Transcranial magnetic stimulation over supramarginal gyrus stimulates primary motor cortex directly and impairs manual dexterity: implications for TMS focality.

Based on human motor cortex, the effective spatial resolution of transcranial magnetic stimulation (TMS) is often described as 5-20 mm, because small changes in TMS coil position can have large effects on motor-evoked potentials (MEPs). MEPs are often studied at rest, with muscles relaxed. During muscle contraction and movement, corticospinal excitability is higher, thresholds for effective stimulation are lower, and MEPs can be evoked from larger regions of scalp, so the effective spatial resolution of TMS is larger. We found that TMS over the supramarginal gyrus (SMG) impaired manual dexterity in the grooved pegboard task. It also resulted in short-latency MEPs in hand muscles, despite the coil being 55 mm away from the motor cortex hand area (M1). MEPs might be evoked by either a specific corticospinal connection from SMG or a remote but direct electromagnetic stimulation of M1. To distinguish these alternatives, we mapped MEPs across the scalp during rest, isotonic contraction, and manual dexterity tasks and ran electric field simulations to model the expected M1 activation from 27 scalp locations and four coil orientations. We also systematically reviewed studies using TMS during movement. Across five experiments, TMS over SMG reliably evoked MEPs during hand movement. These MEPs were consistent with direct M1 stimulation and substantially decreased corticospinal thresholds during natural movement. Systematic review suggested that 54 published experiments may have suffered from similar motor activation confounds. Our results have implications for the assumed spatial resolution of TMS, and especially when TMS is presented within 55 mm of the motor cortex.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS) is often described as having an effective spatial resolution of ∼10 mm, because of the limited area of the scalp on which TMS produces motor-evoked potentials (MEPs) in resting muscles. We find that during natural hand movement TMS evokes MEPs from a much larger scalp area, in particular when stimulating over the supramarginal gyrus 55 mm away. Our results show that TMS can be effective at much larger distances than generally assumed.

No self-advantage in recognizing photographs of one's own hand: experimental and meta-analytic evidence.

Visually recognising one's own body is important both for controlling movement and for one's sense of self. Twenty previous studies asked healthy adults to make rapid recognition judgements about photographs of their own and other peoples' hands. Some of these judgements involved explicit self-recognition: "Is this your hand or another person's?" while others assessed self-recognition implicitly, comparing performance for self and other hands in tasks unrelated to self-other discrimination (e.g., left-versus-right; match-to-sample). We report five experiments with three groups of participants performing left-versus-right (Experiment 1) and self-versus-other discrimination tasks (Experiments 2 to 5). No evidence was found for better performance with self than with other stimuli, but some evidence was found for a self-disadvantage in the explicit task. Manipulating stimulus duration as a proxy for task difficulty revealed strong response biases in the explicit self-recognition task. Rather than discriminating between self and other stimuli, participants seem to treat self-other discrimination tasks as self-detection tasks, raising their criterion and consistently responding 'not me' when the task is difficult. A meta-analysis of 21 studies revealed no overall self-advantage, and suggested a publication bias for reports showing self-advantages in implicit tasks. Although this may appear counter-intuitive, we suggest that there may be no self-advantage in hand recognition.

Repetitive Transcranial Magnetic Stimulation Over the Left Posterior Middle Temporal Gyrus Reduces Wrist Velocity During Emblematic Hand Gesture Imitation.

Results from neuropsychological studies, and neuroimaging and behavioural experiments with healthy individuals, suggest that the imitation of meaningful and meaningless actions may be reliant on different processing routes. The left posterior middle temporal gyrus (pMTG) is one area that might be important for the recognition and imitation of meaningful actions. We studied the role of the left pMTG in imitation using repetitive transcranial magnetic stimulation (rTMS) and two-person motion-tracking. Participants imitated meaningless and emblematic meaningful hand and finger gestures performed by a confederate actor whilst both individuals were motion-tracked. rTMS was applied during action observation (before imitation) over the left pMTG or a vertex control site. Since meaningless action imitation has been previously associated with a greater wrist velocity and longer correction period at the end of the movement, we hypothesised that stimulation over the left pMTG would increase wrist velocity and extend the correction period of meaningful actions (i.e., due to interference with action recognition). We also hypothesised that imitator accuracy (actor-imitator correspondence) would be reduced following stimulation over the left pMTG. Contrary to our hypothesis, we found that stimulation over the pMTG, but not the vertex, during action observation reduced wrist velocity when participants later imitated meaningful, but not meaningless, hand gestures. These results provide causal evidence for a role of the left pMTG in the imitation of meaningful gestures, and may also be in keeping with proposals that left posterior temporal regions play a role in the production of postural components of gesture.

Repetitive transcranial magnetic stimulation reveals a role for the left inferior parietal lobule in matching observed kinematics during imitation.

Apraxia (a disorder of complex movement) suggests that the left inferior parietal lobule (IPL) plays a role in kinematic or spatial aspects of imitation, which may be particularly important for meaningless (i.e. unfamiliar intransitive) actions. Mirror neuron theories indicate that the IPL is part of a frontoparietal system that can support imitation by linking observed and stored actions through visuomotor matching, and have less to say about different subregions of the left IPL, or how different types of action (i.e. meaningful or meaningless) are processed for imitation. We used repetitive transcranial magnetic stimulation (rTMS) to bridge this gap and better understand the roles of the left supramarginal gyrus (SMG) and left angular gyrus (AG) in imitation. We also examined whether these areas are differentially involved in meaningful and meaningless action imitation. We applied rTMS over the left SMG, over the left AG or during a no-rTMS baseline condition, and then asked participants to imitate a confederate's actions whilst the arm and hand movements of both individuals were motion-tracked. rTMS over both the left SMG and the left AG reduced the velocity of participants' finger movements relative to the actor during imitation of finger gestures, regardless of action meaning. Our results support recent claims in apraxia and confirm a role for the left IPL in kinematic processing during gesture imitation, regardless of action meaning.

Involvement of human primary somatosensory cortex in vibrotactile detection depends on task demand.

Detecting and discriminating sensory stimuli are fundamental functions of the nervous system. Electrophysiological and lesion studies suggest that macaque primary somatosensory cortex (SI) is critically involved in discriminating between stimuli, but is not required simply for detecting stimuli. By contrast, transcranial magnetic stimulation (TMS) studies in humans have shown near-complete disruption of somatosensory detection when a single pulse of TMS is delivered over SI. To address this discrepancy, we measured the sensitivity and decision criteria of participants detecting vibrotactile stimuli with individually-tailored fMRI-guided TMS over SI, over a control site not activated by vibrotactile stimuli (inferior parietal lobule, IPL), or away from the head (a no TMS condition). In a one-interval detection task, TMS increased participants' likelihood of reporting 'no' target present regardless of site, but TMS over SI also decreased detection sensitivity, and prevented improvement in tactile sensitivity over time. We then measured tactile thresholds in a series of two-interval forced-choice (2IFC) detection and discrimination tasks with lower dependence on response criteria and short-term memory load. We found that thresholds for detecting stimuli were comparable with TMS over SI and IPL, but TMS over SI specifically and significantly impaired frequency discrimination. We conclude that, in accordance with macaque studies, human SI is required for discriminating between tactile stimuli and for maintaining stimulus representations over time, or under high task demand, but may not be required for simple tactile detection. SIGNIFICANT STATEMENT: Studies on monkeys have suggested that the primary somatosensory cortex is responsible for discriminating between different vibrations on the fingertips, but not just for detecting these vibrations. However, similar studies in humans suggest that the somatosensory cortex is required both for detecting and discriminating between tactile stimuli. We used magnetic brain stimulation to interfere with human somatosensory cortex while healthy volunteers detected and discriminated between vibrations applied to their fingertips. We found that the somatosensory cortex is required for keeping vibrotactile stimuli in memory for short periods of time and for comparing two vibrotactile stimuli, but is not required merely for detecting vibrotactile stimulation. This suggests that human primary somatosensory cortex is not always needed for vibrotactile detection.

Bilateral representations of touch in the primary somatosensory cortex.

According to current textbook knowledge, the primary somatosensory cortex (SI) supports unilateral tactile representations, whereas structures beyond SI, in particular the secondary somatosensory cortex (SII), support bilateral tactile representations. However, dexterous and well-coordinated bimanual motor tasks require early integration of bilateral tactile information. Sequential processing, first of unilateral and subsequently of bilateral sensory information, might not be sufficient to accomplish these tasks. This view of sequential processing in the somatosensory system might therefore be questioned, at least for demanding bimanual tasks. Evidence from the last 15 years is forcing a revision of this textbook notion. Studies in animals and humans indicate that SI is more than a simple relay for unilateral sensory information and, together with SII, contributes to the integration of somatosensory inputs from both sides of the body. Here, we review a series of recent works from our own and other laboratories in favour of interactions between tactile stimuli on the two sides of the body at early stages of processing. We focus on tactile processing, although a similar logic may also apply to other aspects of somatosensation. We begin by describing the basic anatomy and physiology of interhemispheric transfer, drawing on neurophysiological studies in animals and behavioural studies in humans that showed tactile interactions between body sides, both in healthy and in brain-damaged individuals. Then we describe the neural substrates of bilateral interactions in somatosensation as revealed by neurophysiological work in animals and neuroimaging studies in humans (i.e., functional magnetic resonance imaging, magnetoencephalography, and transcranial magnetic stimulation). Finally, we conclude with considerations on the dilemma of how efficiently integrating bilateral sensory information at early processing stages can coexist with more lateralized representations of somatosensory input, in the context of motor control.

When one's sense of agency goes wrong: Absent modulation of time perception by voluntary actions and reduction of perceived length of intervals in passivity symptoms in schizophrenia.

Passivity symptoms in schizophrenia are characterised by an absence of agency for actions, thoughts and other somatic experiences. Time perception and intentional binding have both been linked to agency and schizophrenia but have not been examined in passivity symptoms. Time perception and intentional binding were assessed in people with schizophrenia (n=15 with, n=24 without passivity symptoms) and 43 healthy controls using an interval estimation procedure (200, 400 and 600ms intervals) with active, passive and observed movements. People with passivity symptoms did not display action-modulation of time perception, while those without passivity symptoms estimated intervals to be the same after active and observed movements. Additionally, both clinical samples reported intervals to be shorter with increasing interval length. We propose that impaired predictive processes may produce an overreliance on external cues and, together with shorter perceived intervals, lead to the subjective loss of agency.

Body representations in schizophrenia: an alteration of body structural description is common to people with schizophrenia while alterations of body image worsen with passivity symptoms.

INTRODUCTION: Individuals with schizophrenia, particularly those with passivity symptoms, often feel that their actions and thoughts are controlled by an external agent. Recent evidence has elucidated the role of body representations in the aetiology of passivity symptoms, yet one representation - body structural description - has not yet been examined. Additionally, body image has rarely been examined outside of bodily illusions (e.g., rubber hand experiments) and external validation is required. METHODS: Body structural description was assessed with an in-between task and a matching body parts by location task, and body image with a questionnaire examining body distortion experiences (containing subscales assessing boundary loss, depersonalisation and body size distortions). Individuals with schizophrenia (20 with current, 12 with past and 21 with no history of passivity symptoms) and 48 healthy controls participated in the study. RESULTS: People with schizophrenia (as a group) made more errors on the in-between task, but not on the matching body parts by location task. Individuals with current passivity symptoms reported greater distortions on all subscales relative to the other clinical samples, except for experiences of boundary loss which were common to both passivity symptom groups. CONCLUSIONS: The results indicate that body structural description may be altered in schizophrenia generally and body image alterations are worsened in passivity symptoms, and these alterations likely contribute to the emergence of passivity symptoms.

To eat or not to eat? Kinematics and muscle activity of reach-to-grasp movements are influenced by the action goal, but observers do not detect these differences.

Recent evidence suggests that the mirror neuron system responds to the goals of actions, even when the end of the movement is hidden from view. To investigate whether this predictive ability might be based on the detection of early differences between actions with different outcomes, we used electromyography (EMG) and motion tracking to assess whether two actions with different goals (grasp to eat and grasp to place) differed from each other in their initial reaching phases. In a second experiment, we then tested whether observers could detect early differences and predict the outcome of these movements, based on seeing only part of the actions. Experiment 1 revealed early kinematic differences between the two movements, with grasp-to-eat movements characterised by an earlier peak acceleration, and different grasp position, compared to grasp-to-place movements. There were also significant differences in forearm muscle activity in the reaching phase of the two actions. The behavioural data arising from Experiments 2a and 2b indicated that observers are not able to predict whether an object is going to be brought to the mouth or placed until after the grasp has been completed. This suggests that the early kinematic differences are either not visible to observers, or that they are not used to predict the end-goals of actions. These data are discussed in the context of the mirror neuron system.

Beware 'persuasive communication devices' when writing and reading scientific articles.

Authors rely on a range of devices and techniques to attract and maintain the interest of readers, and to convince them of the merits of the author's point of view. However, when writing a scientific article, authors must use these 'persuasive communication devices' carefully. In particular, they must be explicit about the limitations of their work, avoid obfuscation, and resist the temptation to oversell their results. Here we discuss a list of persuasive communication devices and we encourage authors, as well as reviewers and editors, to think carefully about their use.

Does tool use extend peripersonal space? A review and re-analysis.

The fascinating idea that tools become extensions of our body appears in artistic, literary, philosophical, and scientific works alike. In the last 15 years, this idea has been reframed into several related hypotheses, one of which states that tool use extends the neural representation of the multisensory space immediately surrounding the hands (variously termed peripersonal space, peri-hand space, peri-cutaneous space, action space, or near space). This and related hypotheses have been tested extensively in the cognitive neurosciences, with evidence from molecular, neurophysiological, neuroimaging, neuropsychological, and behavioural fields. Here, I briefly review the evidence for and against the hypothesis that tool use extends a neural representation of the space surrounding the hand, concentrating on neurophysiological, neuropsychological, and behavioural evidence. I then provide a re-analysis of data from six published and one unpublished experiments using the crossmodal congruency task to test this hypothesis. While the re-analysis broadly confirms the previously reported finding that tool use does not literally extend peripersonal space, the overall effect sizes are small and statistical power is low. I conclude by questioning whether the crossmodal congruency task can indeed be used to test the hypothesis that tool use modifies peripersonal space.

Keeping the world at hand: rapid visuomotor processing for hand-object interactions.

The existence of hand-centred visual processing has long been established in the macaque premotor cortex. These hand-centred mechanisms have been thought to play some general role in the sensory guidance of movements towards objects, or, more recently, in the sensory guidance of object avoidance movements. We suggest that these hand-centred mechanisms play a specific and prominent role in the rapid selection and control of manual actions following sudden changes in the properties of the objects relevant for hand-object interactions. We discuss recent anatomical and physiological evidence from human and non-human primates, which indicates the existence of rapid processing of visual information for hand-object interactions. This new evidence demonstrates how several stages of the hierarchical visual processing system may be bypassed, feeding the motor system with hand-related visual inputs within just 70 ms following a sudden event. This time window is early enough, and this processing rapid enough, to allow the generation and control of rapid hand-centred avoidance and acquisitive actions, for aversive and desired objects, respectively.

Correction: Ceiling effects in the Movement Assessment Battery for Children-2 (MABC-2) suggest that non-parametric scoring methods are required.

[This corrects the article DOI: 10.1371/journal.pone.0198426.].

Coding of visual space during motor preparation: Approaching objects rapidly modulate corticospinal excitability in hand-centered coordinates.

Defensive behaviors, such as withdrawing your hand to avoid potentially harmful approaching objects, rely on rapid sensorimotor transformations between visual and motor coordinates. We examined the reference frame for coding visual information about objects approaching the hand during motor preparation. Subjects performed a simple visuomanual task while a task-irrelevant distractor ball rapidly approached a location either near to or far from their hand. After the distractor ball appearance, single pulses of transcranial magnetic stimulation were delivered over the subject's primary motor cortex, eliciting motor evoked potentials (MEPs) in their responding hand. MEP amplitude was reduced when the ball approached near the responding hand, both when the hand was on the left and the right of the midline. Strikingly, this suppression occurred very early, at 70-80 ms after ball appearance, and was not modified by visual fixation location. Furthermore, it was selective for approaching balls, since static visual distractors did not modulate MEP amplitude. Together with additional behavioral measurements, we provide converging evidence for automatic hand-centered coding of visual space in the human brain.

Infants lost in (peripersonal) space?

A significant challenge in developing spatial representations for the control of action is one of multisensory integration. Specifically, we require an ability to efficiently integrate sensory information arriving from multiple modalities pertaining to the relationships between the acting limbs and the nearby external world (i.e. peripersonal space), across changes in body posture and limb position. Evidence concerning the early development of such spatial representations points towards the independent emergence of two distinct mechanisms of multisensory integration. The earlier-developing mechanism achieves spatial correspondence by representing body parts in their typical or default locations, and the later-developing mechanism does so by dynamically remapping the representation of the position of the limbs with respect to external space in response to changes in postural information arriving from proprioception and vision.

The principle of inverse effectiveness in multisensory integration: some statistical considerations.

The principle of inverse effectiveness (PoIE) in multisensory integration states that, as the responsiveness to individual sensory stimuli decreases, the strength of multisensory integration increases. I discuss three potential problems in the analysis of multisensory data with regard to the PoIE. First, due to 'regression towards the mean,' the PoIE may often be observed in datasets that are analysed post-hoc (i.e., when sorting the data by the unisensory responses). The solution is to design discrete levels of stimulus intensity a priori. Second, due to neurophysiological or methodological constraints on responsiveness, the PoIE may be, in part, a consequence of 'floor' and 'ceiling' effects. The solution is to avoid analysing or interpreting data that are too close to the limits of responsiveness, enabling both enhancement and suppression to be reliably observed. Third, the choice of units of measurement may affect whether the PoIE is observed in a given dataset. Both relative (%) and absolute (raw) measurements have advantages, but the interpretation of both is affected by systematic changes in response variability with changes in response mean, an issue that may be addressed by using measures of discriminability or effect-size such as Cohen's d. Most importantly, randomising or permuting a dataset to construct a null distribution of a test parameter may best indicate whether any observed inverse effectiveness specifically characterises multisensory integration. When these considerations are taken into account, the PoIE may disappear or even reverse in a given dataset. I conclude that caution should be exercised when interpreting data that appear to follow the PoIE.

Inverse effectiveness, multisensory integration, and the bodily self: some statistical considerations.

A recent report in Consciousness and Cognition provided evidence from a study of the rubber hand illusion (RHI) that supports the multisensory principle of inverse effectiveness (PoIE). I describe two methods of assessing the principle of inverse effectiveness ('a priori' and 'post-hoc'), and discuss how the post-hoc method is affected by the statistical artefact of 'regression towards the mean'. I identify several cases where this artefact may have affected particular conclusions about the PoIE, and relate these to the historical origins of 'regression towards the mean'. Although the conclusions of the recent report may not have been grossly affected, some of the inferential statistics were almost certainly biased by the methods used. I conclude that, unless such artefacts are fully dealt with in the future, and unless the statistical methods for assessing the PoIE evolve, strong evidence in support of the PoIE will remain lacking.