant correlations between tablet measures and BBT or MPUT were found. Inter-task correlation among tablet-derived measures was weak. Conclusions Most tablet-based dexterity measures showed good-to-excellent reliability (ICC ≥ 0.60) except for unwanted movements during multi-finger tapping. Age-related decline in performance and association with finger force-sensor measures support validity of tablet measures. Tablet-based components of dexterity complement conventional clinical dexterity assessments. Future work is required to establish measurement properties in patients with neurological and psychiatric disorders.

Background: Neural information processing is subject to noise and this leads to variability in neural firing and behavior. Schizophrenia has been associated with both more variable motor control and impaired cortical inhibition, which is crucial for excitatory/inhibitory balance in neural commands. Hypothesis: In this study, we hypothesized that impaired intracortical inhibition in motor cortex would contribute to task-related motor noise in schizophrenia. Methods: We measured variability of force and of electromyographic (EMG) activity in upper limb and hand muscles during a visuomotor grip force-tracking paradigm in patients with schizophrenia (N = 25), in unaffected siblings (N = 17) and in healthy control participants (N = 25). Task-dependent primary motor cortex (M1) excitability and inhibition were assessed using transcranial magnetic stimulation (TMS). Results: During force maintenance patients with schizophrenia showed increased variability in force and EMG, despite similar mean force and EMG magnitudes. Compared to healthy controls, patients with schizophrenia also showed increased M1 excitability and reduced cortical inhibition during grip-force tracking. EMG variability and force variability correlated negatively to cortical inhibition in patients with schizophrenia. EMG variability also correlated positively to negative symptoms. Siblings had similar variability and cortical inhibition compared to controls. Increased EMG and force variability indicate enhanced motor noise in schizophrenia, which relates to reduced motor cortex inhibition. Conclusion: The findings suggest that excessive motor noise in schizophrenia may arise from an imbalance of M1 excitation/inhibition of GABAergic origin. Thus, higher motor noise may provide a useful marker of impaired cortical inhibition in schizophrenia.

Background: The EXOPULSE Mollii method is an innovative full-body suit approach for non-invasive electrical stimulation, primarily designed to reduce disabling spasticity and improve motor function through the mechanism of reciprocal inhibition. This study aimed to evaluate the effectiveness of one session of stimulation with the EXOPULSE Mollii suit at different stimulation frequencies on objective signs of spasticity and clinical measures, and the subjective perceptions of the intervention.Methods: Twenty patients in the chronic phase after stroke were enrolled in a cross-over, double-blind controlled study. Electrical stimulation delivered through EXOPULSE Mollii was applied for 60 min at two active frequencies (20 and 30 Hz) and in OFF-settings (placebo) in a randomized order, every second day. Spasticity was assessed with controlled-velocity passive muscle stretches using the NeuroFlexor hand and foot modules. Surface electromyography (EMG) for characterizing flexor carpi radialis, medial gastrocnemius, and soleus muscles activation, Modified Ashworth Scale and range of motion were used as complementary tests. Finally, a questionnaire was used to assess the participants' perceptions of using the EXOPULSE Mollii suit.Results: At group level, analyses showed no significant effect of stimulation at any frequency on NeuroFlexor neural component (NC) and EMG amplitude in the upper or lower extremities (p > 0.35). Nevertheless, the effect was highly variable at the individual level, with eight patients exhibiting reduced NC (>1 N) in the upper extremity after stimulation at 30 Hz, 5 at 20 Hz and 3 in OFF settings. All these patients presented severe spasticity at baseline, i.e., NC > 8 N. Modified Ashworth ratings of spasticity and range of motion did not change significantly after stimulation at any frequency. Finally, 75% of participants reported an overall feeling of well-being during stimulation, with 25% patients describing a muscle-relaxing effect on the affected hand and/or foot at both 20 and 30 Hz.Conclusions: The 60 min of electrical stimulation with EXOPULSE Mollii suit did not reduce spasticity consistently in the upper and lower extremities in the chronic phase after stroke. Findings suggest a need for further studies in patients with severe spasticity after stroke including repeated stimulation sessions.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04076878, identifier: NCT04076878.

