Background: Ten years ago, we presented evidence that shoulder apprehension is linked to reorganization in brain activation, involving areas associated with motor control, cognitive control of motor behaviour, as well as anxiety and emotional regulation. Purpose: The present study investigates whether a decade-long follow-up after surgery is connected to the normalization of apprehension-related brain activations. Methods: Ten patients (average age 38.6±9.7 years) who had undergone shoulder stabilisation and nine controls (average age 40.6±2.9 years) from the original study (Y0) took part in this ten-year follow-up prospective comparative study (Y10). We replicated the same experimental procedure, which included functional magnetic resonance imaging (fMRI) with videos designed to induce shoulder apprehension, and clinical assessments. Results: In terms of task-related functional imaging, patients exhibited a complete reduction in apprehension-related brain activations at Y10 compared to Y0. In terms of functional connectivity, the differences observed in several brain networks at Y0 between patients and controls nearly completely normalized at Y10. There were no significant structural differences in brain grey matter or white matter observed between Y0 and Y10 in both patients and controls. Regarding clinical parameters, patients showed improvement at Y10 compared to Y0 across all scores. Conclusion: In patients with shoulder apprehension, apprehension-related brain activation patterns showed near-complete normalization ten years after successful shoulder stabilisation, although subjective apprehension remained higher than in healthy controls.

The lumbosacral spinal cord contains neural circuits crucial for locomotion, organized into rostrocaudal levels with distinct somatosensory and motor neuron pools that project to and from the muscles of the lower limbs. However, the specific spinal levels that innervate each muscle and the locations of neuron pools vary significantly between individuals, presenting challenges for targeted therapies and neurosurgical interventions aimed at restoring locomotion. Non-invasive approaches to functionally map the segmental distribution of muscle innervation-orprojectome-are therefore essential. Here, we developed a pipeline dedicated to record blood oxygenation level dependent (BOLD) signals in the lumbosacral spinal cord using functional magnetic resonance imaging (fMRI). We assessed spinal activity across different conditions targeting the extensor/flexor muscles of the right leg (ankle, knee, and hip) in 12 healthy participants. To enhance clinical relevance, we included not only active movements but also two conditions that did not rely on participants' performance: passive stretches and muscle-specific tendon vibration, which activates proprioceptive afferents of the vibrated muscle. BOLD activity patterns were primarily located on the side ipsilateral to the movement, stretch, or vibration, both at the group and participant levels, indicating the BOLD activity being associated with the projectome. The fMRI-derived rostrocaudal BOLD activity patterns exhibited mixed alignment with expected innervation maps from invasive studies, varying by muscle and condition. While some muscles and conditions matched well across studies, others did not. Significant variability among individual participants underscores the need for personalized mapping of projections for targeted therapies and neurosurgical interventions. To support the interpretation of BOLD activity patterns, we developed a decision tree-based framework that combines reconstruction of neural structures from high-resolution anatomical MRI datasets and muscle-specific fMRI activity to produce personalized projectomes. Our findings provide a valuable proof-of-concept for the potential of fMRI to map the lumbosacral spinal cord's functional organization, while shedding light on challenges associated with this endeavor.

Understanding how focal perturbations trigger large-scale network reorganization is essential for uncovering the neural mechanisms that support perception and behaviour. Here we used a transcranial magnetic stimulation (TMS) perturbational approach by applying brief 10 Hz TMS to early visual areas (EVAs) or the medio-temporal (MT) area in healthy participants while recording concurrent functional magnetic resonance imaging (fMRI). TMS delivered during the early stages of motion processing specifically impaired direction discrimination at both sites, whereas disruption of the later processing phase impaired performances only for the MT condition. Despite a similar local increase in BOLD activity induced by EVA and MT stimulation, the broader network responses diverged significantly. Perturbation of EVA elicited a more robust and efficient pattern of functional reorganization, manifesting as more constrained BOLD changes, consistent with greater resilience to focal disruption. In contrast behavioural impairments induced by MT stimulation were accompanied by a disorganized and less-efficient network configuration, characterized by smaller small-world properties and longer path lengths. The decrease in performances induced by MT stimulation scaled with lower clustering coefficients, implying a more random or decentralized network structure. These findings demonstrate that TMS-fMRI coupling provides a powerful framework for causally mapping the relationships between local neural perturbations, large-scale network dynamics and behavioural performance. KEY POINTS: Transcranial magnetic stimulation (TMS)-induced perturbation of the early visual areas (EVAs) or the medio-temporal (MT) area selectively impairs motion direction discrimination. The TMS perturbation is associated with a context-dependent local upscaling of blood-oxygen-level dependent (BOLD) activity in both areas. The two visual areas exhibit distinct topological networks' adaptation in response to TMS, reflecting different levels of network resilience to a focal lesion. TMS-functional magnetic resonance imaging (fMRI) coupling can be used to assess 'causal disconnectomics' and to precisely map how a local perturbation propagates to large-scale behavioural deficits.

