Resting State Functional Networks in Gliomas: Validation With Direct Electric Stimulation of a New Tool for Planning Brain Resections.

BACKGROUND AND OBJECTIVES: Precise mapping of functional networks in patients with brain tumor is essential for tailoring personalized treatment strategies. Resting-state functional MRI (rs-fMRI) offers an alternative to task-based fMRI, capable of capturing multiple networks within a single acquisition, without necessitating task engagement. This study demonstrates a strong concordance between preoperative rs-fMRI maps and the gold standard intraoperative direct electric stimulation (DES) mapping during awake surgery. METHODS: We conducted an analysis involving 28 patients with glioma who underwent awake surgery with DES mapping. A total of 100 DES recordings were collected to map sensorimotor (SMN), language (LANG), visual (VIS), and speech articulation cognitive domains. Preoperative rs-fMRI maps were generated using an updated version of the ReStNeuMap software, specifically designed for rs-fMRI data preprocessing and automatic detection of 7 resting-state networks (SMN, LANG, VIS, speech articulation, default mode, frontoparietal, and visuospatial). To evaluate the agreement between these networks and those mapped with invasive cortical mapping, we computed patient-specific distances between them and intraoperative DES recordings. RESULTS: Automatically detected preoperative functional networks exhibited excellent agreement with intraoperative DES recordings. When we spatially compared DES points with their corresponding networks, we found that SMN, VIS, and speech articulatory DES points fell within the corresponding network (median distance = 0 mm), whereas for LANG a median distance of 1.6 mm was reported. CONCLUSION: Our findings show the remarkable consistency between key functional networks mapped noninvasively using presurgical rs-fMRI and invasive cortical mapping. This evidence highlights the utility of rs-fMRI for personalized presurgical planning, particularly in scenarios where awake surgery with DES is not feasible to protect eloquent areas during tumor resection. We have made the updated tool for automated functional network estimation publicly available, facilitating broader utilization of rs-fMRI mapping in various clinical contexts, including presurgical planning, functional reorganization over follow-up periods, and informing future treatments such as radiotherapy.

Spontaneous unilateral spatial neglect recovery after brain tumour resection: A multimodal diffusion and rs-fMRI case report.

Patients with unilateral spatial neglect (USN) are unable to explore or to report stimuli presented in the left personal and extra-personal space. USN is usually caused by lesion of the right parietal lobe: nowadays, it is also clear the key role of structural connections (the second and the third branch of the right Superior Longitudinal Fasciculus, respectively, SLF II and III) and functional networks (Dorsal and Ventral Attention Network, respectively, DAN and VAN) in USN. In this multimodal case report, we have merged those structural and functional information derived from a patient with a right parietal lobe tumour and USN before surgery. Functional, structural and neuropsychological data were also collected 6 months after surgery, when the USN was spontaneously recovered. Diffusion metrics and Functional Connectivity (FC) of the right SLF and DAN, before and after surgery, were compared with the same data of a patient with a tumour in a similar location, but without USN, and with a control sample. Results indicate an impairment in the right SLF III and a reduction of FC of the right DAN in patients with USN before surgery compared to controls; after surgery, when USN was recovered, patient's diffusion metrics and FC showed no differences compared to the controls. This single case and its multimodal approach reinforce the crucial role of the right SLF III and DAN in the development and recovery of egocentric and allocentric extra-personal USN, highlighting the need to preserve these structural and functional areas during brain surgery.

Integrating direct electrical brain stimulation with the human connectome.

