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Multisensory processing can be assessed by measuring susceptibility to crossmodal illusions such as the Sound-Induced Flash Illusion (SIFI). When a single flash is accompanied by 2 or more beeps, it is perceived as multiple flashes (fission illusion); conversely, a fusion illusion is experienced when more flashes are matched with a single beep, leading to the perception of a single flash. Such illusory perceptions are associated to crossmodal changes in visual cortical excitability. Indeed, increasing occipital cortical excitability, by means of transcranial electrical currents, disrupts the SIFI (ie, fission illusion). Similarly, a reduced fission illusion was shown in patients with episodic migraine, especially during the attack, in agreement with the pathophysiological model of cortical hyperexcitability of this disease. If episodic migraine patients present with reduced SIFI especially during the attack, we hypothesize that chronic migraine (CM) patients should consistently report less illusory effects than healthy controls; drugs intake could also affect SIFI. On such a basis, we studied the proneness to SIFI in CM patients (n = 63), including 52 patients with Medication Overuse Headache (MOH), compared to 24 healthy controls. All migraine patients showed reduced fission phenomena than controls (P

Objective: Sound-induced flash illusions depend on visual cortical excitability. In this study, we explored whether sound-induced flash illusions are perceived differently in migraine, a condition associated with pathologic cortical hyperexcitability. Methods: Sound-induced flash illusions were examined in 59 migraine patients (mean age = 32 ± 16 years; 36 females), 32 without aura and 27 with aura, and in 24 healthy controls (mean age = 42 ± 17 years; 16 females). Patients were studied during attacks and interictally. Visual stimuli (flashes) accompanied by sounds (beeps) were presented in different combinations: a single flash with multiple beeps was given to induce the perception of multiple flashes (“fission” illusion), and multiple flashes with a single beep were used to reduce the number of perceived flashes (“fusion” illusion). Results: For migraineurs, the fission illusion was reduced, especially during the attack, and almost abolished when a single flash was combined with 2 beeps (except for those without aura tested interictally); the fusion illusion was less consistently reported in both migraine groups, but not completely disrupted. Conclusions: Results from this study add novel clues to our understanding of visual cortex hyperexcitability in migraine, especially migraine with aura. Furthermore, these analyses underscore how pathologic changes in cortical excitability affect multisensory interactions. Cross-modal illusions represent a valid tool for exploration of functional connectivity between sensory areas, which likely has an important role in the pathophysiology of migraine.

Recent neuropsychological evidence suggests that acquired brain lesions can, in some instances, abolish the ability to integrate inputs from different sensory modalities, disrupting multisensory perception. We explored the ability to perceive multisensory events, in particular the integrity of audio-visual processing in the temporal domain, in brain-damaged patients with visual field defects (VFD), or with unilateral spatial neglect (USN), by assessing their sensitivity to the 'Sound-Induced Flash Illusion' (SIFI). The study yielded two key findings. Firstly, the 'fission' illusion (namely, seeing multiple flashes when a single flash is paired with multiple sounds) is reduced in both left- and right-brain-damaged patients with VFD, but not in right-brain-damaged patients with left USN. The disruption of the fission illusion is proportional to the extent of the occipital damage. Secondly, a reliable 'fusion' illusion (namely, seeing less flashes when a single sound is paired with multiple flashes) is evoked in USN patients, but neither in VFD patients nor in healthy participants. A control experiment showed that the fusion, but not the fission, illusion is lost in older participants (>50 year-old), as compared with younger healthy participants (

A 2-[18F]-Fluoro-2-Deoxy- D -Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery fromunilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

Both visuo-spatial neglect and visual extinction may occur following right-brain damage. So far, studies on brain-damaged patients have not provided definite evidence about which lesion patterns may lead to the association or dissociation of these deficits. This study was set out to address this issue using Intracranial Electrical Stimulation (IES) in a group of nine patients affected by refractory epilepsy. Cerebral regions associated with visuo-spatial neglect and visual extinction were stimulated, including the right frontal, temporal, and posterior parietal areas. During IES, patients with intracranial implantation involving at least one of these cortical regions were administered with a manual line bisection task (N = 9) to assess visuo-spatial neglect, and a computerized task (N = 8) assessing visual extinction. Results showed that parietal IES induced a rightward bias at the manual bisection task, together with a general improvement in reaction times at bilateral and unilateral visual stimuli detection at the extinction task. The occurrence of visual extinction did not vary across stimulations. By adopting a complementary approach to anatomo-clinical correlation studies, our work corroborates the notion that lesions to the right inferior parietal lobule play a pivotal role in the pathogenesis of visuo-spatial neglect. Importantly, our results also suggest that temporarily interfering with the activity of this region is not sufficient per se to generate visual extinction, which instead may involve a broader and/or different network, possibly extending beyond the cerebral regions considered here, posing important theoretical and clinical implications.

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.

The brain preserves its capacity to integrate information from different senses in many pathological conditions, including stroke. Multisensory integration mechanisms, which may be spared by brain damage, provide a tool for setting up rehabilitation programs of poststroke sensory and cognitive disorders. Indeed, proper multisensory stimulation can ameliorate some unisensory perceptual and spatial impairments of brain-damaged patients. In the case of postchiasmatic visual field defects, intensive audiovisual stimulation of the blind hemifield allows the development of compensatory eye movements, in turn reducing vision-related functional disability in daily living. This approach is effective in both adult stroke patients and in children with cerebral palsy. In the rehabilitation of unilateral spatial neglect, many available treatments are intrinsically multisensory, because they primarily act through a crossmodal reinforcement of spatial representations. This is the case of adaptation to optical prisms displacing the visual scene, a widely used method that affects sensorimotor neuroplasticity. In patients with spatial neglect, prism adaptation induces a remapping of spatial coordinates, enabling the reconstruction of a stable representation of space across different sensory modalities. Other promising therapeutic strategies are offered by multisensory illusions, which can be used for restoring disarranged spatial and body representations, thereby improving the resulting deficits.

