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BACKGROUND Being a parent can be demanding and stressful, especially for people with chronic diseases such as multiple sclerosis (MS). Parenting can be disrupted by flareups, disease worsening, and other MS symptoms, including mobility problems, pain, fatigue, and cognitive impairment. Mood disorders, such as depression and anxiety, have been found to occur at much higher rates in people with MS than in the general population. Surprisingly, less is known about which factors may predict mood disorders in parents with MS. This study aims to identify potential demographic, clinical, and self-reported predictors that contribute to mood disorders measured by the Hospital Anxiety and Depression Scale. METHODS A total of 285 parents with MS completed an anonymous online questionnaire combining sociodemographic, clinical, and family characteristics and scales, validated in Italian, related to coping strategies and social support. Associations between each variable and mood disorders were assessed using univariate and multivariate logistic regression analyses. RESULTS Disability level, emotional and dysfunctional coping strategies, and perceived social support were significant predictors of mood disorders in parents with MS. CONCLUSIONS These findings confirm the importance of identifying risk factors for mood disorders in parents with MS so that early intervention can minimize mood disruptions caused by the disease.

To investigate the impact of the COVID-19 pandemic on physical activity in persons with multiple sclerosis (PwMS).Multicenter international online survey study.The survey was conducted within 11 participating countries. Each country launched the survey using online platforms from May to July 2021.This was an electronic survey study targeting PwMS (N=3725).Not applicable.The survey ascertained physical activity performance and its intensity, the nature of the activities conducted, and the use of technology to support home-based physical activity before and during the pandemic.A total of 3725 respondents completed the survey. Prepandemic, the majority (83%) of respondents reported being physically active, and this decreased to 75% during the pandemic. This change was significant for moderate- and high-intensity activity (Plt;.0001). Activities carried out in physiotherapy centers, gyms, or pools decreased the most. Walking was the most frequently performed activity prepandemic (27%) and increased during the pandemic (33%). A total of 24% of those inactive during the pandemic had no intention of changing their physical activity behavior post pandemic. A total of 58% of the respondents did not use technology to support physical activity during the pandemic. Of those who did use technology, wearables were most used (24%). Of those currently nonactive (25%) expressed a preference for an in-person format to conduct physical activity post pandemic.Physical activity performance, especially activities at moderate and high intensities, decreased during the pandemic in PwMS compared with prepandemic. Walking and using wearables gained popularity as ways to stay active. As we move toward an endemic COVID-19, a call for action to develop interventions focused on walking programs with specific emphasis on increasing physical activity of PwMS is proposed.

Cognitive rehabilitation in multiple sclerosis (MS) aims at reducing patients’ cognitive impairments, improving their awareness and ability to take cognitive difficulties into account in their daily living. However, at this moment, more high-quality randomized trials are needed to draw conclusion about the effectiveness of cognitive interventions in MS. Although existing studies provide clear descriptions of intervention key ingredients (e.g. targeted cognitive domain as well as treatment frequency and duration) and the practical details needed to manage these key elements (e.g. restorative approaches, compensatory strategies, or environmental modifications), other crucial aspects received less attention in rehabilitation research. The aim of this topical review is to try to elucidate some critical issues that were only partly addressed and analyzed by the scientific literature: setting (center-based vs home-based) and mode (individual vs group) of the cognitive rehabilitation treatment.

Although shared behavioral and neural mechanisms between working memory (WM) and motor sequence learning (MSL) have been suggested, the additive and interactive effects of training have not been studied. This study aimed at investigating changes in brain functional connectivity (FC) induced by sequential (WM + MSL and MSL + WM) and combined (WM × MSL) training programs. 54 healthy subjects (27 women; mean age: 30.2 ± 8.6 years) allocated to three training groups underwent twenty-four 40-min training sessions over 6 weeks and four cognitive assessments including functional MRI. A double-baseline approach was applied to account for practice effects. Test performances were compared using linear mixed-effects models and t-tests. Resting state fMRI data were analysed using FSL. Processing speed, verbal WM and manual dexterity increased following training in all groups. MSL + WM training led to additive effects in processing speed and verbal WM. Increased FC was found after training in a network including the right angular gyrus, left superior temporal sulcus, right superior parietal gyrus, bilateral middle temporal gyri and left precentral gyrus. No difference in FC was found between double baselines. Results indicate distinct patterns of resting state FC modulation related to sequential and combined WM and MSL training suggesting a relevance of the order of training performance. These observations could provide new insight for the planning of effective training/rehabilitation.

