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Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0–50, 50–100, and 100–150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffu

Recently, the anatomo-functional specialization of the cerebral areas involved in verbal Short-Term Memory network has been investigated on neurosurgical patients, highlighting how the two main areas of this network, the left Inferior Frontal Gyrus (IFG) and the left Supra-Marginal Gyrus (SMG), can be specialized in the storage of content information and of order information, respectively. In the present experiment, we aimed at replicating this evidence in healthy subjects through the use of repetitive Transcranial Magnetic Stimulation (rTMS). Twenty healthy subjects took part in a within-subjects experiment including three randomized sessions. In two sessions, offline 1 Hz rTMS was applied over either the left IFG or left SMG, while the third was a behavioural-only session. The experimental task was a computerized auditory-verbal digit span. Digit span showed a significant worsening of the accuracy after 1 Hz rTMS applied over both the left IFG and SMG. Furthermore, a reversed distribution of error type was observed: inhibiting IFG significantly increased the content/item errors, while inhibiting SMG increased order errors. We suggest that the SMG is specialized in storing order information, probably independently from the material type.

In the past few years, an increasing number of studies have shown the existence of a Tactile Mirror System in the human brain. This system relies on a shared network of brain areas responding to both the experience of a tactile sensation and to the observation of the same tactile sensations experienced by others. One crucial area of this system is the primary somatosensory cortex (S1). A hypothesis put forward is that the cross-modal responses of the Tactile Mirror System could be a by-product of Hebbian associative learning: the contingency between a seen touch and a felt touch on one’s own body may reinforce the synapses between somatosensory and visual neurons. We developed a novel cross-modal paired associative stimulation (cmPAS) protocol to test the hypothesis that the mirror-like responses of S1 may arise from Hebbian associative plasticity mechanisms. In this new protocol, a Transcranial Magnetic Stimulation (TMS) pulse over S1 is repeatedly paired with the view of a hand being touched. The successful modulation of S1 reactivity by the cmPAS was assessed at a behavioral level, measuring changes in the observer’s tactile acuity as tested with a 2-point discrimination task (2PDT). In the first experiment, we investigated the efficacy of the cmPAS and the temporal specificity of the Hebbian plasticity mechanisms induced by it by varying the inter-stimulus intervals (ISIs) between the TMS pulse and the visual stimuli. In the second experiment, we examined the cortical specificity of our protocol applying TMS also over the primary visual cortex (V1). We found that cmPAS was effective in decreasing participants’ sensory threshold, specifically when the ISI between the visual stimulus and the TMS pulse was of 20 ms, and only when TMS was applied over S1. In the third experiment, we investigated the specificity of the visual stimulus in eliciting changes in the sensory threshold: we assessed the effect of a control condition in which TMS pulses were paired with a pi

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES) are noninvasive brain stimulation (NIBS) tools that are now widely used in neuroscientific research in humans. The fact that both TMS and tES are able to modulate brain plasticity and, in turn, affect behavior is opening up new horizons in the treatment of brain circuit and plasticity disorders. In the present chapter, we will first provide the reader with a brief background on the basic principles of NIBS, describing the electromagnetic and physical foundations of TMS and tES, as well as the current knowledge of the neurophysiologic basis of their effects on brain activity and plasticity. In the main part, we will outline studies aimed at improving persistent symptoms and deficits in patients suffering from neurologic and neuropsychiatric disorders featured by dysfunction of the parietal lobe. The emerging view is that NIBS of parietal areas holds the promise to overcome various sensory, motor, and cognitive disorders that are often refractory to standard medical or behavioral therapies. The chapter closes with an outlook on further developments in this realm, discussing novel therapeutic approaches that could lead to more effective rehabilitation procedures, better suited for the specific parietal lobe dysfunction