Neurological and neurodevelopmental conditions are a major public health concern for which new therapies are urgently needed. The development of effective therapies relies on the precise mapping of the neural substrates causally involved in behaviour generation. Direct electrical stimulation (DES) performed during cognitive and neurological monitoring in awake surgery is currently considered the gold standard for the causal mapping of brain functions. However, DES is limited by the focal nature of the stimulation sites, hampering a real holistic exploration of human brain functions at the network level. We used 4137 DES points derived from 612 glioma patients in combination with human connectome data-resting-state functional MRI, n = 1000 and diffusion weighted imaging, n = 284-to provide a multimodal description of the causal macroscale functional networks subtending 12 distinct behavioural domains. To probe the validity of our procedure, we (i) compared the network topographies of healthy and clinical populations; (ii) tested the predictive capacity of DES-derived networks; (iii) quantified the coupling between structural and functional connectivity; and (iv) built a multivariate model able to quantify single subject deviations from a normative population. Lastly, we probed the translational potential of DES-derived functional networks by testing their specificity and sensitivity in identifying critical neuromodulation targets and neural substrates associated with postoperative language deficits. The combination of DES and human connectome data resulted in an average 29.4-fold increase in whole brain coverage compared to DES alone. DES-derived functional networks are predictive of future stimulation points (97.8% accuracy) and strongly supported by the anatomical connectivity of subcortical stimulations. We did not observe any significant topographical differences between the patients and the healthy population at both group and single subject level. Showcasing concrete clinical applications, we found that DES-derived functional networks overlap with effective neuromodulation targets across several functional domains, show a high degree of specificity when tested with the intracranial stimulation points of a different stimulation technique and can be used effectively to characterize postoperative behavioural deficits. The integration of DES with the human connectome fundamentally advances the quality of the functional mapping provided by DES or functional imaging alone. DES-derived functional networks can reliably predict future stimulation points, have a strong correspondence with the underlying white matter and can be used for patient specific functional mapping. Possible applications range from psychiatry and neurology to neuropsychology, neurosurgery and neurorehabilitation.

The arcuate fasciculus: Combining structure and function into surgical considerations.

BACKGROUND: Two Centuries from today, Karl Friedrich Burdach attributed the nomenclature "arcuate fasciculus" to a white matter (WM) pathway connecting the frontal to the temporal cortices by arching around the Sylvian fissure. Although this label remained essentially unvaried, the concepts related to it and the characterization of the structural properties of this bundle evolved along with the methodological progress of the past years. Concurrently, the functional relevance of the arcuate fasciculus (AF) classically restricted to the linguistic domain has extended to further cognitive abilities. These features make it a relevant structure to consider in a large variety of neurosurgical procedures. OBJECTIVE: Herein, we build on our previous review uncovering the connectivity provided by the Superior Longitudinal System, including the AF, and provide a handy representation of the structural organization of the AF by considering the frequency of defined reports in the literature. By adopting the same approach, we implement an account of which functions are mediated by this WM bundle. We highlight how this information can be transferred to the neurosurgical field by presenting four surgical cases of glioma resection requiring the evaluation of the relationship between the AF and the nearby structures, and the safest approaches to adopt. CONCLUSIONS: Our cumulative overview reports the most common wiring patterns and functional implications to be expected when approaching the study of the AF, while still considering seldom descriptions as an account of interindividual variability. Given its extension and the variety of cortical territories it reaches, the AF is a pivotal structure for different cognitive functions, and thorough understanding of its structural wiring and the functions it mediates is necessary for preserving the patient's cognitive abilities during glioma resection.

Which components of famous people recognition are lateralized? A study of face, voice and name recognition disorders in patients with neoplastic or degenerative damage of the right or left anterior temporal lobes.

We administered to large groups of patients with neoplastic or degenerative damage affecting the right or left ATL, the 'Famous People Recognition Battery' (FPRB), in which subjects are required to recognize the same 40 famous people through their faces, voices and names, to clarify which components of famous people recognition are lateralized. At the familiarity level, we found, as expected, a dissociation between a greater impairment of patients with right ATL lesions on the non-verbal (face and voice) recognition modalities and of those with left ATL lesions on name familiarity. Equally expected were results obtained at the naming level, because the worse naming scores for faces and voices were observed in left-sided patients. Less foregone were, for two reasons, results obtained at the semantic level. First, no difference was found between the two hemispheric groups when scores obtained on the verbal (name) and non-verbal (face and voice) recognition modalities were account for. Second, the face and voice recognition modalities showed a different degree of right lateralization. All groups of patients showed, indeed, both at the familiarity and at the semantic level, a greater difficulty in the recognition of voices regarding faces, but this difference reached significance only in patients with right ATL lesions, suggesting a greater right lateralization of the more complex task of voice recognition. A model aiming to explain the greater right lateralization of the more perceptually demanding voice modality of person recognition is proposed.

