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Abstract Background Motor difficulties are common in many, but not all, autistic individuals. These difficulties can co-occur with other problems, such as delays in language, intellectual, and adaptive functioning. Biological mechanisms underpinning such difficulties are less well understood. Poor motor skills tend to be more common in individuals carrying highly penetrant rare genetic mutations. Such mechanisms may have downstream consequences of altering neurophysiological excitation-inhibition balance and lead to enhanced behavioral motor noise. Methods This study combined publicly available and in-house datasets of autistic (n = 156), typically-developing (TD, n = 149), and developmental coordination disorder (DCD, n = 23) children (age 3–16 years). Autism motor subtypes were identified based on patterns of motor abilities measured from the Movement Assessment Battery for Children 2nd edition. Stability-based relative clustering validation was used to identify autism motor subtypes and evaluate generalization accuracy in held-out data. Autism motor subtypes were tested for differences in motor noise, operationalized as the degree of dissimilarity between repeated motor kinematic trajectories recorded during a simple reach-to-drop task. Results Relatively ‘high’ (n = 87) versus ‘low’ (n = 69) autism motor subtypes could be detected and which generalize with 89% accuracy in held-out data. The relatively ‘low’ subtype was lower in general intellectual ability and older at age of independent walking, but did not differ in age at first words or autistic traits or symptomatology. Motor noise was considerably higher in the ‘low’ subtype compared to ‘high’ (Cohen’s d = 0.77) or TD children (Cohen’s d = 0.85), but similar between autism ‘high’ and TD children (Cohen’s d = 0.08). Enhanced motor noise in the ‘low’ subtype was also most pronounced during the feedforward phase of reaching actions. Limitations The sample size of this work is limited. Future work in larger samples along with independent replication is important. Motor noise was measured only on one specific motor task. Thus, a more comprehensive assessment of motor noise on many other motor tasks is needed. Conclusions Autism can be split into at least two discrete motor subtypes that are characterized by differing levels of motor noise. This suggests that autism motor subtypes may be underpinned by different biological mechanisms.

Abstract Acting in concert with others, a key aspect of our social life, requires behavioral coordination between persons on multiple timescales. When zooming in on the kinematic properties of movements, it appears that small speed fluctuations, called submovements, are embedded within otherwise smooth end-point trajectories. Submovements, by occurring at a faster timescale than that of movements, offer a novel window upon the functional relationship between distinct motor timescales. In this regard, it has previously been shown that when partners visually synchronize their movements, they also coordinate the timing of their submovement by following an alternated pattern. However, it remains unclear whether the mechanisms behind submovement coordination are domain-general or specific to the visual modality, and whether they have relevance for interpersonal coordination also at the scale of whole movements. In a series of solo and dyadic tasks, we show that submovements are also present and coordinated across partners when sensorimotor interactions are mediated by auditory feedback only. Importantly, the accuracy of task-instructed interpersonal coordination at the movement level correlates with the strength of submovement coordination. These results demonstrate that submovement coordination is a potentially fundamental mechanism that participates in interpersonal motor coordination regardless of the sensory domain mediating the interaction.

Abstract Behavioral interpersonal coordination requires smooth negotiation of actions in time and space (joint action—JA). Inhibitory control may play a role in fine-tuning appropriate coordinative responses. To date, little research has been conducted on motor inhibition during JA and on the modulatory influence that premotor areas might exert on inhibitory control. Here, we used an interactive task in which subjects were required to reach and open a bottle using one hand. The bottle was held and stabilized by a co-actor (JA) or by a mechanical holder (vice clamp, no-JA). We recorded two TMS-based indices of inhibition (short-interval intracortical inhibition—sICI; cortical silent period—cSP) during the reaching phase of the task. These reflect fast intracortical (GABAa-mediated) and slow corticospinal (GABAb-mediated) inhibition. Offline continuous theta burst stimulation (cTBS) was used to interfere with dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and control site (vertex) before the execution of the task. Our results confirm a dissociation between fast and slow inhibition during JA coordination and provide evidence that premotor areas drive only slow inhibitory mechanisms, which in turn may reflect behavioral co-adaptation between trials. Exploratory analyses further suggest that PMd, more than PMv, is the key source of modulatory drive sculpting movements, according to the socio-interactive context.

Abstract Aberrant motor-sensory predictive functions have been linked to symptoms of psychosis, particularly reduced attenuation of self-generated sensations and misattribution of self-generated actions. Building on the parallels between prediction of self- and other-generated actions, this study aims to investigate whether individuals with psychosis also demonstrate abnormal perceptions and predictions of others’ actions. Patients with psychosis and matched controls completed a two-alternative object size discrimination task. In each trial, they observed reaching actions towards a small and a large object, with varying levels of temporal occlusion ranging from 10% to 80% of movement duration. Their task was to predict the size of the object that would be grasped. We employed a novel analytic approach to examine how object size information was encoded and read out across progressive levels of occlusion with single-trial resolution. Patients with psychosis exhibited an overall pattern of reduced and discontinuous evidence integration relative to controls, characterized by a period of null integration up to 20% of movement duration, during which they did not read any size information. Surprisingly, this drop in accuracy in the initial integration period was not accompanied by a reduction in confidence. Difficulties in action prediction were correlated with the severity of negative symptoms and impaired functioning in social relationships.