A fundamental component of the self-awareness is the sensation that we are acting with our own body. Thus, a coherent sense of self implies the existence of a tight link between the sense of body ownership and the motor system. Here, we investigated this issue by taking advantage of a well-known experimental manipulation of body ownership, i.e., the rubber hand illusion (RHI), during which the subjects perceive a fake hand as part of their own body. To test the effect of the motor system down-regulation on the RHI susceptibility, we designed a sham-controlled study, where the primary motor cortex (M1) excitability was modulated by off-line low-frequency repetitive transcranial magnetic stimulation (rTMS). After rTMS (real or sham), subjects underwent the RHI either on the right hand, contralateral to the inhibited hemisphere (Experiment 1), or on the left hand, ipsilateral to the inhibited hemisphere (Experiment 2). Only in Experiment 1, the procedure strengthened the illusory experience, as proved by a significant increase, in rTMS compared to Sham, of both subjective (Embodiment/Disembodiment Questionnaires) and objective (Proprioceptive Drift) RHI measures. This evidence demonstrates that, when the M1 activity is down-regulated, the sense of body ownership is attenuated and the subjects become more prone to incorporate an alien body part. This, in turn, supports the existence of a mutual interaction between the sense of body ownership and the motor system, shedding new light on the construction of a coherent sense of self as an acting body

In the rubber hand illusion (RHI), the feeling that a fake hand belongs to oneself can be induced by the simultaneous, congruent touch of the fake visible hand and one's own hidden hand. This condition is also associated with a recalibration of the perceived location of the real hand. A cortical network, including premotor and temporo-parietal areas, has been proposed as the basis of the RHI. However, the causal contribution of these areas to the discrete illusory components remains unclear. We used transcranial direct current stimulation (tDCS) to assess the contribution of the right premotor cortex (rPMc) and the right temporo-parietal junction (rTPJ) to the RHI and explored the role of these areas in modulating the subjective experience of embodiment and the misperception of the hand position. We found that anodal tDCS of both rPMc and rTPJ increased the misjudgement of the real hand location towards the fake hand. Crucially, the difference in proprioceptive displacement evoked by the congruent and incongruent visuo-tactile stroking was minimised when tDCS was applied over the rPMc, while it was amplified when the rTPJ was targeted. The parietal effects of tDCS also extended to the self-report components of the RHI. These findings suggest that the tDCS of rTPJ modulates the RHI depending on the temporal congruency of the visuo-tactile stimulation, while the tDCS of rPMc induces a general recalibration of hand coordinates, regardless of the visuo-tactile congruency. The present results are discussed in the view of a multicomponent model of the RHI

In this study, we assessed the impact of multiple sclerosis (MS) on bodily self-consciousness (BSC) using the Rubber Hand Illusion. Patients with MS showed a dissociation between body ownership and self-location: they did report an explicit ownership of the rubber hand, but they did not point towards it, showing a defective ability of localizing body parts in space. This evidence indicates that MS may affect selective components of BSC, whose impairment may contribute to, and even worsen, the functional disability of MS.

Visuo-motor adaptation to optical prisms displacing the visual scene (prism adaptation, PA) is a method used for investigating visuo-motor plasticity in healthy individuals and, in clinical settings, for the rehabilitation of unilateral spatial neglect. In the standard paradigm, the adaptation phase involves repeated pointings to visual targets, while wearing optical prisms displacing the visual scene laterally. Here we explored differences in PA, and its aftereffects (AEs), as related to the sensory modality of the target. Visual, auditory, and multisensory - audio-visual - targets in the adaptation phase were used, while participants wore prisms displacing the visual field rightward by 10°. Proprioceptive, visual, visual-proprioceptive, auditory-proprioceptive straightahead shifts were measured. Pointing to auditory and to audio-visual targets in the adaptation phase produces proprioceptive, visual-proprioceptive, and auditoryproprioceptive AEs, as the typical visual targets did. This finding reveals that crossmodal plasticity effects involve both the auditory and the visual modality, and their interactions (Experiment 1). Even a shortened PA phase, requiring only 24 pointings to visual and audio-visual targets (Experiment 2), is sufficient to bring about AEs, as compared to the standard 92-pointings procedure. Finally, pointings to auditory targets cause AEs, although PA with a reduced number of pointings (24) to auditory targets brings about smaller AEs, as compared to the 92-pointings procedure (Experiment 3). Together, results from the three experiments extend to the auditory modality the sensorimotor plasticity underlying the typical AEs produced by PA to visual targets. Importantly, PA to auditory targets appears characterized by less accurate pointings and error correction, suggesting that the auditory component of the PA process may be less central to the building up of the AEs, than the sensorimotor pointing activity per se. These findings highlight both

