Transitory Inhibition of the left anterior intraparietal sulcus impairs joint actions: a continuous Theta-Burst stimulation study

Although temporal coordination is a hallmark of motor interactions, joint action (JA) partners do not simply synchronize; they rather dynamically adapt to each other to achieve a joint goal. We created a novel paradigm to tease apart the processes underlying synchronization and JA and tested the causal contribution of the left anterior intraparietal sulcus (aIPS) in these behaviors. Participants had to synchronize their congruent or incongruent movements with a virtual partner in two conditions: (i) being instructed on what specific action to perform, independently from what action the partner performed (synchronization), and (ii) being instructed to adapt online to the partner's action (JA). Offline noninvasive inhibitory brain stimulation (continuous theta-burst stimulation) over the left aIPS selectively modulated interpersonal synchrony in JA by boosting synchrony during congruent interactions and impairing it during incongruent ones, while leaving performance in the synchronization condition unaffected. These results suggest that the left aIPS plays a causal role in supporting online adaptation to a partner's action goal, whereas it is not necessarily engaged in social situations where the goal of the partner is irrelevant. This indicates that, during JAs, the integration of one's own and the partner's action goal is supported by aIPS

Attentional Modulation of Vision Versus Proprioception During Action

To control our actions efficiently, our brain represents our body based on a combination of visual and proprioceptive cues, weighted according to how (un)reliable—how precise—each respective modality is in a given context. However, perceptual experiments in other modalities suggest that the weights assigned to sensory cues are also modulated “top-down” by attention. Here, we asked whether during action, attention can likewise modulate the weights (i.e., precision) assigned to visual versus proprioceptive information about body position. Participants controlled a virtual hand (VH) via a data glove, matching either the VH or their (unseen) real hand (RH) movements to a target, and thus adopting a “visual” or “proprioceptive” attentional set, under varying levels of visuo-proprioceptive congruence and visibility. Functional magnetic resonance imaging (fMRI) revealed increased activation of the multisensory superior parietal lobe (SPL) during the VH task and increased activation of the secondary somatosensory cortex (S2) during the RH task. Dynamic causal modeling (DCM) showed that these activity changes were the result of selective, diametrical gain modulations in the primary visual cortex (V1) and the S2. These results suggest that endogenous attention can balance the gain of visual versus proprioceptive brain areas, thus contextualizing their inf luence on multisensory areas representing the body for action

Neuroplasticity of the Sensorimotor Cortex during Learning

We will discuss some of the current issues in understanding plasticity in the sensorimotor (SM) cortices on the behavioral, neurophysiological, and synaptic levels. We will focus our paper on reaching and grasping movements in the rat. In addition, we will discuss our preliminary work utilizing inhibition of protein kinase Mζ (PKMζ), which has recently been shown necessary and sufficient for the maintenance of long-term potentiation (LTP) (Ling et al., 2002). With this new knowledge and inhibitors to this system, as well as the ability to overexpress this system, we can start to directly modulate LTP and determine its influence on behavior as well as network level processing dependent at least in part due to this form of LTP. We will also briefly introduce the use of brain machine interface (BMI) paradigms to ask questions about sensorimotor plasticity and discuss current analysis techniques that may help in our understanding of neuroplasticity

Corticospinal excitability modulation in resting digit muscles during cyclical movement of the digits of the ipsilateral limb

We investigated how corticospinal excitability of the resting digit muscles was modulated by the digit movement in the ipsilateral limb. Subjects performed cyclical extension-flexion movements of either the right toes or fingers. To determine whether corticospinal excitability of the resting digit muscles was modulated on the basis of movement direction or action coupling between ipsilateral digits, the right forearm was maintained in either the pronated or supinated position. During the movement, the motor evoked potential (MEP) elicited by transcranial magnetic stimulation was measured from either the resting right finger extensor and flexor, or toe extensor and flexor. For both finger and toe muscles, independent of forearm position, MEP amplitude of the flexor was greater during ipsilateral digit flexion as compared to extension, and MEP amplitude of the extensor was greater during ipsilateral digit extension as compared to flexion. An exception was that MEP amplitude of the toe flexor with the supinated forearm did not differ between during finger extension and flexion. These findings suggest that digit movement modulates corticospinal excitability of the digits of the ipsilateral limb such that the same action is preferred. Our results provide evidence for a better understanding of neural interactions between ipsilateral limbs, and may thus contribute to neurorehabilitation after a stroke or incomplete spinal cord injury