Abstract The next generation of brain–machine interfaces are envisioned to couple signal transduction, filtering, and sorting on board with minimum power consumption and maximum bio‐integrability. These functional needs shall be mandatorily met in order to design efficient closed‐loop brain–machine interfaces aimed at treating and monitoring various disorders of the central and peripheral nervous system. Here, the pivotal role is highlighted that organic bioelectronics may have in the contextual development of all these three desiderata, by demonstrating a modular organic‐electronics circuit toward real‐time signal filtering. The inherent filtering capabilities of electrolyte‐gated organic transistor are tuned via adjustment of operational conditions and benchmarked in an electromyography experiment. Additionally, a whole‐organic signal processing circuitry is presented, coupling such transistors with ad hoc designed organic passive components. This provides the possibility to sort complex signals into their constitutive frequency components in real time, thereby delineating innovative strategies to devise organic‐based functional building‐blocks for brain–machine interfaces.

Abstract The observation that different effectors can execute the same movement suggests functional equivalences driven by limb independent representation of action in the central nervous system. A common invariant motor behavior is the speed and curvature coupling (the 1/3 power law), a low dimensional (abstract) descriptor of movement which is resilient to different sensorimotor contexts. Our purpose is to verify the consistency of such motor equivalence during a drawing task, by testing the effect of manual dominance and movement speed on motor performance. We hypothesize that abstract kinematic variables are not the most resistant to speed or limb effector changes. The results show specific effects of speed and hand side on the drawing task. Movement duration, speed-curvature covariation, and maximum velocity were not significantly affected by hand side, while geometrical features were strongly speed and limb dependent. However, intra-trial analysis performed over the successive drawing movements reveals a significant hand side effect on the variability of movement vigor and velocity-curvature relationship (the 1/3 PL). The identified effects of speed and hand dominance on the kinematic parameters suggest different neural strategies, in a pattern that does not go from the most abstract to the least abstract component, as proposed by the traditional hierarchical organization of the motor plan.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impairs normal brain development and socio-cognitive abilities. The pathogenesis of this condition points out the involvement of genetic and environmental factors during in-utero life. Placenta, as an interface tissue between mother and fetus, provides developing fetus requirements and exposes it to maternal environment as well. Therefore, the alteration of DNA methylation as epigenetic consequence of gene-environmental interaction in the placenta could shed light on ASD pathogenesis. In this study, we reviewed the current findings on placental methylation status and its association with ASD. Differentially methylated regions (DMRs) in ASD-developing placenta were found to be mainly enriched in ASD gene loci affecting synaptogenesis, microtubule dynamics, neurogenesis and neuritogenesis. In addition, non-genic DMRs in ASD-placenta proposes an alternative contributing mechanism for ASD development. Our study highlights the importance of placental DNA methylation signature as a biomarker for ASD prediction.

In the current landscape of endothelial cell isolation for building in vitro models of the blood-brain barrier, our work moves towards reproducing the features of the neurovascular unit to achieve glial compliance through an innovative biomimetic coating technology for brain chronic implants. We hypothesized that the autologous origin of human brain microvascular endothelial cells (hBMECs) is the first requirement for the suitable coating to prevent the glial inflammatory response triggered by foreign neuroprosthetics. Therefore, this study established a new procedure to preserve the in vitro viability of hBMECs isolated from gray and white matter specimens taken from neurosurgery patients. Culturing adult hBMECs is generally considered a challenging task due to the difficult survival ex vivo and progressive reduction in proliferation of these cells. The addition of 10 nM β-estradiol 17-acetate to the hBMEC culture medium was found to be an essential and discriminating factor promoting adhesion and proliferation both after isolation and thawing, supporting the well-known protective role played by estrogens on microvessels. In particular, β-estradiol 17-acetate was critical for both freshly isolated and thawed female-derived hBMECs, while it was not necessary for freshly isolated male-derived hBMECs; however, it did counteract the decay in the viability of the latter after thawing. The tumor-free hBMECs were thus cultured for up to 2 months and their growth efficiency was assessed before and after two periods of cryopreservation. Despite the thermal stress, the hBMECs remained viable and suitable for re-freezing and storage for several months. This approach increasing in vitro viability of hBMECs opens new perspectives for the use of cryopreserved autologous hBMECs as biomimetic therapeutic tools, offering the potential to avoid additional surgical sampling for each patient.

A novel organic neuromorphic device performing pattern classification is presented and demonstrated. It features an artificial soma capable of dendritic integration from three pre-synaptic neurons. The time-response of the interface between electrolytic solutions and organic mixed ionic-electronic conductors is proposed as the sole computational feature for pattern recognition, and it is easily tuned in the organic dendritic integrator by simply controlling electrolyte ionic strength. The classifier is benchmarked in speech-recognition experiments, with a sample of 14 words, encoded either from audio tracks or from kinematic data, showing excellent discrimination performances in a planar, miniaturizable, fully passive device, designed to be promptly integrated in more complex architectures where on-board pattern classification is required.

