Cerebellar Direct Current Stimulation Reveals the Causal Role of the Cerebellum in Temporal Prediction.

Temporal prediction (TP) influences our perception and cognition. The cerebellum could mediate this multi-level ability in a context-dependent manner. We tested whether a modulation of the cerebellar neural activity, induced by transcranial Direct Current Stimulation (tDCS), changed the TP ability according to the temporal features of the context and the duration of target interval. Fifteen healthy participants received anodal, cathodal, and sham tDCS (15 min × 2 mA intensity) over the right cerebellar hemisphere during a TP task. We recorded reaction times (RTs) to a target during the task in two contextual conditions of temporal anticipation: rhythmic (i.e., interstimulus intervals (ISIs) were constant) and single-interval condition (i.e., the estimation of the timing of the target was based on the prior exposure of the train of stimuli). Two ISIs durations were explored: 600 ms (short trials) and 900 ms (long trials). Cathodal tDCS improved the performance during the TP task (shorter RTs) specifically in the rhythmic condition only for the short trials and in the single-interval condition only for the long trials. Our results suggest that the inhibition of cerebellar activity induced a different improvement in the TP ability according to the temporal features of the context. In the rhythmic context, the cerebellum could integrate the temporal estimation with the anticipatory motor responses critically for the short target interval. In the single-interval context, for the long trials, the cerebellum could play a main role in integrating representation of time interval in memory with the elapsed time providing an accurate temporal prediction.

Assessment of the psychometric properties of the Italian version of the New Freezing of Gait Questionnaire (NFOG-Q-IT) in people with Parkinson disease: a validity and reliability study.

INTRODUCTION: Freezing of gait (FOG) in Parkinson's disease (PD) is a challenging clinical symptom to assess, due to its episodic nature. A valid and reliable tool is the New FOG Questionnaire (NFOG-Q) used worldwide to measure FOG symptoms in PD. OBJECTIVE: The aim of this study was to translate, to culturally adapt, and to test the psychometric characteristics of the Italian version of the NFOG-Q (NFOG-Q-It). METHODS: The translation and cultural adaptation was based on ISPOR TCA guidelines to finalize the 9-item NFOG-Q-It. Internal consistency was assessed in 181 Italian PD native speakers who experienced FOG using Cronbach's alpha. Cross-cultural analysis was tested using the Spearman's correlation between the NFOG-Q-It and the Modified Hoehn-Yahr Scale (M-H&Y). To assess construct validity, correlations among NFOG-Q-It, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Falls Efficacy Scale-International (FES-I), the 6-min Walking Test (6MWT), the Mini Balance Evaluation System Test (Mini-BESTest) and the Short Physical Performance Battery (SPPB) were investigated. RESULTS: The Italian N-FOGQ had high internal consistency (Cronbach's α = 0.859). Validity analysis showed significant correlations between NFOG-Q-IT total score and M-H&Y scores (r = 0.281 p < 0.001), MDS-UPDRS (r = 0.359 p < 0.001), FES-I (r = 0.230 p = 0.002), Mini BESTest (r = -0.256 p = 0.001) and 6MWT (r = -0.166 p = 0.026). No significant correlations were found with SPPB, MOCA and MMSE. CONCLUSION: The NFOG-It is a valuable and reliable tool for assessing FOG symptoms, duration and frequency in PD subjects. Results provide the validity of NFOG-Q-It by reproducing and enlarging previous psychometric data.

Effectiveness of Physiotherapy on Freezing of Gait in Parkinson's Disease: A Systematic Review and Meta-Analyses.

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.

Open Access Physical Therapy Journals: Do Predatory Journals Publish Lower-Quality Randomized Controlled Trials?

OBJECTIVES: To compare the quality of randomized controlled trials (RCTs) published in predatory and nonpredatory journals in the field of physical therapy. DATA SOURCES: From a list of 18 journals included either on Beall's list (n=9) or in the Directory of Open Access Journals (DOAJ) (n=9), 2 independent assessors extracted all the RCTs published between 2014 and 2017. When journals published more than 40 RCTs, a sample of 40 trials was randomly extracted, preserving the proportions among years. Indexing in PubMed, country of journal publication, and dates of submission or acceptance were also recorded for each journal. MAIN OUTCOME MEASURES: The PEDro (Physiotherapy Evidence Database) scale and duration of the peer review. RESULTS: Four hundred ten RCTs were included. The mean PEDro score of articles published in non-Beall, DOAJ journals was higher than those published in Beall journals (mean score ± SD, 5.8±1.7 vs 4.5±1.5; P<.001), with the differences increasing when the indexing in PubMed was also considered (6.5±1.5 vs 4.4±1.5; P<.001). The peer review duration was significantly longer in non-Beall than in Beall journals (mean duration [d] ± SD, 145.2±92.9 vs 45.4±38.8; P<.001) and in journals indexed in PubMed than in nonindexed journals (136.6±100.7 vs 60.4±55.7; P<.001). Indexing in PubMed was the strongest independent variable associated with the PEDro score (adjusted R2=0.182), but noninclusion on Beall's list explained an additional, albeit small, portion of the PEDro score variance (cumulative adjusted R2=0.214). CONCLUSIONS: Potentially predatory journals publish lower-quality trials and have a shorter peer review process than non-Beall journals included in the DOAJ database.

Functional Correlates of Action Observation of Gait in Patients with Parkinson's Disease.

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.

Motor imagery ability scores are related to cortical activation during gait imagery.

Motor imagery (MI) is the mental execution of actions without overt movements that depends on the ability to imagine. We explored whether this ability could be related to the cortical activity of the brain areas involved in the MI network. To this goal, brain activity was recorded using high-density electroencephalography in nineteen healthy adults while visually imagining walking on a straight path. We extracted Event-Related Desynchronizations (ERDs) in the θ, α, and ß band, and we measured MI ability via (i) the Kinesthetic and Visual Imagery Questionnaire (KVIQ), (ii) the Vividness of Movement Imagery Questionnaire-2 (VMIQ), and (iii) the Imagery Ability (IA) score. We then used Pearson's and Spearman's coefficients to correlate MI ability scores and average ERD power (avgERD). Positive correlations were identified between VMIQ and avgERD of the middle cingulum in the ß band and with avgERD of the left insula, right precentral area, and right middle occipital region in the θ band. Stronger activation of the MI network was related to better scores of MI ability evaluations, supporting the importance of testing MI ability during MI protocols. This result will help to understand MI mechanisms and develop personalized MI treatments for patients with neurological dysfunctions.

Modulation of response times in early-stage Parkinson's disease during emotional processing of embodied and non-embodied stimuli.

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.

How Music Moves Us: Music-induced Emotion Influences Motor Learning.

Music is an important tool for the induction and regulation of emotion. Although learning a sequential motor behaviour is essential to normal motor function, to our knowledge, the role of music-induced emotion on motor learning has not been explored. Our experiment aimed to determine whether listening to different emotional music could influence motor sequence learning. We focused on two sub-components of motor sequence learning: the acquisition of the order of the elements in the sequence (the "what"), and the ability to carry out the sequence, combining the elements in a single, skilled action (the "how"). Twenty subjects performed a motor sequence-learning task with a digitizing tablet in three different experimental sessions. In each session they executed the task while listening to three different musical pieces, eliciting fearful, pleasant, and neutral mood. Eight targets were presented in a pre-set order and subjects were asked to learn the sequence while moving. Music-induced pleasure had an impact on movement kinematics with onset time and peak velocity decreasing and movement time increasing more with respect to neutral music session. Declarative learning, verbal recall of the sequence order, was improved under emotional manipulation, but only for fear-condition. Results suggest that music-induced emotion can influence both sub-components of motor learning in a different way. Music-induced pleasure may have improved motor components of sequence learning by means of increased striatal dopamine availability whereas music-induced fear may facilitate the recruitment of attentional circuits, thus acting on declarative knowledge of the sequence order.

Home-based exercise training by using a smartphone app in patients with Parkinson's disease: a feasibility study.

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.

Mobility and balance rehabilitation in multiple sclerosis: A systematic review and dose-response meta-analysis.

OBJECTIVE: To assess the benefits of neurological rehabilitation and the dose-response relationship for the treatment of mobility and balance in multiple sclerosis. METHODS: We included studies investigating the effects of neurological rehabilitation on mobility and balance with the following eligibility criteria for inclusion: Population, People with Multiple Sclerosis (PwMS); Intervention, method of rehabilitation interventions; Comparison, experimental (specific balance intervention) vs control (no intervention/no specific balance intervention); Outcome, balance clinical scales; Study Design, randomised controlled trials. We conducted a random effects dose-response meta-analysis to assess linear trend estimations and a one stage linear mixed effects meta-regression for estimating dose-response curves. RESULTS: We retrieved 196 studies from a list of 5020 for full text review and 71 studies (n subjects=3306) were included. One study was a cross-over and 70 studies were randomized controlled trials and the mean sample size per study was 46.5 ± 28.6 (mean±SD) with a mean age of 48.3 ± 7.8years, disease duration of 11.6 ± 6.1years, and EDSS of 4.4 ± 1.4points. Twenty-nine studies (40.8%) had the balance outcome as the primary outcome, while 42 studies (59.1%) had balance as secondary outcome or did not specify primary and secondary outcomes. Thirty-three trials (46.5%) had no active intervention as comparator and 38 trials (53.5%) had an active control group. Individual level data from 20 studies (n subjects=1016) were analyzed showing a medium pooled effect size for balance interventions (SMD=0.41; 95% CIs 0.22 to 0.59). Moreover, we analyzed 14 studies (n subjects=696) having balance as primary outcome and BBS as primary endpoint yielding a mean difference of 3.58 points (95% CIs 1.79 to 5.38, p<0.0001). Finally, we performed meta regression of the 20 studies showing an association between better outcome, log of intensity defined as minutes per session (ß=1.26; SEß=0.51; p = 0.02) and task-oriented intervention (ß=0.38; SEß=0.17; p = 0.05). CONCLUSION: Our analyses provide level 1 evidence on the effect of balance intervention to improve mobility. Furthermore, according to principles of neurological rehabilitation, high intensity and task-specific interventions are associated with better treatment outcomes.

Are Motor Imagery Ability scores related to cortical activity during gait imagery?

Motor imagery (MI) is the mental execution of actions without overt movements that depends on the ability to imagine. We explored whether this ability could be related to the cortical activity of the brain areas involved in the MI network. To this goal, brain activity was recorded using high-density electroencephalography (hdEEG) in nineteen healthy adults while visually imagining walking on a straight path. We extracted Event-Related Desynchronizations (ERDs) in the ß band, and we measured MI ability via (i) the Kinesthetic and Visual Imagery Questionnaire (KVIQ), (ii) the Vividness of Movement Imagery Questionnaire-2 (VMIQ), and (iii) the Imagery Ability (IA) score. We then used Pearson's and Spearman's coefficients to correlate MI ability scores and average ERD power (avgERD). VMIQ was positively correlated with avgERD of frontal and cingulate areas, whereas IA SCORE was positively correlated with avgERD of left inferior frontal and superior temporal regions. Stronger activation of the MI network was related to better scores of MI ability evaluations, supporting the importance of testing MI ability during MI protocols. This result will help to understand MI mechanisms and develop personalized MI treatments for patients with neurological dysfunctions.

One cue does not fit all: A systematic review with meta-analysis of the effectiveness of cueing on freezing of gait in Parkinson's disease.

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.

Bias in the measurement of the outcome is associated with effect sizes in randomized clinical trials on exercise therapy for chronic low back pain: a meta-epidemiological study.

OBJECTIVES: To explore the relationships between the risk of bias and treatment effect estimates for exercise therapy interventions on pain intensity and physical functioning outcomes in randomized controlled trials (RCTs) involving patients with chronic low back pain. STUDY DESIGN AND SETTING: A cross-sectional meta-epidemiological study of the 230 RCTs (31,674 participants) in the 2021 'Exercise therapy for chronic low back pain' Cochrane Review were included. Study design characteristics, sample size, prospective trial registration, flowchart information, interventions, and comparisons were extracted. Independent pairs of reviewers assessed the risk of bias using the Cochrane Risk of Bias 2 tool. RESULTS: The metaregression included 220 (pain intensity) and 203 (physical functioning) effect sizes. Unadjusted and adjusted metaregression models showed no significant associations between the bias domains and pain intensity effect sizes. Only domain 'bias in the measurement of the outcome' was significantly associated with physical functioning (standardized mean difference: -0.40, 95% confidence interval: -0.77 to -0.02) when adjusted for flowchart reported (yes/no), prospective trial registration, sample size, and comparator type. CONCLUSION: The risk of bias in the measurement of the outcome could lead to slight overestimates of the effect size for physical functioning. Clinicians should consider this when they read and assess RCT results in this field. We encourage metaresearchers to replicate our findings using a consistent approach for evaluating the risk of bias (i.e., the RoB 2 tool) in other musculoskeletal conditions and interventions to investigate their generalizability.

Neural oscillations during motor imagery of complex gait: an HdEEG study.

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 ß-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 ß 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 ß-band ERDs in a large cortical-subcortical network encompassing mostly frontal and parietal regions. In most of the regions, we found α- and ß-band ERDs in the DT compared with the UW condition. Finally, in the ß band, significant correlations emerged between ERDs and scores in imagery ability tests. Overall we detected MI gait-related α- and ß-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.

Adherence to the PRISMA statement and its association with risk of bias in systematic reviews published in rehabilitation journals: A meta-research study.

BACKGROUND: Systematic reviews (SRs) and meta-analyses are essential resources for the clinicians. They allow to evaluate the strengths and the weaknesses of the evidence to support clinical decision-making if they are adequately reported. Little is known in the rehabilitation field about the completeness of reporting of SRs and its relationship with the risk of bias (ROB). OBJECTIVES: Primary: 1) To evaluate the completeness of reporting of systematic reviews (SRs) published in rehabilitation journals by evaluating their adherence to the PRISMA 2009 checklist, 2) To investigate the relationship between ROB and completeness of reporting. Secondary: To study the association between completeness of reporting and journals and study characteristics. METHODS: A random sample of 200 SRs published between 2011 and 2020 in 68 rehabilitation journals was indexed under the "rehabilitation" category in the InCites database. Two independent reviewers evaluated adherence to the PRISMA checklist and assessed ROB using the ROBIS tool. Overall adherence and adherence to each PRISMA item and section were calculated. Regression analyses investigated the association between completeness of reporting, ROB, and other characteristics (impact factor, publication options, publication year, and study protocol registration). RESULTS: The mean overall PRISMA adherence across the 200 studies considered was 61.4%. Regression analyses show that having a high overall ROB is a significant predictor of lower adherence (B=-7.1%; 95%CI -12.1, -2.0). Studies published in fourth quartile journals displayed a lower overall adherence (B= -7.2%; 95%CI -13.2, -1.3) than those published in first quartile journals; the overall adherence increased (B= 11.9%; 95%CI 5.9, 18.0) if the SR protocol was registered. No association between adherence, publication options, and publication year was found. CONCLUSION: Reporting completeness in rehabilitation SRs is suboptimal and is associated with ROB, impact factor, and study registration. Authors of SRs should improve adherence to the PRISMA guideline, and journal editors should implement strategies to optimize the completeness of reporting.

The effect of music-induced emotion on visual-spatial learning in people with Parkinson's disease: A pilot study.

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.