Selective enhancement of motor cortical plasticity by observed mirror-matched actions

Watching others learn a motor task can enhance an observer's own later performance when learning the same motor task. This is thought to be due to activation of the action observation (or mirror neuron) network. Here we show that the effectiveness of plasticity induced in human motor cortex (M1) is also significantly influenced by the nature of prior action observation. In separate sessions, 17 participants watched a video showing repeated goal-directed movements (action observation) involving either the right hand (congruent condition) or the same video mirror-reversed to simulate the left hand (incongruent condition). Participants then received pulses of transcranial magnetic stimulation over the hand area of left M1 paired with median nerve stimulation of the right hand (paired associative stimulation; PAS). The resting motor-evoked potential (MEP) in right abductor pollicis brevis (APB) increased significantly 20. minutes after PAS, but only when participants had previously watched the congruent video. In this condition, all participants showed an increase in MEP amplitude at 20. minutes post-PAS. There was no change in MEP amplitude following PAS when participants watched the incongruent video. We conclude that prior action observation is a potent modulator of subsequent PAS-induced neuroplasticity, which may have important therapeutic applications

Early, sustained and broadly-tuned discharge of fast-spiking interneurons in the premotor cortex during action planning

Preparatory neural activity in premotor areas is critical for planning and execution of voluntary movements. Previous studies in monkeys and mice have revealed how the discharges of pyramidal, excitatory neurons (PNs) encode a motor plan for an upcoming movement (Afshar et al., 2011; Chen et al., 2017; Li et al., 2015). However, the contribution of GABAergic interneurons, specifically fast-spiking interneurons (FSNs), to voluntary movements remains poorly understood. Putative premotor areas involved in action planning have been demonstrated in rodents. In particular, in mice, a premotor area controlling voluntary licking has been identified in the anterior-lateral motor cortex (ALM) (Komiyama et al., 2010). Also, ALM partially overlaps with the rostral forelimb area (RFA), the previously defined premotor region involved in the control of paw movement in rats and mice (Rouiller et al., 1993; Tennant et al., 2011). To understand the excitatory-inhibitory microcircuit involved in action planning, here I compare directly the response properties of PNs and FSNs during licking behaviour and forelimb retraction in the mouse. Recordings are carried out with both acute electrodes and chronic microelectrode arrays from both the two premotor areas, i.e. the ALM \u2013 responsible for licking \u2013, and RFA \u2013 involved in paw movement. Specifically, in a first set of experiments, I used head-restrained mice that spontaneously lick a reward delivered at random intervals from a drinking spout. Mice voluntary performed either single isolated or a burst of consecutive licks, which I categorized, a posteriori, in single (= 1 lick) and multiple licks ( 65 3 licks). During the task, I extracellularly recorded single units\u2019 activity from ALM, using acute in vivo electrophysiology. I identified putative PNs and FSNs, based on well-established features of their waveforms, and investigated their functional properties during the movement. Unexpectedly, I report that optogenetically-verified FSNs showed an earlier and more sustained activation than PNs. In particular, most of the neurons\u2019 activity anticipated the licking onset, consistently with an involvement of the ALM in movement planning. The majority of the neurons (~90%) increased their firing frequency in correspondence with the movement, but suppressive modulations were also observed in a subset of units. For both PNs and FSNs, I found significantly greater discharge during multiple than single licks and the peak discharge was significantly delayed for both subclasses during multiple licking events. However, FSNs modulated their activity about 100ms earlier than PNs. Furthermore, almost all FSNs showed a peak in their response before the beginning of the sequence of licks. Analysis of mean information content confirms that FSNs predict licking onset not only significantly better, but even earlier, than PNs. Chronic electrode arrays covering both the ALM and RFA were next used to simultaneously probe neural responses during (i) licking and (ii) forelimb pulling in a robotic device (Spalletti et al., 2017). I report that most of the FSNs respond with a stereotyped increase in their firing rates during both licking and pulling. In stark contrast, PNs show a variety of behaviours, dependent on movement type. At least for a minority of them, licking behaviour and forelimb retraction are represented as two different motor acts, reaching significant levels in the PNs. Accordingly, computational analysis shows that PNs carry more independent information than FSNs. Altogether, these data indicate that a global rise of GABAergic inhibition mediated by FSNs firing contributes to early action planning. Next, encouraged by the deeper understanding of the cortical microcircuits underlying movement planning in mice, I exploited this knowledge to explore more complex mechanisms, as action understanding. The neural circuits that integrate performed and observed actions have been found in the premotor cortex of monkeys and named as \u2018mirror neurons system\u2019 (di Pellegrino et al., 1992). Recently, the presence of mirror neurons have been demonstrated in rodents in the anterior cingulate cortex (Carrillo et al., 2019), but whether they could contribute to action understanding in the premotor cortex is still unclear. At behavioural level, the observation of actions can actually lead, in some cases, to the repetition of those same actions. This phenomenon has been named social facilitation, and the underlying motor program has been attributed to the mirror system (Ferrari et al., 2005). Here, I set up a behavioural task similar to the one exploited in monkeys to explore social facilitation in mice. I took advantage of licking behaviour to set up the social facilitation experiment. Therefore, head-restrained mice were allowed to lick water from a feeding needle. I found that mice can actually facilitated to lick more when another individual was engaged in the same action, supporting the hypothesis of a social facilitation in mouse. Altogether these results indicate that the observers\u2019 behaviour was actually influenced by the demonstrators\u2019 one, laying the groundwork for the study of mirror neurons in mice at cellular level