Our motor behavior and interactions with the external world are mediated by many spatial systems. This study investigated the absence of visual control of performance in the manual line bisection task, with the goal of teasing apart the role of the motor component of the visuomotor spatial system. Results show a rightward bias when right-handed individuals bisect lines using their right hand. This effect is traced back to a motor-spatial representation of space centered on the dominant hand. This finding was replicated and further explored in 4 experiments, with the same "open loop" bisection procedure. The mechanism underlying the rightward bias does not interact with the visuo-perceptual processing involved in visual illusions of extension. Besides, this bias no longer appears when perceptual judgments of prebisected lines are required, and is substantially reduced when the influence of visual feedback is minimized by a ballistic movement. The emergence of a leftward shift in left-handed individuals, when using their left hand, confirms the hypothesis of a dominant-hand-centered motor-spatial bias. Finally, when the lines to be bisected are placed to the left or to the right of the midsagittal plane of the participants' trunk, the error shifts overall toward the side of displacement of the stimulus, both in left- and right-handers, independent of the bisection bias, which does not appear related to the egocentric position of the stimulus. We reexamined the spatial biases occurring both in healthy (i.e., pseudoneglect) and neurological (i.e., neglect) populations, by emphasizing the integration mechanism of different spatial coordinate systems. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The knowledge of the size of our own body parts is essential for accurately moving in space and efficiently interact with objects. A distorted perceptual representation of the body size often represents a core diagnostic criterion for some psychopathological conditions. The metric representation of the body was shown to depend on somatosensory afferences: local deafferentation indeed causes a perceptual distortion of the size of the anesthetized body part. A specular effect can be induced by altering the cortical map of body parts in the primary somatosensory cortex. Indeed, the present study demonstrates, in healthy adult participants, that repetitive Transcranial Magnetic Stimulation to the somatosensory cortical map of the hand in both hemispheres causes a perceptual distortion (i.e., an overestimation) of the size of the participants' own hand (Experiments 1-3), which does not involve other body parts (i.e., the foot, Experiment 2). Instead, the stimulation of the inferior parietal lobule of both hemispheres does not affect the perception of the own body size (Experiment 4). These results highlight the role of the primary somatosensory cortex in the building up and updating of the metric of body parts: somatosensory cortical activity not only shapes our somatosensation, it also affects how we perceive the dimension of our body.

Spatial neglect is a debilitating disorder frequently observed after damage to the right cerebral hemisphere. Previous investigations have revealed that prism adaptation (PA) therapy can lead to improvements in neglect-related symptoms. In the typical PA protocol patients repeatedly point toward a visual target while wearing prism goggles. A few years ago, a novel PA procedure, involving a variety of more "ecological" visuo-motor activities during adaptation, less repetitive than a sequence of pointings, was introduced by our research group, and shown to be able to improve neglect-related symptoms to the same extent as the standard pointing task. The ecological procedure was easy to administer and pleasant for the patients. In all previous studies, patients were treated by specialized personnel during hospitalization. In the current study, we investigated the effectiveness of the ecological PA method when performed in a home-based setting, with the help of caregivers and family members. Seven right-brain-damaged patients with chronic left spatial neglect underwent a two-week ecological PA treatment, extended, for two extra weeks, in 6 patients, who were available for this additional rehabilitation session. As a control treatment, patients performed the same activities while wearing neutral goggles, before the PA procedure. Two weeks of ecological PA training proved to be able to significantly improve performance in neuropsychological tests (BIT, Cancellation tasks), a neurological scale (NIH), and functional abilities (CBS), when compared to both the baseline and the neutral control treatment, with improvements being maintained over 6 months. The ecological home-based PA training is effective in alleviating signs of spatial neglect. Importantly, this training is affordable, pleasant, and feasible to be performed in the comfort of the patient's home. Easily extendable to larger patient populations and prolonged periods, this method has a real potential to benefit the quality of life of brain-damaged patients with left spatial neglect.

The right cerebral hemisphere plays a crucial rule in spatial cognition, spanning from perception of elementary features, such as location, color, line orientation or shape to representation of different spaces (3D space, allocentric, egocentric, face, personal, peri-personal, or imaginal). One important aspect of its contribution concerns the perception of space symmetry and the representation of objects and scenes, with reference to the midline or body axis. This representation results from a balance between spatial attention processes depending from the two hemispheres. Healthy participants tend to show a discrete deviation of the midline plane representation toward the left side, that is likely to result from the predominance of the activity of the right cerebral hemisphere, mainly oriented toward the contralateral side of space. The visuospatial abilities of the right hemisphere, especially for the representation of the midline plane are crucially engaged in painting and drawing processes in artists. Interestingly, the distortions created by painters of the Cubism period, characterized by an asymmetry of objects and body representations, a specific enlargement or reduction of parts of space, or even by complex distortions of 3D space are analogous to those classically reported in right-brain-damaged patients (unilateral spatial neglect, hyperschematia, constructional apraxia). Understanding the pathological mechanisms of these representation disorders provides meaningful information to apprehend visual artist creations and esthetic perception of space.

Unilateral spatial neglect is a disabling neurologic deficit, most frequent and severe after right-hemispheric lesions. In most patients neglect involves the left side of space, contralateral to a right-hemispheric lesion. About 50% of stroke patients exhibit neglect in the acute phase. Patients fail to orient, respond to, and report sensory events occurring in the contralateral sides of space and of the body, to explore these portions of space through movements by action effectors (eye, limbs), and to move the contralateral limbs. Neglect is a multicomponent higher-level disorder of spatial awareness, cognition, and attention. Spatial neglect may occur independently of elementary sensory and motor neurologic deficits, but it can mimic and make them more severe. Diagnostic tests include: motor exploratory target cancellation; setting the midpoint of a horizontal line (bisection), that requires the estimation of lateral extent; drawing by copy and from memory; reading, assessing neglect dyslexia; and exploring the side of the body contralateral to the lesion. Activities of daily living scales are also used. Patients are typically not aware of neglect, although they may exhibit varying degrees of awareness toward different components of the deficit. The neural correlates include lesions to the inferior parietal lobule of the posterior parietal cortex, which was long considered the unique neuropathologic correlate of neglect, to the premotor and to the dorsolateral prefrontal cortices, to the posterior superior temporal gyrus, at the temporoparietal junction, to subcortical gray nuclei (thalamus, basal ganglia), and to parietofrontal white-matter fiber tracts, such as the superior longitudinal fascicle. Damage to the inferior parietal lobule of the posterior parietal cortex is specifically associated with the mainly egocentric, perceptual, and exploratory extrapersonal, and with the personal, bodily components of neglect. Productive manifestations, such as perseveration, are not a correlate of posterior parietal cortex damage.

Cortical regional cerebral perfusion was assessed by N, N, N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1, 3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerised tomography (SPECT) in six aphasic and two neglect patients with unilateral subcortical vascular lesions. Assessments were carried out both in the acute phase and after a period ranging from 1 to 6 months after stroke onset. In all patients an almost complete spontaneous recovery occurred and was associated with a significant improvement of cortical perfusion. A relationship between severity of aphasia and degree of cortical hypoperfusion was found, in both the acute and the follow up assessments, in the aphasic subgroup.

The bisection of lines positioned radially (with the two ends of the line close and far, with respect to the participant's body) has been less investigated than that of lines placed horizontally (with their two ends left and right, with respect to the body's midsagittal plane). In horizontal bisection, patients with left neglect typically show a rightward bias for both lines and words, greater with longer stimuli. As for radial bisection, available data indicate that neurologically unimpaired participants make a distal error, while results from right-brain-damaged patients with left spatial neglect are contradictory. We investigated the bisection of radially oriented words, with the prediction that, during bisection, linguistic material would be recoded to its canonical left-to-right format in reading, with the performance of neglect patients being similar to that for horizontal words. Thirteen right-brain-damaged patients (seven with left spatial neglect) and fourteen healthy controls were asked to manually bisect 40 radial and 40 horizontal words (5-10 letters), and 80 lines, 40 radial and 40 horizontal, of comparable length. Right-brain-damaged patients with spatial neglect exhibited a proximal bias in the bisection of short radial words, with the proximal part corresponding to the final right part of horizontally oriented words. This proximal error was not found in patients without neglect and healthy controls. For bisection, short radial words may be recoded to the canonical orthographic horizontal format, unveiling the impact of left neglect on radially oriented stimuli.

The stage at which processing of tactile distance occurs is still debated. We addressed this issue by implementing an adaptation-aftereffect paradigm with passive touch. We demonstrated the presence of a strong aftereffect, induced by the simultaneous presentation of pairs of tactile stimuli. After adaptation to two different distances, one on each hand, participants systematically perceived a subsequent stimulus delivered to the hand adapted to the smaller distance as being larger. We further investigated the nature of the aftereffects, demonstrating that they are orientation- and skin-region-specific, occur even when just one hand is adapted, do not transfer either contralaterally or across the palm and dorsum, and are defined in a skin-centered, rather than an external, reference frame. These characteristics of tactile distance aftereffects are similar to those of low-level visual aftereffects, supporting the idea that distance perception arises at early stages of tactile processing.

Touch has an emotional and communicative meaning, and it plays a crucial role in social perception and empathy. The intuitive link between others' somatosensations and our sense of touch becomes ostensible in mirror-touch synesthesia, a condition in which the view of a touch on another person's body elicits conscious tactile sensations on the observer's own body [1]. This peculiar phenomenon may implicate normal social mirror mechanisms [2]. Here, we show that mirror-touch interference effects, synesthesia-like sensations, and even phantom touches can be induced in nonsynesthetes by priming the primary somatosensory cortex (SI) directly or indirectly via the posterior parietal cortex. These results were obtained by means of facilitatory paired-pulse transcranial magnetic stimulation (ppTMS) contingent upon the observation of touch. For these vicarious effects, the SI is engaged at 150 ms from the onset of the visual touch. Intriguingly, individual differences in empathic abilities, assessed with the Interpersonal Reactivity Index [3], drive the activity of the SI when nonsynesthetes witness others' tactile sensations. This evidence implies that, under normal conditions, touch observation activates the SI below the threshold for perceptual awareness [4]; through the visual-dependent tuning of SI activity by ppTMS, what is seen becomes felt, namely, mirror-touch synesthesia. On a broader perspective, the visual responsivity of the SI may allow an automatic and unconscious transference of the sensation that another person is experiencing onto oneself, and, in turn, the empathic sharing of somatosensations [2]. © 2014 Elsevier Ltd.

Macro- and micro-somatognosia refer to rare disorders of the cerebral representation of the body whereby patients perceive body parts as disproportionately large or small. Here we report the experimental study of a patient who, following a left lateral medullary stroke (Wallenberg's syndrome, including vestibular deficits) complained of a persistent somatosensory illusory sensation of swelling, confined to the left side of his face (i.e., left macrosomatognosia). This hemifacial somatosensory distortion was associated with a left facial anesthesia, and a neuropathic pain affecting the three branches of the left trigeminal nerve. In this study, we first document quantitatively the patient's somatosensory illusion by using a somatosensory-to-visual matching task in which the patient modified the picture of his own face to fit his left-sided somatosensory misperception. The patient's performance revealed that macrosomatognosia was confined to the second branch of the left trigeminal nerve. Perception of the size of visual objects was comparatively preserved. Second, we investigated the effects of two peripheral stimulations, which may affect the spatial component of somatosensory deficits (caloric vestibular stimulation, CVS; transcutaneous electrical nervous stimulation, TENS) and pain (TENS). Left CVS abolished the facial somatosensory illusion, for about 30min, but had no effect on the left facial pain. Conversely, left TENS substantially reduced the neuropathic pain during stimulation, but had no effect on macrosomatognosia, indicating a double dissociation between the two disorders. These results reveal that facial macrosomatognosia may be regarded as a high-order deficit of somatosensory perception of the shape and volume of the face, which fits the definition of 'hyperschematia' (i.e., when the body takes up too much room) originally proposed by Bonnier (1905). Our data also indicate that CVS may favor the restoration of the conscious representation of the shape and size of the face. Overall, these findings lend support to the view that afferent inputs from the vestibular system can affect in a specific fashion the activity of cerebral structures involved in the building up and updating of the topological description of body parts.

Objective: Adaptation to prisms displacing the visual scene rightward is a therapeutic tool for left unilateral spatial neglect (USN). We aimed at comparing the effects of the classic adaptation procedure (repeated pointing toward visual targets, control treatment, C), with those of a novel adaptation method, involving ecological visuomotor activities (experimental treatment, E). Method: In 10 right-brain-damaged USN patients, each treatment was given for 1 week, with a crossover design, for a total of 20 sessions, twice per day. USN was assessed by cancellation, reading, and drawing tasks, and by a standardized scale. Neurological severity was assessed by the National Institutes of Health (NIH) stroke scale (Brott et al., 1989), disability by the Functional Independence Measure (FIM) scale. Results: The 2-week treatments (EC, CE) were equally effective, improving both USN, confirming previous reports (Frassinetti, Angeli, Meneghello, Avanzi, & Làdavas, 2002) and, importantly, disability. The improvement was independent of baseline performance, duration of disease, and neurological severity. Recovery took place after the first week, continued in the second week, and was stable at the follow-up of 3 months. The improvement of USN, measured by cancellation performance, and, in part, that of disability, measured through the FIM scale, were mediated by the size of the leftward aftereffects, suggesting a causal relationship between prism exposure and recovery. The E protocol was better tolerated. Conclusions: Daily life visuomotor activities, associated with prism exposure, are a useful tool for rehabilitating USN patients. This new treatment may widen the compliance with prism exposure treatments and their feasibility within home-based programs.