In this study, we investigated the contribution of tactile and proprioceptive cues to the development of the sense of body ownership by testing the susceptibility of 4- to 5-year-old children, 8- to 9-year-old children, and adults to the somatic rubber-hand illusion (SRHI). We found that feelings of owning a rubber hand in the SHRI paradigm, as assessed by explicit reports (i.e., questionnaire), are already present by age 4 and do not change throughout development. In contrast, the effect of the illusion on the sense of hand position, as assessed by a pointing task, was present only in 8- to 9-year-old children and adults; the magnitude of such capture increased with age. Our findings reveal that tactile-proprioceptive interactions contributed differently to the two aspects characterizing the SRHI: Although the contribution of such interactions to an explicit sense of self was similar across age groups, their contribution to the more implicit recalibration of hand position is still developing by age 9

Coding the direction of others' gestures is a fundamental human ability, since it allows the observer to attend and react to sources of potential interest in the environment. Shifts of attention triggered by action observation have been reported to occur early in infancy. Yet, the neurophysiological underpinnings of such action priming and the properties of gestures that might be crucial for it remain unknown. Here, we addressed these issues by recording electroencephalographic activity (EEG) from 6-month-old infants cued with spatially non-predictive hand grasping toward or away from the position of a target object, i.e., valid and invalid trials, respectively. Half of the infants were cued with a gesture executable by a human hand (possible gesture) and the other half with a gesture impossible to be executed by a human hand. Results show that the amplitude enhancement of the posterior N290 component in response to targets in valid trials, as compared to invalid trials, was present only for infants seeing possible gestures, while it was absent for infants seeing impossible gestures. These findings suggest that infants detect the biomechanical properties of human movements when processing hand gestures, relying on this information to orient their visual attention toward the target object.

Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS are still unclear, as well as, it is not fully understood how the stimulation of a given cerebral region may affect the activity of anatomically connected regions. In a previous study it has been investigated the tDCS anodal’s effect on the cortical excitability, by a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal networks. In the present study, we used the same technique and methodological settings in order to explore local and global cortical excitability modulation during and after cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 minutes of tDCS over the right PPC, while EEG was recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for four temporal windows: 0-50, 50-100, 100-150 and 150-200 milliseconds. The global index was computed on all 60 channels. The local indexes were computed in four clusters of electrodes: left and right, in frontal and parietal regions. The preliminary results on fifteen subjects show no differences in both sessions during and after cathodal tDCS compared to pre-stimulation session. These results are consistent with the literature in which

Motor execution, planning, and learning are altered by transcranial Direct Current Stimulation (tDCS). The potential of this technique for modulating action monitoring and awareness has not been explored so far. Optimal motor control relies on internal representations of the intended, predicted, and actual action. The brain is equipped with a ‘‘comparator” system, which monitors and detects the congruence between planned and performed movements; based on this comparison motor awareness is constructed.

Objective: The alien hand syndrome (AHS) is a rare neuropsychological disorder characterized by involuntary,yet purposeful, hand movements. Patients with the AHS typically complain about a loss of agencyassociated with a feeling of estrangement for actions performed by the affected limb. The present studyexplores the integrity of the body representation in AHS, focusing on 2 main processes: multisensoryintegration and visual self-recognition of body parts. Three patients affected by AHS following a righthemispherestroke, with clinical symptoms akin to the posterior variant of AHS, were tested and theirperformance was compared with that of 18 age-matched healthy controls. Method: AHS patients and controlsunderwent 2 experimental tasks: a same-different visual matching task for body postures, which assessed theability of using your own body schema for encoding others' body postural changes (Experiment 1), and anexplicit self-hand recognition task, which assessed the ability to visually recognize your own hands (Experiment2). Results: As compared to controls, all AHS patients were unable to access a reliable multisensoryrepresentation of their alien hand and use it for decoding others' postural changes; however, they could relyon an efficient multisensory representation of their intact (ipsilesional) hand. Two AHS patients also presentedwith a specific impairment in the visual self-recognition of their alien hand, but normal recognition of theirintact hand. Conclusion: This evidence suggests that the AHS following a right-hemisphere stroke mayinvolve a disruption of the multisensory representation of the alien limb; instead, self-hand recognitionmechanisms may be spared.

