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The ability to predict the weight of objects is important for skilled and dexterous manipulation during activities of daily living. The observation of other people moving objects might represent an important source of information on object features and help to plan the correct motor interaction with it. In aging, an impaired ability to evaluate the object weight might have negative drawbacks in term of the safety of the person. The aim of this study was to investigate the role of aging in the ability to discriminate the object weight during action observation. Twenty older adults (Old) and twenty young subjects (Young) performed a two-interval forced-choice task consisting in the observation of a couple of videos showing an actor moving a box of different weights. The observer had to evaluate which video showed the heavier box. Handgrip strength was acquired from all subjects. Sensitivity analysis was performed and psychometric curves were built on participants' responses. The results showed a diminished sensitivity in the object weight discrimination in Old than in Young group. The analysis of the psychometric curves revealed that this impairment pertained both the light and heavy boxes and the minimum difference to discriminate different weights was greater in Old than in Young. At last, the sensitivity and the discrimination ability significantly correlated with individuals' handgrip strength. These findings allow us to deeply characterize the impairments older adults have in discriminating the weight of an object moved by another individual., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Albergoni, Biggio, Faelli, Ruggeri, Avanzino, Bove and Bisio.)

The difficulty in assessing FOG and the variety of existing cues, hamper to determine which cueing modality should be applied and which FOG-related aspect should be targeted to reach personalized treatments for FOG. This systematic review aimed to highlight: i) whether cues could reduce FOG and improve FOG-related gait parameters, ii) which cues are the most effective, iii) whether medication state (ON-OFF) affects cues-related results. Thirty-three repeated measure design studies assessing cueing effectiveness were included and subdivided according to gait tasks (gait initiation, walking, turning) and to the medication state. Main results reveal that: preparatory phase of gait initiation benefit from visual and auditory cues; spatio-temporal parameters (e.g., step and stride length) are improved by visual cues during walking; turning time and step time variability are reduced by applying auditory and visual cues. Some findings on the potential benefits of cueing on FOG and FOG gait-related parameters were found. Questions remain about which are the best behavioral strategies according to FOG features and PD clinical characteristics., Competing Interests: Conflict of interest The Authors have no financial or other conflicts of interest associated with this publication to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Parkinson's disease (PD) patients experience deterioration in mobility with consequent inactivity and worsened health and social status. Physical activity and physiotherapy can improve motor impairments, but several barriers dishearten PD patients to exercise regularly. Home-based approaches (e.g., via mobile apps) and remote monitoring, could help in facing this issue., Objective: This study aimed at testing the feasibility, usability and training effects of a home-based exercise program using a customized version of Parkinson Rehab® application., Methods: Twenty PD subjects participated in a two-month minimally supervised home-based training. Daily session consisted in performing PD-specific exercises plus a walking training. We measured: (i) feasibility (training adherence), usability and satisfaction (via an online survey); (ii) safety; (iii) training effects on PD severity, mobility, cognition, and mood. Evaluations were performed at: baseline, after 1-month of training, at the end of training (T2), and at 1-month follow-up (T3)., Results: Eighteen out of twenty participants completed the study without important adverse events. Participants' adherence was 91% ± 11.8 for exercise and 105.9% ± 30.6 for walking training. Usability and satisfaction survey scored 70.9 ± 7.7 out of 80. Improvements in PD severity, mobility and cognition were found at T2 and maintained at follow-up., Conclusion: The home-based training was feasible, safe and seems to positively act on PD-related symptoms, mobility, and cognition in patients with mild to moderate stage of PD disease. Additionally, the results suggest that the use of a mobile app might increase the amount of daily physical activity in our study population. Remote monitoring and tailored exercise programs appear to be key elements for promoting exercise. Future studies in a large cohort of PD participants at different stages of disease are needed to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Putzolu, Manzini, Gambaro, Cosentino, Bonassi, Botta, Ravizzotti, Avanzino, Pelosin and Mezzarobba.)

This study aimed to investigate the role of sensorimotor expertise in evaluating relative weight of a lifted object during the observation of a sport-specific gesture, namely the deadlift. Fifty-six participants, assigned to three groups according to their experience in weight lifting, powerlifters, CrossFit® practitioners and naïve participants (controls), performed a perceptual weight judgments task. Participants observed videos showing a powerlifter executing a deadlift at the 80%, 90% and 100% of 1 repetition maximum (1RM) and answered a question about the weight of the lifted object. Participants' response accuracy and variability were evaluated. Findings showed that powerlifters were more accurate than controls. No differences appeared between powerlifter and CrossFit® practitioners, and between CrossFit® practitioners and controls. Response variability was similar in the three groups. These findings suggest that a fine sensorimotor expertise specific for the observed gesture is crucial to detect the weight of the object displayed in the observed movement, since it might allow detecting small changes in the observed movement kinematics, which we speculate are at the basis of the object weight recognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Albergoni, Biggio, Faelli, Pesce, Ruggeri, Avanzino, Bove and Bisio.)

Purpose: Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study., Methods: Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials., Results: There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI., Conclusions: Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder., Competing Interests: R. E. Sondergaard holds a Natural Sciences and Engineering Research Council of Canada (NSERC) studentship and N. D. J. Strzalkowski held University of Calgary Eyes High, Parkinson Alberta and Parkinson Foundation postdoctoral fellowships. Funding was also provided by NSERC (RGPIN/04126-2017) to Z. H. T. Kiss and Dystonia Medical Research Foundation of Canada grant (Z.H.T.K. and D.M.). The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

In healthy people, motor resonance mechanisms are flexible to negative emotional contextual clues with greater motor resonance during the observation of a reach to grasp movement performed in an environment eliciting disgust. The link between emotion and motor control has become an interesting topic in Parkinson's disease (PD). Here, we aimed to study the response of the mirror neuron system, specifically motor resonance, to an emotion-enriched context in people with PD. Corticospinal excitability was recorded in a total of 44 participants, divided into two groups (23 PD patients and 21 healthy subjects). We recorded motor-evoked potentials from a muscle involved in the grasping movement while participants were watching the same reach-to-grasp movement embedded in surrounds with negative emotional valence, but different levels of arousal: sadness (low arousal) and disgust (high arousal). Basic motor resonance mechanisms were less efficient in PD than controls. Responsiveness to emotional contextual clues eliciting sadness was similar between PD and controls, whereas responsiveness to emotional contextual clues eliciting disgust was impaired in PD patients. Our findings show reduced motor resonance flexibility to the disgusting context, supporting the hypothesis that PD patients may have a deficit in "translating" an aversive motivational state into a physiologic response. The amygdala, which is implicated in the appraisal of fearful stimuli and response to threatening situations, might be implicated in this process., Competing Interests: The study's authors affirm that there were no financial or commercial relationships that might be viewed as having a potential conflict of interest., (Copyright © 2022 Giovanna Lagravinese et al.)

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management., (© 2022. Fondazione Società Italiana di Neurologia.)