We study how obsessive-compulsive disorder (OCD) affects the complexity and time-reversal symmetry-breaking (irreversibility) of the brain resting-state activity as measured by magnetoencephalography (MEG). Comparing MEG recordings from OCD patients and age/sex matched control subjects, we find that irreversibility is more concentrated at faster time scales and more uniformly distributed across different channels of the same hemisphere in OCD patients than in control subjects. Furthermore, the interhemispheric asymmetry between homologous areas of OCD patients and controls is also markedly different. Some of these differences were reduced by 1-year of Kundalini Yoga meditation treatment. Taken together, these results suggest that OCD alters the dynamic attractor of the brain's resting state and hint at a possible novel neurophysiological characterization of this psychiatric disorder and how this therapy can possibly modulate brain function.

Organic Electrochemical Transistors (OECTs) are suitable for developing ultra-sensitive bioelectronic sensors. In the organic electrochemical transistors architecture, the source-drain channel is made of a conductive polymer film either cast from a formulated dispersion or electrodeposited from a monomer solution. The commercial poly(3,4-ethylenedioxidethiophene)/poly(styrene sulfonate) (PEDOT:PSS) water dispersion is the workhorse of organic bioelectronics for its high conductance, low impact and ease of processability. In this study, a hybrid organic electrochemical transistors channel fabrication strategy is presented, where electrochemical deposition of a PEDOT/X (with X indicating the counterion) is performed on a dispersion-cast PEDOT:PSS film. Six different counterions where used: X = PSS, Nafion, Hyaluronate, Dextran sulfate, Dexamethasone phosphate and tauroursodeoxycholic acid, each potentially endowing organic electrochemical transistors with additional functions such as ion exchange and pharmacological activity upon release of X. The PEDOT/X-PEDOT:PSS bilayers were characterized by means of electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and focused ion beam tomography combined with scanning electron microscopy (FIB-SEM). In addition, their respective organic electrochemical transistorss were characterized and compared to PEDOT:PSS organic electrochemical transistors. Our results show that the hybrid bilayer strategy is viable to fabricate multifunctional organic electrochemical transistorss with biologically-relevant function, thereby retaining the outstanding figures of merit of commercial PEDOT:PSS.

Social behaviors rely on the coordination of multiple effectors within one’s own body as well as between the interacting bodies. However, little is known about how coupling at the interpersonal level impacts coordination among body parts at the intrapersonal level, especially in ecological, complex, situations. Here, we perturbed interpersonal sensorimotor communication in violin players of an orchestra and investigated how this impacted musicians’ intrapersonal movements coordination. More precisely, first section violinists were asked to turn their back to the conductor and to face the second section of violinists, who still faced the conductor. Motion capture of head and bow kinematics showed that altering the usual interpersonal coupling scheme increased intrapersonal coordination. Our perturbation also induced smaller yet more complex head movements, which spanned multiple, faster timescales that closely matched the metrical levels of the musical score. Importantly, perturbation differentially increased intrapersonal coordination across these timescales. We interpret this behavioral shift as a sensorimotor strategy that exploits periodical movements to effectively tune sensory processing in time and allows coping with the disruption in the interpersonal coupling scheme. As such, head movements, which are usually deemed to fulfill communicative functions, may possibly be adapted to help regulate own performance in time.

Abstract Successful translation of organic transistors as sensors and transducers to clinical settings is hampered by safety and stability issues. The operation of such devices demands driving voltages across the biotic/abiotic interface, which may result in undesired electrochemical reactions that may harm both the patient and the device. In this study, a novel operational mode is presented for electrolyte‐gated organic transistors that avoid these drawbacks: the common‐drain/grounded‐source configuration. This approach reverts the standard common‐source/common‐ground configuration and achieves maximum signal amplification while applying null net bias across the electrolyte, with no parasitic currents. The viability of the proposed configuration is demonstrated by recording in vivo the somatosensory evoked activity from the barrel cortex of rats. The main inherent advantage of transistors with respect to passive electrodes is preserved in the proposed scheme: a superior signal‐to‐noise ratio is achieved which enables the detection of evoked activity at the single‐trial level. Then, common‐drain/grounded‐source organic transistors are proposed as ideal candidate devices for a harmless translational recording platform.

Abstract Next‐generation neural interfaces for bidirectional communication with the central nervous system aim to achieve the intimate integration with the neural tissue with minimal neuroinflammatory response, high spatio‐temporal resolution, very high sensitivity, and readout stability. The design and manufacturing of devices for low power/low noise neural recording and safe and energy‐efficient stimulation that are, at the same time, conformable to the brain, with matched mechanical properties and biocompatibility, is a convergence area of research where neuroscientists, materials scientists, and nanotechnologists operate synergically. The biotic–abiotic neural interface, however, remains a formidable challenge that prompts for new materials platforms and innovation in device layouts. Conductive polymers (CP) are attractive materials to be interfaced with the neural tissue and to be used as sensing/stimulating electrodes because of their mixed ionic‐electronic conductivity, their low contact impedance, high charge storage capacitance, chemical versatility, and biocompatibility. This manuscript reviews the state‐of‐the‐art of poly(3,4‐ethylenedioxythiophene)‐based neural interfaces for extracellular recording and stimulation, focusing on those technological approaches that are successfully demonstrated in vivo. The aim is to highlight the most reliable and ready‐for‐clinical‐use solutions, in terms of materials technology and recording performance, other than spot major limitations and identify future trends in this field.

Summary: Most animal species group together and coordinate their behavior in quite sophisticated manners for mating, hunting, or defense purposes. In humans, coordination at a macroscopic level (the pacing of movements) is evident both in daily life (e.g., walking) and skilled (e.g., music and dance) behaviors. By examining the fine structure of movement, we here show that interpersonal coordination is established also at a microscopic – submovement – level. Natural movements appear as marked by recurrent (2–3 Hz) speed breaks, i.e., submovements, that are traditionally considered the result of intermittency in (visuo)motor feedback-based control. In a series of interpersonal coordination tasks, we show that submovements produced by interacting partners are not independent but alternate tightly over time, reflecting online mutual adaptation. These findings unveil a potential core mechanism for behavioral coordination that is based on between-persons synchronization of the intrinsic dynamics of action-perception cycles.

The role of pre-synaptic DC bias is investigated in three-terminal organic neuromorphic architectures based on electrolyte-gated organic transistors—EGOTs. By means of pre-synaptic offset it is possible to finely control the number of discrete conductance states in short-term plasticity experiments, to obtain, at will, both depressive and facilitating response in the same neuromorphic device and to set the ratio between two subsequent pulses in paired-pulse experiments. The charge dynamics leading to these important features are discussed in relationship with macroscopic device figures of merit such as conductivity and transconductance, establishing a novel key enabling parameter in devising the operation of neuromorphic organic electronics.

Developmental coordination disorder (DCD) is a common neurodevelopmental condition characterized by disabling motor impairments being visible from the first years of life. Over recent decades, research in this field has gained important results, showing alterations in several processes involved in the regulation of motor behavior (e.g., planning and monitoring of actions, motor learning, action imitation). However, these studies mostly pursued a behavioral approach, leaving relevant questions open concerning the neural correlates of this condition. In this narrative review, we first survey the literature on motor control and sensorimotor impairments in DCD. Then, we illustrate the contributions to the field that may be achieved using transcranial magnetic stimulation (TMS) of the motor cortex. While still rarely employed in DCD research, this approach offers several opportunities, ranging from the clarification of low-level cortical electrophysiology to the assessment of the motor commands transmitted throughout the corticospinal system. We propose that TMS may help to investigate the neural correlates of motor impairments reported in behavioral studies, thus guiding DCD research toward a brain-oriented acknowledgment of this condition. This effort would help translational research to provide novel diagnostic and therapeutic tools.

Movements overtly sample sensory information, making sensory analysis an active-sensing process. In this study, we show that visual information sampling is not just locked to the (overt) movement dynamics but to the internal (covert) dynamics of cortico-motor control. We asked human participants to perform continuous isometric contraction while detecting unrelated and unpredictable near-threshold visual stimuli. The motor output (force) shows zero-lag coherence with brain activity (recorded via electroencephalography) in the beta-band, as previously reported. In contrast, cortical rhythms in the alpha-band systematically forerun the motor output by 200 milliseconds. Importantly, visual detection is facilitated when cortico-motor alpha (not beta) synchronization is enhanced immediately before stimulus onset, namely, at the optimal phase relationship for sensorimotor communication. These findings demonstrate an ongoing coupling between visual sampling and motor control, suggesting the operation of an internal and alpha-cycling visuomotor loop.

Modulation of cortical beta rhythm (15–30 Hz) is present during preparation for and execution of voluntary movements as well as during somatosensory stimulation. A rebound in beta synchronization is observed after the end of voluntary movements as well as after somatosensory stimulation and is believed to describe the return to baseline of sensorimotor networks. However, the contribution of efferent and afferent signals to the beta rebound remains poorly understood. Here, we applied electrical median nerve stimulation (MNS) to the right side followed by transcranial magnetic stimulation (TMS) on the left primary motor cortex after either 15 or 25 ms. Because the afferent volley reaches the somatosensory cortex after about 20 ms, TMS on the motor cortex was either anticipating or following the cortical arrival of the peripheral stimulus. We show modulations in different beta sub-bands and in both hemispheres, following a pattern of greater resynchronization when motor signals are paired with a peripheral one. The beta rebound in the left hemisphere (stimulated) is modulated in its lower frequency range when TMS precedes the cortical arrival of the afferent volley. In the right hemisphere (unstimulated), instead, the increase is limited to higher beta frequencies when TMS is delivered after the arrival of the afferent signal. In general, we demonstrate that the temporal integration of afferent and efferent signals plays a key role in the genesis of the beta rebound and that these signals may be carried in parallel by different beta sub-bands.

Action Execution (AE) and Action Observation (AO) share an extended cortical network of activated areas. During coordinative action these processes also overlap in time, potentially giving rise to behavioral interference effects. The neurophysiological mechanisms subtending the interaction between concurrent AE and AO are substantially unknown. To assess the effect of AO on observer’s corticomotor drive, we run one electromyography (EMG) and three Transcranial Magnetic Stimulation (TMS) studies. Participants were requested to maintain a steady hand opening or closing posture while observing the same or a different action (hand opening and closing in the main TMS study). By measuring Cortical Silent Periods (CSP), an index of GABAB-mediated corticospinal inhibitory strength, we show a selective reduction of inhibitory motor drive for mismatching AE-AO pairs. The last two TMS experiments, show that this mismatch is computed according to a muscle-level agonist-antagonist representation. Combined, our results suggest that corticospinal inhibition may be the central neurophysiological mechanism by which one’s own motor execution is adapted to the contextual visual cues provided by other’s actions.