The emergence of 7T clinical MRI technology has sparked our interest in its ability to discern the complex structures of the hand. Our primary objective was to assess the sensory and motor nerve structures of the hand, specifically nerves and Pacinian corpuscles, with the dual purpose of aiding diagnostic endeavors and supporting reconstructive surgical procedures. Ethical approval was obtained to carry out 7T MRI scans on a cohort of volunteers. Four volunteers assumed a prone position, with their hands (N = 8) positioned in a “superman” posture. To immobilize and maintain the hand in a strictly horizontal position, it was affixed to a plastic plate. Passive B0 shimming was implemented. Once high-resolution 3D images had been acquired using a multi-transmit head coil, advanced post-processing techniques were used to meticulously delineate the nerve fiber networks and mechanoreceptors. Across all participants, digital nerves were consistently located on the phalanges area, on average, between 2.5 and 3.5 mm beneath the skin, except within flexion folds where the nerve was approximately 1.8 mm from the surface. On the phalanges area, the mean distance from digital nerves to joints was approximately 1.5 mm. The nerves of the fingers were closer to the bone than to the surface of the skin. Furthermore, Pacinian corpuscles exhibited a notable clustering primarily within the metacarpal zone, situated on the palmar aspect. Our study yielded promising results, successfully reconstructing and meticulously describing the anatomy of nerve fibers spanning from the carpus to the digital nerve division, alongside the identification of Pacinian corpuscles, in four healthy volunteers (eight hands).

Understanding the causal relationship between a focal lesion and network (re)organization is crucial to accurately predict the resulting large-scale symptoms of a lesion. In this study, we applied short trains of 10 Hz TMS to healthy participants over the early visual areas (EVA) or the medio-temporal area (hMT+/MT) during a motion discrimination task and at rest, while concurrent fMRI was acquired. TMS applied in the early stage of motion processing induced a specific deficit in judging motion direction in both sites, while global motion perception was preserved. This was associated with a common suppression of local brain activity and network activity. In contrast, we report distinct topological network properties depending on the disrupted site. Networks associated with EVA perturbation displayed a more robust and efficient functional reorganization, suggesting that EVA might be more resilient to focal perturbations. While contributing to a better understanding of the impact and potential mechanisms of TMS perturbation, these results provide a model for focal lesions in the visual motion processing system. Highlights TMS-induced perturbation of the early visual areas (EVA) or the mediotemporal area (hMT+/V5) area selectively impairs motion direction discrimination. The TMS perturbation is associated with a local down-scaling of BOLD activity in both areas, potentially specific to task-related neuronal populations during motion discrimination. The two visual areas display distinct topological networks’ adaptations in response to TMS, reflecting different levels of networks resilience to a focal lesion. TMS-fMRI coupling can be used to assess ‘disconnectomics’ and to precisely map how a local perturbation propagates to large-scale behavioural deficits. Graphical abstract