The Müller-Lyer figure is a powerful illusion in both vision and touch, although it is still unclear whether the visual and haptic illusory effects are due to modality-specific or shared processes. In order to investigate the hypothesis of a common underlying mechanism, the performance of 24 undergraduates in a manual bisection task of the Judd variant of the Müller-Lyer figure was assessed under visual, haptic, and visuo-haptic presentations (Experiment 1). In the bimodal condition participants saw the arrowheads on the front and touched the shaft on the back of a stimulus-supporting board. Illusory effects were comparable in touch and vision and were present, albeit reduced, in the bimodal visuo-haptic condition. In Experiment 2 we used the bimodal task of Experiment 1, manipulating the spatial position of the horizontal shaft on the backside of the board. The visual arrowheads affected haptic bisection, bringing about the illusory effects, only when the shaft was aligned with them. In conclusion, illusory effects transfer cross-modally from vision to haptics only in the presence of spatial coincidence, which appears to be a crucial factor for cross-modal integration. Implications for multisensory processes are discussed.

Sixteen patients with unilateral subcortical haemorrhagic or ischaemic stroke, confirmed by CT, were evaluated for the presence of aphasia and neglect. Compared with patients without neuropsychological deficits, left brain-damaged aphasic and right brain-damaged neglect patients showed a significantly greater reduction of cortical perfusion on N,N,N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1,3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerized tomography (SPECT). These results suggest that major cortical derangement is the crucial factor for the appearance of aphasia or neglect after a subcortical stroke. These remote effects, which are related to the size of the subcortical lesion, are interpreted in terms of interruption of neural connections (diaschisis).

Phonological processing and short-term memory were investigated in a patient with slowly progressive anarthria. The patient, who had an auditory-verbal span in the lower unimpaired range, showed preserved phonological similarity and word length effects with auditory presentation. These phonological effects of immediate retention were absent with visual input. The patient was also unable to perform phonological judgments on written verbal material. Under unattended speech interference her visual span improved, with an increase of visual confusion errors. In the light of a model including a main auditory-verbal storage component (the phonological short-term input store, STS), and a rehearsal process, that, after phonological recoding, conveys visually presented verbal material to the phonological STS, the patient's pattern of impairment is interpreted as a selective deficit in the process of phonological recoding. This prevents visual-verbal material from accessing the phonological STS, that is, therefore, insulated from visual inputs.

In everyday life, many diverse bits of information, simultaneously derived from the different sensory channels, converge into discrete brain areas, and are ultimately synthetized into unified percepts. Such a multisensory integration can dramatically alter the phenomenal experience of both environmental events and our own body. Crossmodal illusions are one intriguing product of multisensory integration. This review describes and discusses the main clinical applications of the most known crossmodal illusions in rehabilitation settings. We consider evidence highlighting the contribution of crossmodal illusions to restore, at least in part, defective mechanisms underlying a number of disorders of body representation related to pain, sensory, and motor impairments in neuropsychological and neurological diseases, and their use for improving neuroprosthetics. This line of research is enriching our understanding of the relationships between multisensory functions and the pathophysiological mechanisms at the basis of a number of brain disorders. The review illustrates the potential of crossmodal illusions for restoring disarranged spatial and body representations, and, in turn, different pathological symptoms.

Background and objectives Evidence of abnormal color vision processing in migraine comes from observation of positive symptoms during visual aura, effects of strong color contrast triggering attacks and of colored-spectacles reducing migraine frequency. Although the central or peripheral basis of such color misperception remains unclear, several authors reported a selective deficit of shortwavelength cones (S-cones) [1]. Sound-induced flash illusions (SIFI) are a simple way to describe visual distorsion induced by acoustic perception. SIFI critically depend on excitability of primary visual cortex (V1) as they are reduced by facilitatory anodal transcranial direct current stimulation (tDCS) over V1 in healthy subjects [2]. We observed diminished SIFI in episodic migraine patients, especially in those with aura (MA) and during the attack [3] in agreement with the hypothesis of visual cortex hyperexcitability. Aim of the present study was to explore the potential correlation between cones dysfunction (evaluated by colorimetric scales) and visual cortex hyperexcitability (tested by SIFI) in episodic migraine without aura patients (MoA). Materials and methods Twenty-two MoA patients (4 M; mean age 35.8±11.1 years) and 12 unimpaired healthy volunteers with no family history of migraine (9 M; mean age 27.7±13.2 years) were enrolled. Migraine patients were tested interictally. None of the patients enrolled had taken any prophylactic drug during the 3 months prior to the

The sound-induced flash illusions (SIFI) represent a valid tool to explore multimodal perception and are critically dependent on visual and acoustic cortical excitability [1, 2]. In a previous study [3], we observed a significant reduction of illusions in migraine patients with respect to healthy controls, probably due to a condition of visual cortex hyperexcitability. Aim of the present study was to evaluate SIFI perceptions in healthy women and patients with menstrual migraine and to describe the effects of cyclical change of steroid hormones and cortical responsiveness.

Perception of the external world is based on the integration of inputs from different sensory modalities. Recent experimental findings suggest that this phenomenon is present in lower-level cortical areas at early processing stages. The mechanisms underlying these early processes and the organization of the underlying circuitries are still a matter of debate. Here, we investigate audiovisual interactions by means of a simple neural network consisting of two layers of visual and auditory neurons. We suggest that the spatial and temporal aspects of audio-visual illusions can be explained within this simple framework, based on two main assumptions: auditory and visual neurons communicate via excitatory synapses; and spatio-temporal receptive fields are different in the two modalities, auditory processing exhibiting a higher temporal resolution, while visual processing a higher spatial acuity. With these assumptions, the model is able: i) to simulate the sound-induced flash fission illusion; ii) to reproduce psychometric curves assuming a random variability in some parameters; iii) to account for other audio-visual illusions, such as the sound-induced flash fusion and the ventriloquism illusions; and iv) to predict that visual and auditory stimuli are combined optimally in multisensory integration. In sum, the proposed model provides a unifying summary of spatio-temporal audio-visual interactions, being able to both account for a wide set of empirical findings, and be a framework for future experiments. In perspective, it may be used to understand the neural basis of Bayesian audio-visual inference. © 2014 Elsevier Inc.

In line bisection right-brain-damaged patients with left spatial neglect show a rightward deviation, with respect to the line's physical center. In word bisection ortho-phonological features of the stimulus' final (right-sided) part modulate performance of both patients and healthy participants (Veronelli, Vallar, Marinelli, Primativo, & Arduino, 2014). We investigated the role of linguistic factors in sentence bisection, in patients with and without neglect, and control participants. The effects of information in the right-sided part of the sentence (Experiment #1), and of lexical and syntactic violations (Experiment #2) were assessed. Neglect patients showed an overall rightward bias, larger than those of patients without neglect and controls. The neglect patients' bias was modulated by stimulus type, decreasing from lines, to letter strings and to all types of sentences. In sum, in visuo-manual sentence bisection a basic linguistic mechanism, such as sentence readability, brings about a more leftward appreciation of the stimulus, reducing the neglect patients' rightward bias. (C) 2014 Elsevier Inc. All rights reserved.

