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• The cerebellum receives sensory information for adaptive motor coordination and motor planning. • We tested the effect of median nerve stimulation (ES) on cerebellar brain inhibition (CBI). • We found reduced CBI when the ES was delivered 25 or 35 ms prior to CBI testing. 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. 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. 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). 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. To test the interaction between somatosensory inputs and cerebello-cortical pathway may be important in a variety of motor tasks and neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

• Instructed-delay reaction time task involving concentric and eccentric contraction. • CSE tested from 300 ms before up to 40 ms after an imperative signal. • CSE significantly differs between contractions around the imperative signal. • Role of preparatory inhibition and attentional processing in eccentric contractions. 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_50) and a significant increase 40 ms after it (Post_40) with respect to the MEPs recorded at Pre_150. Finally, CSE in eccentric contraction was lower before the Go cue (Pre_50) and greater after it (Post_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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Working memory (WM) is already impaired in early-HD and in pre-manifest HD (pre-HD) • We recorded neuronal oscillations with hdEEG in pre- and early-HD during a WM task. • We analyzed θ, β, gamma low, γ LOW and γ HIGH ERS/ERD during WM update, maintenance and readout. • θ oscillations were generally reduced in HD during the update and readout phases. • In HD, γ oscillations during WM task correlated with disease burden score. We recently demonstrated specific spectral signatures associated with updating of memory information, working memory (WM) maintenance and readout, with relatively high spatial resolution by means of high-density electroencephalography (hdEEG). WM is impaired already in early symptomatic HD (early-HD) and in pre-manifest HD (pre-HD). The aim of this study was to test whether hdEEG coupled to source localization allows for the identification of neuronal oscillations in specific frequency bands in 16 pre-HD and early-HD during different phases of a WM task. We examined modulation of neural oscillations by event-related synchronization and desynchronization (ERS/ERD) of θ, β, gamma low, γ LOW and γ HIGH EEG bands in a-priori selected large fronto-parietal network, including the insula and the cerebellum. We found: (i) Reduced θ oscillations in HD with respect to controls in almost all the areas of the WM network during the update and readout phases; (ii) Modulation of β oscillations, which increased during the maintenance phase of the WM task in both groups; (iii) correlation of γ HIGH oscillations during WM task with disease burden score in HD patients. Our data show reduced phase-specific modulation of oscillations in pre-HD and early-HD, even in the presence of preserved dynamic of modulation. Particularly, reduced synchronization in the θ band in the areas of the WM network, consistent with abnormal long-range coordination of neuronal activity within this network, was found in update and readout phases in HD groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Recent work suggests that wearables can augment conventional measures of Parkinson's disease (PD). We evaluated the relationship between conventional measures of disease and motor severity (e.g., MDS-UPDRS part III), laboratory-based measures of gait and balance, and daily-living physical activity measures in patients with PD.Methods: Data from 125 patients (age: 71.7 ± 6.5 years, Hoehn and Yahr: 1-3, 60.5% men) were analyzed. The MDS-UPDRS-part III was used as the gold standard of motor symptom severity. Gait and balance were quantified in the laboratory. Daily-living gait and physical activity metrics were extracted from an accelerometer worn on the lower back for 7 days.Results: In multivariate analyses, daily-living physical activity and gait metrics, laboratory-based balance, demographics and subject characteristics together explained 46% of the variance in MDS-UPDRS-part III scores. Daily-living measures accounted for 62% of the explained variance, laboratory measures 30%, and demographics and subject characteristics 7% of the explained variance. Conversely, demographics and subject characteristics, laboratory-based measures of gait symmetry, and motor symptom severity together explained less than 30% of the variance in total daily-living physical activity. MDS-UPDRS-part III scores accounted for 13% of the explained variance, i.e., <4% of all the variance in total daily-living activity.Conclusions: Our findings suggest that conventional measures of motor symptom severity do not strongly reflect daily-living activity and that daily-living measures apparently provide important information that is not captured in a conventional one-time, laboratory assessment of gait, balance or the MDS-UPDRS. To provide a more complete evaluation, wearable devices should be considered. [ABSTRACT FROM AUTHOR]