Personal space regulation is affected by unilateral temporal lesions beyond the amygdala.

We constantly face situations involving interactions with others that require us to automatically adjust our physical distances to avoid discomfort or anxiety. A previous case study has demonstrated that the integrity of both amygdalae is essential to regulate interpersonal distances. Despite unilateral lesion to the amygdala, as to other sectors of the medial temporal cortex, are known to also affect social behavior, their role in the regulation of interpersonal distances has never been investigated. Here, we sought to fill this gap by testing three patients with unilateral temporal lesions following surgical resections, including one patient with a lesion mainly centered on the amygdala and two with lesions to adjacent medial temporal cortex, on two versions of the stop distance paradigm (i.e. in a virtual reality environment and in a real setting). Our results showed that all three patients set shorter interpersonal distances compared to neurotypical controls. In addition, compared to controls, none of the patients adjusted such physical distances depending on facial emotional expressions, despite they preserved ability to categorize them. Finally, patients' heart rate responses differed from controls when viewing approaching faces. Our findings bring compelling evidence that unilateral lesions within the medial temporal cortex, not necessarily restricted to the amygdala, are sufficient to alter interpersonal distance, thus shedding new light on the neural circuitry regulating distance in social interactions.

Segregated circuits for phonemic and semantic fluency: A novel patient-tailored disconnection study.

Phonemic and semantic fluency are neuropsychological tests widely used to assess patients' language and executive abilities and are highly sensitive tests in detecting language deficits in glioma patients. However, the networks that are involved in these tasks could be distinct and suggesting either a frontal (phonemic) or temporal (semantic) involvement. 42 right-handed patients (26 male, mean age = 52.5 years, SD=±13.3) were included in this retrospective study. Patients underwent awake (54.8%) or asleep (45.2%) surgery for low-grade (16.7%) or high-grade-glioma (83.3%) in the frontal (64.3%) or temporal lobe (35.7%) of the left (50%) or right (50%) hemisphere. Pre-operative tractography was reconstructed for each patient, with segmentation of the inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), third branch of the superior longitudinal fasciculus (SLF-III), frontal aslant tract (FAT), and cortico-spinal tract (CST). Post-operative percentage of damage and disconnection of each tract, based on the patients' surgical cavities, were correlated with verbal fluencies scores at one week and one month after surgery. Analyses of differences between fluency scores at these timepoints (before surgery, one week and one month after surgery) were performed; lesion-symptom mapping was used to identify the correlation between cortical areas and post-operative scores. Immediately after surgery, a transient impairment of verbal fluency was observed, that improved within a month. Left hemisphere lesions were related to a worse verbal fluency performance, being a damage to the left superior frontal or temporal gyri associated with phonemic or semantic fluency deficit, respectively. At a subcortical level, disconnection analyses revealed that fluency scores were associated to the involvement of the left FAT and the left frontal part of the IFOF for phonemic fluency, and the association was still present one month after surgery. For semantic fluency, the correlation between post-surgery performance emerged for the left AF, UF, ILF and the temporal part of the IFOF, but disappeared at the follow-up. This approach based on the patients' pre-operative tractography, allowed to trace for the first time a dissociation between white matter pathways integrity and verbal fluency after surgery for glioma resection. Our results confirm the involvement of a frontal anterior pathway for phonemic fluency and a ventral temporal pathway for semantic fluency. Finally, our longitudinal results suggest that the frontal executive pathway requires a longer interval to recover compared to the semantic one.

The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe.

Background: People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients' well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods: An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results: Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion: We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents' opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

The role of the default mode network in longitudinal functional brain reorganization of brain gliomas.