Although mind wandering (MW) is associated with various psychological aspects frequently affected in people with Multiple Sclerosis (PwMS), there is lack of validated tools to assess MW in this clinical population.This psychometric study aimed to assess structural and construct validity and reliability of a brief Italian version of Mind Wandering (MW) Scale that measures two different dimensions of MW, i.e., spontaneous (MW-S) and deliberate (MW-D).Structural validity of the MW Scale was assessed by explorative factor analysis (EFA). To investigate construct validity, mood (Hospital Anxiety Depression Scale) and personality (10-items Big Five Inventory Test) were correlated with MW constructs. Reliability was assessed by Cronbach's α for internal consistency and intraclass correlation coefficients.EFA confirmed two distinct constructs of MW, i.e., MW-S and MW-D, also in PwMS. This tool appropriately fits the graded response model, supporting validity (about 79% of hypotheses for convergent and discriminant constructs confirmed) and internal consistency (MW-S: Cronbach's α = 0.84; MW-D: Cronbach's α = 0.88).MW Scale could be a useful tool to measure MW also in PwMS. As MW seems to be connected to clinical manifestations of MS, a detailed assessment of MW should be encouraged in clinical practice.

Machine learning (ML) applied to patient-reported (PROs) and clinical-assessed outcomes (CAOs) could favour a more predictive and personalized medicine. Our aim was to confirm the important role of applying ML to PROs and CAOs of people with relapsing-remitting (RR) and secondary progressive (SP) form of multiple sclerosis (MS), to promptly identifying information useful to predict disease progression. For our analysis, a dataset of 3398 evaluations from 810 persons with MS (PwMS) was adopted. Three steps were provided: course classification; extraction of the most relevant predictors at the next time point; prediction if the patient will experience the transition from RR to SP at the next time point. The Current Course Assignment (CCA) step correctly assigned the current MS course with an accuracy of about 86.0%. The MS course at the next time point can be predicted using the predictors selected in CCA. PROs/CAOs Evolution Prediction (PEP) followed by Future Course Assignment (FCA) was able to foresee the course at the next time point with an accuracy of 82.6%. Our results suggest that PROs and CAOs could help the clinician decision-making in their practice.

Background Since combining information from different domains could be useful to increase prediction accuracy over and above what can be achieved at the level of single category of markers, this study aimed to identify distinct and predominant subtypes, i.e., cognitive phenotypes, in people with multiple sclerosis (PwMS) considering both cognitive impairment and mood disorders. Methods A latent class analysis (LCA) was applied on data from 872 PwMS who were tested with Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT) and Hospital Anxiety and Depression Scale (HADS). Furthermore, the distribution of demographic (i.e., age, gender, years of education) and clinical characteristics (i.e., disease duration, disease course, disability level) was examined amongst the identified phenotypes. Results Based on model fit and parsimony criteria, LCA identified four cognitive phenotypes: 1) only memory difficulties (n = 247; 28.3%); 2) minor memory and language deficits with mood disorders (n = 185; 21.2%); 3) moderate memory, language and attention impairments (n = 164; 18.8%); 4) severe memory, language, attention, information processing and executive functions difficulties (n = 276; 31.7%). Conclusions Since less is known about the progressive deterioration of cognition in PwMS, a taxonomy of distinct subtypes that consider information from different clustered domains (i.e., cognition and mood) represents both a challenge and opportunity for an advanced understanding of cognitive impairments and development of tailored cognitive treatments in MS.

It has been theorized that hemispheric dominance and more segregated information processing have evolved to overcome long conduction delays through the corpus callosum (transcallosal conduction delay - TCD) but that this may still impact behavioral performance, mostly in tasks requiring high timing accuracy. Nevertheless, a thorough understanding of the temporal features of interhemispheric communication is lacking. Here, we aimed to assess the relationship between TCD and behavioral performance with a noninvasive directional cortical measure of TCD obtained from transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) in the motor system. Twenty-one healthy right-handed subjects were tested. TEPs were recorded during an ipsilateral silent period (iSP) paradigm and integrated with diffusion tensor imaging (DTI) and an in-phase bimanual thumb-opposition task. Linear mixed models were applied to test relationships between measures. We found TEP indexes of transcallosal communication at ∼15 ms both after primary motor cortex stimulation (M1-P15) and after dorsal premotor cortex stimulation (dPMC-P15). Both M1-and dPMC-P15 were predicted by mean diffusivity in the callosal body. Moreover, M1-P15 was positively related to iSP. Importantly, M1-P15 latency was linked to bimanual coordination with direction-dependent effects, so that asymmetric TCD was the best predictor of bimanual coordination. Our findings support the idea that transcallosal timing in signal transmission is essential for interhemispheric communication and can impact the final behavioral outcome. However, they challenge the view that a short conduction delay is always beneficial. Rather, they suggest that the effect of the conduction delay may depend on the direction of information flow.