Neural and motor basis of inter-individual interactions

The goal of my Ph.D. work was to investigate the behavioral markers and the brain activities responsible for the emergence of sensorimotor communication. Sensorimotor communication can be defined as a form of communication consisting into flexible exchanges based on bodily signals, in order to increase the efficiency of the inter-individual coordination. For instance, a soccer player carving his movements to inform another player about his intention. This form of interaction is highly dependent of the motor system and the ability to produce appropriate movements but also of the ability of the partner to decode these cues. To tackle these facets of human social interaction, we approached the complexity of the problem by splitting my research activities into two separate lines of research. First, we pursued the examination of motor-based humans\u2019 capability to perceive and \u201cread\u201d other\u2019s behaviors in focusing on single-subject experiment. The discovery of mirror neurons in monkey premotor cortex in the early nineties (di Pellegrino et al. 1992) motivated a number of human studies on this topic (Rizzolatti and Craighero 2004). The critical finding was that some ventral premotor neurons are engaged during visual presentation of actions performed by conspecifics. More importantly, those neurons were shown to encode also the actual execution of similar actions (i.e. irrespective of who the acting individual is). This phenomenon has been highly investigated in humans by using cortical and cortico-spinal measures (for review see, fMRI: Molenberghs, Cunnington, and Mattingley 2012; TMS: Naish et al. 2014; EEG: Pineda 2008). During single pulse TMS (over the primary motor cortex), the amplitude of motor evoked potentials (MEPs) provides an index of corticospinal recruitment. During action observation the modulation of this index follow the expected changes during action execution (Fadiga et al. 1995). However, dozens of studies have been published on this topic and revealed important inconsistencies. For instance, MEPs has been shown to be dependent on observed low-level motor features (e.g. kinematic features or electromyography temporal coupling; Gangitano, Mottaghy, and Pascual-Leone 2001; Borroni et al. 2005; Cavallo et al. 2012) as well as high level movement properties (e.g. action goals; Cattaneo et al. 2009; Cattaneo et al. 2013). Furthermore, MEPs modulations do not seem to be related to the observed effectors (Borroni and Baldissera 2008; Finisguerra et al. 2015; Senna, Bolognini, and Maravita 2014), suggesting their independence from low-level movement features. These contradictions call for new paradigms. Our starting hypothesis here is that the organization and function of the mirror mechanism should follow that of the motor system during action execution. Hence, we derived three action observation protocols from classical motor control theories: 1) The first study was motivated by the fact that motor redundancy in action execution do not allow the presence of a one-to-one mapping between (single) muscle activation and action goals. Based on that, we showed that the effect of action observation (observation of an actor performing a power versus a precision grasp) are variable at the single muscle level (MEPs; motor evoked potentials) but robust when evaluating the kinematic of TMS-evoked movements. Considering that movements are based on the coordination of multiple muscle activations (muscular synergies), MEPs may represent a partial picture of the real corticospinal activation. Inversely, movement kinematics is both the final functional byproduct of muscles coordination and the sole visual feedback that can be extracted from action observation (i.e. muscle recruitment is not visible). We conclude that TMS-evoked kinematics may be more reliable in representing the state of the motor system during action observation. 2) In the second study, we exploited the inter-subject variability inherent to everyday whole-body human actions, to evaluate the link between individual motor signatures (or motor styles) and other\u2019s action perception. We showed no group-level effect but a robust correlation between the individual motor signature recorded during action execution and the subsequent modulations of corticospinal excitability during action observation. However, results were at odds with a strict version of the direct matching hypothesis that would suggest the opposite pattern. In fact, the more the actor\u2019s movement was similar to the observer\u2019s individual motor signature, the smaller was the MEPs amplitude, and vice versa. These results conform to the predictive coding hypothesis, suggesting that during AO, the motor system compares our own way of doing the action (individual motor signature) with the action displayed on the screen (actor\u2019s movement). 3) In the third study, we investigated the neural mechanisms underlying the visual perception of action mistakes. According to a strict version of the direct matching hypothesis, the observer should potentially reproduce the neural activation present during the actual execution of action errors (van Schie et al. 2004). Here, instead of observing an increase of cortical inhibition, we showed an early (120 ms) decrease of intracortical inhibition (short intracortical inhibition) when a mismatch was present between the observed action (erroneous) and the observer\u2019s expectation. As proposed by the predictive coding framework, the motor system may be involved in the generation of an error signal potentially relying on an early decrease of intracortical inhibition within the corticomotor system. The second line of research aimed at the investigation of how sensorimotor communication flows between agents engaged in a complementary action coordination task. In this regard, measures of interest where related to muscle activity and/or kinematics as the recording of TMS-related indexes would be too complicated in a joint-action scenario. 1) In the first study, we exploited the known phenomenon of Anticipatory Postural Adjustments (APAs). APAs refers to postural adjustments made in anticipation of a self- or externally-generated disturbance in order to cope for the predicted perturbation and stabilize the current posture. Here we examined how observing someone else lifting an object we hold can affect our own anticipatory postural adjustments of the arm. We showed that the visual information alone (joint action condition), in the absence of efference copy (present only when the subject is unloading by himself the object situated on his hand), were not sufficient to fully deploy the needed anticipatory muscular activations. Rather, action observation elicited a dampened APA response that is later augmented by the arrival of tactile congruent feedback. 2) In a second study, we recorded the kinematic of orchestra musicians (one conductor and two lines of violinists). A manipulation was added to perturb the normal flow of information conveyed by the visual channel. The first line of violinist where rotated 180\ub0, and thus faced the second line. Several techniques were used to extract inter-group (Granger Causality method) and intra-group synchronization (PCA for musicians and autoregression for conductors). The analyses were directed to two kinematic features, hand and head movements, which are central for functionally different action. The hand is essential for instrumental actions, whereas head movements encode ancillary expressive actions. During the perturbation, we observed a complete reshaping of the whole patterns of communication going in the direction of a distribution of the leadership between conductor and violinists, especially for what regards head movements. In fact, in the perturbed condition, the second line acts as an informational hub connecting the first line to the conductor they no longer can see. This study evidences different forms of communications (coordination versus synchronization) flowing via different channels (ancillary versus instrumental) with different time-scales

