Efficacy of Repetitive Transcranial Magnetic Stimulation for Acute Central Post-stroke Pain: A Case Study.

Although rare, central post-stroke pain remains one of the most refractory forms of neuropathic pain. Repetitive transcranial magnetic stimulation (rTMS) has been reported to be effective in chronic cases. However, there are no data on the effects in the acute and subacute phases after stroke. In this study, we present a case of a patient with thalamic stroke with acute onset of pain and paresthesia who was responsive to rTMS. After a right thalamic stroke, a 32-year-old woman presented with drug-resistant pain and paresthesia on the left side of the body. There were no motor or sensory deficits, except for blunted thermal sensation and allodynia on light touch. Ten daily sessions were performed, where 10 Hz rTMS was applied to the hand area of the right primary motor cortex, 40 days after stroke. Before rTMS treatment (T0), immediately after treatment conclusion (T1), and 1 month after treatment (T2), three pain questionnaires were administered, and cortical responses to single and paired-pulse TMS were assessed. Eight healthy participants served as controls. At T0, when the patient was experiencing the worst pain, the excitability of the ipsilesional motor cortex was reduced. At T1 and T2, the pain scores and paresthesia' spread decreased. The clinical improvement was paralleled by the recovery in motor cortex excitability of the affected hemisphere, in terms of both intra- and inter-hemispheric connections. In this subacute central post-stroke pain case, rTMS treatment was associated with decreased pain and motor cortex excitability changes.

Phonemic fluency improved after inhibitory transcranial magnetic stimulation in a case of chronic aphasia.

Twenty-six months after a left hemispheric ischemic stroke an aphasic patient showed a significant improvement in verbal fluency following ten daily sessions of inhibitory 1 Hz repetitive transcranial magnetic stimulation over the right cortex homologous to the Broca's area.No improvement was observed for other linguistic functions or for executive ones. Results confirm the segregation of neural circuitries subtending phonemic and semantic fluency and suggest a selective usefulness of the repetitive transcranial magnetic stimulation treatment.

Dynamic expansion of alert responses to incoming painful stimuli following tool use.

Peripersonal space is the region closely surrounding our bodies. Within its boundaries, avoidance of threatening objects is crucial for surviving. Here we explored autonomic responses to painful stimuli with respect to the dynamic properties of the peripersonal space in healthy individuals. To this aim, in a series of experiments, we measured the Skin Conductance Response (SCR) to a noxious stimulus approaching and touching the hand, or stopping at different distances (far, near) from it. Results showed that the anticipatory response to an incoming threat is reduced if the stimulus targets a spatial position far away from the body, as compared to a near or bodily location. However, responses to far stimuli change if the boundaries of reachable space are extended further away by active tool use. Noteworthy, SCR is not influenced by a training consisting of a spatial attention task, without active tool use. This evidence sheds novel light on the adaptive role of peripersonal space, showing its importance for the coding of incoming threatening stimuli and its plasticity induced by contingent experience, such as tool use.

Sharing social touch in the primary somatosensory cortex.

Touch has an emotional and communicative meaning, and it plays a crucial role in social perception and empathy. The intuitive link between others' somatosensations and our sense of touch becomes ostensible in mirror-touch synesthesia, a condition in which the view of a touch on another person's body elicits conscious tactile sensations on the observer's own body [1]. This peculiar phenomenon may implicate normal social mirror mechanisms [2]. Here, we show that mirror-touch interference effects, synesthesia-like sensations, and even phantom touches can be induced in nonsynesthetes by priming the primary somatosensory cortex (SI) directly or indirectly via the posterior parietal cortex. These results were obtained by means of facilitatory paired-pulse transcranial magnetic stimulation (ppTMS) contingent upon the observation of touch. For these vicarious effects, the SI is engaged at 150 ms from the onset of the visual touch. Intriguingly, individual differences in empathic abilities, assessed with the Interpersonal Reactivity Index [3], drive the activity of the SI when nonsynesthetes witness others' tactile sensations. This evidence implies that, under normal conditions, touch observation activates the SI below the threshold for perceptual awareness [4]; through the visual-dependent tuning of SI activity by ppTMS, what is seen becomes felt, namely, mirror-touch synesthesia. On a broader perspective, the visual responsivity of the SI may allow an automatic and unconscious transference of the sensation that another person is experiencing onto oneself, and, in turn, the empathic sharing of somatosensations [2].

Face age modulates gaze following in young adults.

Gaze-following behaviour is considered crucial for social interactions which are influenced by social similarity. We investigated whether the degree of similarity, as indicated by the perceived age of another person, can modulate gaze following. Participants of three different age-groups (18-25; 35-45; over 65) performed an eye movement (a saccade) towards an instructed target while ignoring the gaze-shift of distracters of different age-ranges (6-10; 18-25; 35-45; over 70). The results show that gaze following was modulated by the distracter face age only for young adults. Particularly, the over 70 year-old distracters exerted the least interference effect. The distracters of a similar age-range as the young adults (18-25; 35-45) had the most effect, indicating a blurred own-age bias (OAB) only for the young age group. These findings suggest that face age can modulate gaze following, but this modulation could be due to factors other than just OAB (e.g., familiarity).

Understanding others' feelings: the role of the right primary somatosensory cortex in encoding the affective valence of others' touch.

Brain imaging studies in humans have shown the existence of a shared somatosensory representation in the primary somatosensory cortex (S1), putatively involved in understanding others' sensations (Keysers et al., 2010); however, the role of S1 in such a high-level process is still unknown. To ascertain the causal involvement of S1, and its possible hemispheric lateralization, in encoding the affective valence of emotional scenes, depicting, or not, a tactile event, we gave to healthy participants a picture-based affective go/no-go task and low-frequency repetitive transcranial magnetic stimulation (rTMS). The dorsolateral prefrontal cortex (DLPFC) was chosen as control site. rTMS over the right, but not the left, S1 selectively increased the participants' latencies in the affective go/no-go task, but only when the affective state was conveyed by touch; intriguingly, this interfering effect was associated with the empathic ability to adopt the subjective perspective of others. The left, not the right, DLPFC is also involved in affective go/no-go performance, but regardless of the sight of touch, and independently of empathic abilities. This novel evidence demonstrates the crossmodal role of right S1 in encoding the pleasant and aversive consequences of others' sensations evoked by touch.

Multisensory processing after a brain damage: clues on post-injury crossmodal plasticity from neuropsychology.

Current neuropsychological evidence demonstrates that damage to sensory-specific and heteromodal areas of the brain not only disrupts the ability of combining sensory information from multiple sources, but can also cause altered multisensory experiences. On the other hand, there is also evidence of behavioural benefits induced by spared multisensory mechanisms. Thus, crossmodal plasticity can be viewed in both an adaptive and maladaptive context. The emerging view is that different crossmodal plastic changes can result following damage to sensory-specific and heteromodal areas, with post-injury crossmodal plasticity representing an attempt of a multisensory system to reconnect the various senses and by-pass injured areas. Changes can be considered adaptive when there is compensation for the lesion-induced sensory impairment. Conversely, it may prove maladaptive when atypical or even illusory multisensory experiences are generated as a result of re-arranged multisensory networks. This theoretical framework posits new intriguing questions for neuropsychological research and places greater emphasis on the study of multisensory phenomena within the context of damage to large-scale brain networks, rather than just focal damage alone.

Visual perception of bodily interactions in the primary somatosensory cortex.

Brain imaging studies in humans have revealed the existence of a visuo-tactile system, which matches observed touch with felt touch. In this system, the primary somatosensory cortex (SI) appears to play a causal role in the visual processing of tactile events. Whether this visuo-tactile mechanism for touch in SI applies to the sight of 'any' touch, or whether it is restricted to the domain of body-related tactile experiences remains unresolved. To address this issue, repetitive transcranial magnetic stimulation (rTMS) was used to determine whether activity in SI is strictly related to the visual processing of human body-part interactions, or is also involved in processing the contact between inanimate objects, or between human body-parts and objects. The results show that rTMS over SI selectively impaired the processing of a contralateral visual stimulus depicting a human body-part being touched by a human agent, while it did not affect the visual perception of contact between objects, or between human body-parts and objects. Correlation analysis shows that this effect was associated with the intensity and embodiment of the observed touched. This result suggests that SI is more suited to represent social touch, contributing to our understanding of the effect of interpersonal tactile interactions between people.

Seeing touch in the somatosensory cortex: a TMS study of the visual perception of touch.

Recent studies suggest the existence of a visuo-tactile mirror system, comprising the primary (SI) and secondary (SII) somatosensory cortices, which matches observed touch with felt touch. Here, repetitive transcranial magnetic stimulation (rTMS) was used to determine whether SI or SII play a functional role in the visual processing of tactile events. Healthy participants performed a visual discrimination task with tactile stimuli (a finger touching a hand) and a control task (a finger moving without touching). During both tasks, rTMS was applied over either SI or SII, and to the occipital cortex. rTMS over SI selectively reduced subject performance for interpreting whether a contralateral visual tactile stimulus contains a tactile event, whereas SII stimulation impaired visual processing regardless of the tactile component. These findings provide evidence for a multimodal sensory-motor system with mirror properties, where somatic and visual properties of action converge. SI, a cortical area traditionally viewed as modality-specific, is selectively implicated in the visual processing of touch. These results are in line with the existence of a sensory mirror system mediating the embodied simulation concept.

Neuromodulation of multisensory perception: a tDCS study of the sound-induced flash illusion.

This study explores whether brain polarization could be effective in modulating multisensory audiovisual interactions in the human brain, as measured by the 'sound-induced flash illusion' (Shams et al., 2000). In different sessions, healthy participants performed the task while receiving anodal, cathodal, or sham tDCS (2 mA, 8 min) to the occipital, temporal, or posterior parietal cortices. We found that up- or down-regulating cortical excitability by tDCS can facilitate or reduce audiovisual illusions, depending on the current polarity, the targeted area, and the illusory percept. Specifically, the perceptual 'fission' of a single flash, due to multiple beeps, was increased after anodal tDCS of the temporal cortex, and decreased after anodal stimulation of the occipital cortex. A reversal of such effects was induced by cathodal tDCS. Conversely, the perceptual 'fusion' of multiple flashes due to a single beep was unaffected by tDCS. This evidence adds novel clues on the cortical substrate of the generation of the sound-flash illusion, and opens new attractive possibilities for modulating multisensory perception in humans: tDCS appears to be an effective tool to modulate the conscious visual experience associated with multisensory interactions, by noninvasively shifting cortical excitability within occipital or temporal areas.

Enhancing multisensory spatial orienting by brain polarization of the parietal cortex.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces polarity-specific excitability changes in the human brain, therefore altering physiological, perceptual and higher-order cognitive processes. Here we investigated the possibility of enhancing attentional orienting within and across different sensory modalities, namely visual and auditory, by polarization of the posterior parietal cortex (PPC), given the putative involvement of this area in both unisensory and multisensory spatial processing. In different experiments, we applied anodal or sham tDCS to the right PPC and, for control, anodal stimulation of the right occipital cortex. Using a redundant signal effect (RSE) task, we found that anodal tDCS over the right PPC significantly speeded up responses to contralateral targets, regardless of the stimulus modality. Furthermore, the effect was dependant on the nature of the audiovisual enhancement, being stronger when subserved by a probabilistic mechanism induced by blue visual stimuli, which probably involves processing in the PPC. Hence, up-regulating the level of excitability in the PPC by tDCS appears a successful approach for enhancing spatial orienting to unisensory and crossmodal stimuli. Moreover, audiovisual interactions mostly occurring at a cortical level can be selectively enhanced by anodal PPC tDCS, whereas multisensory integration of stimuli, which is also largely mediated at a subcortical level, appears less susceptible to polarization of the cortex.