In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term "hyperschematia" for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with "hyperschematia" includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left "hyperschematia" involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal "hyperschematia"). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, "hypeschematia" is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings.

Right-brain-damaged patients with left unilateral spatial neglect typically set the mid-point of horizontal lines to the right of the objective center. By contrast, healthy participants exhibit a reversed bias (pseudoneglect). The same effect has been described also when bisecting orthographic strings. In particular, for this latter kind of stimulus, some recent studies have shown that visuo-perceptual characteristics, like stimulus length, may contribute to both the magnitude and the direction bias of the bisection performance (Arduino et al. in Neuropsychologia 48:2140-2146, 2010). Furthermore, word stress was shown to modulate reading performances in both healthy participants, and patients with left spatial neglect and neglect dyslexia (Cubelli and Beschin in Brain Lang 95:319-326, 2005; Rusconi et al. in Neuropsychology 18:135-140, 2004). In Experiment I, 22 right-brain-damaged patients (11 with left visuo-spatial neglect) and 11 matched neurologically unimpaired control participants were asked to set the subjective mid-point of word letter strings, and of lines of comparable length. Most patients exhibited an overall disproportionate rightward bias, sensitive to stimulus length, and similar for words and lines. Importantly, in individual patients, biases differed according to stimulus type (words vs. lines), indicating that at least partly different mechanisms may be involved. In Experiment II, the putative effects on the bisection bias of ortho-phonological information (i.e., word stress endings), arising from the non-neglected right hand side of the stimulus were investigated. The orthographic cue induced a rightward shift of the perceived mid-point in both patients and controls, with short words stressed on the antepenultimate final sequence inducing a smaller rightward deviation with respect to short words stressed on the penultimate final sequence. In conclusion, partly different mechanisms, including both visuo-spatial and lexical factors, may support line and word bisection performance of right-brain-damaged patients with left spatial neglect, and healthy participants.

Right-brain-damaged patients with unilateral spatial neglect are usually unaware (anosognosic) about their spatial deficits. However, in the scientific literature there is a lack of systematic and quantitative evaluation of this kind of unawareness, despite the negative impact of anosognosia on rehabilitation programs. This study investigated anosognosia for neglect-related impairments at different clinical tasks, by means of a quantitative assessment. Patients were tested in two different conditions (before and after execution of each task), in order to evaluate changes in the level of awareness of neglect-related behaviours triggered by task execution. Twenty-nine right-brain-damaged patients (17 with left spatial neglect) and 27 neurologically unimpaired controls entered the study. Anosognosia for spatial deficits is not pervasive, with different tasks evoking different degrees of awareness about neglect symptoms. Indeed, patients showed a largely preserved awareness about their performance in complex visuo-motor spatial and reading tasks; conversely, they were impaired in evaluating their spatial difficulties in line bisection and drawing from memory, showing over-estimation of their performance. The selectivity of the patients' unawareness of specific manifestations of spatial neglect is further supported by their preserved awareness of performance at a linguistic task, and by the absence of anosognosia for hemiplegia. This evidence indicates that discrete processes are involved in the aware monitoring of cognitive and motor performance, which can be selectively compromised by brain damage. Awareness of spatial difficulties is supported by a number of distinct components, and influenced by the specific skills required to perform a given task. (C) 2014 Elsevier Ltd. All rights reserved.

We studied the effects of transcutaneous electrical nerve stimulation (TENS) in six right-brain-damaged patients with left unilateral spatial neglect (USN), using both standard clinical tests (reading, line, and letter cancelation, and line bisection), and electrophysiological measures (steady-state visual-evoked potentials, SSVEP). TENS was applied on left neck muscles for 15', and measures were recorded before, immediately after, and 60' after stimulation. Behavioral results showed that the stimulation temporarily improved the deficit in all patients. In cancelation tasks, omissions and performance asymmetries between the two hand-sides were reduced, as well as the rightward deviation in line bisection. Before TENS, SSVEP average latency to stimuli displayed in the left visual half-field [LVF (160 ms)] was remarkably longer than to stimuli shown in the right visual half-field [RVF (120 ms)]. Immediately after TENS, latency to LVF stimuli was 130 ms; 1 h after stimulation the effect of TENS faded, with latency returning to baseline. TENS similarly affected also the latency SSVEP of 12 healthy participants, and their line bisection performance, with effects smaller in size. The present study, first, replicates evidence concerning the positive behavioral effects of TENS on the manifestations of left USN in right-brain-damaged patients; second, it shows putatively related electrophysiological effects on the SSVEP latency. These behavioral and novel electrophysiological results are discussed in terms of specific directional effects of left somatosensory stimulation on egocentric coordinates, which in USN patients are displaced toward the side of the cerebral lesion. Showing that visual-evoked potentials latency is modulated by proprioceptive stimulation, we provide electrophysiological evidence to the effect that TENS may improve some manifestations of USN, with implications for its rehabilitation.

This study assessed whether numerical magnitude affects the setting of basic spatial coordinates and reference frames, namely the subjective straight ahead. Three tasks were given to 24 right-handed healthy participants: a proprioceptive and a visuo-proprioceptive task, requiring pointing to the subjective straight ahead, and a visual task, requiring a perceptual judgment about the straight ahead position of a light moving left-to-right, or right-to-left. A control task, requiring the bisection of rods of different lengths, was also given. The four tasks were performed under conditions of passive auditory numerical (i.e., listening to small, “2”, and large, “8”, numbers), and neutral auditory-verbal (“blah”) stimulation. Numerical magnitude modulates the participants’ deviations in the visual straight ahead task, when the movement of the light is from left to right, with the small number bringing about a leftward deviation, the large number a rightward deviation. This result suggests that the spatial effects induced by the activation of the mental number line extend to an egocentric frame of reference. A similar directional modulation was found in the rod bisection task, in line with previous evidence. No effects of numerical magnitude were found on the proprioceptive and visuo-proprioceptive straight ahead tasks. These results suggest that the spatial effects induced by the activation of the mental number line extend to an egocentric frame of reference but only when a portion of horizontal space has to be “actively” explored.

Prism adaptation improves a wide range of manifestations of left spatial neglect in right-brain-damaged patients. The typical paradigm consists in repeated pointing movements to visual targets, while patients wear prism goggles that displace the visual scene rightwards. Recently, we demonstrated the efficacy of a novel adaptation procedure, involving a variety of every-day visuo-motor activities. This “ecological” procedure proved to be as effective as the repetitive pointing adaptation task in ameliorating symptoms of spatial neglect, and was better tolerated by patients. However, the absence of adaptation and aftereffects measures for the ecological treatment did not allow for a full comparison of the two procedures. This is important in the light of recent findings showing that the magnitude of prism-induced aftereffects may predict recovery from spatial neglect. Here, we investigated prism-induced adaptation and aftereffects after ecological and pointing adaptation procedures. Forty-eight neurologically healthy participants (young and aged groups) were exposed to rightward shifting prisms while they performed the ecological or the pointing procedures, in separate days. Before and after prism exposure, participants performed proprioceptive, visual, and visual-proprioceptive tasks to assess prism-induced aftereffects. Participants adapted to the prisms during both procedures. Importantly, the ecological procedure induced greater aftereffects in the proprioceptive task (for both the young and the aged groups) and in the visual-proprioceptive task (young group). A similar trend was found for the visual task in both groups. Finally, participants rated the ecological procedure as more pleasant, less monotonous, and more sustainable than the pointing procedure. These results qualify ecological visuo-motor activities as an effective prism-adaptation procedure, suitable for the rehabilitation of spatial neglect.

Brain imaging studies in humans have shown the existence of a shared somatosensory representation in the primary somatosensory cortex (S1), putatively involved in understanding others' sensations (Keysers et al., 2010); however, the role of S1 in such a high-level process is still unknown. To ascertain the causal involvement of S1, and its possible hemispheric lateralization, in encoding the affective valence of emotional scenes, depicting, or not, a tactile event, we gave to healthy participants a picture-based affective go/no-go task and low-frequency repetitive transcranial magnetic stimulation (rTMS). The dorsolateral prefrontal cortex (DLPFC) was chosen as control site. rTMS over the right, but not the left, S1 selectively increased the participants' latencies in the affective go/no-go task, but only when the affective state was conveyed by touch; intriguingly, this interfering effect was associated with the empathic ability to adopt the subjective perspective of others. The left, not the right, DLPFC is also involved in affective go/no-go performance, but regardless of the sight of touch, and independently of empathic abilities. This novel evidence demonstrates the crossmodal role of right S1 in encoding the pleasant and aversive consequences of others' sensations evoked by touch. © 2013 the authors.

Crossmodal illusions clearly show how perception, rather than being a modular and self-contained function, can be dramatically altered by interactions between senses. Here, we provide evidence for a novel crossmodal "physiological" illusion, showing that sounds can boost visual cortical responses in such a way to give rise to a striking illusory visual percept. In healthy participants, a single-pulse transcranial magnetic stimulation (sTMS) delivered to the occipital cortex evoked a visual percept, i.e., a phosphene. When sTMS is accompanied by two auditory beeps, the second beep induces in neurologically unimpaired participants the perception of an illusory second phosphene, namely the sound-induced phosphene illusion. This perceptual "fission" of a single phosphene, due to multiple beeps, is not matched by a "fusion" of double phosphenes due to a single beep, and it is characterized by an early auditory modulation of the TMS-induced visual responses (~80 ms). Multiple beeps also induce an illusory feeling of multiple TMS pulses on the participants' scalp, consistent with an audio-tactile fission illusion. In conclusion, an auditory stimulation may bring about a phenomenological change in the conscious visual experience produced by the transcranial stimulation of the occipital cortex, which reveals crossmodal binding mechanisms within early stages of visual processing. © 2013 Springer-Verlag Berlin Heidelberg.

Objective: Right-brain-damaged patients with left spatial neglect make perseveration errors in target cancellation tasks. A recent study (Ronchi, Posteraro, Fortis, Bricolo, & Vallar, 2009) showed that perseveration occurred more frequently in star than in letter cancellation, possibly due to different stimulus disposition. In this study we investigated the role of the spatial organization of targets (scattered vs. arranged) of the star and letter cancellation tasks in eliciting omission and perseveration errors; the role of impairments of divided attentional resources; and the lesion correlates of perseveration. Method: Thirty-three right-brain-damaged patients (27 with neglect, and six without neglect; 17 showing perseveration, 16 of them with spatial neglect) were given two versions of the star and letter cancellation tasks (with stimuli scattered or in rows), and a dual task. Results: A scattered target disposition increased omission and perseveration errors. Target type modulated differently omission and perseveration, with the former being more elicited by verbal targets, and the latter occurring more frequently in the star cancellation task, with scattered stimuli. Perseveration behavior was unrelated to deficits of divided attention, as assessed by the dual task. Lesion analysis indicated damage to the right insula as a neural correlate of perseveration. Conclusions: A display including nonverbal (star) and scattered targets brings about more perseveration errors. Target type and organization modulate in a different fashion omission and perseveration, suggesting the involvement of independent pathological mechanisms, which, however, do not implicate deficits of divided attention. The role of insular damage in motor perseveration in spatial neglect is discussed.

The representation of body parts holds a special status in the brain, due to their prototypical shape and the contribution of multisensory (visual and somatosensory-proprioceptive) information. In a previous study (Sposito et al., 2010), we showed that patients with left unilateral spatial neglect exhibit a rightward bias in setting the mid-point of their left forearm, which becomes larger when bisecting a cylindrical object comparable in size. This body part advantage, found also in control participants, suggests partly different processes for computing the extent of body parts and objects. In this study we tested 16 right-brain-damaged patients, and 10 unimpaired participants, on a manual bisection task of their own (real) left forearm, or a size-matched fake forearm. We then explored the effects of adaptation to rightward displacing prism exposure, which brings about leftward aftereffects. We found that all participants showed prism adaptation and aftereffects, with right-brain-damaged patients exhibiting a reduction of the rightward bias for both real and fake forearm, with no overall differences between them. Second, correlation analyses highlighted the role of visual and proprioceptive information for the metrics of body parts. Third, single-patient analyses showed dissociations between real and fake forearm bisections, and the effects of prism adaptation, as well as a more frequent impairment with fake body parts. In sum, the rightward bias shown by right-brain-damaged patients in bisecting body parts is reduced by prism exposure, as other components of the neglect syndrome; discrete spatial representations for real and fake body parts, for which visual and proprioceptive codes play different roles, are likely to exist. Multisensory information seems to render self bodily segments more resistant to the disruption brought about by right-hemisphere injury.

There is evidence that humans represent numbers in the form of a mental number line (MNL). Here we show that the MNL modulates the representation of visual and haptic space both in healthy individuals and right-brain-damaged patients, both with and without left unilateral spatial neglect (USN). Participants were asked to estimate the midpoint of visually or haptically explored rods while listening to task-irrelevant stimuli: a small digit ("2"), a large digit ("8"), or a non-numerical auditory stimulus ("blah"). In a control silent condition, the bisection error of USN patients was biased rightwards (namely, the marker of USN) only in the visual modality. Regardless of the direction of the bisection error committed in silent trials, listening to the small digit shifted the perceived midline leftwards, and listening to the large digit shifted the perceived midline rightwards, compared to a control condition in which a neutral syllable ("blah") was presented. The shift induced by listening to numbers occurred independently of the modality of response (i.e., both in vision and haptics), and in every group of participants. Interestingly, the effect of auditory numbers processing on space estimation was overall larger for haptically than for visually explored space in all participants. In conclusion, the present data show that listening to irrelevant numbers affects space perception also in patients with left USN, indicating that the spatial representation and attention processes disrupted by USN are not involved in these numerical magnitude-spatial effects.

This study explores whether brain polarization could be effective in modulating multisensory audiovisual interactions in the human brain, as measured by the 'sound-induced flash illusion' (Shams et al., 2000). In different sessions, healthy participants performed the task while receiving anodal, cathodal, or sham tDCS (2 mA, 8 min) to the occipital, temporal, or posterior parietal cortices. We found that up- or down-regulating cortical excitability by tDCS can facilitate or reduce audiovisual illusions, depending on the current polarity, the targeted area, and the illusory percept. Specifically, the perceptual 'fission' of a single flash, due to multiple beeps, was increased after anodal tDCS of the temporal cortex, and decreased after anodal stimulation of the occipital cortex. A reversal of such effects was induced by cathodal tDCS. Conversely, the perceptual 'fusion' of multiple flashes due to a single beep was unaffected by tDCS. This evidence adds novel clues on the cortical substrate of the generation of the sound-flash illusion, and opens new attractive possibilities for modulating multisensory perception in humans: tDCS appears to be an effective tool to modulate the conscious visual experience associated with multisensory interactions, by noninvasively shifting cortical excitability within occipital or temporal areas. (C) 2010 Elsevier Ltd. All rights reserved.

Numerical magnitude is believed to be represented along a mental number line (MNL), and there is evidence to suggest that the activation of the MNL affects the perception and representation of external space. In the present study, we investigated whether a spatial motor task affects numerical processing in the auditory modality. Blindfolded participants were presented with a numerical interval bisection task, while performing a tapping task with either their left or right hand, either in the fronto-central, fronto-left, or fronto-right peripersonal space. Results showed that tapping significantly influenced the participants' numerical bisection, with tapping in the left side of space increasing the original tendency to err leftward, and tapping to the right reducing such bias. Importantly, the effect depended on the side of space in which the tapping activity was performed, regardless of which hand was used. Tapping with either the left or right hand in the fronto-central space did not affect the participants' bias. These findings offer novel support for the existence of bidirectional interactions between external and internal representations of space. © 2010 Springer-Verlag.

Unilateral spatial neglect has been mainly investigated in the visual modality; only a few studies compared spatial neglect in different sensory modalities, and explored their multisensory interactions, with controversial results. We investigated the integration between vision and haptics, through a bisection task of a crossmodal length illusion, the Judd variant of the Müller-Lyer illusion. We examined right-brain-damaged patients with (n=7) and without (n=7) left unilateral spatial neglect, and neurologically unimpaired participants (n=14) in the bisection of Judd stimuli under visual, haptic, and visuo-haptic presentation. Neglect patients showed the characteristic rightward bias in the bisection of a baseline stimulus in the visual modality, but not in the haptic and visuo-haptic conditions. The illusory effects were preserved in each group and in each modality, indicating that the processing of the length illusion is independent of the presence of deficits of spatial attention and representation. Spatial neglect can be modality-specific, but visual and tactile sensory inputs are properly integrated.

The Müller-Lyer illusion occurs both in vision and in touch, and transfers cross-modally from vision to haptics [Mancini, F., Bricolo, E., & Vallar, G. Multisensory integration in the Müller-Lyer illusion: From vision to haptics. Quarterly Journal of Experimental Psychology, 63, 818–830, 2010]. Recent evidence suggests that the neural underpinnings of the Müller-Lyer illusion in the visual modality involve the bilateral lateral occipital complex (LOC) and right superior parietal cortex (SPC). Conversely, the neural correlates of the haptic and cross-modal illusions have never been investigated previously. Here we used repetitive TMS (rTMS) to address the causal role of the regions activated by the visual illusion in the generation of the visual, haptic, and cross-modal visuo-haptic illusory effects, investigating putative modality-specific versus cross-modal underlying processes. rTMS was administered to the right and the left hemisphere, over occipito-temporal cortex or SPC. rTMS over left and right occipito-temporal cortex impaired both unisensory (visual, haptic) and cross-modal processing of the illusion in a similar fashion. Conversely, rTMS interference over left and right SPC did not affect the illusion in any modality. These results demonstrate the causal involvement of bilateral occipito-temporal cortex in the representation of the visual, haptic, and cross-modal Müller-Lyer illusion, in favor of the hypothesis of shared underlying processes. This indicates that occipito-temporal cortex plays a cross-modal role in perception both of illusory and nonillusory shapes.

Body parts are represented in the brain in a very specific fashion, as compared to other three-dimensional objects, with reference to their prototypic shape and multisensory coding. However, evidence is lacking about the spatial representation of body parts. To address this issue, in Experiment 1 we first compared the metric representation of body parts and of non-bodily objects in 14 right-brain-damaged patients with left unilateral spatial neglect (USN), and in 14 neurologically unimpaired control participants. Participants bisected, by manual pointing, a three-dimensional object, or their own left forearm. Patients showed the well-known ipsilesional rightward displacement of the subjective midpoint, in both forearm and solid bisection. Both USN patients and control participants were overall more accurate in the bisection of their own forearm, relative to the extracorporeal object. In four patients this advantage of the forearm was significant in a single-case analysis, while two patients showed the opposite dissociation, being more accurate with the solid object. In Experiment 2 neurologically unimpaired participants were more accurate in the bisection of a fake forearm, as well as of their own forearm, as compared to the extrapersonal object. Overall, the results indicate that the representation of the metric of the body is more reliable than that of extrapersonal objects, and also more resistant to the disruption of spatial representations brought about by USN, possibly due to the prototypical shape of body parts. Furthermore, the double dissociation found in USN patients suggests that the metrics of body parts and of extrapersonal objects are supported by independent spatial processes.

Neglect dyslexia (ND) is reviewed, based on published single-patient and group studies. ND is frequently associated with right hemispheric damage and unilateral spatial neglect (USN), and typically involves the left side of the letter string. Left-brain-damaged patients showing ND, ipsilateral (left) or contralateral (right) to the side of the left-sided hemispheric lesion, have also been reported, as well as a few patients with bilateral damage, with more frequently left than right ND. As USN, ND is temporarily ameliorated by lateralized stimulations (vestibular caloric, visual prism adaptation). ND may occur independent of USN, suggesting the damage to specific visuospatial representational/attentional systems, supporting reading. ND errors comprise omission, substitution, and, less frequently, addition of letters on one side of the stimulus, resulting in words or nonwords, also with reference to the stimulus' linguistic features. Patients with ND may show preserved lexical-morphological effects and implicit processing, up to the semantic level, of the misread string. This preserved processing is a feature of ND, shared with the USN syndrome. The mechanisms modulating error type and lexical-morphological effects are partly independent of each other. Different levels of representation of the letter string may be affected, giving rise to egocentric, stimulus-centred, and word-centred patterns of impairment. The anatomical correlates of ND include the temporo-parieto-occipital regions. © 2010 Springer-Verlag.

One possible pathological mechanism underlying the rightward bisection error of right-brain-damaged patients with left spatial neglect is a leftward relaxation of the spatial representational medium. This view was originally based on the finding that patients with left neglect, required to extend horizontal segments, in order to double their original length, may exhibit a relative left overextension of the drawn lines (Bisiach et al., 1994). We investigated this putative distortion of representational space using a 16 cm ‘line segmentation’ task (Experiment 1). Were the representation of space relaxed contralesionally, a progressive increase from right to left of the size of the drawn segments would be expected. Right-brain-damaged patients with left unilateral neglect (N=12) performed the segmentation task with no left versus right differences, as right-brain-damaged patients without neglect (N=8), and neurologically unimpaired control subjects (N=10), did. Experiments 2 and 3 explored the effects of sample length (1, 2, 4, and 8 cm), by which the 16 cm lines had to be segmented. Neglect patients produced longer left-sided segments only for the 8 cm sample (i.e. half of the length of the segment). This set of experiments suggests an impairment in the segmentation task only with the larger (8 cm) sample, when a more global level of processing may be involved. Experiment 4 assessed this hypothesis by a ‘part/whole’ bisection task, using 8 cm lines, presented either embedded in a longer 16 cm line or in isolation. Neglect patients made a larger rightward bisection error when the segment was not embedded. The suggestion is made that the lateral distortion of the representation of space in neglect patients (i.e. a leftward relaxation of the spatial medium) concerns tasks where a more ‘global’ representation of the visual stimulus has to be set up. The different demands of the segmentation and bisection tasks are discussed.

Vocabulary acquisition is such a major aspect of language learning in children, but also in adults when learning a foreign language, that a dedicated vocabulary learning device may exist within the language organ. To identify the relevant brain systems, we performed regional cerebral blood flow measurements in normal subjects while they were learning a list of neologisms or a list of word–nonword pairs. Structures implicated in phonological short-term memory (Broca's area, left temporo-parietal junction) were steadily activated during nonwords learning, while the left temporal lobe neocortical and paralimbic structures (parahippocampal region), associated with long-term memory, contributed to learning in a time-dependent manner, with maximal activation at the beginning of the process. The neural system specifically activated when learning new vocabulary was strongly lateralized to the left hemisphere. This evidence refines current models of memory function and supports theories which emphasise the importance of phonological competence in hemispheric dominance for language.

A review of published brain-damaged patients showing delusional beliefs concerning the contralesional side of the body (somatoparaphrenia) is presented. Somatoparaphrenia has been reported, with a few exceptions, in right-brain-damaged patients, with motor and somatosensory deficits, and the syndrome of unilateral spatial neglect. Somatoparaphrenia, most often characterized by a delusion of disownership of left-sided body parts, may however occur without associated anosognosia for motor deficits, and personal neglect. Also somatosensory deficits may not be a core pathological mechanism of somatoparaphrenia, and visual field disorders may be absent. Deficits of proprioception, however, may play a relevant role. Somatoparaphrenia is often brought about by extensive right-sided lesions, but patients with posterior (parietal-temporal), and insular damage are on record, as well as a few patients with subcortical lesions. Possible pathological factors include a deranged representation of the body concerned with ownership, mainly right-hemisphere-based, and deficits of multisensory integration. Finally, the rubber hand illusion, that brings about a bodily misattribution in neurologically unimpaired participants, as somatoparaphrenia does in brain-damaged patients, is briefly discussed.

In recent years, a growing amount of evidence concerning the relationships between numerical and spatial representations has been interpreted, by and large, in favour of the mental number line hypothesis—namely, the analogue continuum where numbers are spatially represented (Dehaene, 1992; Dehaene, Piazza, Pinel, & Cohen, 2003). This numerical representation is considered the core of number meaning and, accordingly, needs to be accessed whenever numbers are semantically processed. The present study explored, by means of a length reproduction task, whether besides the activation of lateralized spatial codes, numerical processing modulates the mental representation of a horizontal spatial extension. Mis-estimations of length induced by Arabic numbers are interpreted in terms of a cognitive illusion, according to which the elaboration of magnitude information brings about an expansion or compression of the mental representation of spatial extension. These results support the hypothesis that visuo-spatial resources are involved in the representation of numerical magnitude.

Perseveration in target cancellation tasks and in drawing by copy and from memory was investigated in 21 right-brain-damaged patients, seven with no evidence of left visuo-spatial neglect, and 14 with neglect. Eight such neglect patients showed perseveration in both cancellation and drawing tasks, although no correlation was found with the severity of neglect. Patients with perseveration were not disproportionately impaired in tasks assessing executive (fluency, Stroop colour-word interference, and Weigl's sorting test), and visuo-spatial short-term memory function. In the context of a two-component hypothesis, graphic perseveration (the first component) is a specific disorder that manifests in a variety of tasks, particularly those requiring serial graphic production. Unilateral spatial neglect (the second component) may trigger and facilitate the production of perseveration errors, with a contra-ipsilateral gradient of increasing severity.

The present study investigated the effects of the duration of the stimulus on the reading performance of right-brain-damaged patients with left neglect dyslexia. Three Italian patients read aloud words and nonwords, under conditions of unlimited time of stimulus exposure and of timed presentation. In the untimed condition, the majority of the patients' errors involved the left side of the letter string (i.e., neglect dyslexia errors). Conversely, in the timed condition, although the overall level of performance decreased, errors were more evenly distributed across the whole letter string (i.e., visual - nonlateralized - errors). This reduction of neglect errors with a reduced time of presentation of the stimulus may reflect the read out of elements of the letter string from a preserved visual storage component, such as iconic memory. Conversely, a time-unlimited presentation of the stimulus may bring about the rightward bias that characterizes the performance of neglect patients, possibly by a capture of the patients' attention by the final (rightward) letters of the string. (c) 2005 Elsevier Ltd. All rights reserved.