Contextualizing action observation in the predictive brain: Causal contributions of prefrontal and middle temporal areas

Available online 16 May 2018Context facilitates the recognition of forthcoming actions by pointing to which intention is likely to drive them. This intention is thought to be estimated in a ventral pathway linking MTG with frontal regions and to further impact on the implementation of sensory predictions within the action observation network (AON). Additionally, when conflicting intentions are estimated from context, the DLPFC may bias action selection. However, direct evidence for the contribution of these areas to context-embedded action representations in the AON is still lacking. Here, we used a perturb-and-measure TMS-approach to disrupt neural activity, separately in MTG and DLPFC and subsequently measure cortico-spinal excitability while observing actions embedded in congruent, incongruent or ambiguous contexts. Context congruency was manipulated in terms of compatibility between observed kinematics and the action goal suggested by the ensemble of objects depicted in the environment. In the control session (vertex), we found an early facilitation and later inhibition for kinematics embedded in congruent and incongruent contexts, respectively. MTG stimulation altered the differential modulation of M1 response to congruent vs. incongruent contexts, suggesting this area specifies prior representations about appropriate object graspability. Interestingly, all effects were abolished after DLPFC stimulation highlighting its critical role in broader contextual modulation of the AON activity.This work was supported by grants from the European Commission (MCSA-H2020-NBUCA, grant N. 656881), the Ministero Istruzione Universita' e Ricerca (Futuro In Ricerca, FIR 2012, Prot. N. RBFR12F0BD; to C.U.), and from Istituto di Ricovero e Cura a Carattere Scientifico ‘E. Medea’ (Ricerca Corrente 2014, Ministero Italiano della Salute; to C.U.)

Cortical Sensorimotor Mechanisms for Neural Control of Skilled Manipulation

abstract: The human hand is a complex biological system. Humans have evolved a unique ability to use the hand for a wide range of tasks, including activities of daily living such as successfully grasping and manipulating objects, i.e., lifting a cup of coffee without spilling. Despite the ubiquitous nature of hand use in everyday activities involving object manipulations, there is currently an incomplete understanding of the cortical sensorimotor mechanisms underlying this important behavior. One critical aspect of natural object grasping is the coordination of where the fingers make contact with an object and how much force is applied following contact. Such force-to-position modulation is critical for successful manipulation. However, the neural mechanisms underlying these motor processes remain less understood, as previous experiments have utilized protocols with fixed contact points which likely rely on different neural mechanisms from those involved in grasping at unconstrained contacts. To address this gap in the motor neuroscience field, transcranial magnetic stimulation (TMS) and electroencephalography (EEG) were used to investigate the role of primary motor cortex (M1), as well as other important cortical regions in the grasping network, during the planning and execution of object grasping and manipulation. The results of virtual lesions induced by TMS and EEG revealed grasp context-specific cortical mechanisms underlying digit force-to-position coordination, as well as the spatial and temporal dynamics of cortical activity during planning and execution. Together, the present findings provide the foundation for a novel framework accounting for how the central nervous system controls dexterous manipulation. This new knowledge can potentially benefit research in neuroprosthetics and improve the efficacy of neurorehabilitation techniques for patients affected by sensorimotor impairments.Dissertation/ThesisDoctoral Dissertation Neuroscience 201

The dorsal visual stream revisited: Stable circuits or dynamic pathways?

In both macaque and human brain, information regarding visual motion flows from the extrastriate area V6 along two different paths: a dorsolateral one towards areas MT/V5, MST, V3A, and a dorsomedial one towards the visuomotor areas of the superior parietal lobule (V6A, MIP, VIP). The dorsolateral visual stream is involved in many aspects of visual motion analysis, including the recognition of object motion and self motion. The dorsomedial stream uses visual motion information to continuously monitor the spatial location of objects while we are looking and/or moving around, to allow skilled reaching for and grasping of the objects in structured, dynamically changing environments. Grasping activity is present in two areas of the dorsal stream, AIP and V6A. Area AIP is more involved than V6A in object recognition, V6A in encoding vision for action. We suggest that V6A is involved in the fast control of prehension and plays a critical role in biomechanically selecting appropriate postures during reach to grasp behaviors.In everyday life, numerous functional networks, often involving the same cortical areas, are continuously in action in the dorsal visual stream, with each network dynamically activated or inhibited according to the context. The dorsolateral and dorsomedial streams represent only two examples of these networks. Many others streams have been described in the literature, but it is worthwhile noting that the same cortical area, and even the same neurons within an area, are not specific for just one functional property, being part of networks that encode multiple functional aspects. Our proposal is to conceive the cortical streams not as fixed series of interconnected cortical areas in which each area belongs univocally to one stream and is strictly involved in only one function, but as interconnected neuronal networks, often involving the same neurons, that are involved in a number of functional processes and whose activation changes dynamically according to the context

Role of Anterior Cingulate Cortex in Saccade Control

Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions. Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed a resting-state fMRI study to identify areas within the ACC that are functionally connected to the frontal eye fields (FEF). It has been shown that FEF is involved in saccade generation. Therefore, the ACC areas that are functionally connected to FEF could be hypothesized to have a role in saccade control. Then, I performed simultaneous electrophysiological recordings in the ACC and FEF. Furthermore, I explored whether ACC exerts control over FEF. My results show that ACC is involved in cognitive control of saccades. Furthermore, the ACC and FEF neurons communicate through synchronized theta and beta band activity in these areas. The results of this thesis shine light on the mechanisms by which these brain areas communicate. Moreover, my findings support the notion that ACC and FEF have a unique oscillatory property, and more specifically ACC has a prominent theta band, and to a lesser extent beta band activity