Motor imagery and motor illusion: from plasticity to a translational approach

Motor imagery e illusione motoria: dalla plasticit\ue0 ad un approccio traslazional

Sensorimotor experience in virtual environments

The goal of rehabilitation is to reduce impairment and provide functional improvements resulting in quality participation in activities of life, Plasticity and motor learning principles provide inspiration for therapeutic interventions including movement repetition in a virtual reality environment, The objective of this research work was to investigate functional specific measurements (kinematic, behavioral) and neural correlates of motor experience of hand gesture activities in virtual environments stimulating sensory experience (VE) using a hand agent model. The fMRI compatible Virtual Environment Sign Language Instruction (VESLI) System was designed and developed to provide a number of rehabilitation and measurement features, to identify optimal learning conditions for individuals and to track changes in performance over time. Therapies and measurements incorporated into VESLI target and track specific impairments underlying dysfunction. The goal of improved measurement is to develop targeted interventions embedded in higher level tasks and to accurately track specific gains to understand the responses to treatment, and the impact the response may have upon higher level function such as participation in life. To further clarify the biological model of motor experiences and to understand the added value and role of virtual sensory stimulation and feedback which includes seeing one\u27s own hand movement, functional brain mapping was conducted with simultaneous kinematic analysis in healthy controls and in stroke subjects. It is believed that through the understanding of these neural activations, rehabilitation strategies advantaging the principles of plasticity and motor learning will become possible. The present research assessed successful practice conditions promoting gesture learning behavior in the individual. For the first time, functional imaging experiments mapped neural correlates of human interactions with complex virtual reality hands avatars moving synchronously with the subject\u27s own hands, Findings indicate that healthy control subjects learned intransitive gestures in virtual environments using the first and third person avatars, picture and text definitions, and while viewing visual feedback of their own hands, virtual hands avatars, and in the control condition, hidden hands. Moreover, exercise in a virtual environment with a first person avatar of hands recruited insular cortex activation over time, which might indicate that this activation has been associated with a sense of agency. Sensory augmentation in virtual environments modulated activations of important brain regions associated with action observation and action execution. Quality of the visual feedback was modulated and brain areas were identified where the amount of brain activation was positively or negatively correlated with the visual feedback, When subjects moved the right hand and saw unexpected response, the left virtual avatar hand moved, neural activation increased in the motor cortex ipsilateral to the moving hand This visual modulation might provide a helpful rehabilitation therapy for people with paralysis of the limb through visual augmentation of skills. A model was developed to study the effects of sensorimotor experience in virtual environments, and findings of the effect of sensorimotor experience in virtual environments upon brain activity and related behavioral measures. The research model represents a significant contribution to neuroscience research, and translational engineering practice, A model of neural activations correlated with kinematics and behavior can profoundly influence the delivery of rehabilitative services in the coming years by giving clinicians a framework for engaging patients in a sensorimotor environment that can optimally facilitate neural reorganization

On sensorimotor function and the relationship between proprioception and motor learning

Research continues to explore the mechanisms that mediate successful motor control. Behaviourally-relevant modulation of muscle commands is dependent on sensory signals. Proprioception -- the sense of body position -- is one signal likely to be crucial for motor learning. The present thesis explores the relationship between human proprioception and motor learning. First we investigated changes to sensory function during the adaptation of arm movements to novel forces. Subjects adapted movements in the presence of directional loads over the course of learning. Psychophysical estimates of perceived hand position showed that motor learning resulted in sensed hand position becoming \emph{biased} in the direction of the experienced load. This biasing of perception occurred for four different perturbation directions and remained even after washout movements. Therefore, motor learning can result in systematic changes to proprioceptive function. In a second experiment we investigated proprioceptive changes after subjects learned highly accurate movements to targets. Subjects demonstrated improved acuity of the hand\u27s position following this type of motor learning. Interestingly, improved acuity did not generalize to the entire workspace but was instead restricted to local positions within the region of the workspace where motor learning occurred. These results provide evidence that altered sensory function from motor learning may also include sensory acuity improvements. Subsequently the duration of acuity improvements was assessed. Improved acuity of hand position was observed immediately after motor learning and 24h later, but was not reliably different from baseline at 1h or 4h. Persistent sensory change may thus be similar to retention of motor learning and may involve a sleep-dependent component. In the fourth study we investigated the ability of proprioceptive training to improve motor learning. Subjects had to match the position and speed of desired trajectories. At regular intervals during motor motor learning, subjects were presented with the desired trajectory either only visually, or with both vision and and passive proprioceptive movement through the desired trajectory using a robot. Subjects who received proprioceptive guidance indeed performed better in matching both velocity and position of desired movements, suggesting a role for passive proprioceptive training in improving motor learning

Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates

What brain mechanisms underlie autism and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the iSTART model, which proposes how cognitive, emotional, timing, and motor processes may interact together to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes.Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

Observation of Implied Motion in a Work of Art Modulates Cortical Connectivity and Plasticity [C. Concerto, C. Infortuna, L. Mineo, M. Pereira, D. Freedberg, E. Chusid, E. Aguglia, F. Battaglia, Journal of Exercise Rehabilitation 12(5)]

Following the discovery of mirror neurons, much attention has been de-voted to understanding the neural responses evoked by observation of implied motion in works of art. Neuroimaging studies have demonstrated that dorsal premotor cortex (PMd) is commonly involved during observation of movements but the role of the inhibitory and excitatory connections between PMd and primary motor cortex (M1) during observation of implied motion remains uncertain. In this study, using high and low frequency repetitive transcranial magnetic stimulation (rTMS), we examined PMd–M1 connectivity and plasticity during observation of Michelangelo’s frescos with and without implied motion (Sistine Chapel, 1508–1512). We found that observation of implied motion in a painting specifically reduces the activity of inhibitory PMd–M1 connections. On the contrary PMd–M1 facilitatory connections, as examined by means of 5-Hz rTMS, were not modulated during observation of the painting. Our data suggest that observation of implied motion in a painting modulates PMd–M1 connectivity and plasticity. These results are consistent with the hypothesis that art with implied motion might be used as a plasticity-based intervention in rehabilitation

Rehabilitative devices for a top-down approach

In recent years, neurorehabilitation has moved from a "bottom-up" to a "top down" approach. This change has also involved the technological devices developed for motor and cognitive rehabilitation. It implies that during a task or during therapeutic exercises, new "top-down" approaches are being used to stimulate the brain in a more direct way to elicit plasticity-mediated motor re-learning. This is opposed to "Bottom up" approaches, which act at the physical level and attempt to bring about changes at the level of the central neural system. Areas covered: In the present unsystematic review, we present the most promising innovative technological devices that can effectively support rehabilitation based on a top-down approach, according to the most recent neuroscientific and neurocognitive findings. In particular, we explore if and how the use of new technological devices comprising serious exergames, virtual reality, robots, brain computer interfaces, rhythmic music and biofeedback devices might provide a top-down based approach. Expert commentary: Motor and cognitive systems are strongly harnessed in humans and thus cannot be separated in neurorehabilitation. Recently developed technologies in motor-cognitive rehabilitation might have a greater positive effect than conventional therapies

Is that me in the mirror? Depersonalisation modulates tactile mirroring mechanisms

Our sense of self is thought to develop through sensory-motor contingencies provided, not only by observing one's own body, but also by mirroring interactions with others. This suggests that there is a strong link between mirroring mechanisms and the bodily self. The present study tested whether this link is expressed at early, implicit stages of the mirroring process or at later, more cognitive stages. We also provide, to the best of our knowledge, the first demonstration of how inter-individual differences in our sense of bodily self may affect mirroring mechanisms. We used somatosensory event-related potentials (SEPs) to investigate the temporal dynamics of mirroring highly self-related information (viewed touch on one's own face) compared to other-related information (viewed touch on a stranger's face), in individuals with low and high levels of depersonalisation, a mental condition characterised by feeling detached or estranged from one's self and body. For the low-depersonalisation group, mirroring for self-related events (P45) preceded mirroring for other-related events (N80). At later stages (P200), mirroring was stronger for other-related than self-related events. This shows that early, implicit and later, more cognitive processes play different relative roles in mirroring self- and other-related bodily events. Critically, mirroring differed in the high-depersonalisation group, specifically for self-related events. An absence of early, implicit mirroring for self-related events over P45 suggests that the associated processes may be the neural correlates of the disembodiment experienced in depersonalisation. A lack of differential mirroring for self- and other-related events over P200 may reflect compensatory mechanisms that redress deficiencies in mirroring at earlier stages, which may break down to give rise to symptoms of depersonalisation. Alternatively, or in addition, they may represent an attenuation of processes related to self-other distinction. Our study thus shows that mirroring, especially for events on one's own face, can be strongly affected by how connected the observer feels to their own bodily self