The study of patients after glioma resection offers a unique opportunity to investigate brain reorganization. It is currently unknown how the whole-brain connectomic profile evolves longitudinally after surgical resection of a glioma and how this may be associated with tumor characteristics and cognitive outcome. In this longitudinal study, we investigate the impact of tumor lateralization and grade on functional connectivity (FC) in highly connected networks, or hubs, and cognitive performance. Twenty-eight patients (17 high-grade, 11 low-grade gliomas) underwent longitudinal pre/post-surgery resting-state fMRI scans and neuropsychological assessments (73 total measures). FC matrices were constructed considering as functional hubs the default mode (DMN) and fronto-parietal networks. No-hubs included primary sensory functional networks and any other no-hubs nodes. Both tumor hemisphere and grade affected brain reorganization post-resection. In right-hemisphere tumor patients, regardless of grade and relative to left-hemisphere gliomas, FC increased longitudinally after the intervention, both in terms of FC within hubs (phubs = 0.0004) and FC between hubs and no-hubs (phubs-no-hubs = 0.005). Regardless of tumor side, only lower-grade gliomas showed longitudinal FC increases relative to high-grade tumors within a precise hub network, the DMN. The neurocognitive profile was longitudinally associated with spatial features of the connectome, mainly within the DMN. We provide evidence that clinical glioma features, such as lateralization and grade, affect post-surgical longitudinal functional reorganization and cognitive recovery. The data suggest a possible role of the DMN in supporting cognition, providing useful information for prognostic prediction and surgical planning.

Classifyber, a robust streamline-based linear classifier for white matter bundle segmentation.

Virtual delineation of white matter bundles in the human brain is of paramount importance for multiple applications, such as pre-surgical planning and connectomics. A substantial body of literature is related to methods that automatically segment bundles from diffusion Magnetic Resonance Imaging (dMRI) data indirectly, by exploiting either the idea of connectivity between regions or the geometry of fiber paths obtained with tractography techniques, or, directly, through the information in volumetric data. Despite the remarkable improvement in automatic segmentation methods over the years, their segmentation quality is not yet satisfactory, especially when dealing with datasets with very diverse characteristics, such as different tracking methods, bundle sizes or data quality. In this work, we propose a novel, supervised streamline-based segmentation method, called Classifyber, which combines information from atlases, connectivity patterns, and the geometry of fiber paths into a simple linear model. With a wide range of experiments on multiple datasets that span from research to clinical domains, we show that Classifyber substantially improves the quality of segmentation as compared to other state-of-the-art methods and, more importantly, that it is robust across very diverse settings. We provide an implementation of the proposed method as open source code, as well as web service.

Multisensory stimulation for the rehabilitation of unilateral spatial neglect.

Unilateral spatial neglect (USN) is a neuropsychological syndrome, typically caused by lesions of the right hemisphere, whose features are the defective report of events occurring in the left (contralesional) side of space and the inability to orient and set up actions leftwards. Multisensory integration mechanisms, largely spared in USN patients, may temporally modulate spatial orienting. In this pilot study, the effects of an intensive audio-visual Multisensory Stimulation (MS) on USN were assessed, and compared with those of a treatment that ameliorates USN, Prismatic Adaptation (PA). Twenty USN stroke patients received a 2-week treatment (20 sessions, twice per day) of MS or PA. The effects of MS and PA were assessed by a set of neuropsychological clinical tests (target cancellation, line bisection, sentence reading, personal neglect, complex drawing) and the Catherine Bergego Scale for functional disability. Results showed that MS brought about an amelioration of USN deficits overall comparable to that induced by PA; personal neglect was improved only by MS, not by PA. The clinical gains of the MS treatment were not influenced by duration of disease and lesion volume, and they persisted up to one month post-treatment. In conclusion, MS represents a novel and promising rehabilitation procedure for USN.

Planning Brain Tumor Resection Using a Probabilistic Atlas of Cortical and Subcortical Structures Critical for Functional Processing: A Proof of Concept.

BACKGROUND: Functional preoperative planning for resection of intrinsic brain tumors in eloquent areas is still a challenge. Predicting subcortical functional framework is especially difficult. Direct electrical stimulation (DES) is the recommended technique for resection of these lesions. A reliable probabilistic atlas of the critical cortical epicenters and subcortical framework based on DES data was recently published. OBJECTIVE: To propose a pipeline for the automated alignment of the corticosubcortical maps of this atlas with T1-weighted MRI. METHODS: To test the alignment, we selected 10 patients who underwent resection of brain lesions by using DES. We aligned different cortical and subcortical functional maps to preoperative volumetric T1 MRIs (with/without gadolinium). For each patient we quantified the quality of the alignment, and we calculated the match between the location of the functional sites found at DES and the functional maps of the atlas. RESULTS: We found an accurate brain extraction and alignment of the functional maps with both the T1 MRIs of each patient. The matching analysis between functional maps and functional responses collected during surgeries was 88% at cortical and, importantly, 100% at subcortical level, providing a further proof of the correct alignment. CONCLUSION: We demonstrated quantitatively and qualitatively the reliability of this tool that may be used for presurgical planning, providing further functional information at the cortical level and a unique probabilistic prevision of distribution of the critical subcortical structures. Finally, this tool offers the chance for multimodal planning through integrating this functional information with other neuroradiological and neurophysiological techniques.

Effects of supra-total resection in neurocognitive and oncological outcome of high-grade gliomas comparing asleep and awake surgery.

PURPOSE: Awake surgery is an established technique for resection of low-grade gliomas, while its possible benefit for resection of high-grade gliomas (HGGs) needs further confirmations. This retrospective study aims to compare overall survival, extent of resection (EOR) and cognitive outcome in two groups of HGGs patients submitted to asleep or awake surgery. METHODS: Thirty-three patients submitted to Gross Total Resection of contrast-enhancing area of HGGs were divided in two homogeneous groups: awake (AWg; N = 16) and asleep surgery (ASg; N = 17). All patients underwent to an extensive neuropsychological assessment before surgery (time_1), 1-week (time_2) and 4-months (time_3) after surgery. We performed analyses to assess differences in cognitive performances between groups, cognitive outcomes in each group and EOR. A comparison of overall survival (OS) between the two groups was conducted. RESULTS: Statistical analyses showed no differences between groups at time_2 and time_3 in each cognitive domain, excluding selective attention that resulted higher in the AWg before surgery. Regarding cognitive outcomes, we found a reversible worsening of memory and constructional praxis, and a significant recovery at time_3, similar for both groups. Assessment of time_3 in respect to time_1 never showed differences (all ps > .074). Moreover we found a significant lower level of tumor infiltration after surgery for AWg (p < .05), with an influence on OS (p < .05). Indeed, patients of AWg showed a significant longer OS in comparison to those in the ASg (p < .01). This result was confirmed even considering only wildtype Glioblastoma (p < .05). CONCLUSION: These results indicate that awake surgery, and in general a supra-total resection of enhancing area, can improve OS in HGGs patients, preserving neuro-cognitive profile and quality of life.

A Case of Right Temporal Lobectomy for Brain Tumor With Selective Semantic Pictorial Disorder.

Disagreement exists regarding representational and connectionist interpretations of semantic knowledge subserved by the right versus left anterior temporal lobes (ATLs). These interpretations predict a different pattern of impairment in patients with a right unilateral ATL lesion. We conducted a neuropsychological study of a selective semantic pictorial defect exhibited by a 57-year-old man who had undergone a right temporal lobectomy due to the presence of a glioblastoma. The patient was given the Thematic and Taxonomic Semantic task, in which individuals must select, within triplets of words or pictures, the best associates of living or nonliving stimuli, related by thematic or taxonomic links, and presented in the verbal or pictorial modality. The selectivity of the defect was documented by a comparison between the results obtained by our patient and those obtained by healthy controls on living items and on pictures with a thematic relation. The selectivity of the defect was confirmed by a within-subject analysis of the results obtained on all of the task's triplets and those obtained on the stimuli representing living entities with a taxonomic relation. The selectivity of this semantic pictorial defect mainly concerning living entities is consistent with the representational account of semantic defects observed in our patient. In the present case report, a right temporal lobectomy resulted in a selective semantic pictorial defect with the qualitative features predicted by the representational account of semantic defects observed after a unilateral ATL lesion.

Whole-Brain Network Connectivity Underlying the Human Speech Articulation as Emerged Integrating Direct Electric Stimulation, Resting State fMRI and Tractography.

Production of fluent speech in humans is based on a precise and coordinated articulation of sounds. A speech articulation network (SAN) has been observed in multiple brain studies typically using either neuroimaging or direct electrical stimulation (DES), thus giving limited knowledge about the whole brain structural and functional organization of this network. In this study, seven right-handed patients underwent awake surgery resection of low-grade gliomas (4) and cavernous angiomas. We combined pre-surgical resting state fMRI (rs-fMRI) and diffusion MRI together with speech arrest sites obtained intra-operatively with DES to address the following goals: (i) determine the cortical areas contributing to the intrinsic functional SAN using the speech arrest sites as functional seeds for rs-fMRI; (ii) evaluate the relative contribution of gray matter terminations from the two major language dorsal stream bundles, the superior longitudinal fasciculus (SLF III) and the arcuate fasciculus (AF); and (iii) evaluate the possible pre-surgical prediction of SAN with rs-fMRI. In all these right-handed patients the intrinsic functional SAN included frontal, inferior parietal, temporal, and insular regions symmetrically and bilaterally distributed across the two hemispheres regardless of the side (four right) of speech arrest evocation. The SLF III provided a much higher density of terminations in the cortical regions of SAN in respect to AF. Pre-surgical rs-fMRI data demonstrated moderate ability to predict the SAN. The set of functional and structural data provided in this multimodal study characterized, at a whole-brain level, a distributed and bi-hemispherical network subserving speech articulation.

The role of premotor and parietal cortex during monitoring of involuntary movement: A combined TMS and tDCS study.

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.

Improving left spatial neglect through music scale playing.

The study assessed whether the auditory reference provided by a music scale could improve spatial exploration of a standard musical instrument keyboard in right-brain-damaged patients with left spatial neglect. As performing music scales involves the production of predictable successive pitches, the expectation of the subsequent note may facilitate patients to explore a larger extension of space in the left affected side, during the production of music scales from right to left. Eleven right-brain-damaged stroke patients with left spatial neglect, 12 patients without neglect, and 12 age-matched healthy participants played descending scales on a music keyboard. In a counterbalanced design, the participants' exploratory performance was assessed while producing scales in three feedback conditions: With congruent sound, no-sound, or random sound feedback provided by the keyboard. The number of keys played and the timing of key press were recorded. Spatial exploration by patients with left neglect was superior with congruent sound feedback, compared to both Silence and Random sound conditions. Both the congruent and incongruent sound conditions were associated with a greater deceleration in all groups. The frame provided by the music scale improves exploration of the left side of space, contralateral to the right hemisphere, damaged in patients with left neglect. Performing a scale with congruent sounds may trigger at some extent preserved auditory and spatial multisensory representations of successive sounds, thus influencing the time course of space scanning, and ultimately resulting in a more extensive spatial exploration. These findings offer new perspectives also for the rehabilitation of the disorder.

"How Did I Make It?": Uncertainty about Own Motor Performance after Inhibition of the Premotor Cortex.

Optimal motor performance requires the monitoring of sensorimotor input to ensure that the motor output matches current intentions. The brain is thought to be equipped with a "comparator" system, which monitors and detects the congruence between intended and actual movement; results of such a comparison can reach awareness. This study explored in healthy participants whether the cathodal transcranial direct current stimulation (tDCS) of the right premotor cortex (PM) and right posterior parietal cortex (PPC) can disrupt performance monitoring in a skilled motor task. Before and after tDCS, participants underwent a two-digit sequence motor task; in post-tDCS session, single-pulse TMS (sTMS) was applied to the right motor cortex, contralateral to the performing hand, with the aim of interfering with motor execution. Then, participants rated on a five-item questionnaire their performance at the motor task. Cathodal tDCS of PM (but not sham or PPC tDCS) impaired the participants' ability to evaluate their motor performance reliably, making them unconfident about their judgments. Congruently with the worsened motor performance induced by sTMS, participants reported to have committed more errors after sham and PPC tDCS; such a correlation was not significant after PM tDCS. In line with current computational and neuropsychological models of motor control and awareness, the present results show that a mechanism in the PM monitors and compares intended versus actual movements, evaluating their congruence. Cathodal tDCS of the PM impairs the activity of such a "comparator," disrupting self-confidence about own motor performance.