Impaired manual dexterity is commonly observed in schizophrenia. However, a quantitative description of key sensorimotor components contributing to impaired dexterity is lacking. Whether the key components of dexterity are differentially affected and how they relate to clinical characteristics also remains unclear. We quantified the degree of dexterity in 35 stabilized patients with schizophrenia and in 20 age-matched control subjects using four visuomotor tasks: (i) force tracking to quantify visuomotor precision, (ii) sequential finger tapping to measure motor sequence recall, (iii) single-finger tapping to assess temporal regularity, and (iv) multi-finger tapping to measure independence of finger movements. Diverse clinical and neuropsychological tests were also applied. A patient subgroup (N = 15) participated in a 14-week cognitive remediation protocol and was assessed before and after remediation. Compared to control subjects, patients with schizophrenia showed greater error in force tracking, poorer recall of tapping sequences, decreased tapping regularity, and reduced degree of finger individuation. A composite performance measure discriminated patients from controls with sensitivity = 0.79 and specificity = 0.9. Aside from force-tracking error, no other dexterity components correlated with antipsychotic medication. In patients, some dexterity components correlated with neurological soft signs, Positive and Negative Syndrome Scale (PANSS), or neuropsychological scores. This suggests differential cognitive contributions to these components. Cognitive remediation lead to significant improvement in PANSS, tracking error, and sequence recall (without change in medication). These findings show that multiple aspects of sensorimotor control contribute to impaired manual dexterity in schizophrenia. Only visuomotor precision was related to antipsychotic medication. Good diagnostic accuracy and responsiveness to treatment suggest that manual dexterity may represent a useful clinical marker in schizophrenia.

BACKGROUND:Focal dystonia has been associated with deficient processing of sense of effort cues. However, corresponding studies are lacking in cervical dystonia (CD). We hypothesized that dystonic muscle activity would perturb neck force control based on sense of effort cues. METHODS:Neck extension force control was investigated in 18 CD patients with different clinical features (7 with and 11 without retrocollis) and in 19 control subjects. Subjects performed force-matching and force-maintaining tasks at 5% and 20% of maximum voluntary contraction (MVC). Three task conditions were tested: i) with visual force feedback, ii) without visual feedback (requiring use of sense of effort), iii) without visual feedback, but with neck extensor muscle vibration (modifying muscle afferent cues). Trapezius muscle activity was recorded using electromyography (EMG). RESULTS:CD patients did not differ in task performance from healthy subjects when using visual feedback (ANOVA, p>0.7). In contrast, when relying on sense of effort cues (without visual feedback, 5% MVC), force control was impaired in patients without retrocollis (p = 0.006), but not in patients with retrocollis (p>0.2). Compared to controls, muscle vibration without visual feedback significantly affected performance in patients with retrocollis (p

Manual dexterity measures can be useful for early detection of age-related functional decline and for prediction of cognitive decline. However, what aspects of sensorimotor function to assess remains unclear. Manual dexterity markers should be able to separate impairments related to cognitive decline from those related to healthy aging. In this pilot study, we aimed to compare manual dexterity components in patients diagnosed with cognitive decline (mean age: 84 years, N = 11) and in age comparable cognitively intact elderly subjects (mean age: 78 years, N = 11). In order to separate impairments due to healthy aging from deficits due to cognitive decline we also included two groups of healthy young adults (mean age: 26 years, N = 10) and middle-aged adults (mean age: 41 years, N = 8). A comprehensive quantitative evaluation of manual dexterity was performed using three tasks: (i) visuomotor force tracking, (ii) isochronous single finger tapping with auditory cues, and (iii) visuomotor multi-finger tapping. Results showed a highly significant increase in force tracking error with increasing age. Subjects with cognitive decline had increased finger tapping variability and reduced ability to select the correct tapping fingers in the multi-finger tapping task compared to cognitively intact elderly subjects. Cognitively intact elderly subjects and those with cognitive decline had prolonged force release and reduced independence of finger movements compared to young adults and middle-aged adults. The findings suggest two different patterns of impaired manual dexterity: one related to cognitive decline and another related to healthy aging. Manual dexterity tasks requiring updating of performance, in accordance with (temporal or spatial) task rules maintained in short-term memory, are particularly affected in cognitive decline. Conversely, tasks requiring online matching of motor output to sensory cues were affected by age, not by cognitive status. Remarkably, no motor impairments were detected in patients with cognitive decline using clinical scales of hand function. The findings may have consequences for the development of manual dexterity markers of cognitive decline.