We recently demonstrated, by means of short latency afferent inhibition (SAI), that before an imagined movement, during the reaction time (RT), SAI decreases only in the movement-related muscle (sensorimotor modulation) and that a correlation exists between sensorimotor modulation and motor imagery (MI) ability. Excitatory anodal transcranial direct current stimulation (a-tDCS) on M1 could enhance the MI outcome; however, mechanisms of action are not completely known. Here, we assessed if a-tDCS on M1 prior to an MI task could affect sensorimotor modulation. Participants imagined abducting the index or little finger in response to an acoustic signal. SAI was evaluated from the first dorsal interosseus after the "go" signal, before the expected electromyographic (EMG) activity. Participants received 20-min 1.5 mA a-tDCS or sham-tDCS on M1 on two different days, in random order. Results showed that a-tDCS on M1 increases the sensorimotor modulation consisting of a weakening of SAI after the Go signal with respect to sham-tDCS, in the movement-related muscle right before the beginning of MI. These results suggest that a-tDCS on M1 further potentiate those circuits responsible for sensorimotor modulation in the RT phase of MI. Increased sensorimotor modulation during MI may be one of the mechanisms involved in MI improvement after a-tDCS over M1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bonassi, Lagravinese, Putzolu, Botta, Bove, Pelosin and Avanzino.)

Balance and walking are fundamental to support common daily activities. Relatively accurate characterizations of normal and impaired gait features were attained at the kinematic and muscular levels. Conversely, the neural processes underlying gait dynamics still need to be elucidated. To shed light on gait-related modulations of neural activity, we collected high-density electroencephalography (hdEEG) signals and ankle acceleration data in young healthy participants during treadmill walking. We used the ankle acceleration data to segment each gait cycle in four phases: initial double support, right leg swing, final double support, left leg swing. Then, we processed hdEEG signals to extract neural oscillations in alpha, beta, and gamma bands, and examined event-related desynchronization/synchronization (ERD/ERS) across gait phases. Our results showed that ERD/ERS modulations for alpha, beta, and gamma bands were strongest in the primary sensorimotor cortex (M1), but were also found in premotor cortex, thalamus and cerebellum. We observed a modulation of neural oscillations across gait phases in M1 and cerebellum, and an interaction between frequency band and gait phase in premotor cortex and thalamus. Furthermore, an ERD/ERS lateralization effect was present in M1 for the alpha and beta bands, and in the cerebellum for the beta and gamma bands. Overall, our findings demonstrate that an electrophysiological source imaging approach based on hdEEG can be used to investigate dynamic neural processes of gait control. Future work on the development of mobile hdEEG-based brain-body imaging platforms may enable overground walking investigations, with potential applications in the study of gait disorders., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Gait is a common but rather complex activity that supports mobility in daily life. It requires indeed sophisticated coordination of lower and upper limbs, controlled by the nervous system. The relationship between limb kinematics and muscular activity with neural activity, referred to as neurokinematic and neuromuscular connectivity (NKC/NMC) respectively, still needs to be elucidated. Recently developed analysis techniques for mobile high-density electroencephalography (hdEEG) recordings have enabled investigations of gait-related neural modulations at the brain level. To shed light on gait-related neurokinematic and neuromuscular connectivity patterns in the brain, we performed a mobile brain/body imaging (MoBI) study in young healthy participants. In each participant, we collected hdEEG signals and limb velocity/electromyography signals during treadmill walking. We reconstructed neural signals in the alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-50 Hz) frequency bands, and assessed the co-modulations of their power envelopes with myogenic/velocity envelopes. Our results showed that the myogenic signals have larger discriminative power in evaluating gait-related brain-body connectivity with respect to kinematic signals. A detailed analysis of neuromuscular connectivity patterns in the brain revealed robust responses in the alpha and beta bands over the lower limb representation in the primary sensorimotor cortex. There responses were largely contralateral with respect to the body sensor used for the analysis. By using a voxel-wise analysis of variance on the NMC images, we revealed clear modulations across body sensors; the variability across frequency bands was relatively lower, and below significance. Overall, our study demonstrates that a MoBI platform based on hdEEG can be used for the investigation of gait-related brain-body connectivity. Future studies might involve more complex walking conditions to gain a better understanding of fundamental neural processes associated with gait control, or might be conducted in individuals with neuromotor disorders to identify neural markers of abnormal gait., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Bonassi, Samogin, Taberna, Porcaro, Pelosin, Avanzino and Mantini.)

Purpose: Strong evidence shows that symptoms in individuals with Parkinson's Disease (PD) restrict both their independence and social participation, leading to a low Quality of Life (QoL). Conversely, a reduced QoL has a negative impact on symptoms. The aim is to evaluate the correlation between QoL and severity of PD by assessing the presence of an optimal cut-off point on the Parkinson's disease questionnaire (PDQ-39) as related to the Hoehn &Yahr (H&Y) scale in a cohort of Italian adults with PD., Methods: A multicenter, cross-sectional study was performed. This study was conducted on a cohort of consecutive individuals. All participants were evaluated with the PDQ-39, and the severity of PD was recorded according to the H&Y scale by a neurologist. Receiver op-erating characteristic (ROC) curves and coordinates, visually inspected, were used to find cut-off points with optimal sensitivity and specificity. These were in turn used to determine the optimal PDQ-39 cut-off score for identifying disease severity according to H&Y stages., Results: 513 individuals were included in the study. The ROC curve analysis showed that QoL worsened with an increase in disease severity and age. Moreover, QoL was worse in females., Conclusions: The results of this study allowed for the correlation of QoL and disease severity in a cohort of individuals with PD. With this cut-off point, it is now possible to make a determination of QoL of an individual with PD at a certain stage of the disease, in a specific age range, and of a particular gender.

Visual processing of emotional stimuli has been shown to engage complex cortical and subcortical networks, but it is still unclear how it affects sensorimotor integration processes. To fill this gap, here, we used a TMS protocol named short-latency afferent inhibition (SAI), capturing sensorimotor interactions, while healthy participants were observing emotional body language (EBL) and International Affective Picture System (IAPS) stimuli. Participants were presented with emotional (fear- and happiness-related) or non-emotional (neutral) EBL and IAPS stimuli while SAI was tested at 120 ms and 300 ms after pictures presentation. At the earlier time point (120 ms), we found that fear-related EBL and IAPS stimuli selectively enhanced SAI as indexed by the greater inhibitory effect of somatosensory afferents on motor excitability. Larger early SAI enhancement was associated with lower scores at the Behavioural Inhibition Scale (BIS). At the later time point (300 ms), we found a generalized SAI decrease for all kind of stimuli (fear, happiness or neutral). Because the SAI index reflects integrative activity of cholinergic sensorimotor circuits, our findings suggest greater sensitivity of such circuits during early (120 ms) processing of threat-related information. Moreover, the correlation with BIS score may suggest increased attention and sensory vigilance in participants with greater anxiety-related dispositions. In conclusion, the results of this study show that sensorimotor inhibition is rapidly enhanced while processing threatening stimuli and that SAI protocol might be a valuable option in evaluating emotional-motor interactions in physiological and pathological conditions., (© 2022. The Author(s).)

