Brain Networks Modulation during Simple and Complex Gait: A "Mobile Brain/Body Imaging" Study.

Walking encompasses a complex interplay of neuromuscular coordination and cognitive processes. Disruptions in gait can impact personal independence and quality of life, especially among the elderly and neurodegenerative patients. While traditional biomechanical analyses and neuroimaging techniques have contributed to understanding gait control, they often lack the temporal resolution needed for rapid neural dynamics. This study employs a mobile brain/body imaging (MoBI) platform with high-density electroencephalography (hd-EEG) to explore event-related desynchronization and synchronization (ERD/ERS) during overground walking. Simultaneous to hdEEG, we recorded gait spatiotemporal parameters. Participants were asked to walk under usual walking and dual-task walking conditions. For data analysis, we extracted ERD/ERS in α, ß, and γ bands from 17 selected regions of interest encompassing not only the sensorimotor cerebral network but also the cognitive and affective networks. A correlation analysis was performed between gait parameters and ERD/ERS intensities in different networks in the different phases of gait. Results showed that ERD/ERS modulations across gait phases in the α and ß bands extended beyond the sensorimotor network, over the cognitive and limbic networks, and were more prominent in all networks during dual tasks with respect to usual walking. Correlation analyses showed that a stronger α ERS in the initial double-support phases correlates with shorter step length, emphasizing the role of attention in motor control. Additionally, ß ERD/ERS in affective and cognitive networks during dual-task walking correlated with dual-task gait performance, suggesting compensatory mechanisms in complex tasks. This study advances our understanding of neural dynamics during overground walking, emphasizing the multidimensional nature of gait control involving cognitive and affective networks.

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.

Sensorimotor Expectations Bias Motor Resonance during Observation of Object Lifting: The Causal Role of pSTS.

Transcranial magnetic stimulation studies have highlighted that corticospinal excitability is increased during observation of object lifting, an effect termed "motor resonance." This facilitation is driven by movement features indicative of object weight, such as object size or observed movement kinematics. Here, we investigated in 35 humans (23 females) how motor resonance is altered when the observer's weight expectations, based on visual information, do not match the actual object weight as revealed by the observed movement kinematics. Our results highlight that motor resonance is not robustly driven by object weight but easily masked by a suppressive mechanism reflecting the correctness of weight expectations. Subsequently, we investigated in 24 humans (14 females) whether this suppressive mechanism was driven by higher-order cortical areas. For this, we induced "virtual lesions" to either the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) before having participants perform the task. Importantly, virtual lesion of pSTS eradicated this suppressive mechanism and restored object weight-driven motor resonance. In addition, DLPFC virtual lesion eradicated any modulation of motor resonance. This indicates that motor resonance is heavily mediated by top-down inputs from both pSTS and DLPFC. Together, these findings shed new light on the theorized cortical network driving motor resonance. That is, our findings highlight that motor resonance is not only driven by the putative human mirror neuron network consisting of the primary motor and premotor cortices as well as the anterior intraparietal sulcus, but also by top-down input from pSTS and DLPFC.SIGNIFICANCE STATEMENT Observation of object lifting activates the observer's motor system in a weight-specific fashion: Corticospinal excitability is larger when observing lifts of heavy objects compared with light ones. Interestingly, here we demonstrate that this weight-driven modulation of corticospinal excitability is easily suppressed by the observer's expectations about object weight and that this suppression is mediated by the posterior superior temporal sulcus. Thus, our findings show that modulation of corticospinal excitability during observed object lifting is not robust but easily altered by top-down cognitive processes. Finally, our results also indicate how cortical inputs, originating remotely from motor pathways and processing action observation, overlap with bottom-up motor resonance effects.

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.

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.

Sensorimotor inhibition during emotional processing.

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

Transcranial direct current stimulation alters sensorimotor modulation during cognitive representation of movement.

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.

Motor Resonance Flexibility to Emotion-Enriched Context in Parkinson's Disease Patients.

In healthy people, motor resonance mechanisms are flexible to negative emotional contextual clues with greater motor resonance during the observation of a reach to grasp movement performed in an environment eliciting disgust. The link between emotion and motor control has become an interesting topic in Parkinson's disease (PD). Here, we aimed to study the response of the mirror neuron system, specifically motor resonance, to an emotion-enriched context in people with PD. Corticospinal excitability was recorded in a total of 44 participants, divided into two groups (23 PD patients and 21 healthy subjects). We recorded motor-evoked potentials from a muscle involved in the grasping movement while participants were watching the same reach-to-grasp movement embedded in surrounds with negative emotional valence, but different levels of arousal: sadness (low arousal) and disgust (high arousal). Basic motor resonance mechanisms were less efficient in PD than controls. Responsiveness to emotional contextual clues eliciting sadness was similar between PD and controls, whereas responsiveness to emotional contextual clues eliciting disgust was impaired in PD patients. Our findings show reduced motor resonance flexibility to the disgusting context, supporting the hypothesis that PD patients may have a deficit in "translating" an aversive motivational state into a physiologic response. The amygdala, which is implicated in the appraisal of fearful stimuli and response to threatening situations, might be implicated in this process.

Modulation of Response Times During Processing of Emotional Body Language.

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.