Although acquired dystonia may develop following ischaemic/haemorrhagic stroke, the relationship between cerebrovascular disease and idiopathic dystonia has been poorly investigated. This cross sectional study aimed at evaluating the impact of cerebrovascular risk factors on the clinical expression of idiopathic adult onset dystonia (IAOD), with reference to dystonia localization and dystonia-associated features. Data were obtained from the Italian Dystonia Registry. Patients with IAOD were stratified into two groups according to the presence of diabetes mellitus and/or arterial hypertension and/or dyslipidemia and/or heart disease. The two groups were compared for demographic features, dystonia phenotype, and dystonia-associated features (sensory trick, tremor, eye symptoms in blepharospasm, and neck pain in cervical dystonia). A total of 1108 patients participated into the study. Patients who reported one cerebrovascular factor or more (n = 555) had higher age and longer disease duration than patients who did not. On multivariable logistic regression analysis, blepharospasm was the only localization, and sensory trick was the only dystonia-associated feature that was significantly associated with cerebrovascular risk factors. Linear regression analysis showed that the strength of the association between cerebrovascular factors and blepharospasm/sensory trick increased with increasing the number of cerebrovascular factors per patient. Results of the present study showed that cerebrovascular risk factors may be associated with specific features of IAOD that is development of blepharospasm and sensory trick. Further studies are needed to better understand the meaning and the mechanisms underlying this association. • We assessed the impact of vascular risk factors (VRFs) on idiopathic dystonia. • VRFs may be associated with specific phenotypes of idiopathic dystonia. • This may suggest that VRFs-related lesions changes impact on idiopathic dystonia. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Cues variety hinder to determine which cueing modality to use for more personalized treatment of Freezing of Gait (FOG). • This systematic review explores cueing effectiveness on FOG related parameters during gait initiation, walking and turning. • Gait initiation (APAs) and turning (turning time, step time CV, FOG episodes) can be improved by visual and auditory cueing. • During walking visual cueing can ameliorate step and stride length but not FOG episodes. • Freezing features (subtypes and triggers) should be considered when designing a FOG-tailored cue trial. [ABSTRACT FROM AUTHOR]

The present study was designed to explore the changes in motor performance and motor resonance after multiple sessions of action observation (AO) training. Subjects were exposed to the observation of a video showing finger tapping movements executed at 3 Hz, a frequency higher than the spontaneous one (2 Hz) for four consecutive days. Motor performance and motor resonance were tested before the AO training on the first day, and on the last day. Results showed that multiple sessions of AO training induced a shift of the speed of execution of finger tapping movements toward the observed one and a change in motor resonance. Before the 3 Hz-AO training cortical excitability was highest during the observation of the 2 Hz video. This motor resonance effect was lost after one single session of 3 Hz-AO training whereas after multiple sessions of 3 Hz-AO training cortical excitability was highest during the observation of the 3 Hz video. Our study shows for the first time that multiple sessions of AO training are able not only to induce performance gains but also to change the way by which the observer's motor system recognizes a certain movement as belonging to the individual motor repertoire. These results may encourage the development of novel rehabilitative protocols based on multiple sessions of action observation aimed to regain a correct movement when its spontaneous speed is modified by pathologies or to modify the innate temporal properties of certain movements. [ABSTRACT FROM AUTHOR]

Rehabilitation is considered as an adjuvant to pharmacological and surgical treatments for Parkinson's disease (PD) to maximize functional ability and minimize secondary complications. Originally, approaches were based on empirical experience, but growing evidence suggests that exercise-dependent plasticity constitutes the main mechanism underlying the effects of physiotherapy. Exercise increases synaptic strength and influences neurotransmission, thus potentiating functional circuitry in PD. In addition, exercise is a pivotal element of motor learning. PD patients retain a sufficient capacity of motor learning, though learning rates and performance are reduced in comparison to normal controls. Recent meta-analyses demonstrated that rehabilitation could induce short-lasting, but clinically important benefits, particularly for gait and balance. However, the interventions are largely heterogeneous (stretching, muscle strengthening, balance, postural exercises, occupational therapy, cueing, treadmill training), and there is still no consensus about the optimal approach. Innovative techniques have been recently proposed: virtual reality and exergaming, motor imagery and action observation, robot-assisted physiotherapy and non-conventional therapies (e.g.: dance, martial arts). The rehabilitative program for PD should be "goal-based" (targeted to practicing and learning specific activities in the core areas), but a number of practice variables (intensity, specificity, complexity) need to be identified and the program should tailored to the individual patients' characteristics. [ABSTRACT FROM AUTHOR]