The aim of this study was to investigate differences between usual and complex gait motor imagery (MI) task in healthy subjects using high-density electroencephalography (hdEEG) with a MI protocol. We characterized the spatial distribution of α- and β-bands oscillations extracted from hdEEG signals recorded during MI of usual walking (UW) and walking by avoiding an obstacle (Dual-Task, DT). We applied a source localization algorithm to brain regions selected from a large cortical-subcortical network, and then we analyzed α and β bands Event-Related Desynchronizations (ERDs). Nineteen healthy subjects visually imagined walking on a path with (DT) and without (UW) obstacles. Results showed in both gait MI tasks, α- and β-band ERDs in a large cortical-subcortical network encompassing mostly frontal and parietal regions. In most of the regions, we found α- and β-band ERDs in the DT compared with the UW condition. Finally, in the β band, significant correlations emerged between ERDs and scores in imagery ability tests. Overall we detected MI gait-related α- and β-band oscillations in cortical and subcortical areas and significant differences between UW and DT MI conditions. A better understanding of gait neural correlates may lead to a better knowledge of pathophysiology of gait disturbances in neurological diseases., (© 2022. The Author(s).)

Treadmill training with virtual reality (TT + VR) has been shown to improve gait performance and to reduce fall risk in Parkinson's disease (PD). However, there is no consensus on the optimal training duration. This study is a sub-study of the V-TIME randomized clinical trial (NCT01732653). In this study, we explored the effect of the duration of training based on the motor-cognitive interaction on motor and cognitive performance and on fall risk in subjects with PD. Patients in Hoehn and Yahr stages II-III, aged between 40 and 70 years, were included. In total, 96 patients with PD were assigned to 6 or 12 weeks of TT + VR intervention, and 77 patients completed the full protocol. Outcome measures for gait and cognitive performance were assessed at baseline, immediately after training, and at 1- and 6-month follow-up. The incident rate of falls in the 6-month pre-intervention was compared with that in the 6-month post-intervention. Dual-task gait performance (gait speed, gait speed variability and stride length under cognitive dual task and obstacle negotiation, and the leading foot clearance in obstacle negotiation) improved similarly in both groups with gains sustained at 6-month follow-up. A higher decrease in fall rate and fear of falling were observed in participants assigned to the 12-week intervention than the 6-week intervention. Improvements in cognitive functions (i.e., executive functions, visuospatial ability, and attention) were seen only in participants enrolled in 12-week training up to 1-month follow-up but vanished at the 6-month evaluation. Our results suggest that a longer TT + VR training leads to greater improvements in cognitive functions especially those directly addressed by the virtual environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pelosin, Ponte, Putzolu, Lagravinese, Hausdorff, Nieuwboer, Ginis, Rochester, Alcock, Bloem, Nieuwhof, Cereatti, Della Croce, Mirelman and Avanzino.)

Introduction: Emotional states have been shown to influence cognitive processes including visual-spatial learning. Parkinson's Disease (PD), besides manifesting with the cardinal motor symptoms, presents cognitive and affective disturbances. Here we aimed at investigating whether manipulation of the emotional state by means of music was able to influence the performance of a visual-spatial learning task in a group of PD participants., Methods: Ten PD patients and 11 healthy elderly (ELD) were asked to perform a visual-spatial learning task while listening two musical pieces evoking a neutral emotion or fear. Targets were presented on a screen in a preset order over four blocks and subjects were asked to learn the sequence order by attending to the display. At the end of each block, participants were asked to verbally recall the sequence and a score was assigned (Verbal Score, VS)., Results: Analysis of variance-type statistic test on the VS disclosed a significant effect of Music and sequence Blocks (p = 0.01 and p < 0.001, respectively) and a significant interaction between Group and sequence Blocks. Sequence learning occurred across the training period in both groups, but PD patients were slower than ELD and at the end of the training period learning performance was worse in PD with respect to ELD. In PD patients, like in ELD, fear-inducing music has a detrimental effect on visual-spatial learning performances, which are slower and decreased., Conclusion: These findings confirm an impairment in visual-spatial learning in PD and indicates that the emotional state influences this learning ability similarly to healthy controls., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective. Electroencephalography (EEG) is a widely used technique to address research questions about brain functioning, from controlled laboratorial conditions to naturalistic environments. However, EEG data are affected by biological (e.g. ocular, myogenic) and non-biological (e.g. movement-related) artifacts, which-depending on their extent-may limit the interpretability of the study results. Blind source separation (BSS) approaches have demonstrated to be particularly promising for the attenuation of artifacts in high-density EEG (hdEEG) data. Previous EEG artifact removal studies suggested that it may not be optimal to use the same BSS method for different kinds of artifacts. Approach. In this study, we developed a novel multi-step BSS approach to optimize the attenuation of ocular, movement-related and myogenic artifacts from hdEEG data. For validation purposes, we used hdEEG data collected in a group of healthy participants in standing, slow-walking and fast-walking conditions. During part of the experiment, a series of tone bursts were used to evoke auditory responses. We quantified event-related potentials (ERPs) using hdEEG signals collected during an auditory stimulation, as well as the event-related desynchronization (ERD) by contrasting hdEEG signals collected in walking and standing conditions, without auditory stimulation. We compared the results obtained in terms of auditory ERP and motor-related ERD using the proposed multi-step BSS approach, with respect to two classically used single-step BSS approaches. Main result s. The use of our approach yielded the lowest residual noise in the hdEEG data, and permitted to retrieve stronger and more reliable modulations of neural activity than alternative solutions. Overall, our study confirmed that the performance of BSS-based artifact removal can be improved by using specific BSS methods and parameters for different kinds of artifacts. Significance. Our technological solution supports a wider use of hdEEG-based source imaging in movement and rehabilitation studies, and contributes to the further development of mobile brain/body imaging applications., (Creative Commons Attribution license.)

Objective: Transcranial magnetic stimulation (TMS) delivered over the cerebellum 5-7 ms prior to a stimulus over the contralateral primary motor cortex (M1) reduces the excitability of M1 output, a phenomenon termed cerebellar brain inhibition (CBI). The cerebellum receives sensory information for adaptive motor coordination and motor planning. Here, we explored through TMS whether a peripheral electrical stimulus modulates CBI., Methods: We studied the effect of right median nerve electrical stimulation (ES) on CBI from right cerebellum (conditioning stimulus, CS) to left M1 (test stimulus, TS) in 12 healthy subjects. The following ES-CS inter-stimulus intervals (ISIs) were tested: 25, 30 and 35 ms. CS-TS ISI was set at 5 ms., Results: We found significantly weaker CBI when the ES was delivered 25 ms (p < 0.001) and 35 ms (p < 0.001) earlier the CS over the ipsilateral cerebellum and a trend for 30 ms ES-CS ISI (p = 0.07)., Conclusions: We hypothesize that the activation of cerebellar interneurons together with intrinsic properties of Purkinje cells may be responsible of the decreased CBI when the peripheral stimulation preceded the cerebellar stimulation of 25 and 35 ms., Significance: To test the interaction between somatosensory inputs and cerebello-cortical pathway may be important in a variety of motor tasks and neuropsychiatric disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Specific neural mechanisms operate at corticospinal levels during eccentric and concentric contractions. Here, we investigated the difference in corticospinal excitability (CSE) when preparing these two types of contraction. In this study we enrolled 16 healthy participants. They were asked to perform an instructed-delay reaction time (RT) task involving a concentric or an eccentric contraction of the right first dorsal interosseus muscle, as a response to a proprioceptive cue (Go signal) presented 1 s after a warning signal. We tested CSE at different time points ranging from 300 ms before up to 40 ms after a Go signal. CSE increased 300-150 ms before the Go signal for both contractions. Interestingly, significant changes in CSE in the time interval around the Go signal (from -150 ms to +40 ms) were only revealed in eccentric contraction. We observed a significant decrease in excitability immediately before the Go cue (Pre&#95;50) and a significant increase 40 ms after it (Post&#95;40) with respect to the MEPs recorded at Pre&#95;150. Finally, CSE in eccentric contraction was lower before the Go cue (Pre&#95;50) and greater after it (Post&#95;40) compared to the concentric contraction. A similar result was also found in NoMov paradigm, used to disentangle the effects induced by movement preparation from those induced by the movement preparation linked to the proprioceptive cue. We could conclude that different neural mechanisms observed during concentric and eccentric contractions are mirrored with a different time-specific modulation of CSE in the preparatory phase to the movement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Day-to-day walking-related activities frequently involve the simultaneous performance of two or more tasks (i.e., dual task). Dual task ability is influenced by higher order cognitive and cortical control mechanisms. Recently, it has been shown that the concomitant execution of an attention-demanding task affected postural control in subject with cervical dystonia (CD). However, no study has investigated whether dual tasking might deteriorate gait performance in CD patients. To investigate whether adding a concomitant motor and cognitive tasks could affect walking performance in CD subjects.17 CD patients and 19 healthy subjects (HS) participated in this pilot case-control study. Gait performance was evaluated during four walking tasks: usual, fast, cognitive dual task and obstacle negotiation. Spatiotemporal parameters, dual-task cost and coefficients of variability (CV%) were measured by GaitRite ® and were used to detect differences between groups. Balance performance was also assessed with Mini-BEST and Four Step Square tests. In CD participants, correlation analysis was computed between gait parameters and clinical data. Significant differences in complex gait and balance performance were found between groups. CD patients showed lower speed, longer stance time and higher CV% and dual-task cost compared to HS. In CD, altered gait parameters correlated with balance performance and were not associated with clinical features of CD. Our findings suggest that complex walking performance is impaired in patients with CD and that balance and gait deficits might be related., (© 2021. The Author(s).)

Recent studies provide novel insights into the meso-scale organization of the brain, highlighting the co-occurrence of different structures: classic assortative (modular), disassortative, and core-periphery. However, the spectral properties of the brain meso-scale remain mostly unexplored. To fill this knowledge gap, we investigated how the meso-scale structure is organized across the frequency domain. We analyzed the resting state activity of healthy participants with source-localized high-density electroencephalography signals. Then, we inferred the community structure using weighted stochastic block-model (WSBM) to capture the landscape of meso-scale structures across the frequency domain. We found that different meso-scale modalities co-exist and are diversely organized over the frequency spectrum. Specifically, we found a core-periphery structure dominance, but we also highlighted a selective increase of disassortativity in the low frequency bands (<8 Hz), and of assortativity in the high frequency band (30-50 Hz). We further described other features of the meso-scale organization by identifying those brain regions which, at the same time, (a) exhibited the highest degree of assortativity, disassortativity, and core-peripheriness (i.e., participation) and (b) were consistently assigned to the same community, irrespective from the granularity imposed by WSBM (i.e., granularity-invariance). In conclusion, we observed that the brain spontaneous activity shows frequency-specific meso-scale organization, which may support spatially distributed and local information processing., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: It is not clear how specific gait measures reflect disease severity across the disease spectrum in Parkinson's disease (PD)., Objective: To identify the gait and mobility measures that are most sensitive and reflective of PD motor stages and determine the optimal sensor location in each disease stage., Methods: Cross-sectional wearable-sensor records were collected in 332 patients with PD (Hoehn and Yahr scale I-III) and 100 age-matched healthy controls. Sensors were adhered to the participant's lower back, bilateral ankles, and wrists. Study participants walked in a ~15-meter corridor for 1 minute under two walking conditions: (1) preferred, usual walking speed and (2) walking while engaging in a cognitive task (dual-task). A subgroup (n = 303, 67% PD) also performed the Timed Up and Go test. Multiple machine-learning feature selection and classification algorithms were applied to discriminate between controls and PD and between the different PD severity stages., Results: High discriminatory values were found between motor disease stages with mean sensitivity in the range 72%-83%, specificity 69%-80%, and area under the curve (AUC) 0.76-0.90. Measures from upper-limb sensors best discriminated controls from early PD, turning measures obtained from the trunk sensor were prominent in mid-stage PD, and stride timing and regularity were discriminative in more advanced stages., Conclusions: Applying machine-learning to multiple, wearable-derived features reveals that different measures of gait and mobility are associated with and discriminate distinct stages of PD. These disparate feature sets can augment the objective monitoring of disease progression and may be useful for cohort selection and power analyses in clinical trials of PD. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

A crucial ability for athletes playing sports that involve coincidence timing actions is the motor timing ability. The efficiency of perceptual and motor processes underlying the motor timing ability has been related to the motor experience gained in interceptive sports, such as tennis. In the present study, the motor timing ability in young tennis players (TP) and age-matched control participants (CTRL) was compared by means of a synchronization paradigm. Participants were asked to perform finger-opposition movements in synch to a metronome beating 0.5 and 2 Hz in (1) a bimanual coordination test, which compared the performance of the dominant hand with that of the contralateral hand, and (2) a movement lateralization test, which compared the motor performance of the dominant hand during single-hand and bimanual tasks (BTs). The motor performance was evaluated through movement strategy [defined by touch duration (TD), inter-tapping interval (ITI), and movement frequency] and movement accuracy (temporal accuracy defined by the synchronization error and spatial accuracy defined by the percentage of correct touches-%CORR&#95;SEQ). Results showed that motor expertise significantly influences movement strategy in the bimanual coordination test; TD of TP was significantly higher than those of CTRL, specifically at 0.5 Hz. Furthermore, overall ITI values of TP were lower than those of CTRL. Lastly, in the movement lateralization test, the %CORR&#95;SEQ executed with the right dominant hand by TP in the BT was significantly higher than those of CTRL. A discussion about the role of motor expertise in the timing ability and the related neurophysiological adaptations is provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bisio, Faelli, Pelosin, Carrara, Ferrando, Avanzino and Ruggeri.)

Language impairment in Parkinson's disease (PD) has been investigated at different levels of linguistic skills. Only a few studies dealt with pragmatic abilities in PD, and these suggest an impairment of pragmatic skills, which might affect quality of life. However, previous studies enrolled patients with heterogeneous symptom severity. The goal of this study is twofold: first, to investigate whether pragmatic skills are compromised at the early stage of PD; second, to explore whether an early pragmatic impairment is explained by a decay of a specific cognitive function. We assessed pragmatic abilities (discourse production, comprehension of narratives, humour, and figurative language), and a cluster of cognitive functions (memory, verbal fluency, inhibition, shifting, and ToM) in a sample of early PD patients and a group of age-matched healthy controls. Early PD patients showed impaired general pragmatic skills (the ability to perform different pragmatic tasks in language production and comprehension), as well as a deficit in the production and comprehension individual scores. Our results suggest that good general cognitive skills (a good overall cognitive level) and high education support patients' pragmatic competence. Inhibitory processes have been found to predict patients' ability to understand figurative language, such as metaphors, and this might be related to frontal lobe dysfunctions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Adult-onset focal dystonia can spread to involve one, or less frequently, two additional body regions. Spread of focal dystonia to a third body site is not fully characterized., Materials and Methods: We retrospectively analyzed data from the Italian Dystonia Registry, enrolling patients with segmental/multifocal dystonia involving at least two parts of the body or more. Survival analysis estimated the relationship between dystonia features and spread to a third body part., Results: We identified 340 patients with segmental/multifocal dystonia involving at least two body parts. Spread of dystonia to a third body site occurred in 42/241 patients (17.4%) with focal onset and 10/99 patients (10.1%) with segmental/multifocal dystonia at onset. The former had a greater tendency to spread than patients with segmental/multifocal dystonia at onset. Gender, years of schooling, comorbidity, family history of dystonia/tremor, age at dystonia onset, and disease duration could not predict spread to a third body site. Among patients with focal onset in different body parts (cranial, cervical, and upper limb regions), there was no association between site of focal dystonia onset and risk of spread to a third body site., Discussion and Conclusion: Spread to a third body site occurs in a relative low percentage of patients with idiopathic adult-onset dystonia affecting two body parts. Regardless of the site of dystonia onset and of other demographic/clinical variables, focal onset seems to confer a greater risk of spread to a third body site in comparison to patients with segmental/multifocal dystonia at onset., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The pathophysiological mechanisms underlying freezing of gait (FOG) are poorly defined. MRI studies in FOG showed a distinct pattern of cortical atrophy and decreased functional connectivity (FC) within motor and cognitive networks. Furthermore, reduced rs-FC within midbrain, frontal, and temporal areas has been also described. This study investigated the patterns of whole-brain FC alterations within midbrain inter-connected regions in PD-FOG patients, and whether these patterns are linked to midbrain structural damage using a multi-modal imaging approach, combing structural and functional imaging techniques. Methods: Thirty three PD patients (16 PD-FOG, 17 PD noFOG), and 21 sex- and age-matched healthy controls (HCs) were prospectively enrolled. All subjects underwent MRI scan at 1.5T, whereas only PD patients underwent clinical and cognitive assessment. Grey matter (GM) integrity was measured using voxel-based morphometry (VBM). VBM findings served as basis to localize midbrain damage, and were further used as a seed region for investigating whole-brain FC alterations using rs-fMRI. Results: In rs-fMRI, patients with PD and FOG demonstrated significant decrease of midbrain-cortical FC levels in the R PCG, right postcentral, and supramarginal gyri compared to controls and the middle cingulate compared to noFOG group. Based on the regression analysis, MOCA, UPDRS-III total score, and FOG severity scores were associated with FC levels in several frontal, parietal and temporal regions. Discussion: The present results suggest that midbrain structural damage as well as decreased FC within the brainstem functional network might contribute to FOG occurrence in PD patients., Competing Interests: EP: received research grants from Italian Ministry of Health and the Michael J. Fox foundation. LA: received research grants from Italian Ministry of Health and Gossweiler Foundation. MI: received research grants from NIH, DOD, NMSS, FISM, and Teva Neuroscience; received fees for participating in advisory boards from Roche, Biogen, Merck and Genzyme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Droby, Pelosin, Putzolu, Bommarito, Marchese, Mazzella, Avanzino and Inglese.)

Action observation combined with proprioceptive stimulation able to induce a kinesthetic illusion of movement (AO-KI) was shown to elicit a plastic increase in primary motor cortex (M1) excitability, with promising applications in rehabilitative interventions. Nevertheless, the known individual variability in response to combined stimulation protocols limits its application. The aim of this study was to examine whether a relationship exists between changes in M1 excitability during AO-KI and the long-lasting changes in M1 induced by AO-KI. Fifteen volunteers received a conditioning protocol consisting in watching a video showing a thumb-opposition movement and a simultaneous proprioceptive stimulation that evoked an illusory kinesthetic experience of their thumbs closing. M1 excitability was evaluated by means of single-pulse transcranial magnetic stimulation before, DURING the conditioning protocol, and up to 60 min AFTER it was administered. M1 excitability significantly increased during AO-KI with respect to a rest condition. Furthermore, AO-KI induced a long-lasting increase in M1 excitability up to 60 min after administration. Finally, a significant positive correlation appeared between M1 excitability changes during and after AO-KI; that is, participants who were more responsive during AO-KI showed greater motor cortical activity changes after it. These findings suggest that M1 response during AO-KI can be considered a neurophysiological marker of individual responsiveness to the combined stimulation since it was predictive of its efficacy in inducing long-lasting M1 increase excitability. This information would allow knowing in advance whether an individual will be a responder to AO-KI., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Working memory (WM) performance is very often measured using the n-back task, in which the participant is presented with a sequence of stimuli, and required to indicate whether the current stimulus matches the one presented n steps earlier. In this study, we used high-density electroencephalography (hdEEG) coupled to source localization to obtain information on spatial distribution and temporal dynamics of neural oscillations associated with WM update, maintenance and readout. Specifically, we a priori selected regions from a large fronto-parietal network, including also the insula and the cerebellum, and we analyzed modulation of neural oscillations by event-related desynchronization and synchronization (ERD/ERS). During update and readout, we found larger θ ERS and smaller β ERS respect to maintenance in all the selected areas. γ LOW and γ HIGH bands oscillations decreased in the frontal and insular cortices of the left hemisphere. In the maintenance phase we observed decreased θ oscillations and increased β oscillations (ERS) in most of the selected posterior areas and focally increased oscillations in γ LOW and γ HIGH bands in the frontal and insular cortices of the left hemisphere. Finally, during WM readout, we also found a focal modulation of the γ LOW band in the left fusiform cortex and cerebellum, depending on the response trial type (true positive vs. true negative). Overall, our study demonstrated specific spectral signatures associated with updating of memory information, WM maintenance, and readout, with relatively high spatial resolution., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The investigation of how humans perceive and respond to emotional signals conveyed by the human body has been for a long time secondary compared with the investigation of facial expressions and emotional scenes recognition. The aims of this behavioral study were to assess the ability to process emotional body postures and to test whether motor response is mainly driven by the emotional content of the picture or if it is influenced by motor resonance. Emotional body postures and scenes (IAPS) divided into three clusters (fear, happiness, and neutral) were shown to 25 healthy subjects (13 males, mean age ± SD: 22.3 ± 1.8 years) in a three-alternative forced choice task. Subjects were asked to recognize the emotional content of the pictures by pressing one of three keys as fast as possible in order to estimate response times (RTs). The rating of valence and arousal was also performed. We found shorter RTs for fearful body postures as compared with happy and neutral postures. In contrast, no differences across emotional categories were found for the IAPS stimuli. Analysis on valence and arousal and the subsequent item analysis showed an excellent reliability of the two sets of images used in the experiment. Our results show that fearful body postures are rapidly recognized and processed, probably thanks to the automatic activation of a series of central nervous system structures orchestrating the defensive threat reactions, strengthening and supporting previous neurophysiological and behavioral findings in body language processing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Botta, Lagravinese, Bove, Avenanti and Avanzino.)

Theory of mind (ToM) refers to an individual's ability to attribute mental states to predict and explain another person's behavior. It has been shown that patients with cervical dystonia (CD) present impaired ToM ability supporting the idea that CD is a network disorder. An emerging hypothesis is that different phenotypes of CD reflect distinct key nodes in the malfunctioning cerebral network. The aim of the present study was to investigate whether the presence of tremor as additional phenotypic feature of CD influences the ability to attribute a cognitive or emotional state to another person. We enrolled 35 patients with CD, 21 with tremor (CD-T) and 14 without tremor (CD-NT) and 47 age-matched healthy subjects (HS). The Emotion Attribution Task (EAT) was adopted to assess the affective ToM ability while the Advanced Test (AT) was used to investigate the cognitive ToM ability. Results showed that CD patients' performance was worse than HS in recognizing the emotional feelings expressed in the EAT situations, with no difference between CD-T and CD-NT. Regarding cognitive ToM, both CD-T and CD-NT performed worse than HS in the AT task. However, it also emerged that CD-T were more impaired in AT task than CD-NT. Our results indicate that both affective and cognitive aspects of ToM are impaired in CD and that cognitive ToM is more impaired in patients presenting tremor respect to those without. These findings support the hypothesis that the cerebral network responsible of motor and non-motor impairments is more widespread in CD-T than CD-NT.

Background: Action observation (AO) relies on the mirror neuron system (MNS) and has been proposed as a rehabilitation tool in Parkinson's disease (PD), in particular for gait disorder such as freezing of gait (FOG). In this study, we aimed to explore the brain functional correlates of the observation of human gait in PD patients with (FOG+) and without (FOG-) FOG and to investigate a possible relationship between AO-induced brain activation and gait performance., Methods: Fifty-four participants were enrolled in the study (15 PD FOG+; 18 PD FOG-; 21 healthy subjects (HS)) which consisted of two tasks in two separate days: (i) gait assessment and (ii) task-fMRI during AO of gait. Differences between patients with PD (FOG+ and FOG-) and HS were assessed at the level of behavioral and functional analysis., Results: Gait parameters, including gait velocity, stride length, and their coefficients of variability (CV), were different in PD patients compared to HS, whereas gait performance was similar between FOG+ and FOG-. The PD group, compared to HS, presented reduced functional activation in the frontal, cingulum, and parietooccipital regions. Reduced activity was more pronounced in the FOG+ group, compared to both HS and FOG- groups. Gait variability positively correlated with precuneus neural activity in the FOG+ group. Discussion . Patients with PD present a reduced functional activity during AO of gait, especially if FOG+. A baseline knowledge of the neural correlates of AO of gait in the clinical routine "on" status would help for the design of future AO rehabilitative interventions., Competing Interests: EP reports grant from Michael J. Fox Foundation; EP and LA report honoraria for participating at Fox Trial Finder projects of the MJF Foundation; MI received research grants from NIH, DOD, NMSS, FISM, and Teva Neuroscience; RM, GB, MP, CC, and AB have no conflict of interest to report., (Copyright © 2020 Giulia Bommarito et al.)

Introduction: Cervical dystonia (CD) is one of the most common forms of adult-onset isolated dystonia. Recently, CD has been classified according to the site of onset and spread, in different clinical subgroups, that may represent different clinical entities or pathophysiologic subtypes. In order to support this hypothesis, in this study we have evaluated whether different subgroups of CD, that clinically differ for site of onset and spread, also imply different sensorimotor features. Methods: Clinical and demographic data from 842 patients with CD from the Italian Dystonia Registry were examined. Motor features (head tremor and tremor elsewhere) and sensory features (sensory trick and neck pain) were investigated. We analyzed possible associations between motor and sensory features in CD subgroups [focal neck onset, no spread (FNO-NS); focal neck onset, segmental spread (FNO-SS); focal onset elsewhere with segmental spread to neck (FOE-SS); segmental neck involvement without spread (SNI)]. Results: In FNO-NS, FOE-SS, and SNI subgroups, head tremor was associated with the presence of tremor elsewhere. Sensory trick was associated with pain in patients with FNO-NS and with head tremor in patients with FNO-SS. Conclusion: The frequent association between head tremor and tremor elsewhere may suggest a common pathophysiological mechanism. Two mechanisms may be hypothesized for sensory trick: a gating mechanism attempting to reduce pain and a sensorimotor mechanism attempting to control tremor., (Copyright © 2020 Di Biasio, Marchese, Abbruzzese, Baldi, Esposito, Silvestre, Tescione, Berardelli, Fabbrini, Ferrazzano, Pellicciari, Eleopra, Devigili, Bono, Santangelo, Bertolasi, Altavista, Moschella, Barone, Erro, Albanese, Scaglione, Liguori, Cotelli, Cossu, Ceravolo, Coletti Moja, Zibetti, Pisani, Petracca, Tinazzi, Maderna, Girlanda, Magistrelli, Misceo, Romano, Minafra, Modugno, Aguggia, Cassano, Defazio and Avanzino.)

Time processing is a multifaceted skill crucial for managing different aspects of life. In the current work, we explored the relationship between interoception and time processing by examining research on clinical models. We investigated whether time processing deficits are associated with dysfunction of the interoceptive system and/or insular cortex activity, which is crucial in decoding internal body signaling. Furthermore, we explored whether insular activation predicts the subjective experience of time (i.e., the subjective duration of a target stimulus to be timed). Overall, our work suggests that alteration of the interoceptive system could be a common psychophysiological hallmark of mental disorders affected by time processing deficits., (Copyright © 2020 Vicario, Nitsche, Salehinejad, Avanzino and Martino.)

Background: Sleep disturbances and nocturnal hypokinesia are common in Parkinson's disease (PD). Recent work using wearable technologies showed fewer nocturnal movements in PD when compared with controls. However, it is unclear how these manifest across the disease spectrum., Objectives: We assessed the prevalence of sleep disturbances and nocturnal hypokinesia in early and advanced PD and their relation to nonmotor symptoms and dopaminergic medication., Methods: A total of 305 patients with PD with diverse disease severity (Hoehn and Yahr [H&Y] stage 1 = 47, H&Y stage 2 = 181, H&Y stage 3 = 77) and 205 healthy controls continuously wore a tri-axial accelerometer on the lower back for at least 2 days. Lying, turning, and upright -time at night were extracted from the acceleration signals. Percent upright time and nighttime walking were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed were used to evaluate nocturnal movements., Results: Nocturnal lying time was similar among all groups (healthy controls, 7.5 ± 1.2 hours; H&Y stage 1, 7.3 ± 0.9 hours; H&Y stage 2, 7.2 ± 1.3 hours; H&Y stage 3, 7.4 ± 1.6 hours; P = 0.501). However, patients with advanced PD had more upright periods, whereas the number and velocity of their turns were reduced (P ≤ 0.021). Recently diagnosed patients (<1 year from diagnosis) were similar to controls in the number of nocturnal turns (P = 0.148), but showed longer turning time (P = 0.001) and reduced turn magnitude (P = 0.002). Reduced nocturnal movements were associated with increased PD motor severity and worse dysautonomia and cognition and with dopaminergic medication., Conclusions: Using wearable sensors for continuous monitoring of movement at night may offer an unbiased measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Complex motor tasks are learned through training which results in lasting improvement in sensorimotor performance and accuracy. Learning a motor skill is commonly attained via physical execution. However, research has shown that cognitive training, such as motor imagery (MI), effectively facilitates skill learning. Neurophysiological findings suggest that learning-induced plasticity in the human motor cortex, subserving consolidation and retention of motor skills, is stronger after movement execution (ME) than after MI training. Here, we designed an experimental task able to test for the fast and slow learning phases and for retention of motor skills for both MI and ME. We hypothesize that differences between MI and ME training would emerge in terms of reduced consolidation and retention of motor skills. Twenty-four young healthy subjects were divided into two groups, performing MI or ME training. Participants wore sensor-engineered gloves and their sensorimotor performance was assessed over a period of 15 days with 4-days training. We analysed the touch duration (TD), the inter-tapping interval (ITI), movement rate and accuracy. Results showed that (i) during the first phase of acquisition of motor skills, sensorimotor performance improved similarly in MI and ME groups; (ii) during the second learning phase movement rate increased more in ME than MI group and this difference was mainly driven by differences in the duration of TD; (iii) consolidation deficits with MI training reflected in impaired retention of the acquired skills, as TD and ITI were larger and movement rate was lower in the MI group with respect to the ME, till to 10 days after the last training session. Explicit component of motor learning, accuracy, was maintained in retention phase in both groups. Following our hypothesis, our findings show that MI training is as effective as ME within the first learning phase, but consolidation and retention of motor skills are less effective following MI training. This study highlights MI limitations and suggests option to enhance MI, as by providing an external sensory feedback., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The ability to predict temporal outcome of body movement is abnormal in idiopathic dystonia and can be altered by cerebellar neuromodulation. Tremor in cervical dystonia might be associated with performance on motion perception tasks., Methods: A total of 15 cervical dystonia patients with and 14 without tremor and 15 age-matched healthy participants estimated the termination of videos showing different movements (handwriting a sentence, ball reaching a target) after these were darkened at different time intervals., Results: Cervical dystonia patients with tremor exhibited greater absolute timing error across all intervals of the hand motion task (group × task interaction effect, F 2,41 = 4.57; P = 0.016). The percentage of responses in anticipation for both motion tasks did not differ across groups, suggesting lack of timing error directionality., Conclusions: Temporal processing of perceived motion in cervical dystonia is associated with the presence of tremor. Cortico-cerebellar network abnormalities in cervical dystonia might account for motion processing changes in these patients. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME)., Methods: One hundred and nine older fallers, 38 fallers with mild cognitive impairment (MCI), and 128 fallers with Parkinson's disease (PD) were randomly assigned to one of two active interventions: treadmill training only or treadmill training combined with a virtual reality component. Participants were tested before and after the interventions. Free-living walking activity was characterized by volume, pattern, and variability of ambulatory bouts using an accelerometer positioned on the lower back for 1 week. To evaluate that relationship between fall risk and activity, a normalized index was determined expressing fall rates relative to activity exposure (FRA index), with higher scores indicating a higher risk of falls per steps taken., Results: At baseline, the FRA index was higher for fallers with PD compared to those with MCI and older fallers. Walking activity did not change after the intervention for the groups but the FRA index decreased significantly for all groups (p ≤ .035)., Conclusions: This work showed that V-TIME interventions reduced falls risk without concurrent change in walking activity. We recommend using the FRA index in future fall prevention studies to better understand the nature of intervention programs., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background . People with Parkinson's disease and freezing of gait (FOG+) have more falls, postural instability and cognitive impairment compared with FOG-. Objective . To conduct a secondary analysis of the V-TIME study, a randomized, controlled investigation showing a greater reduction of falls after virtual reality treadmill training (TT + VR) compared with usual treadmill walking (TT) in a mixed population of fallers. We addressed whether these treadmill interventions led to similar gains in FOG+ as in FOG-. Methods . A total of 77 FOG+ and 44 FOG- were assigned randomly to TT + VR or TT. Participants were assessed pre- and posttraining and at 6 months' follow-up. Main outcome was postural stability assessed by the Mini Balance Evaluation System Test (Mini-BEST) test. Falls were documented using diaries. Other outcomes included the New Freezing of Gait Questionnaire (NFOG-Q) and the Trail Making Test (TMT-B). Results . Mini-BEST scores and the TMT-B improved in both groups after training ( P = .001), irrespective of study arm and FOG subgroup. However, gains were not retained at 6 months. Both FOG+ and FOG- had a greater reduction of falls after TT + VR compared with TT ( P = .008). NFOG-Q scores did not change after both training modes in the FOG+ group. Conclusions . Treadmill walking (with or without VR) improved postural instability in both FOG+ and FOG-, while controlling for disease severity differences. As found previously, TT + VR reduced falls more than TT alone, even among those with FOG. Interestingly, FOG itself was not helped by training, suggesting that although postural instability, falls and FOG are related, they may be controlled by different mechanisms.

Freezing of gait is considered one of the most disabling gait disorders in patients with PD. An effective treatment for freezing of gait is missing, thus current management requires a multidisciplinary approach. Among treatment options, physiotherapy is acknowledged to be crucial; however, a systematic review that demonstrates its efficacy is missing. This review aims at examining the short- and long-term effects of physiotherapy in improving freezing of gait in PD patients. Five electronic databases were searched for English-language full-text articles, and only randomized controlled trials were considered. The freezing of gait questionnaire was selected as the primary outcome measure because it is the only validated measure used to evaluate the severity and impact of freezing of gait on patients' daily life. From 1,130 trials, 19 relevant studies, including 913 patients, were selected. The included studies varied for sample size, methodology, and type of intervention. None of the studies had a low risk of bias, but the majority of randomized control trials presented a low risk for at least 6 of 13 biases. Our findings provide evidence for short-term effectiveness of physiotherapy in improving freezing of gait (physiotherapy vs. no treatment: effect size = -0.28 [-0.45, -0.11], P = 0.001; physiotherapy vs. control: effect size = 0.43 [-0.65, -0.21], P < 0.0001), particularly when tailored interventions are applied. These results seem to be maintained at the follow-up examinations (effect size = -0.52 [-0.78, -0.26]; P = 0.001). Promising findings on the potential benefits of physiotherapy in improving freezing of gait were found, although further randomized control trial studies are still needed. Questions remain on the type and duration of intervention that best fits for treating freezing of gait symptom in PD. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Background: Falls are frequent in Parkinson's disease and aging. Impairments in the cholinergic-mediated attentional supervision of gait may contribute to increased fall risk, especially when obstacles challenge gait. Interventions combining motor-cognitive approaches have been shown to improve motor performance, cognitive skills, and falls number. Here, we hypothesized that an intervention simulating an attention-demanding walking condition could affect not only complex gait performance and fall risk but also short-latency afferent inhibition (SAI), as a marker of cholinergic activity., Methods: Thirty-nine participants at falls risk (24 Parkinson's disease participants and 15 older adults) were recruited in a randomized controlled trial. Participants were assigned to treadmill training or treadmill training with non-immersive virtual reality intervention and trained three times a week for 6 weeks. SAI, a transcranial magnetic stimulation paradigm, was used to assess cholinergic activity. Gait kinematics was measured during usual walking and while negotiating physical obstacles. Transcranial magnetic stimulation and gait assessments were performed pre, post, and 6 months post-intervention., Results: Treadmill training combined with non-immersive virtual reality induced an increase in inhibition of the SAI protocol on cortical excitability, improved obstacle negotiation performance, and induced a reduction of the number of falls compared with treadmill training. Furthermore, the more SAI increased after training, the more the obstacle negotiation performance improved and fall rate decreased., Conclusions: We provide evidence that an innovative rehabilitation approach targeting cognitive components of complex motor actions can induce changes in cortical cholinergic activity, as indexed by SAI, thereby enabling functional gait improvements., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Goal: Functional connectivity (FC) is an important indicator of the brain's state in different conditions, such as rest/task or health/pathology. Here we used high-density electroencephalography coupled to source reconstruction to assess frequency-specific changes of FC during resting state. Specifically, we computed the Small-World Propensity (SWP) index to characterize network small-world architecture across frequencies. Methods: We collected resting state data from healthy participants and built connectivity matrices maintaining the heterogeneity of connection strengths. For a subsample of participants, we also investigated whether the SWP captured FC changes after the execution of a working memory (WM) task. Results: We found that SWP demonstrated a selective increase in the alpha and low beta bands. Moreover, SWP was modulated by a cognitive task and showed increased values in the bands entrained by the WM task. Conclusions: SWP is a valid metric to characterize the frequency-specific behavior of resting state networks.

Objective: To determine whether different phenotypes of cervical dystonia (CD) express different types and levels of somatosensory impairment., Methods: We assessed somatosensory function in patients with CD with and without tremor (n = 12 each) and in healthy age-matched controls (n = 22) by measuring tactile temporal discrimination thresholds of the nondystonic forearm and proprioceptive acuity in both the dystonic (head/neck) and nondystonic body segments (forearm/hand) using a joint position-matching task. The head or the wrist was passively displaced along different axes to distinct joint positions by the experimenter or through a robotic exoskeleton. Participants actively reproduced the experienced joint position, and the absolute joint position-matching error between the target and the reproduced positions served as a marker of proprioceptive acuity., Results: Tactile temporal discrimination thresholds were significantly elevated in both CD subgroups compared to controls. Proprioceptive acuity of both the dystonic and nondystonic body segments was elevated in patients with CD and tremor with respect to both healthy controls and patients with CD without tremor. That is, tactile abnormalities were a shared dysfunction of both CD phenotypes, while proprioceptive dysfunction was observed in patients with CD with tremor., Conclusions: Our findings suggest that the pathophysiology in CD can be characterized by 2 abnormal neural processes: a dysfunctional somatosensory gating mechanism involving the basal ganglia that triggers involuntary muscle spasms and abnormal processing of proprioceptive information within a defective corticocerebellar loop, likely affecting the feedback and feedforward control of head positioning. This dysfunction is expressed mainly in CD with tremor., (© 2020 American Academy of Neurology.)

Background: Acute peripheral trauma is a controversial risk factor for idiopathic dystonia., Materials and Methods: We retrospectively analyzed data from the Italian Dystonia Registry regarding the occurrence of acute peripheral trauma severe enough to require medical attention in 1382 patients with adult-onset idiopathic dystonia and 200 patients with acquired adult-onset dystonia., Results: Patients with idiopathic and acquired dystonia showed a similar burden of peripheral trauma in terms of the number of patients who experienced trauma (115/1382 vs. 12/200, p = 0.3) and the overall number of injuries (145 for the 1382 idiopathic patients and 14 for the 200 patients with secondary dystonia, p = 0.2). Most traumas occurred before the onset of idiopathic or secondary dystonia but only a minority of such injuries (14 in the idiopathic group, 2 in the acquired group, p = 0.6) affected the same body part as that affected by dystonia. In the idiopathic group, the elapsed time between trauma and dystonia onset was 8.1 ± 9.2 years; only six of the 145 traumas (4.1%) experienced by 5/1382 idiopathic patients (0.36%) occurred one year or less before dystonia onset; in the acquired dystonia group, the two patients experienced prior trauma to the dystonic body part 5 and 6 years before dystonia development., Discussion and Conclusion: Our data suggest that the contribution of peripheral acute trauma to idiopathic dystonia is negligible, if anything, and likely involves only a small subset of patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© The Author(s) 2020. Published by Oxford University Press.)

Introduction: Perception of verticality is fundamental for postural stability that is often impaired in patients with Parkinson's disease (PD). Haptic perception of verticality has not been fully investigated in PD. The aim of the study was to assess subjective haptic vertical (SHV) in PD patients in relation to postural and balance impairments., Methods: 39 PD patients (mean age 72.87 ± 5.78) and 28 gender and age-matched healthy elderly (ELD, mean age 69.16 ± 13.89) were enrolled. The Pull test and the Activities-specific Balance Confidence (ABC) were used for evaluating balance performance, whereas measurement of posture was performed using the Physical Analyzer System ® . For evaluating SHV, participants were instructed to provide their subjective vertical by manipulating with two hands a road while standing with their eyes closed., Results: SHV data showed that PD subjects had a greater deviation from the objective vertical than controls (p < 0.001). Significant differences in balance performance (ABC and Pull test) and postural alignment were found between PD and ELD. Only in PD participants, SHV deviations significantly correlated with the lateral inclination of the trunk (r = 0.618, p < 0.001), pull test (r = 0.519; p = 0.001) and ABC (r = 0.471, p = 0.002) scores., Conclusions: The perception of verticality, driven by multimodal sensory integration, is defective in PD subjects. Deficits in SHV correlated with postural alignment and balance performances, independently from age, disease severity or cognitive decline. Our findings support that PD pathology is associated with a decline in haptic perception suggesting that perception per se might have a causal role in postural and balance deficits., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Before movement onset, during the reaction time, excitability of M1 is selectively modulated by somatosensory inputs, only in the movement-related muscle. If a similar mechanism operates before the onset of mental movements, then somatosensory afferent inputs are exploited during cognitive representation of movement. We assessed sensorimotor modulation through short latency afferent inhibition (SAI) paradigm before the onset of executed and imagined movements. Participants performed or imagined an abduction of index or little finger, in response to an acoustic signal. SAI was evaluated between a Warning and a Go signal and 100 ms after the Go signal, before the real or expected EMG activity. Results showed a reduction of SAI after the Go signal, in the movement-related muscle, during motor imagery as well as movement execution. There was a positive correlation between the individual degree of sensorimotor modulation during executed and mental movements and between the sensorimotor modulation during mental movements and motor imagery ability. Sensorimotor modulation operates during the cognitive representation of movement with selective disinhibition of the cortical representation of the muscle involved in the task. Sensorimotor modulation mechanisms prior to mental and executed movements likely share overlapping circuits., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)