Introduction: Arm and hand function deficits are commonly in people with multiple sclerosis (PwMS). The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) is a novel self-administered instrument specifically developed to evaluate upper limb function in MS. The aim of this study was to translate and adapt the AMSQ into Italian and to assess its psychometric properties in PwMS. Validity (structural, construct, and known-groups) and reliability (internal consistency, test-retest, and measurement error) were assessed. Materials and methods: From June 2017 to February 2018, a prospective cohort of PwMS among those followed as outpatients at the Rehabilitation Services of the Italian Multiple Sclerosis Society (AISM) of Genoa, Padua, and Vicenza was involved in the study. Construct validity of AMSQ was determined by examining correlations with the Italian version of ABILHAND, Modified Fatigue Impact Scale (MFIS), and Functional Independence Measure (FIM). Results: A total of 234 PwMS were enrolled. The mean AMSQ total score was 67.3 (SD = 38.4). Factor analysis results suggested one factor. As expected, moderate to high correlation coefficients were found between AMSQ and ABILHAND (− 0.79), MFIS (0.50) and its subsets, and FIM (− 0.60) and its subsets involving upper limb functioning. PwMS with higher EDSS reported worse total score of AMSQ than patients with low disability. The internal consistency of the 31 items was high (Cronbach’s α, 0.98). Test-retest reliability, as measured with ICC, was 0.96 (95% IC, 0.93–0.98), and measurement error was about 8.3 points showing good reliability. Discussion: AMSQ has been adapted and validated, it is a reliable questionnaire for Italian PwMS.

The aim of this study was to investigate the correlation between a field test assessing aerobic capacity (namely, the 12 minute-walk/run test, 12m-WRT) and the performance of students of distinct school-grade levels at two different working memory (WM)-related tasks. Forty participants (21 males, 19 females, mean age 19.18 ± 6.18 years, range 10-24) have been assessed using the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT) as WM measures, and a walk/run test of 12 minutes to indirectly measure the aerobic capacity (VO2max). We found significant correlations between VO2max and PASAT and between VO2max and SDMT. Two different trends were identified in relation to the individual level of formal education. In particular, aerobic fitness showed higher predictive values on WM performance when investigated with PASAT in primary and secondary school students, whilst increasing predictive values of physical condition on SDMT’s scores were observed with the progressing of students’ school career, reaching maximal values in university students. No significant correlations were observed between age and the cognitive tests, nor between age and VO2max. The present findings suggest that the 12m-WRT is associated with WM performance, showing different correlation with PASAT and SDMT according to the school-grade level. This might be due to the different effects that aerobic fitness has on specific neural substrates during development and opens avenues to research new tools able to monitor the health of the brain in young subjects.

Cognitive impairment and related abnormal brain activity are common in people with multiple sclerosis (PwMS). Adaptive training based on working memory (WM) has been shown to ameliorate cognitive symptoms, although the effects at a neural level are unclear. The aim of this study was to expand the existing research on the effects of an adaptive WM rehabilitative intervention on brain functional activity in PwMS. A sample of eighteen PwMS performed an 8-week home-based cognitive rehabilitation treatment based on adaptive WM training. PwMS were assessed before and after treatment using a validated neuropsychological battery and undergoing an fMRI session while carrying out a cognitive task (i.e., Paced Visual Serial Addition Test - PVSAT). fMRI activations were compared to the activation pattern elicited by eighteen matched healthy subjects performing the same task. At baseline, we found abnormal brain activity during PVSAT in PwMS when compared to healthy subjects, with a pattern including several bilateral activation clusters. Following rehabilitation, PwMS improved cognitive performance, as evaluated by the neuropsychological battery, and showed a different activation map with clusters mainly located in the right cerebellum and in the left hemisphere. The only significant cluster in the right hemisphere was located in the inferior parietal lobule, and the BOLD signal extracted in this area significantly correlated with cognitive performance both before and after the treatment. We suggest that WM training can improve the cognitive performance and reduce the abnormal activation of PwMS by partially maintaining or even restoring brain cognitive function.

Background Mood disorders, such as depression and anxiety, are frequent in people with Multiple Sclerosis (PwMS). Although anxiety has a well-recognized negative influence on family, work and social life, it has received less attention than depression. Thus, it is still under debate which risk factors can predict anxiety, its evolution over time and the extent of its effect on disability progression. Objective The aim of this retrospective study was to identify potential demographic, clinical and self-reported predictors that contribute to clinically significant anxiety at one-year follow up, measured by the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS). Methods Data was acquired from a cohort of 608 subjects with MS, and included domains potentially meaningful for clinically significant anxiety. Associations between each variable and clinically significant anxiety at one-year follow-up were assessed with univariate and multivariate logistic regression analyses. Results Lower educational level, relapsing-remitting disease course, presence of clinically significant anxiety at baseline, higher depression and fatigue perception were significant predictors for clinically significant anxiety at one-year follow up. Conclusion Findings confirm the importance of identifying risk factors for clinically significant anxiety in predicting prognosis and planning early intervention.

Humans can acquire information on others’ motor outputs (action prediction) and intentions (action understanding) according to their individual motor repertoire and to the detected gesture’s features (e.g. temporal patterns). We aimed at dissociating between action prediction and action understanding abilities in soccer players and novices observing soccer action videos including correct timing pass (CTP) or delayed pass (DP). First, we used an occluding paradigm to evaluate participants’ ability to predict the correct time to pass the ball. Although soccer players showed reduced reaction times, all subjects showed a similar pattern of performance: during DP observation, responses appeared delayed with respect to the other conditions but anticipated with respect to the observed DP. In a separate experiment, we investigated the ability to recognize CTP vs DP and the modulation of primary motor cortex (M1) excitability associated to video observation. Only soccer players showed selective modulation of M1 according to the plausibility of the observed action, with increased excitability during the observation of the CTP and in a phase preceding the DP. In conclusion, action prediction ability seems to be independent from the individual motor repertoire. By contrast, only subjects with previously acquired sensorimotor skills are able to infer the observed action’s long-term intention.

Wearable sensors are designed to be worn on the body or embedded into portable devices (e.g. smartphones and smartwatches), allowing continuous patient-based monitoring, objective outcomes measuring, and feedback delivering on daily-life activities. Within the medicine domain, there has been a rapid increase in the development, testing, and use of wearable technologies especially in the context of neurological diseases. Although wearables represent promising tools also in multiple sclerosis (MS), the research on their application in MS is still ongoing, and further studies are required to assess their reliability and accuracy to monitor body functions and disability in people with MS (pwMS). Here, we provided a comprehensive overview of the opportunities, potential challenges, and limitations of the wearable technology use in MS. In particular, we classified previous findings within this field into macro-categories, considered crucial for disease management: assessment, monitoring, intervention, advice, and education. Given the increasing pivotal role played by wearables, current literature suggests that for pwMS, the time is right to shift from a center-based traditional therapeutic paradigm toward a personalized patient-based disease self-management. On this way, we present two ongoing initiatives aimed at implementing a continuous monitoring of pwMS and, consequently, providing timely and appropriate care interventions.

The aim of this work was to investigate changes in motor performance and in the brain activation pattern during finger movements, following upper limb motor training in multiple sclerosis. Thirty people with multiple sclerosis with mild upper limb sensorimotor deficits were randomly allocated to one of two groups: the experimental group (n = 15) received an upper limb treatment based on voluntary task-oriented movements; the control group (n = 15) underwent passive mobilization of shoulder, elbow, wrist and fingers. All participants completed three treatment sessions per week for eight weeks. Before and after the intervention, all participants were evaluated for motor performance by means of Action Research Arm Test, Nine Hole Peg Test, and grip strength by a dynamometer, and for brain activations by functional magnetic resonance imaging during right finger opposition movements. Similar effects on motor performance were found in the two groups. A significant improvement with time was found in both groups at NHPT and in GRIP strength; a similar trend was found at ARAT. However, only the experimental group showed increased lateralization towards more normal brain activation following treatment, with activation clusters mainly located in the left brain hemisphere and right cerebellum. In conclusion, both active and passive interventions were effective in improving motor performance. However, only the treatment based on voluntary task-oriented movements could induce changes in brain activity that may have reflected skill acquisition by the right hand, reducing the activation of compensatory areas and decreasing brain resource demand.

Action observation is known to enhance sensorimotor system activation, and such effect has been linked to neural priming and response facilitation mechanisms. This facilitation effect, however, has been primarily studied by focusing on high-level motor proficiency, whereas evidence on the effect of observing poorly performed actions is still lacking. We then devised a study to investigate neural correlates of the observation of suboptimal motor acts as mirrored by corticospinal activation (via transcranial magnetic stimulation (TMS), Experiment 1) and by modulation of cortical oscillatory activity (via electroencephalography (EEG), Experiment 2). 40 participants were presented with four randomly reiterated videos. Videos depicted a healthy confederate, a minimally impaired multiple sclerosis (MS) patient, a mildly impaired MS patient, or a confederate trying to simulate mild motor difficulties performing a test concerning fine motor abilities. In Experiment 1 we analyzed TMS-induced motor-evoked potentials during the observation of videos. In Experiment 2 EEG data were analyzed in the frequency-domain. Analyses highlighted both increased corticospinal excitability and desynchronized alpha-beta oscillations during the observation of poorly performed motor acts performed by the mildly impaired MS patient. Further, we observed gradually increasing beta activity across videos reiterations, specifically for the minimally impaired patient’s video. Reported findings corroborate the hypotheses that the action-observation network and the motor system might be involved in processes evoked in the attempt to understand and predict observed actions which do not belong to the onlookers’ motor repertoire, reflecting in an increased sensorimotor activity.

Writing is a means of communication which requires complex motor, perceptual and cognitive skills. If one of these abilities gets lost following traumatic events or due to neurological diseases, handwriting could deteriorate. Occupational therapy practitioners provide rehabilitation services for people with impaired handwriting. However, to determine the effectiveness of handwriting interventions no studies assessed whether the proposed treatments improved the kinematics of writing movement or had an effect at the level of the central nervous system. There is need to find new quantitative methodologies able to describe the behavioral and the neural outcomes of the rehabilitative interventions for handwriting. In the present study we proposed a combined approach that allowed evaluating the kinematic parameters of handwriting movements, acquired by means of a magnetic resonance-compatible tablet, and their neural correlates obtained simultaneously from a functional magnetic resonance imaging (fMRI) examination. Results showed that the system was reliable in term of reproducibility of the kinematic data during a test/re-test procedure. Further, despite the modifications with respect to an ecological writing movement condition, the kinematic parameters acquired inside the MR-environment were descriptive of individuals’ movement features. At last, the imaging protocol succeeded to show the activation of the cerebral regions associated with the production of writing movement in healthy people. From these findings, this methodology seems to be promising to evaluate the handwriting movement deficits and the potential alterations in the neural activity in those individuals who have handwriting difficulties. Finally, it would provide a mean to quantitatively assess the effect of a rehabilitative treatment.

Background Cognitive impairment is common in multiple sclerosis (MS), but the definition of the best cognitive rehabilitation tools and features is still an open issue among researchers. The aims of the present study were to evaluate the effectiveness of COGNI-TRAcK (a customized application software delivering personalized working memory-based exercises) on cognitively impaired people with MS and to investigate the effects of an adaptive vs. a non-adaptive cognitive training administered by means of COGNI-TRAcK. Methods Twenty eight patients (20 women, age 47.5 ± 9.3 years, Expanded Disability Status Scale score 3.8 ± 1.9) were randomized in two homogeneous groups, both performing a 8-week home-based cognitive rehabilitation treatment by means of COGNI-TRAcK. The study group (ADAPT-gr) underwent an adaptive training given by the automatic adjustment of tasks difficulty to the subjects’ performance, whilst the control group (CONST-gr) was trained at constant difficulty levels. Before and after the treatment, patients’ cognitive status was assessed using a gold standard neuropsychological evaluation. Moreover, the mostly affected cognitive domains in MS (i.e., attention, concentration and information processing speed) were also assessed 6 months after the end of the treatment. Results The analysis of variance showed a significant Group*Time interaction in six out of ten tests of the cognitive evaluation. Post-hoc analysis revealed a significant improvement between the performances before and after the intervention only in the ADAPT-gr in tests evaluating verbal memory acquisition (p

International audience; Motor imagery is a mental process during which subjects internally simulate a movement without any motor output. Mental and actual movement durations are similar in healthy adults (isochrony) while temporal discrepancies (anisochrony) could be an expression of neurological deficits on action representation. It is unclear whether patients with multiple sclerosis (PwMS) preserve the capacity to simulate their own movements. This study investigates the ability of PwMS to predict their own actions by comparing temporal features of dominant and non-dominant actual and mental actions. Fourteen PwMS and nineteen healthy subjects (HS) were asked to execute and to imagine pointing arm movements among four pairs of targets of different sizes. Task duration was calculated for both actual and mental movements by an optoelectronic device. Results showed temporal consistency and target-by-target size modulation in actual movements through the four cycles for both groups with significantly longer actual and mental movement durations in PwMS with respect to HS. An index of performance (IP) was used to examine actual/mental isochrony properties in the two groups. Statistical analysis on IP showed in PwMS significantly longer actual movement durations with respect to mental movement durations (anisochrony), more relevant for the non-dominant than dominant arm. Mental prediction of motor actions is not well preserved in MS where motor and cognitive functional changes are present. Differences in performing imagined task with dominant and non-dominant arm could be related to increased cognitive effort required for performing non-dominant movements.