Converging evidence on voluntary actions underlays the existence of a motor monitoring system able to compare the predicted and the actual consequences of our movements. In this context, both the premotor cortex (PMC) and the posterior parietal cortex (PPC) play a role in action monitoring and awareness. The present study explores the role of PMC and PPC in monitoring involuntary muscle contractions induced by transcranial magnetic stimulation (TMS) over the hand motor area. To this aim, the effects of transcranial direct current stimulation (tDCS) over PMC and PPC were examined. Thirty-six healthy subjects were asked to perform a motor monitoring task (i.e., to verbally report hand twitches induced by TMS) after 10 min of tDCS. Through three experiments, the effects of cathodal, anodal and sham tDCS over the left and the right hemispheres were compared. Our results show that cathodal tDCS over the right PMC does not affect the monitoring of involuntary movements. By contrast, tDCS over both the right and the left PPC affects motor monitoring, depending on the current polarity: while cathodal tDCS increases the feeling of phantom-like movements (which actually did not occur), anodal tDCS impairs the ability to detect involuntary hand twitches (which actually took place). These findings show that the PMC is not involved in motor monitoring of involuntary movements; rather, the PPC, where multisensory stimuli converge and are processed, seems to play a crucial role.

OBJECTIVES: The safety, painless, and tolerability features of transcranial Direct Current Stimulation (tDCS) have prompted the research on the therapeutic effects of this technique in stroke; however, an in-depth and unarguable examination of the adverse effects of tDCS in stroke patients is still lacking. This review analyzes the reported adverse effects in stroke, looking for factors that may induce side-effects. MATERIALS AND METHODS: A comprehensive search of articles published from 1998 to 2015 describing tDCS application in stroke patients performed through data extraction from MEDLINE/PubMed database. RESULTS: Only 11.62% of published papers reported the occurrence of tDCS adverse effects in stroke patients. The most common was itching (70%), followed by burning sensation (40%), headache (40%), tingling (30%), sleepiness (20%), difficulty of concentration, mild fatigue, skin redness, and dizziness (10%). No significant difference was found between studies "Reporting" vs. "Non-reporting" adverse effects regarding tDCS parameters (intensity, current density, duration of stimulation, and number of sessions). CONCLUSION: In the majority of stroke patients, tDCS did not induce any severe adverse effect. Regrettably, many published papers did not provide a careful description of exclusion criteria, nor a systematic report of side effects. Our work emphasizes the need of a more meticulous description of the adopted exclusion criteria and of the induced adverse effects, in order to optimize the therapeutic use of tDCS and to better delineate its safety parameters in stroke

The development of the ability to recognize the whole human body shape has long been investigated in infants, while less is known about their ability to recognize the shape of single body parts, and in particular their biomechanical constraints. This study aimed to explore whether 9- and 12-month-old infants have knowledge of a hand-grasping movement (i.e., pincer grip), being able to recognize violations of the hand's anatomical constraints during the observation of that movement. Using a preferential looking paradigm, we showed that 12-month-olds discriminate between biomechanically possible and impossible pincer grips, preferring the former over the latter (Experiment 1). This capacity begins to emerge by 9 months of age, modulated by infants' own sensorimotor experience with pincer grip (Experiment 2). Our findings indicate that the ability to visually discriminate between pincer grasps differing in their biomechanical properties develops between 9 and 12 months of age, and that experience with self-produced hand movements might help infants in building a representation of the hand that encompasses knowledge of the physical constraints of this body part.

Coding the direction of others' gestures is a fundamental human ability, since it allows the observer to attend and react to sources of potential interest in the environment. Shifts of attention triggered by action observation have been reported to occur early in infancy. Yet, the neurophysiological underpinnings of such action priming and the properties of gestures that might be crucial for it remain unknown. Here, we addressed these issues by recording electroencephalographic activity (EEG) from 6-month-old infants cued with spatially non-predictive hand grasping toward or away from the position of a target object, i.e., valid and invalid trials, respectively. Half of the infants were cued with a gesture executable by a human hand (possible gesture) and the other half with a gesture impossible to be executed by a human hand. Results show that the amplitude enhancement of the posterior N290 component in response to targets in valid trials, as compared to invalid trials, was present only for infants seeing possible gestures, while it was absent for infants seeing impossible gestures. These findings suggest that infants detect the biomechanical properties of human movements when processing hand gestures, relying on this information to orient their visual attention toward the target object.

BACKGROUND: Despite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP. OBJECTIVE: The objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees. METHODS: A prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) b

Among the other senses touch is the first to develop and it represents the primary means through which infants learn about their surrounding world from very early in life. Evidence in human adults indicates that touch is crucial not only for own corporeal sensations, but also for understanding others’ tactile sensations likely through mirroring mechanisms. In recent years, there has been a growing interest on how infants process tactile stimulations on their own body but, to date, no study has explored how they process others’ touching gestures. In this talk, I will first present results from experiments exploring how newborns visually process others’ gestures that involve a tactile event. To explore this ability, we measured looking times and orienting responses in a visual preference task in which 2-day-old newborns were simultaneously presented with two videos depicting a gesture not involving a touch (no-touching gesture) and a gesture involving a contact (touching gesture) between human body parts (face, hand) and/or an object (spoon). Results have shown that only in the case of a human body-to-body contact, newborns could differentiate between a touching and a no-touching gesture. Crucially, newborns’ early sensitivity to touch vanished when they were presented with gestures that involved an object as the agent of the touch. Another interesting issue refers to the development of mirroring mechanisms for touch. Recent lines of evidence in human adults have shown that viewing touch may vicariously activate a putative tactile mirror system, comprising the somatosensory cortices (SI and SII). I will present evidence of the origins of such ‘tactile mirror system’, showing the vicarious activation of the somatosensory cortex during touch observation, as indexed by somatosensory evoked potentials (SEPs), in 8-month-old infants.

In the last decade, in the field of neuromodulation, we have observed an increase in the popularity of approaches that combine transcranial electrical stimulation (tES) with additional methods to establish, in vivo, the neurophysiological consequences of a given experimental or therapeutic manipulation. We are at the beginning of the development of multimodal approaches, and several methods are available that can be combined with tES to study brain functions. This chapter aims to introduce the reader to some basic principles of this multimodal approach. We begin with a brief definition of multimodal association and a description of the advantages of such an approach. Afterwards, we provide a more specific description of how we can combine tES with electroencephalography (EEG). We show that EEG is a feasible and reliable way to track electrophysiological changes induced by tES, deepening our understanding of the mechanisms of action of this tool and revealing the key role of several stimulation features. In neuropsychiatric diseases, a combined tES-EEG approach may allow the prediction of clinical responses to tES, the discrimination of responders from non-responders, improvement in the efficacy of tES, and the tracking of tES-induced neuroplastic changes associated with recovery.

Contemporary strategies to promote motor recovery following stroke focus on repetitive voluntary movements. Although successful movement relies on efficient sensorimotor integration, functional outcomes often bias motor therapy toward motor-related impairments such as weakness, spasticity and synergies; sensory therapy and reintegration is implied, but seldom targeted. However, the planning and execution of voluntary movement requires that the brain extracts sensory information regarding body position and predicts future positions, by integrating a variety of sensory inputs with ongoing and planned motor activity. Neurological patients who have lost one or more of their senses may show profoundly affected motor functions, even if muscle strength remains unaffected. Following stroke, motor recovery can be dictated by the degree of sensory disruption. Consequently, a thorough account of sensory function might be both prognostic and prescriptive in neurorehabilitation. This review outlines the key sensory components of human voluntary movement, describes how sensory disruption can influence prognosis and expected outcomes in stroke patients, reports on current sensory-based approaches in post-stroke motor rehabilitation, and makes recommendations for optimizing rehabilitation programs based on sensory stimulation.