Background: Objective measures of physical and cognitive fatigability do not correlate with subjective Parkinson's disease (PD)-related fatigue. The relationship of subjective PD-related fatigue to tasks combining cognitive and motor effort has never been explored.Methods: Forty-four right-handed, non-demented PD patients, 22 with (PD-F) and 22 without (PD-NF) fatigue, were tested using a sensor-engineered glove on their more affected hand. Patients performed sequential opposition finger movements following a metronome at 2 Hz for 5 min (cued task), and for another minute following a 2-min rest. The same task was repeated without sustained auditory cueing. Movement time (inter-tapping interval, ITI) and rate, touch duration, percentage of correct sequences and clinical measures (motor and fatigue severity, depression, sleep impairment and apathy) were analysed.Results: In the cued task, motor performance worsened over time (significantly increased ITI and decreased movement rate on the third to fifth minute) in PD-F patients only. In the uncued task, motor performance deteriorated similarly in the two groups. PD-F and PD-NF patients differed in ITI and movement rate deterioration over time only in the cued task, independently from motor severity, depression and sleep impairment. The severity of subjective fatigue complaints significantly correlated with motor performance deterioration in the cued task.Conclusions: PD-related fatigue is associated with performance on an externally cued, attention-controlled motor task, but not with an uncued version of the same task. The finding supports a link between PD-related fatigue and attention-demanding motor tasks, proposing a model of inducible fatigue applicable to future clinical and neuroimaging research. [ABSTRACT FROM AUTHOR]

Background Affective “Theory of Mind” (ToM) is the specific ability to represent own and others' emotional states and feelings. Several studies examined affective ToM ability in patients with Parkinson's disease (PD), using the “Reading the Mind in the Eyes test” (RMET). However, there has been no agreement as to whether or not affective ToM ability is impaired in PD and such discrepancy may be due to the heterogeneous clinical presentation of PD. Affective disturbance has been linked to the akinetic-rigid form of PD and to gait disturbances, like freezing of gait (FOG). Particularly, FOG has been associated with dysfunction in striatum ability of processing affective inputs. Here we hypothesized that the presence of FOG can be associated with impaired affective ToM ability in PD patients. Methods We evaluated ToM by means of RMET and executive functions using the Tower Of London (ToL) test in 29 PD patients (15 with FOG and 14 without FOG) and 19 healthy age-matched subjects. Results Our results showed that affective ToM is abnormal in PD patients, compared to healthy subjects and that it is more impaired in patients with FOG than in patients without FOG. Further, PD patients with FOG performed worse than PD patients without FOG on the ToL test. Conclusion The affective aspects of ToM can be associated to FOG in patients with PD, thus supporting the idea that FOG is caused by a complex interplay between motor, cognitive and affective factors, rather than being a pure motor problem. [ABSTRACT FROM AUTHOR]

Abstract: Motor performance recovery after a demanding finger motor task does not follow the excitability dynamics of primary motor cortex (M1), which remains depressed also when performance is restored. Thus, other neural circuits are supposed to cope with central fatigue, re-establishing adequate motor performance levels. A hint that the basal ganglia (BG) can be involved in this process is provided by studies showing an association of central fatigue with the BG. To investigate this possibility, we conducted an fMRI study with simultaneous motor performance recording in 20 healthy volunteers at different stages of a demanding finger motor task: baseline, central fatigue induced by 5-min sequence repetition, performance recovery after a short rest period. When motor performance was recovered, we observed a significant activation with respect to baseline in subcortical structures belonging to different BG circuits (putamen and globus pallidus), involving the limbic system functionally interacting with the BG (amygdala). Then, to assess whether the BG activation was exclusively related to the fatigue and recovery processes or to increasing automatism in motor performance, a control fMRI experiment based on a shorter motor task duration was carried out on 14 healthy subjects. In this case, the task repetition did not induce decreased performance, and no significant effect on the BOLD signal change was found in BG regions of interest with respect to baseline. All these findings suggest that motor and non-motor BG circuits run parallel and converge in a common motor path to successfully compensate motor performance deterioration in a central fatigue condition. [Copyright &y& Elsevier]

Abstract: Objective: To study short interval intracortical inhibition (SICI) in a rare patient with segmental dystonia of the left upper limb due to a vascular lesion in the contralateral putamen without corticospinal tract involvement. Methods: Paired-pulse transcranial magnetic stimulation (TMS) was applied to both hemispheres in a conditioning-test paradigm. Six interstimulus intervals (ISIs) and 4 conditioning stimulation intensities were investigated in two separate sessions. Results: Motor evoked potentials upon single-pulse TMS were within the normal range, whereas paired-pulse TMS revealed major changes in cortical excitability, proving that SICI was bilaterally absent. Conclusions: The bilateral impairment of SICI cannot be considered the cause of dystonic contractions, but just a predisposing factor. Significance: The absence of SICI might be regarded as a condition able to promote maladaptive plastic changes triggered by focal lesions in the putamen. [Copyright &y& Elsevier]

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. • Motor imagery (MI) is as effective as actual training within the 1st learning phase. • Learning processes are less efficient in the 2nd learning phase with MI training. • Consolidation deficits reflect in impaired retention of motor skills with MI training. [ABSTRACT FROM AUTHOR]

Background: Given that patients with Parkinson's Disease (PD) and Freezing of Gait (FoG) may lack the cognitive resources necessary to activate the motor imagery (MI) process, investigating how to boost MI vividness and accuracy could be a valuable therapeutic strategy in MI Practice (MIP)., Objective: We aim to evaluate the priming effect of visual, or auditory, or attentional stimuli in enhancing MI ability by using quantitative data on gait and turning performance., Methods: Nineteen PD participants with FoG underwent four one-week sessions of MIP, with pre and post clinical assessments. Each session included MI alone or one of three booster MI tasks (Attentional, Action observation, or Auditory) before imagining and executing walking straight and performing a 180° turn. Gait and turning performances were evaluated using six inertial sensors before and after each session., Results: Our findings showed that both MI and boosted MI induced similar improvement in gait (speed and stride length) and 180° (step number and velocity) and 360° turning (velocity, angle) parameters compared to baseline. When differences among "booster" tasks were analyzed, results showed that Auditory and Attentional boosted MI were superior to MI alone in some gait and turning parameters. At the end of the 4 sessions, MI ability measured by means of Kinesthetic and Visual Imagery Questionnaire and Gait Imagery Questionnaire and FoG symptoms were also improved., Conclusion: Our preliminary results suggest that boosting MI is a feasible strategy for enhancing MI ability and addressing FoG symptoms. Auditory and Attentional conditions appear to enhance the priming effect of MI on gait and turning performance more effectively., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paolo Bernardis is Guest Associate Editor in Emotion Science and Rewiev Editor in Motor Neuroscience. Martina Putzolu reports financial support was provided by Ministry of University. Alessandro Botta reports a relationship with EU Joint Programme Neurodegenerative Disease Research that includes: employment. Gaia Bonassi reports a relationship with Ministry of University that includes: employment. Roberta Marchese reports a relationship with Ministry of Health that includes: funding grants. Roberta Marchese reports a relationship with Zambon Pharmaceutical Laboratories that includes: consulting or advisory. Roberta Marchese reports a relationship with Bial that includes: consulting or advisory. Roberta Marchese reports a relationship with AbbVie Inc that includes: consulting or advisory. Laura Avanzino reports financial support was provided by Ministry of University. Laura Avanzino reports a relationship with EU Joint Programme Neurodegenerative Disease Research that includes: funding grants. Laura Avanzino reports a relationship with The Michael J Fox Foundation that includes: funding grants. Laura Avanzino reports a relationship with Zambon Pharmaceutical Laboratories that includes: consulting or advisory. Laura Avanzino reports a relationship with Bial that includes: consulting or advisory. Laura Avanzino is the Review Editor of Frontiers, section Movement Disorders and, Intervention for Rehabilitation. Elisa Pelosin reports financial support was provided by Ministry of University. Elisa Pelosin reports a relationship with Ministry of University - PRIN that includes: funding grants. Elisa Pelosin reports a relationship with The Michael J Fox Foundation that includes: funding grants. Elisa Pelosin reports a relationship with The Michael J Fox Foundation that includes: consulting or advisory. Elisa Pelosin is an Associate Editor of Archives of Physiotherapy, section neurology. If there are other authors, they 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals., Objectives: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD., Methods: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale., Results: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction., Conclusion: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects., (© 2024. The Author(s).)

Background: Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread., Objective: To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD., Methods: Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed., Results: Women predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia., Conclusions: Our findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Valence (positive and negative) and content (embodied vs non-embodied) characteristics of visual stimuli have been shown to influence motor readiness, as tested with response time paradigms. Both embodiment and emotional processing are affected in Parkinson's disease (PD) due to basal ganglia dysfunction. Here we aimed to investigate, using a two-choice response time paradigm, motor readiness when processing embodied (emotional body language [EBL] and emotional facial expressions [FACS]) vs non-embodied (emotional scenes [IAPS]) stimuli with neutral, happy, and fearful content. We enrolled twenty-five patients with early-stage PD and twenty-five age matched healthy participants. Motor response during emotional processing was assessed by measuring response times (RTs) in a home-based, forced two-choice discrimination task where participants were asked to discriminate the emotional stimulus from the neutral one. Rating of valence and arousal was also performed. A clinical and neuropsychological evaluation was performed on PD patients. Results showed that RTs for PD patients were longer for all conditions compared to HC and that RTs were generally longer in both groups for EBL compared to FACS and IAPS, with the sole exception retrieved for PD, where in discriminating fearful stimuli, RTs for EBL were longer compared to FACS but not to IAPS. Furthermore, in PD only, when discriminating fearful respect to neutral stimuli, RTs were shorter when discriminating FACS compared to IAPS. This study shows that PD patients were faster in discriminating fearful embodied stimuli, allowing us to speculate on mechanisms involving an alternative, compensatory, emotional motor pathway for PD patients undergoing fear processing., (© 2024. The Author(s).)

Step length is an important diagnostic and prognostic measure of health and disease. Wearable devices can estimate step length continuously (e.g., in clinic or real-world settings), however, the accuracy of current estimation methods is not yet optimal. We developed machine-learning models to estimate step length based on data derived from a single lower-back inertial measurement unit worn by 472 young and older adults with different neurological conditions, including Parkinson's disease and healthy controls. Studying more than 80,000 steps, the best model showed high accuracy for a single step (root mean square error, RMSE = 6.08 cm, ICC(2,1) = 0.89) and higher accuracy when averaged over ten consecutive steps (RMSE = 4.79 cm, ICC(2,1) = 0.93), successfully reaching the predefined goal of an RMSE below 5 cm (often considered the minimal-clinically-important-difference). Combining machine-learning with a single, wearable sensor generates accurate step length measures, even in patients with neurologic disease. Additional research may be needed to further reduce the errors in certain conditions., (© 2024. The Author(s).)

Action observation (AO) and motor imagery (MI) has emerged as promising tool for physiotherapy intervention in Parkinson's disease (PD). This narrative review summarizes why, how, and when applying AO and MI training in individual with PD. We report the neural underpinning of AO and MI and their effects on motor learning. We examine the characteristics and the current evidence regarding the effectiveness of physiotherapy interventions and we provide suggestions about their implementation with technologies. Neurophysiological data suggest a substantial correct activation of brain networks underlying AO and MI in people with PD, although the occurrence of compensatory mechanisms has been documented. Regarding the efficacy of training, in general evidence indicates that both these techniques improve mobility and functional activities in PD. However, these findings should be interpreted with caution due to variety of the study designs, training characteristics, and the modalities in which AO and MI were applied. Finally, results on long-term effects are still uncertain. Several elements should be considered to optimize the use of AO and MI in clinical setting, such as the selection of the task, the imagery or the video perspectives, the modalities of training. However, a comprehensive individual assessment, including motor and cognitive abilities, is essential to select which between AO and MI suite the best to each PD patients. Much unrealized potential exists for the use AO and MI training to provide personalized intervention aimed at fostering motor learning in both the clinic and home setting.

Numerous lines of research indicate that our social brain involves a network of cortical and subcortical brain regions that are responsible for sensing and controlling body movements. However, it remains unclear whether movement disorders have a systematic impact on social cognition. To address this question, we conducted a systematic review examining the influence of hyperkinetic movement disorders (including Huntington disease, Tourette syndrome, dystonia, and essential tremor) on social cognition. Following the PRISMA guidelines and registering the protocol in the PROSPERO database (CRD42022327459), we analyzed 50 published studies focusing on theory of mind (ToM), social perception, and empathy. The results from these studies provide evidence of impairments in ToM and social perception in all hyperkinetic movement disorders, particularly during the recognition of negative emotions. Additionally, individuals with Huntington's Disease and Tourette syndrome exhibit empathy disorders. These findings support the functional role of subcortical structures (such as the basal ganglia and cerebellum), which are primarily responsible for movement disorders, in deficits related to social cognition.

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

Tendon vibration of a limb elicits illusory movements in the direction that the vibrated muscle would be stretched, followed by a transient perception of movement in the opposite direction, that was demonstrated to correspond to a "cortical" aftereffect (Goodwin et al. Science 175:1382-1384, 1972). Primary motor cortex (M1) excitability of the non-vibrated antagonist muscle of the vibrated muscle increased during vibration and decreased thereafter. The cortical aftereffect is of interest when considering the possibility to use tendon vibration in rehabilitation for restoring unbalance activity between antagonistic muscles but, due to its short-lasting duration, has not been explored so far. We investigated the possibility to consolidate the cortical aftereffect by combining tendon vibration with a concomitant high-frequency 5-Hz repetitive transcranial magnetic stimulation (rTMS) protocol. The distal tendon of the flexor carpi radialis muscle (FCR) was vibrated and concomitantly a 2-min 5-Hz rTMS protocol was administered on the left hemi-scalp hot spot of the vibrated FCR or its antagonist muscle (extensor carpi radialis (ECR)). We found that this protocol induced a pattern of unbalanced M1 excitability between vibrated muscle and its antagonist with increased excitability of the FCR and decreased excitability of ECR cortical areas, which persisted up to 30 min.

Objective: It is under debate whether the cerebellum plays a role in dystonia pathophysiology and in the expression of clinical phenotypes. We investigated a typical cerebellar function (anticipatory movement control) in patients with cervical dystonia (CD) with and without tremor., Methods: Twenty patients with CD, with and without tremor, and 17 healthy controls were required to catch balls of different load: 15 trials with a light ball, 25 trials with a heavy ball (adaptation) and 15 trials with a light ball (post-adaptation). Arm movements were recorded using a motion capture system. We evaluated: (i) the anticipatory adjustment (just before the impact); (ii) the extent and rate of the adaptation (at the impact) and (iii) the aftereffect in the post-adaptation phase., Results: The anticipatory adjustment was reduced during adaptation in CD patients with tremor respect to CD patients without tremor and controls. The extent and rate of adaptation and the aftereffect in the post-adaptation phase were smaller in CD with tremor than in controls and CD without tremor., Conclusion: Patients with cervical dystonia and tremor display an abnormal predictive movement control., Significance: Our findings point to a possible role of cerebellum in the expression of a clinical phenotype in dystonia., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is tightly linked also to sensory dysfunction. Accurate motor control requires an optimal processing of afferent inputs from different sensory systems, in particular visual and somatosensory (e.g., touch and proprioception). Several experimental studies indicate that sensory-motor integration - the process through which sensory information is used to plan, execute, and monitor movements - is impaired in focal dystonia. The neural degenerations associated with these alterations affect not only the basal ganglia-thalamic-frontal cortex loop, but also the parietal cortex and cerebellum. The present review outlines the experimental studies describing impaired sensory-motor integration in focal dystonia, establishes their relationship with changes in specific neural mechanisms, and provides new insight towards the implementation of novel intervention protocols. Based on the reviewed state-of-the-art evidence, the theoretical framework summarized in the present article will not only result in a better understanding of the pathophysiology of dystonia, but it will also lead to the development of new rehabilitation strategies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that the known motor problems in Parkinson's disease that are generally characterized as a failure of sensorimotor integration may, in fact, have a sensory origin.

Background: Hemifacial spasm (HFS) is a common movement disorder., Objective: To evaluate possible differences in the demographic and clinical features between primary and secondary HFS., Design: In-person interview using a standardized questionnaire to collect demographic and clinical data., Setting: A multicenter study that included patients with HFS attending 3 Italian academic centers. Patients Two hundred fourteen patients with HFS., Main Outcome Measure: A complete neurological examination assessed the current muscle distribution of spasm and the presence of synkinetic movements between upper and lower facial muscles., Results: The study sample comprised 214 patients with HFS, 81 men and 133 women, having a mean +/- SD age of 65.9 +/- 12.3 years; 164 patients were classified as having primary HFS and 50 patients (48 postparalytic and 2 symptomatic cases) were classified as having secondary HFS. Patients with primary and those with secondary HFS had similar mean +/- SD ages at onset (54.9 +/- 13.5 vs 57.0 +/- 12.8 years), male-female ratios (63:101 vs 18:32), right-sided-left-sided HFS (77:86 [1 bilateral] vs 21:28 [1 bilateral]), and frequencies of familial cases (2.9% vs 2.0%), respectively. Most patients (65.0%) with primary HFS had initial symptoms of periocular muscle contractions alone and had subsequent involvement of the lower facial muscles. Most patients (72.0%) with secondary HFS reported initial involvement of the upper and lower facial muscles simultaneously. Signs of synkinesis were present in primary (43.3%) and secondary (58.0%) HFS., Conclusions: Patients with primary and those with secondary HFS share common demographic and clinical features, including sex distribution, age at onset, affected side of HFS, synkinesis, and rarity of familial cases. Signs of synkinesis were present in significant proportions of patients with primary or secondary HFS. The 2 forms differed in clinical presentation.