Functional magnetic resonance imaging (fMRI) has revolutionized the investigation of brain function. Similar approaches can be translated to probe spinal mechanisms. However, imaging the spinal cord remains challenging, notably due to its size and location. Technological advances are gradually tackling these issues, though there is yet no consensus on optimal acquisition protocols. In this study, we assessed the performance of three sequences during a simple motor task and at rest, in 15 healthy humans. Building upon recent literature, we selected three imaging protocols: a sequence integrating outer volume suppression (OVS) and two sequences implementing inner field-of-view imaging (ZOOMit) with different spatial and temporal resolutions. Images acquired using the OVS sequence appeared more prone to breathing-induced signal fluctuations, though they exhibited a higher temporal signal-to-noise ratio than ZOOMit sequences. Conversely, the spatial signal-to-noise ratio was higher for the two ZOOMit schemes. In spite of these differences in signal properties, all sequences yielded comparable performance in detecting group-level task-related activity, observed in the expected spinal levels. Nevertheless, our results suggest a superior sensitivity and robustness of patterns imaged using the OVS acquisition scheme. To analyze the data acquired at rest, we deployed a dynamic functional connectivity framework, SpiCiCAP, and we evaluated the ability of the three acquisition schemes to disentangle intrinsic spinal signals. We demonstrated that meaningful subdivisions of the spinal cord's functional architecture could be uncovered for all three sequences, with similar spatio-temporal properties across acquisition parameters. Cleaner and more stable components were, however, obtained using ZOOMit sequences. This study emphasizes the potential of fMRI as a robust tool to image spinal activity in vivo and it highlights specificities and similarities of three acquisition methods. This represents a key step towards the establishment of standardized spinal cord fMRI protocols.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its relationship with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the link between the somatotopic organization of PR and FRs and their activation properties remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict the relationship between PR and FRs activations. Using three complementary measures (cross-activations, pattern similarity and resting-state connectivity), we show that the relationship between PR and FRs activations were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting-state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of PR and FRs activations reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional properties, rather the structure of the sensory space (e.g., the hand shape) better describes the observed results.

When performing willed actions, we have the unified and coherent experience of owning and controlling our body. Body ownership is believed to emerge from the integration of coherent multisensory signals, while agency is believed to emerge from the coherence between predicted and perceived outcomes of actions. As a consequence, body ownership and agency can both be modulated by multisensory conflicts. The contribution of active movement generation to ownership and agency has not been parametrically explored. Here, we investigated the contribution of interaction force between the agent and the environment to the sense of hand ownership (SO) and the sense of hand agency (SA). By combining robotics and virtual reality, we manipulated the sensorimotor and visual information during immersive scenarios to induce and quantify altered states of SO and SA. First, we demonstrated that SO and SA could be successfully manipulated by our experimental paradigms. Second, we showed that interaction force strongly contributes to SA, but to a lesser extent to SO. Finally, we showed that SO and SA interact beyond their common multisensory basis. Our results, based on two independent studies, provide a direct link between sensorimotor interactions and subjective body experience and demonstrate a new dissociation between SO and SA.

Functional magnetic resonance Brain Imaging (fMRI) is a key non-invasive imaging technique for the study of human brain activity. Its millimetric spatial resolution is at the cost of several constraints: participants must remain static and experience artificial stimuli, making it difficult to generalize neuroscientific results to naturalistic and ecological conditions. Immersive Virtual Reality (VR) provides alternatives to such stimuli through simulation, but still requires an active first-person exploration of the environment to evoke a strong sense of presence in the virtual environment. Here, we report how to compensate for the inability to freely move in VR by leveraging on principles of embodiment for a virtual avatar, to eventually evoke a strong sense of presence with a minimal motion of the participant. We validated the functionality of the platform in a study where healthy participants performed several basic research tasks in an MR-specific immersive virtual environment. Our results show that our approach can lead to high sense of presence, strong body ownership, and sense of agency for a virtual avatar, with low movement-related MRI artifacts. Moreover, to exemplify the versatility of the platform, we reproduced several behavioral and fMRI results in the perceptual, motor, and cognitive domains. We discuss how to leverage such technology for neuroscience research and provide recommendations on efficient ways to implement and develop it successfully.

ABSTRACT Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its interactions with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the relationship between the somatotopic organization and the cortical functional interactions between PR and FRs remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that the PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict palm-finger functional interactions. Using three complementary measures of functional interactions (co-activations, pattern similarity and resting-state connectivity), we show that palm-finger functional interactions were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting-state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of palm-finger functional interactions reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional interactions, rather the structure of the sensory space (e.g. the hand shape) better predicts the observed functional interactions.

INTRODUCTION:Orbitofrontal reality filtering (ORFi) is a memory mechanism that distinguishes whether a thought is relevant to present reality or not. In adults, it is mediated by the orbitofrontal cortex (OFC). This region is still not fully developed in preteenagers, but ORFi is already active from age 7. Here, we probe the neural correlates of ORFi in early adolescents, hypothesizing that OFC mediates the sense of reality in this population.METHODS:Functional magnetic resonance images (fMRI) were acquired in 22 early adolescents during a task composed of two runs: run 1 measuring recognition capacity; run 2 measuring ORFi; each containing two types of images (conditions): distractors (D: images seen for the first time in the current run) and targets (T: images seen for the second time in the current run). Group region of interest (ROI) analysis was performed in a flexible factorial design with two factors (run and condition) using SPM12.RESULTS:We found significant main effects for the experimental run and condition. The bilateral OFC activation was higher during ORFi than during the first run. Additionally, the OFC was more active while processing distractors than targets.CONCLUSION:These results confirm, for the first time, the role of OFC in reality filtering in early adolescents.

The spinal cord is the main interface between the brain and the periphery. It notably plays a central role in motor control, as spinal motoneurons activate skeletal muscles involved in voluntary movements. Yet, the spinal mechanisms underlying human movement generation have not been completely elucidated. In this regard, functional magnetic resonance imaging (fMRI) represents a potential tool to probe spinal cord function non-invasively and with high spatial resolution. Nonetheless, a thorough characterization of this approach is still lacking, currently limiting its impact. Here, we aimed at systematically quantifying to which extent fMRI can reveal spinal cord activity along the rostrocaudal direction. We investigated changes in the blood oxygenation level dependent signal of the human cervical spinal cord during bimanual upper limb movements (wrist extension, wrist adduction and finger abduction) in nineteen healthy volunteers. Prior to scanning, we recorded the muscle activity associated with these movements in order to reconstruct the theoretical motor-pool output pattern using an anatomy-based mapping of the electromyographic (EMG) waveforms. EMG-derived spinal maps were characterized by distinct rostrocaudal patterns of activation, thus confirming the task-specific features of the different movements. Analogous activation patterns were captured using spinal cord fMRI. Finally, an additional fMRI dataset was acquired from a subset of the participants (n = 6) to deploy a multivoxel pattern analysis, which allowed successful decoding of movements. These combined results suggest that spinal cord fMRI can be used to image rostrocaudal activation patterns reflecting the underlying activity of the motoneuron pools innervating the task-related muscles. Spinal cord fMRI offers the prospect of a novel tool to study motor processes and potentially their modification following neurological motor disorders.

Primary somatosensory cortex (S1) processes somatosensory information and is composed of multiple subregions. In particular, tactile information from the skin is encoded in three subregions, namely Brodmann areas (BAs) 3b, 1 and 2, with each area representing a complete map of the contralateral body. Although, much is known about the somatotopic organization of the hand in human S1, less research has been carried out regarding the somatotopic maps of the foot and leg in S1. Moreover, a latero-medial S1 organization along the superior part of the postcentral gyrus has been reported when moving from hip to toes, yet to date there is no study investigating leg/foot maps within the different subregions of S1. Using ultra-high field MRI (7T), we mapped six cortical representations of the lower limb (hip to toes) at the single subject level and performed this analysis separately for BAs 3b, 1 and 2. Analyzing the BOLD responses associated with tactile stimulations of the mapped foot and leg regions on each side, we quantified the extent and the strength of activation to determine somatotopic organization. In addition, we investigated whether each mapped representation also responded to the stimulation of other body parts (i.e. response selectivity) and conducted dissimilarity analysis relating these anatomical and functional properties of S1 to the physical structure of the lower limbs. Our data reveal somatotopy for the leg, but not for the foot in all investigated BAs, with large inter-subject variability. We found only minor differences between the properties of the three investigated BAs, suggesting that S1 maps for the lower limbs differ from those described for the hand. We also describe greater extent/strength of S1 activation for the big toe representation (compared to the other mapped representations) within all BAs, suggesting a possible homology between the first digit of upper and lower extremity in humans, and report different patterns of selectivity in the foot representations (i.e. lower selectivity) compared to the other leg representations (i.e. greater selectivity). These data provide a detailed description of human S1 subregions for the foot and leg, highlight the importance of high-resolution mapping studies and of single subject analysis, and indicate potential differences between the lower and the upper limb.

Neuroprosthetics research in amputee patients aims at developing new prostheses that move and feel like real limbs. Targeted muscle and sensory reinnervation (TMSR) is such an approach and consists of rerouting motor and sensory nerves from the residual limb towards intact muscles and skin regions. Movement of the myoelectric prosthesis is enabled via decoded electromyography activity from reinnervated muscles and touch sensation on the missing limb is enabled by stimulation of the reinnervated skin areas. Here we ask whether and how motor control and redirected somatosensory stimulation provided via TMSR affected the maps of the upper limb in primary motor (M1) and primary somatosensory (S1) cortex, as well as their functional connections. To this aim, we tested three TMSR patients and investigated the extent, strength, and topographical organization of the missing limb and several control body regions in M1 and S1 at ultra high-field (7 T) functional magnetic resonance imaging. Additionally, we analysed the functional connectivity between M1 and S1 and of both these regions with fronto-parietal regions, known to be important for multisensory upper limb processing. These data were compared with those of control amputee patients (n = 6) and healthy controls (n = 12). We found that M1 maps of the amputated limb in TMSR patients were similar in terms of extent, strength, and topography to healthy controls and different from non-TMSR patients. S1 maps of TMSR patients were also more similar to normal conditions in terms of topographical organization and extent, as compared to non-targeted muscle and sensory reinnervation patients, but weaker in activation strength compared to healthy controls. Functional connectivity in TMSR patients between upper limb maps in M1 and S1 was comparable with healthy controls, while being reduced in non-TMSR patients. However, connectivity was reduced between S1 and fronto-parietal regions, in both the TMSR and non-TMSR patients with respect to healthy controls. This was associated with the absence of a well-established multisensory effect (visual enhancement of touch) in TMSR patients. Collectively, these results show how M1 and S1 process signals related to movement and touch are enabled by targeted muscle and sensory reinnervation. Moreover, they suggest that TMSR may counteract maladaptive cortical plasticity typically found after limb loss, in M1, partially in S1, and in their mutual connectivity. The lack of multisensory interaction in the present data suggests that further engineering advances are necessary (e.g. the integration of somatosensory feedback into current prostheses) to enable prostheses that move and feel as real limbs.

Technical advances in the field of Brain‐Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole‐brain level. Here, we provide a comprehensive and detailed report of the areas active during on‐line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG‐based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI‐actions. Our data revealed an extended cortical‐subcortical network involved in operating a motor‐imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971–2989, 2017 . © 2017 Wiley Periodicals, Inc.

Exteroceptive bodily signals (including tactile, proprioceptive and visual signals) are important information contributing to self-consciousness. Moreover, prominent theories proposed that visceral signals about internal bodily states are equally or even more important for self-consciousness. Neuroimaging studies have described several brain regions which process signals related to bodily self-consciousness (BSC) based on the integration of exteroceptive signals (e. g. premotor cortex, angular gyrus, supramarginal gyrus and extrastriate body area), and that another brain region, the insula/operculum which is involved in interoception and interoceptive awareness, processes signals critical for self-awareness. Providing evidence for the integration of exteroceptive and interoceptive bodily signals, recent behavioral experiments have demonstrated that the manipulation of interoceptive (e. g. cardiac) signals, coupled with exteroceptive (e. g. visual) signals, also modulates BSC. Does this integration occur within or outside the structures described above? To this end, we adapted a recently designed protocol that uses cardio-visual stimulation to induce altered states of BSC to fMRI. Additionally, we measured neural activity in a classical interoceptive task. We found six brain regions (bilateral Rolandic operculum, bilateral supramarginal gyrus, right frontal inferior operculum and left temporal superior gyrus) that were activated differently during the interoception task as opposed to a control task. The brain regions which showed the highest selectivity for BSC based on our cardio-visual manipulation were found in the bilateral Rolandic operculum. Given our findings, we propose that the Rolandic operculum processes integrated exteroceptive-interoceptive signals that are necessary for interoceptive awareness as well as BSC.

It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex.