Effects of a Robot-Assisted Arm Training Plus Hand Functional Electrical Stimulation on Recovery After Stroke: A Randomized Clinical Trial.

OBJECTIVE: To compare the effects of unilateral, proximal arm robot-assisted therapy combined with hand functional electrical stimulation with intensive conventional therapy for restoring arm function in survivors of subacute stroke. DESIGN: This was a single-blinded, randomized controlled trial. SETTING: Inpatient rehabilitation university hospital. PARTICIPANTS: Patients (N=40) diagnosed as having ischemic stroke (time since stroke <8wk) and upper limb impairment were enrolled. INTERVENTIONS: Participants randomized to the experimental group received 30 sessions (5 sessions/wk) of robot-assisted arm therapy and hand functional electrical stimulation (RAT+FES). Participants randomized to the control group received a time-matched intensive conventional therapy. MAIN OUTCOME MEASURES: The primary outcome was arm motor recovery measured with the Fugl-Meyer Motor Assessment. Secondary outcomes included motor function, arm spasticity, and activities of daily living. Measurements were performed at baseline, after 3 weeks, at the end of treatment, and at 6-month follow-up. Presence of motor evoked potentials (MEPs) was also measured at baseline. RESULTS: Both groups significantly improved all outcome measures except for spasticity without differences between groups. Patients with moderate impairment and presence of MEPs who underwent early rehabilitation (<30d post stroke) demonstrated the greatest clinical improvements. CONCLUSIONS: RAT+FES was no more effective than intensive conventional arm training. However, at the same level of arm impairment and corticospinal tract integrity, it induced a higher level of arm recovery.

Bilateral M1 anodal transcranial direct current stimulation in post traumatic chronic minimally conscious state: a pilot EEG-tDCS study.

OBJECTIVE: We tested the preliminary effects of bilateral anodal transcranial direct current stimulation (tDCS) in patients with disorders of consciousness. DESIGN: Open label pilot study. SUBJECTS: Ten chronic (greater than 12 months) patients in a minimally conscious state (MCS) following severe traumatic brain injury. METHODS: The patients received 10 sessions of bilateral M1 anodal tDCS. Behavioural changes were assessed with the Coma Recovery Scale-Revised (CRS-R) before stimulation (T-1, T0), after five sessions (T1), at the end of the stimulation (T2), after two weeks (T3) and after three months (T4). Moreover, an EEG assessment was conducted. RESULTS: Eight out of 10 patients showed new clinical signs of consciousness; specifically, a 2-point CRS-R improvement was detected in the last follow-up (p = 0.004). EEG upper α bandwidth was greater in the parietal site at T1 (p < 0.034). In addition, we found a significant correlation between behavioral and EEG indices at T1 (r =  0.89; p =  0.001). CONCLUSION: This preliminary study presents several limitations (small sample size and no control group). However, it provides important initial data that can be used to design randomized clinical trials testing this novel approach in MCS and to further explore EEG as a neural marker for the effects of tDCS.

Facial expressions as a model to test the role of the sensorimotor system in the visual perception of the actions.

A long-term debate concerns whether the sensorimotor coding carried out during transitive actions observation reflects the low-level movement implementation details or the movement goals. On the contrary, phonemes and emotional facial expressions are intransitive actions that do not fall into this debate. The investigation of phonemes discrimination has proven to be a good model to demonstrate that the sensorimotor system plays a role in understanding actions acoustically presented. In the present study, we adapted the experimental paradigms already used in phonemes discrimination during face posture manipulation, to the discrimination of emotional facial expressions. We submitted participants to a lower or to an upper face posture manipulation during the execution of a four alternative labelling task of pictures randomly taken from four morphed continua between two emotional facial expressions. The results showed that the implementation of low-level movement details influence the discrimination of ambiguous facial expressions differing for a specific involvement of those movement details. These findings indicate that facial expressions discrimination is a good model to test the role of the sensorimotor system in the perception of actions visually presented.

The effects of body exposure on self-body image and esthetic appreciation in anorexia nervosa.

Repeated exposures to thin-idealized body shapes may alter women's perceptions of what normal (e.g., accepted) and ideal (e.g., desired) bodies in a cultural environment look like. The aim of the present study was to investigate whether exposure to thin and round body shapes may change the subsequent esthetic appreciation of others' bodies and the perceptual and cognitive-affective dimensions of self-body image in patients suffering from anorexia nervosa (AN). Thirteen AN patients and 13 matched healthy controls were exposed to pictures of either thin or round unfamiliar body models and, before and after exposure, they were required to either express liking judgments about round and slim figures of unfamiliar bodies (esthetic task) or to adjust distorted pictures of their own body to their perceptual (How do you see yourself?), affective (How do you feel yourself?), metacognitive (How do others see you?) and ideal (How would you like to look like?) body image (self-body adjustment task). Brief exposures to round models increased liking judgments of round figures in both groups. However, only in AN patients, exposure to round models induced an increase in thin figures liking, which positively correlated with their preoccupation with dieting. Furthermore, exposure to round bodies in AN patients, but not in controls, increased the distortion for the perceptual body image and decreased the size of the ideal one. No differences between the two groups were obtained after adaptation to thin models. Our results suggest that AN patients' perception of their own and others' body is more easily malleable by exposure to round figures as compared to controls. Crucially, this mechanism may strongly contribute to the development and maintenance of self-body image disturbances.

Distinct contributions of extrastriate body area and temporoparietal junction in perceiving one's own and others' body.

The right temporoparietal cortex plays a critical role in body representation. Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate their causative roles in perceptual representations of one's own and others' body. Healthy women adjusted size-distorted pictures of their own body or of the body of another person according to how they perceived the body (subjective task) or how others perceived it (intersubjective task). In keeping with previous reports, at baseline, we found an overall underestimation of body size. Crucially, EBA-rTMS increased the underestimation bias when participants adjusted the images according to how others perceived their own or the other woman's body, suggesting a specific role of EBA in allocentric body representations. Conversely, TPJ-rTMS increased the underestimation bias when participants adjusted the body of another person, either a familiar other or a close friend, in both subjective and intersubjective tasks, suggesting an involvement of TPJ in representing others' bodies. These effects were body-specific, since no TMS-induced modulation was observed when participants judged a familiar object. The results suggest that right EBA and TPJ play active and complementary roles in the complex interaction between the perceptions of one's own and other people's body.

Conscious and unconscious representations of observed actions in the human motor system.

Action observation activates the observer's motor system. These motor resonance responses are automatic and triggered even when the action is only implied in static snapshots. However, it is largely unknown whether an action needs to be consciously perceived to trigger motor resonance. In this study, we used single-pulse TMS to study the facilitation of corticospinal excitability (a measure of motor resonance) during supraliminal and subliminal presentations of implied action images. We used a forward and backward dynamic masking procedure that successfully prevented the conscious perception of prime stimuli depicting a still hand or an implied abduction movement of the index or little finger. The prime was followed by the supraliminal presentation of a still or implied action probe hand. Our results revealed a muscle-specific increase of motor facilitation following observation of the probe hand actions that were consciously perceived as compared with observation of a still hand. Crucially, unconscious perception of prime hand actions presented before probe still hands did not increase motor facilitation as compared with observation of a still hand, suggesting that motor resonance requires perceptual awareness. However, the presentation of a masked prime depicting an action that was incongruent with the probe hand action suppressed motor resonance to the probe action such that comparable motor facilitation was recorded during observation of implied action and still hand probes. This suppression of motor resonance may reflect the processing of action conflicts in areas upstream of the motor cortex and may subserve a basic mechanism for dealing with the multiple and possibly incongruent actions of other individuals.

Coherent activity within and between hemispheres: cortico-cortical connectivity revealed by rTMS of the right posterior parietal cortex.

Introduction: Low frequency (1 Hz) repetitive transcranial stimulation (rTMS) applied over right posterior parietal cortex (rPPC) has been shown to reduce cortical excitability both of the stimulated area and of the interconnected contralateral homologous areas. In the present study, we investigated the whole pattern of intra- and inter-hemispheric cortico-cortical connectivity changes induced by rTMS over rPPC. Methods: To do so, 14 healthy participants underwent resting state EEG recording before and after 30 min of rTMS at 1 Hz or sham stimulation over the rPPC (electrode position P6). Real stimulation was applied at 90% of motor threshold. Coherence values were computed on the electrodes nearby the stimulated site (i.e., P4, P8, and CP6) considering all possible inter- and intra-hemispheric combinations for the following frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-50 Hz). Results and discussion: Results revealed a significant increase in coherence in delta, theta, alpha and beta frequency bands between rPPC and the contralateral homologous sites. Moreover, an increase in coherence in theta, alpha, beta and gamma frequency bands was found between rPPC and right frontal sites, reflecting the activation of the fronto-parietal network within the right hemisphere. Summarizing, subthreshold rTMS over rPPC revealed cortico-cortical inter- and intra-hemispheric connectivity as measured by the increase in coherence among these areas. Moreover, the present results further confirm previous evidence indicating that the increase of coherence values is related to intra- and inter-hemispheric inhibitory effects of rTMS. These results can have implications for devising evidence-based rehabilitation protocols after stroke.

Evidence of motor resonance in stroke patients with severe upper limb function impairments.

For the past fifteen years, observation of actions has proved to be effective in the motor rehabilitation of stroke. Despite this, no evidence has ever been provided that this practice is able to activate the efferent motor system of a limb unable to perform the observed action due to stroke. In fact, transcranial magnetic stimulation cannot easily be used in these patients, and the fMRI evidence is inconclusive. This creates a logical problem, as the effectiveness of action observation in functional recovery is attributed to its ability to evoke action simulation, up to sub-threshold muscle activation (i.e., motor resonance), in healthy individuals. To provide the necessary proof-of-concept, patients with severe upper limb function impairments and matched control participants were submitted to a verified action prediction paradigm. They were asked to watch videos showing gripping movements towards a graspable or an ungraspable object, and to press a button the instant the agent touched the object. The presence of more accurate responses for the graspable object trials is considered an indirect evidence of motor resonance. Participants were required to perform the task in two sessions which differed in the hand used to respond. Despite the serious difficulty of movement, 8 out of 18 patients were able to perform the task with their impaired hand. We found that the responses given by the paretic hand showed a modulation of the action prediction time no different from that showed by the non-paretic hand, which, in turn, did not differ from that showed by the matched control participants. The present proof-of-concept study shows that action observation involves the efferent motor system even when the hand used to respond is unable to perform the observed action due to a cortical lesion, providing the missing evidence to support the already established use of Action Observation Training (AOT) in motor rehabilitation of stroke.

Proactive gaze is present during biological and non-biological motion observation.

Others' action observation activates in the observer a coordinated hand-eye motor program, covert for the hand (i.e. motor resonance), and overt for the eye (i.e. proactive gaze), similar to that of the observed agent. The biological motion hypothesis of action anticipation claims that proactive gaze occurs only in the presence of biological motion, and that kinematic information is sufficient to determine the anticipation process. The results of the present study did not support the biological motion hypothesis of action anticipation. Specifically, proactive gaze was present during observation of both a biological accelerated-decelerated motion and a non-biological constant velocity motion (Experiment 1), in the presence of a barrier able to restrict differences between the two kinematics to the motion profile of individual markers prior to contact (Experiment 2), but only if an object was present at the end point of the movement trajectory (Experiment 3). Furthermore, proactive gaze was found independently of the presence of end effects temporally congruent with the instant in which the movement stopped (Experiments 4, and 5). We propose that the involvement of the observer's motor system is not restricted to when the agent moves with natural kinematics, and it is mandatory whenever the presence of an agent or a goal is evident, regardless of physical appearance, natural kinematics, and the possibility to identify the action behind the stimulus.

Efficacy of Facial Exercises in Facial Expression Categorization in Schizophrenia.

Embodied cognition theories suggest that observation of facial expression induces the same pattern of muscle activation, and that this contributes to emotion recognition. Consequently, the inability to form facial expressions would affect emotional understanding. Patients with schizophrenia show a reduced ability to express and perceive facial emotions. We assumed that a physical training specifically developed to mobilize facial muscles could improve the ability to perform facial movements, and, consequently, spontaneous mimicry and facial expression recognition. Twenty-four inpatient participants with schizophrenia were randomly assigned to the experimental and control group. At the beginning and at the end of the study, both groups were submitted to a facial expression categorization test and their data compared. The experimental group underwent a training period during which the lip muscles, and the muscles around the eyes were mobilized through the execution of transitive actions. Participants were trained three times a week for five weeks. Results showed a positive impact of the physical training in the recognition of others' facial emotions, specifically for the responses of "fear", the emotion for which the recognition deficit in the test is most severe. This evidence suggests that a specific deficit of the sensorimotor system may result in a specific cognitive deficit.

Reaction time inhibition from subliminal cues: is it related to inhibition of return?

Task-irrelevant visual cues with near zero visibility proved apt to retard reaction time for the detection of supraliminal visual targets presented at the cued location. The time course of the effect was similar to that of the so-called inhibition-of return (IOR), which is assumed to be due to the withdrawal of attention from the inhibited location. However the present subliminal cues consistently failed to induce an RT facilitation prior to the RT inhibition, contrary to what would be expected if the cue were able to attract attention to the cued location. Since the RT inhibition from subliminal cues could not be attributed to the withdrawal of attention from the cued location, it can be argued that such cues acted both outside of consciousness and without the influence of attention. Therefore, the RT inhibitory effect seems best accounted for by an automatic, unconscious and attention-independent self-inhibition of response tendencies instructed by irrelevant information, akin to that postulated by (Eimer, M., & Schlaghecken, F. (1998). Effects of masked stimuli on motor activation: behavioural and electrophysiological evidence. Journal of Experimental Psychology Human Perception and Performance, 24, 1737-1747.) to explain the negative compatibility effect.

Equal kinematics and visual context but different purposes: Observer's moral rules modulate motor resonance.

Motor resonance is considered to be an index of the automatic under threshold motor replica of the observed action. Similar actions may be quite different in terms of long-term goals (e.g., grasp to eat vs grasp to throw) and, recently, it has been proposed that the distal goal subtly modulates movements execution, and that observers automatically use these differences in kinematics to discriminate between different intentions. This interpretation is in line with computational approaches proposing that in the agent the generative process causes that intention shapes the kinematics, and in the observer the recognition process causes that the kinematics cues the intention. Given the close entanglement between the two processes, here we investigated whether the mere knowledge of agent's intentions induces in the observer a generative process able to modulate motor resonance. We used transcranial magnetic stimulation to examine motor evoked potentials in the Opponens Pollicis muscle to verify if observer's knowledge of agent's positive, negative, or neutral intentions on a third person influences corticospinal excitability during observation of the same action performed with equal kinematics, and in the same visual context. Results showed that the observation of an action executed with the intention to induce negative effects determined a reduction of motor resonance, revealing the presence of a specific inhibition to reenact an action that results in unpleasant consequences in the other. These data suggest that the information at the intention level activates a generative process which overcomes the replica of kinematics at the goal level, and shapes motor resonance according with observer's mind and not with agent's intention, revealing the possibility of a mere cognitive influence on motor resonance based on individual's ethical values.

NMR structure of the p63 SAM domain and dynamical properties of G534V and T537P pathological mutants, identified in the AEC syndrome.

The p63 protein is crucial for epidermal development, and its mutations cause the extrodactyly ectodermal dysplasia and cleft lip/palate syndrome. The three-dimensional solution structure of the p63 sterile alpha-motif (SAM) domain (residues 505-579), a region crucial to explaining the human genetic disease ankyloblepharonectodermal dysplasia-clefting syndrome (AEC), has been determined by nuclear magnetic resonance spectroscopy. The structure indicates that the domain is a monomer with the characteristic five-helix bundle topology observed in other SAM domains. It includes five tightly packed helices with an extended hydrophobic core to form a globular and compact structure. The dynamics of the backbone and the global correlation time of the molecule have also been investigated and compared with the dynamical properties obtained through molecular dynamics simulation. Attempts to purify the pathological G534V and T537P mutants, originally identified in AEC, were not successful because of the occurrence of unspecific proteolytic degradation of the mutated SAM domains. Analysis of the structural dynamic properties of the G534V and T537P mutants through molecular dynamics simulation and comparison with the wild type permits detection of differences in the degree of freedom of individual residues and discussion of the possible causes for the pathology.

Resonating with the ghost of a hand: A TMS experiment.

An impressive body of literature in the past 20 years has revealed a possible role played by cortical motor areas in action perception. One question that has been of interest is whether these areas are selectively tuned to process the actions of biological agents. However, no experiments directly testing the effects of the main characteristics identifying a biological agent (physical appearance and movement kinematics) on corticospinal excitability (CS) are present in literature. To fill this gap, we delivered single-pulse transcranial magnetic stimulation to the primary motor cortex and we recorded motor evoked potentials from contralateral hand muscles during observation of point-light-displays stimuli representing a hand having lost its physical appearance (Experiment 1) and kinematics characteristics (Experiment 2). Results showed that physical appearance, natural kinematics, and the possibility to identify the action behind the stimulus are not necessary conditions to modulate CS excitability during stimuli observation. We propose that the involvement of the motor system can be mandatory whenever the perceived movement, executed by a human, by an animal or by an object, is recognized as reproducible in its final outcome (e.g., position in space, direction of movement, posture of a body part, to-be-produced sound, specific interaction with an object, etc.), and that the peculiar relationship existing between others' actions and the actions executed by the observer could just represent the extreme in which the motor system is able to almost perfectly reproduce the observed stimulus as it unfolds and, consequently, contribute to stimulus perception in the most efficient way.

Altered exposure-related reshaping of body appreciation in adolescent patients with anorexia nervosa.

Several studies suggest a relation between repeated exposure to extremely thin bodies in media and the perceptual and emotional disturbances of body representation in anorexia nervosa (AN). In this study, we utilized an exposure paradigm to investigate how perceptual experience modulates body appreciation in adolescents with AN as compared to healthy adolescents. Twenty AN patients and 20 healthy controls were exposed to pictures of thin or round models and were then required to express liking judgments about bodies of variable weight. Brief exposure to round models increased the liking judgments of round bodies but not those of thin bodies in healthy adolescents. Furthermore, exposure to round models increased the liking judgments of both thin and round bodies in adolescents with AN. Patients did not show any change of liking judgments after exposure to thin models. These results point to weak norm-based reshaping of body appreciation in AN patients.

An object-identity probability cueing paradigm during grasping observation: the facilitating effect is present only when the observed kinematics is suitable for the cued object.

Electrophysiological and psychophysical data indicate that grasping observation automatically orients attention toward the incoming interactions between the actor's hand and the object. The aim of the present study was to clarify if this effect facilitates the detection of a graspable object with the observed action as compared to an ungraspable one. We submitted participants to an object-identity probability cueing experiment in which the two possible targets were of the same dimensions but one of them presented sharp tips at one extreme while the other presented flat faces. At the beginning of each trial the most probable target was briefly shown. After a variable interval, at the same position, the same (75%) or a different target (25%) was presented. Participants had to press a key in response to target appearance. Superimposed to the video showing cue and target, an agent performing the reaching and grasping of the target was presented. The kinematics of the action was or was not suitable for grasping the cued target, according to the absence or presence of the sharp tips. Results showed that response was modulated by the probability of target identity but only when the observed kinematics was suitable to grasp the attended target. A further experiment clarified that response modulation was never present when the superimposed video always showed the agent at a rest position. These findings are discussed at the light of neurophysiological and psychophysical literature, considering the relationship between the motor system and the perception of objects and of others' actions. We conclude that the prediction of the mechanical events that arise from the interactions between the hand and the attended object is at the basis of the capability to select a graspable object in space.

No causal effect of left hemisphere hyperactivity in the genesis of neglect-like behavior.

Spatial neglect is traditionally explained as an imbalance of the interhemispheric reciprocal inhibition exerted by the two hemispheres: after a right lesion, the contralesional hemisphere becomes disinhibited and its enhanced activity suppresses the activity in the lesioned one. Even though the hyperexcitability of the left hemisphere is the theoretical framework of several rehabilitation interventions using non-invasive brain stimulation protocols in neglect, no study has yet investigated directly the actual state of cortical excitability of the contralesional hemisphere immediately after the brain lesion. The present study represents the first attempt to directly assess the interhemispheric rivalry model adopting a novel approach based on the induction of neglect-like biases in healthy participants. Applying repetitive transcranial magnetic stimulation (rTMS) over the right posterior parietal cortex while concurrently recording the EEG activity allows to measure specific neurophysiological markers of cortical activity (i.e. TMS-evoked potentials, TEPs) both over the stimulated right hemisphere and over the contralateral homologous area. Besides the effectiveness of the protocol used in modulating behavior, our results show an inhibition of the cortical excitability of the directly stimulated parietal cortex (right hemisphere) and, most importantly, a comparable reduction of cortical excitability of the homologous contralateral (left) area. TEPs and additional electrophysiological measures reliably provide strong evidence for a bilateral hypo-activation following TMS induction of neglect-like biases. These results suggest that the parietal imbalance typically found in neglect patients could reflect a long-term maladaptive plastic reorganization that follows a brain lesion.