Language and action share similar organizational principles. Both are thought to be hierarchical and recursive in nature. Here we address the relationship between language and action from developmental and neurophysiological perspectives. We discuss three major aspects: The extent of the analogy between language and action; the necessity to extend research on the yet largely neglected aspect of action syntax; the positive contribution of a developmental approach to this topic. We elaborate on the claim that adding an ontogenetic approach will help to obtain a comprehensive picture about both the interplay between language and action and its development, and to answer the question whether the underlying mechanisms of detecting syntactic violations of action sequences are similar to or different from the processing of language syntactic violations.

Transcranial magnetic stimulation was used to investigate corticospinal output changes in 10 professional piano players during motor imagery of triad chords in C major to be “mentally” performed with three fingers of the right hand (thumb, index, and little finger). Five triads were employed in the task; each composed by a stable 3rd interval (C4-E4) and a varying third note that could generate a 5th (G4), a 6th (A4), a 7th (B4), a 9th (D5), or a 10th (E5) interval. The 10th interval chord was thought to be impossible in actual execution for biomechanical reasons, as long as the thumb and the index finger remained fixed on the 3rd interval. Chords could be listened from loudspeakers, read on a staff, or listened and read at the same time while performing the imagery task. The corticospinal output progressively increased along with task demands in terms of mental representation of hand extension. The effects of audio, visual, or audiovisual musical stimuli were generally similar, unless motor imagery of kinetically impossible triads was required. A specific three-effector motor synergy was detected, governing the representation of the progressive mental extension of the hand. Results demonstrate that corticospinal facilitation in professional piano players can be modulated according to the motor plan, even if simply “dispatched” without actual execution. Moreover, specific muscle synergies, usually encoded in the motor cortex, emerge along the cross-modal elaboration of musical stimuli and in motor imagery of musical performances.

Ancient Greek and Latin philosophers were already aware of the difficulty in discriminating between ‘objects’ intended as material entities belonging to the physical, external world, and ‘objects’ intended as internal representations of that world. Descartes was the first making a clear, rational distinction between the physical objects (res extensa) and their representations (res cogitans). However, from a theoretical point of view this remains an open question. Empirical evidence coming from neurophysiology may provide some insight to this vexata quaestio. Despite the classical view, segregating perceptual and executive functions in different sets of brain areas, a large percentage of sensory (visual) and motor neurons are indeed visuomotor. In other terms, the same cell specifically discharges during observation of manipulable objects and during the grasping action directed towards them. Accordingly, objects and objects-related concepts (representations) seem to be the two faces of the same medal. Objects, often created by us, are loci of interaction with our body and their brain representation automatically implies motor interaction. This concept is very close to the classical idea of motor affordance originally proposed by Gibson. Motor control of the grasping hand, visuomotor transformation of objects into hand poses and the relationship between pragmatic and semantic representations of objects/actions are interrelated functions resulting from a continuous interaction between parietal and frontal areas. In humans a similar picture emerges from neuroimaging and transcranial magnetic stimulation studies and prompts interesting links with language as well. In my presentation I will show and discuss the most recent 'state of the art' of the topic integrating the perspective with some recent experimental results from our laboratory.

Observing others' actions desynchronizes electroencephalographic (EEG) rhythms and modulates corticospinal excitability as assessed by transcranial magnetic stimulation (TMS). However, it remains unclear if these measures reflect similar neurofunctional mechanisms at the individual level. In the present study, a within-subject experiment was designed to assess these two neurophysiological indexes and to quantify their mutual correlation. Participants observed reach-to-grasp actions directed towards a small (precision grip) or a large object (power grip). We focused on two specific time points for both EEG and TMS. The first time point (t1) coincided with the maximum hand aperture, i.e. the moment at which a significant modulation of corticospinal excitability is expected. The second (t2), coincided with the EEG resynchronization occurring at the end of the action, i.e. the moment at which a hypothetic minimum for action observation effect is expected. Results showed a Mu rhythm bilateral desynchronization at t1 with differential resynchronization at t2 in the two hemispheres. Beta rhythm was more desynchronized in the left hemisphere at both time points. These EEG differences, however, were not influenced by grip type. Conversely, motor potentials evoked by TMS in an intrinsic hand muscle revealed an interaction effect of grip and time. No significant correlations between Mu/Beta rhythms and motor evoked potentials were found. These findings are discussed considering the spatial and temporal resolution of the two investigated techniques and argue over two alternative explanations: i. each technique provides different measures of the same process or ii. they describe complementary features of the action observation network in humans.

Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity) and clinical practice (e.g., before resecting brain tumors involving the motor cortex). However, compilation of motor maps based on the motor threshold (MT) requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs) through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12) the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS) significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8), while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help to study the functional significance of short-term plasticity in motor learning and recovery from brain injuries. Besides this advantage, particularly in the case of human patients or experimental animals that are less trained to remain at rest, shorter mapping time is physically and mentally less demanding and might allow the evaluation of motor maps in awake individuals as well.

Glassy carbon (GC) has high potential to serve as a biomaterial in neural applications because it is biocompatible, electrochemically inert and can be incorporated in polyimide-based implantable devices. Miniaturization and applicability of GC is, however, thought to be partially limited by its electrical conductivity. For this study, ultra-conformable polyimide-based electrocorticography (ECoG) devices with different-diameter GC electrodes were fabricated and tested in vitro and in rat models. For achieving conformability to the rat brain, polyimide was patterned in a finger-like shape and its thickness was set to 8 µm. To investigate different electrode sizes, each ECoG device was assigned electrodes with diameters of 50, 100, 200 and 300 µm. They were electrochemically characterized and subjected to 10 million biphasic pulses—for achieving a steady-state—and to X-ray photoelectron spectroscopy, for examining their elemental composition. The electrodes were then implanted epidurally to evaluate the ability of each diameter to detect neural activity. Results show that their performance at low frequencies (up to 300 Hz) depends on the distance from the signal source rather than on the electrode diameter, while at high frequencies (above 200 Hz) small electrodes have higher background noises than large ones, unless they are coated with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS).

The Shared Origin of Language and Action – Motor system organization shows some interesting parallels with language organization. Here we point out possible commonalities between Action and Language, basing our claims on neurophysiological, neuroanatomical and neuroimaging data. Furthermore, we speculate that the motor system may have furnished the basic computational capabilities for the emergence of both semantics and syntax.

This paper investigates a biologically motivated model of peripersonal space through its implementation on a humanoid robot. Guided by the present understanding of the neurophysiology of the fronto-parietal system, we developed a computational model inspired by the receptive fields of polymodal neurons identified, for example, in brain areas F4 and VIP. The experiments on the iCub humanoid robot show that the peripersonal space representation i) can be learned efficiently and in real-time via a simple interaction with the robot, ii) can lead to the generation of behaviors like avoidance and reaching, and iii) can contribute to the understanding the biological principle of motor equivalence. More specifically, with respect to i) the present model contributes to hypothesizing a learning mechanisms for peripersonal space. In relation to point ii) we show how a relatively simple controller can exploit the learned receptive fields to generate either avoidance or reaching of an incoming stimulus and for iii) we show how the robot can select arbitrary body parts as the controlled end-point of an avoidance or reaching movement.

Conventional structural Magnetic Resonance (MR) techniques can accurately identify brain tumors but do not provide exhaustive information about the integrity of the surrounding/embedded white matter (WM). In this study, we used Diffusion-Weighted (DW) MRI tractography to explore tumor-induced alterations of WM architecture without any a priori knowledge about the fiber paths under consideration. We used deterministic multi-fiber tractography to analyze 16 cases of histologically classified brain tumors (meningioma, low-grade glioma, high-grade glioma) to evaluate the integrity of WM bundles in the tumoral region, in relation to the contralateral unaffected hemisphere. Our new tractographic approach yielded measures of WM involvement which were strongly correlated with the histopathological features of the tumor (r = 0.83, p = 0.0001). In particular, the number of affected fiber tracts were significantly (p = 0.0006) different among tumor types. Our method proposes a new application of diffusion tractography for the detection of tumor aggressiveness in those cases in which the lesion does not involve any major/known WM paths and when a priori information about the local fiber anatomy is lacking.

Motor resonance mechanisms are known to affect humans' ability to interact with others, yielding the kind of "mutual understanding" that is the basis of social interaction. However, it remains unclear how the partner's action features combine or compete to promote or prevent motor resonance during interaction. To clarify this point, the present study tested whether and how the nature of the visual stimulus and the properties of the observed actions influence observer's motor response, being motor contagion one of the behavioral manifestations of motor resonance. Participants observed a humanoid robot and a human agent move their hands into a pre-specified final position or put an object into a container at various velocities. Their movements, both in the object- and non-object- directed conditions, were characterized by either a smooth/curvilinear or a jerky/segmented trajectory. These trajectories were covered with biological or non-biological kinematics (the latter only by the humanoid robot). After action observation, participants were requested to either reach the indicated final position or to transport a similar object into another container. Results showed that motor contagion appeared for both the interactive partner except when the humanoid robot violated the biological laws of motion. These findings suggest that the observer may transiently match his/her own motor repertoire to that of the observed agent. This matching might mediate the activation of motor resonance, and modulate the spontaneity and the pleasantness of the interaction, whatever the nature of the communication partner.

Parietal and premotor cortices of the macaque monkey contain distinct populations of neurons which, in addition to their motor discharge, are also activated by visual stimulation. Among these visuomotor neurons, a population of grasping neurons located in the anterior intraparietal area (AIP) shows discharge modulation when the own hand is visible during object grasping. Given the dense connections between AIP and inferior frontal regions, we aimed at investigating whether two hand-related frontal areas, ventral premotor area F5 and primary motor cortex (area F1), contain neurons with similar properties. Two macaques were involved in a grasping task executed in various light/dark conditions in which the to-be-grasped object was kept visible by a dim retro-illumination. Approximately 62% of F5 and 55% of F1 motor neurons showed light/dark modulations. To better isolate the effect of hand-related visual input, we introduced two further conditions characterized by kinematic features similar to the dark condition. The scene was briefly illuminated (i) during hand preshaping (pre-touch flash, PT-flash) and (ii) at hand-object contact (touch flash, T-flash). Approximately 48% of F5 and 44% of F1 motor neurons showed a flash-related modulation. Considering flash-modulated neurons in the two flash conditions, ∼40% from F5 and ∼52% from F1 showed stronger activity in PT- than T-flash (PT-flash-dominant), whereas ∼60% from F5 and ∼48% from F1 showed stronger activity in T- than PT-flash (T-flash-dominant). Furthermore, F5, but not F1, flash-dominant neurons were characterized by a higher peak and mean discharge in the preferred flash condition as compared to light and dark conditions. Still considering F5, the distribution of the time of peak discharge was similar in light and preferred flash conditions. This study shows that the frontal cortex contains neurons, previously classified as motor neurons, which are sensitive to the observation of meaningful phases of the own grasping action. We conclude by discussing the possible functional role of these populations.

The representation of actions within the action-observation network is thought to rely on a distributed functional organization. Furthermore, recent findings indicate that the action-observation network encodes not merely the observed motor act, but rather a representation that is independent from a specific sensory modality or sensory experience. In the present study, we wished to determine to what extent this distributed and 'more abstract' representation of action is truly supramodal, i.e. shares a common coding across sensory modalities. To this aim, a pattern recognition approach was employed to analyze neural responses in sighted and congenitally blind subjects during visual and/or auditory presentation of hand-made actions. Multivoxel pattern analyses-based classifiers discriminated action from non-action stimuli across sensory conditions (visual and auditory) and experimental groups (blind and sighted). Moreover, these classifiers labeled as 'action' the pattern of neural responses evoked during actual motor execution. Interestingly, discriminative information for the action/non action classification was located in a bilateral, but left-prevalent, network that strongly overlaps with brain regions known to form the action-observation network and the human mirror system. The ability to identify action features with a multivoxel pattern analyses-based classifier in both sighted and blind individuals and independently from the sensory modality conveying the stimuli clearly supports the hypothesis of a supramodal, distributed functional representation of actions, mainly within the action-observation network.

Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices. The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device. Taken together, neural activity recording and microstimulation techniques allow us to embed a portion of the central nervous system within a closed-loop system, whose behavior emerges from the combined dynamical properties of its neural and artificial components. In this study we asked if it is possible to concurrently regulate this bidirectional brain-machine interaction so as to shape a desired dynamical behavior of the combined system. To this end, we followed a well-known biological pathway. In vertebrates, the communications between brain and limb mechanics are mediated by the spinal cord, which combines brain instructions with sensory information and organizes coordinated patterns of muscle forces driving the limbs along dynamically stable trajectories. We report the creation and testing of the first neural interface that emulates this sensory-motor interaction. The interface organizes a bidirectional communication between sensory and motor areas of the brain of anaesthetized rats and an external dynamical object with programmable properties. The system includes (a) a motor interface decoding signals from a motor cortical area, and (b) a sensory interface encoding the state of the external object into electrical stimuli to a somatosensory area. The interactions between brain activities and the state of the external object generate a family of trajectories converging upon a selected equilibrium point from arbitrary starting locations. Thus, the bidirectional interface establishes the possibility to specify not only a particular movement trajectory but an entire family of motions, which includes the prescribed reactions to unexpected perturbations.

In 1979, Gibson first advanced the idea that the sight of graspable objects automatically activates in the observer the repertoire of actions necessary to interact with them, even in the absence of any intention to act ("affordance effect"). The neurophysiological substrate of this effect was later identified in a class of bimodal neurons, the so-called "canonical" neurons, located within monkey premotor cortex. In humans, even if different behavioral studies supported the existence of affordance effect, neurophysiological investigations exploring its neural substrates showed contradictory results. Here, by means of Transcranial Magnetic Stimulation (TMS), we explored the time-course of the "affordance effect" elicited by the observation of everyday-life graspable objects on motor cortex of resting observers. We recorded motor evoked potentials (MEP) from three intrinsic hand muscles (two "synergic" for grasping, OP and FDI and one "neutral", ADM). We found that objects' vision determined an increased excitability at 120 milliseconds after their presentation. Moreover, this modulation was proved to be specific to the cortical representations of synergic muscles. From an evolutionary perspective, this timing perfectly fits with a fast recruitment of the motor system aimed at rapidly and accurately choosing the appropriate motor plans in a competitive environment filled with different opportunities.

Non-verbal communication enables efficient transfer of information among people. In this context, classic orchestras are a remarkable instance of interaction and communication aimed at a common aesthetic goal: musicians train for years in order to acquire and share a non-linguistic framework for sensorimotor communication. To this end, we recorded violinists' and conductors' movement kinematics during execution of Mozart pieces, searching for causal relationships among musicians by using the Granger Causality method (GC). We show that the increase of conductor-to-musicians influence, together with the reduction of musician-to-musician coordination (an index of successful leadership) goes in parallel with quality of execution, as assessed by musical experts' judgments. Rigorous quantification of sensorimotor communication efficacy has always been complicated and affected by rather vague qualitative methodologies. Here we propose that the analysis of motor behavior provides a potentially interesting tool to approach the rather intangible concept of aesthetic quality of music and visual communication efficacy.

We investigate the use of phonetic motor invariants (MIs), that is, recurring kinematic patterns of the human phonetic articulators, to improve automatic phoneme discrimination. Using a multi-subject database of synchronized speech and lips/tongue trajectories, we first identify MIs commonly associated with bilabial and dental consonants, and use them to simultaneously segment speech and motor signals. We then build a simple neural network-based regression schema (called Audio-Motor Map, AMM) mapping audio features of these segments to the corresponding MIs. Extensive experimental results show that (a) a small set of features extracted from the MIs, as originally gathered from articulatory sensors, are dramatically more effective than a large, state-of-the-art set of audio features, in automatically discriminating bilabials from dentals; (b) the same features, extracted from AMM-reconstructed MIs, are as effective as or better than the audio features, when testing across speakers and coarticulating phonemes; and dramatically better as noise is added to the speech signal. These results seem to support some of the claims of the motor theory of speech perception and add experimental evidence of the actual usefulness of MIs in the more general framework of automated speech recognition.

BACKGROUND: A vast body of social and cognitive psychology studies in humans reports evidence that external rewards, typically monetary ones, undermine intrinsic motivation. These findings challenge the standard selfish-rationality assumption at the core of economic reasoning. In the present work we aimed at investigating whether the different modulation of a given monetary reward automatically and unconsciously affects effort and performance of participants involved in a game devoid of visual and verbal interaction and without any perspective-taking activity. METHODOLOGY/PRINCIPAL FINDINGS: Twelve pairs of participants were submitted to a simple motor coordination game while recording the electromyographic activity of First Dorsal Interosseus (FDI), the muscle mainly involved in the task. EMG data show a clear effect of alternative rewards strategies on subjects' motor behavior. Moreover, participants' stock of relevant past social experiences, measured by a specifically designed questionnaire, was significantly correlated with EMG activity, showing that only low social capital subjects responded to monetary incentives consistently with a standard rationality prediction. CONCLUSIONS/SIGNIFICANCE: Our findings show that the effect of extrinsic motivations on performance may arise outside social contexts involving complex cognitive processes due to conscious perspective-taking activity. More importantly, the peculiar performance of low social capital individuals, in agreement with standard economic reasoning, adds to the knowledge of the circumstances that makes the crowding out/in of intrinsic motivation likely to occur. This may help in improving the prediction and accuracy of economic models and reconcile this puzzling effect of external incentives with economic theory.

BACKGROUND: Several studies bring evidence that action observation elicits contagious responses during social interactions. However automatic imitative tendencies are generally inhibited and it remains unclear in which conditions mere action observation triggers motor behaviours. In this study, we addressed the question of contagious postural responses when observing human imbalance. METHODOLOGY/PRINCIPAL FINDINGS: We recorded participants' body sway while they observed a fixation cross (control condition), an upright point-light display of a gymnast balancing on a rope, and the same point-light display presented upside down. Our results showed that, when the upright stimulus was displayed prior to the inverted one, centre of pressure area and antero-posterior path length were significantly greater in the upright condition compared to the control and upside down conditions. CONCLUSIONS/SIGNIFICANCE: These results demonstrate a contagious postural reaction suggesting a partial inefficiency of inhibitory processes. Further, kinematic information was sufficient to trigger this reaction. The difference recorded between the upright and upside down conditions indicates that the contagion effect was dependent on the integration of gravity constraints by body kinematics. Interestingly, the postural response was sensitive to habituation, and seemed to disappear when the observer was previously shown an inverted display. The motor contagion recorded here is consistent with previous work showing vegetative output during observation of an effortful movement and could indicate that lower level control facilitates contagion effects.

Brain-machine interfaces (BMIs) are mostly investigated as a means to provide paralyzed people with new communication channels with the external world. However, the communication between brain and artificial devices also offers a unique opportunity to study the dynamical properties of neural systems. This review focuses on bidirectional interfaces, which operate in two ways by translating neural signals into input commands for the device and the output of the device into neural stimuli. We discuss how bidirectional BMIs help investigating neural information processing and how neural dynamics may participate in the control of external devices. In this respect, a bidirectional BMI can be regarded as a fancy combination of neural recording and stimulation apparatus, connected via an artificial body. The artificial body can be designed in virtually infinite ways in order to observe different aspects of neural dynamics and to approximate desired control policies.

Automatic imitation is the tendency to reproduce observed actions involuntarily. Though this topic has been widely treated, at present little is known about the automatic imitation of the kinematic features of an observed movement. The present study was designed to understand if the kinematics of a previously seen stimulus primes the executed action, and if this effect is sensitive to the kinds of stimuli presented. We proposed a simple imitation paradigm in which a dot or a human demonstrator moved in front of the participant who was instructed either to reach the final position of the stimulus or to imitate its motion with his or her right arm. Participants' movements were automatically contaminated by stimulus velocity when it moved according to biological laws, suggesting that automatic imitation was kinematic dependent. Despite that the performance, in term of reproduced velocity, improved in a context of voluntary imitation, subjects did not replicate the observed motions exactly. These effects were not affected by the kind of stimuli used, i.e., motor responses were influenced in the same manner after dot or human observation. These findings support the existence of low-level sensory-motor matching mechanisms that work on movement planning and represent the basis for higher levels of social interaction.

BACKGROUND: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. METHODOLOGY/PRINCIPAL FINDINGS: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. CONCLUSIONS/SIGNIFICANCE: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications.