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Background Working memory (WM) abilities are frequently impaired in neurological disorders affecting fronto-parietal cortical/sub-cortical structures. WM deficits negatively influence interventional outcomes and everyday functioning. This study thus aimed at the following: (a) developing and standardizing an ecologically valid task for WM assessment ( Ice Cream Test, ICT); (b) validating and norming a novel WM test (Digit Ordering Test, DOT), as well as providing updated norms for digit span (DS) tasks, in an Italian population sample; (c) introducing a novel scoring procedure for measuring WM. Methods One-hundred and sixty-eight Italian healthy participants—73 male, 95 females; age: 48.4 ± 19.1 (18–86); education: 12.1 ± 4.8 (4–21)—underwent a thorough WM assessment—DOT, ICT, and both forward and backward DS tasks (FDS, BDS). The ICT requires participants to act as waiters who have to keep track of customers’ orders. For each task, WM and total (T) outcomes were computed, i.e., the number of elements in the longest sequence and that of recalled sequences, respectively. Norms were derived via the equivalent score (ES) method. Results DS ratios (DSRs) were computed for both WM/S and T outcomes on raw DS measures (BDS divided by FDS). Age and education significantly predicted all WM tasks; sex affected FDS and DSR-T scores (males > females). WM measures were highly internally related. Discussion The present work provides Italian practitioners with a normatively updated, multi-component, adaptive battery for WM assessment (WoMAB) as well as with novel outcomes which capture different WM facets—WM capacity and attentive monitoring abilities.

The benefits of mindfulness meditation among clinical and non-clinical populations have been largely reported in literature. Existing mindfulness-based programs are particularly useful in targeting specific populations while researchers have pointed out the possibility of developing programs adapted to the audience and the context. In this two-groups pre-post experimental design we developed a mindfulness-based social intervention program to target individuals from the general population. Here we present a two-groups pre-post experimental design to investigate its effectiveness on participants&rsquo, psychological functioning assessed by eight self-reported questionnaires (CORE-OM, FFMQ, SWLS, PANAS, PSS, SCS, WEMWBS, SHS) which encompass different domains of well-being, mindfulness and emotional functioning. Participants, recruited on voluntary basis, were randomly allocated to treated or passive control groups and were aware of group allocation. The intervention comprises a 12-week meditation training in a big group that represents the social aspect of meditation. Data were analysed via a linear mixed effect model and intention to treat. Statistically significant results were obtained for global score of CORE-OM (&beta, = &minus, 0.20 [&minus, 0.30, &minus, 0.10], p = 0.0002), FFMQ (&beta, = 0.20 [0.12, 0.28], p &lt, 0.0001), SWLS (&beta, = 1.43 [0.42, 2.45], p = 0.006), positive PANAS (&beta, = 1.99 [0.95, 3.04], p = 0.0002), negative PANAS (&beta, 1.67 [&minus, 2.92, 0.43], p = 0.009), PSS (&beta, 2.98 [&minus, 4.25, 1.71], p &lt, 0.0001), WEMWBS (&beta, = 4.38 [2.93, 5.83], p &lt, 0.0001) and SHS (&beta, 2.45], p = 0.006). Our intervention is causally associated with an improvement of the psychological functioning and hence can be considered as a preventive measure that may potentially reduce the risk of developing psychological problems and improve the subject&rsquo, s general well-being. Given the voluntary recruitment, our inference only applies to those individuals who have decided to experience meditation as a way to well-being and not to a random person from the general population.

There are few things as irrefutable as the evidence that our limbs belong to us. However, persons with body integrity dysphoria (BID) [1] deny the ownership of one of their fully functional limbs and seek its amputation [2]. We tapped into the brain mechanisms of BID, examining sixteen men desiring the removal of the left healthy leg. The primary sensorimotor area of the to-be-removed leg and the core area of the conscious representation of body size and shape (the right superior parietal lobule [rSPL]) [3, 4] were less functionally connected to the rest of the brain. Furthermore, the left premotor cortex, reportedly involved in the multisensory integration of limb information [5-7], and the rSPL were atrophic. The more atrophic the rSPL, the stronger the desire for amputation, and the more an individual pretended to be an amputee by using wheelchairs or crutches to solve the mismatch between the desired and actual body. Our findings illustrate the pivotal role of the connectivity of the primary sensorimotor limb area in the mediation of the feeling of body ownership. They also delineate the morphometric and functional alterations in areas of higher-order body representation possibly responsible for the dissatisfaction with a standard body configuration. The neural correlates of BID may foster the understanding of other neuropsychiatric disorders involving the bodily self. Ultimately, they may help us understand what most of us take for granted, i.e., the experience of body and self as a seamless unity.

The sense of body ownership is a fundamental feature that refers to the ability to recognize our body as our own, allowing us to interact properly with the outside world. Usually, it is explored by means of the Rubber Hand Illusion (RHI) during which a dummy hand is incorporated in the mental representation of one's own body throughout a multisensory (visuo-tactile) integration mechanism. Particular attention has been paid to the neurofunctional counterparts of this mechanism highlighting the pivotal role of an occipito-parieto-frontal network involving the Ventral Premotor area (PMv). To date, the specific role of the PMv in generating the sense of ownership is still unknown. In this study, we aimed at exploring the role of PMv in generating and experiencing the RHI. Off-line repetitive Transcranial Magnetic Stimulation (rTMS) was applied to a group of 24 healthy participants whilst changes in proprioceptive judgment and self-reported illusion sensations were collected and analysed separately. The PMv was not directly implicated in generating the sense of ownership. Indeed, its inhibition affected the explicit detection of the visuo-tactile congruence without interfering with the illusion experience itself. We hypothesized that the conscious visuo-tactile congruence detection may be independent from the conscious illusion experience. Also, our results support the view that the RHI grounds on a complex interaction between bottom-up and top-down processes, as the visuo-tactile integration per se may be not sufficient to trigger the subjective illusion.

Spinal cord injury can cause cognitive impairments even when no cerebral lesion is appreciable. As patients are forced to explore the environment in a non-canonical position (i.e., seated on a wheelchair), a modified relation with space can explain motor-related cognitive differences compared to non-injured individuals. Peripersonal space is encoded in motor terms, that is, in relation to the representation of action abilities and is strictly related to the affordance of reachability. In turn, affordances, the action possibilities suggested by relevant properties of the environment, are related to the perceiver's peripersonal space and motor abilities. One might suppose that these motor-related cognitive abilities are compromised when an individual loses the ability to move. We shed light on this issue in 10 patients with paraplegia and 20 matched controls. All have been administered an affordances-related reachability judgement task adapted from Costantini, Ambrosini, Tieri, Sinigaglia, and Committeri (2010, Experimental Brain Research, 207, 95) and neuropsychological tests. Our findings demonstrate that patients and controls show the same level of accuracy in estimating the location of their peripersonal space boundaries, but only controls show the typical overestimation of reaching range. Secondly, patients show a higher variability in their judgements than controls. Importantly, this finding is related to the patients' ability to perform everyday tasks. Finally, patients are not faster in making their judgements on reachability in peripersonal space, while controls are. Our results suggest that not moving freely or as usual in the environment impact decoding of action-related properties even when the upper limbs are not compromised.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading.

Proprioception acquires a crucial role in estimating the configuration of our body segments in space when visual information is not available. Proprioceptive accuracy is assessed by asking participants to match the perceived position of an unseen body landmark through reaching movements. This task was also adopted to study the perceived hand structure by computing the relative distances between averaged proprioceptive judgments (hand Localization Task). However, the pattern of proprioceptive errors leading to the misperceived hand structure is unexplored. Here, we aimed to characterize this pattern across different hand landmarks, having different anatomo-physiological properties and cortical representations. Furthermore, we sought to describe the error consistency and its stability over time. To this purpose, we analyzed the proprioceptive errors of 43 healthy participants during the hand Localization Task. We found larger but more consistent errors for the fingertips compared to the knuckles, possibly due to poorer proprioceptive signal, compensated by other sources of spatial information. Furthermore, we found a shift (overlap effect) and a temporal drift of the hand perceived position towards the shoulder of origin, which was consistent within and between subjects. The overlap effect had a greater influence on lateral compared to medial landmarks, leading to the hand width overestimation. Our results are compatible with domain-general and body-specific spatial biases affecting the proprioceptive localization of the hand landmarks, thus the apparent hand structure misperception.

Background and purpose: The number of people suffering from stroke is strongly increasing, giving rise to multiple cognitive deficits which frequently prevent a full recovery. The identification of both spared and impaired cognitive domains has a key role to plan adequate interventions. However, the existing standard tests are either too expensive in terms of time and efforts for patients in acute stage or they derived from instruments addressing different pathologies such as dementia. Methods: We developed a brief neuropsychological battery (mental performance in acute stroke, MEPS) to assess different cognitive domains (language, memory, praxis, visual perception) in acute stroke patients. MEPS was validated by enrolling a sample of 204 patients suffering from stroke in acute stage, and 263 healthy controls participants. Results: The results indicated an adequate construct validity and a high ability in discriminating patients from healthy controls. Conclusions: MEPS can be considered a simple and highly valuable bedside battery, easy to administer, with values of sensitivity and specificity suitable to be proposed as a screening tool for patients with acute stroke.

Distorted representations of the body are observed in healthy individuals as well as in neurological and psychiatric disorders. Distortions of the body model have been attributed to the somatotopic cerebral representation. Recently, it has been demonstrated that visual biases also contribute to those distortions. To better understand the sources of such distortions, we compared the metric representations across five body parts affording different degrees of tactile sensitivity and visual accessibility. We evaluated their perceived dimensions using a Line Length Judgment task. We found that most body parts were underestimated in their dimensions. The estimation error relative to their length was predicted by their tactile acuity, supporting the influence of the cortical somatotopy on the body model. However, tactile acuity did not explain the distortions observed for the width. Visual accessibility in turn does appear to mediate body distortions, as we observed that the dimensions of the dorsal portion of the neck were the only ones accurately perceived. Coherent with the multisensory nature of body representations, we argue that the perceived dimensions of body parts are estimated by integrating visual and somatosensory information, each weighted differently, based on their availability for a given body part and a given spatial dimension.

Scientific evidence plays an important role in the therapeutic decision-making process. What happens when physicians are forced to make therapeutic decisions under uncertainty? The absence of scientific guidelines at the beginning of a pandemic due to an unknown virus, such as COVID-19, could influence the perceived legitimacy of the application of non-evidence-based therapeutic approaches. This paper reports on a test of this hypothesis, in which we administered an ad hoc questionnaire to a sample of 64 Italian physicians during the first wave of the COVID-19 pandemic in Italy (April 2020). The questionnaire statements regarding the legitimacy of off-label or experimental drugs were framed according to three different scenarios (Normality, Emergency and COVID-19). Furthermore, as the perception of internal bodily sensations (i.e., interoception) modulates the decision-making process, we tested participants’ interoceptive sensibility using the Multidimensional Assessment of Interoceptive Awareness (MAIA). The results showed that participants were more inclined to legitimate non-evidence-based therapeutic approaches in the COVID-19 and Emergency scenarios than the Normality scenario. We also found that scores on the MAIA Trusting subscale positively predicted this difference. Our findings demonstrate that uncertain medical scenarios, involving a dramatic increase in patient volume and acuity, can increase risk-taking in therapeutic decision-making. Furthermore, individual characteristics of health care providers, such as interoceptive ability, should be taken into account when constructing models to prevent the breakdown of healthcare systems in cases of severe emergency.

It is largely recognized that the mesial temporal lobe and its substructure support declarative long-term memory (LTM). So far, different theories have been suggested, and the organization of declarative verbal LTM in the brain is still a matter of debate. In the current study, we retrospectively selected 151 right-handed patients with temporal lobe epilepsy with and without hippocampal sclerosis, with a homogeneous (seizure-free) clinical outcome. We analyzed verbal memory performance within a normalized scores context, by means of prose recall and word paired-associate learning tasks. Patients were tested at presurgical baseline, 6months, 2 and 5years after anteromesial temporal lobe surgery, using parallel versions of the neuropsychological tests. Our main finding revealed a key involvement of the left temporal lobe and, in particular, of the left hippocampus in prose recall rather than word paired-associate task. We also confirmed that shorter duration of epilepsy, younger age, and withdrawal of antiepileptic drugs would predict a better memory outcome. When individual memory performance was taken into account, data showed that females affected by left temporal lobe epilepsy for longer duration were more at risk of presenting a clinically pathologic LTM at 5years after surgery. Taken together, these findings shed new light on verbal declarative memory in the mesial temporal lobe and on the behavioral signature of the functional reorganization after the surgical treatment of temporal lobe epilepsy.

A pediatric cognitive screening tool has been shaped in three versions according to school class to assess spatial and temporal orientation, language, reading, writing, drawing, number knowledge, memory, praxis and executive functions in children aged 6-13. It has been standardized on an Italian sample of 807 children. Raw scores were adjusted for critical variables (child's age and parents' education) and a cut-off for the resulting global cognitive score was made available for clinical practice. In line with previous research, adapting the Mini-Mental State Examination to pediatric neuropsychological assessment turned out to be useful in estimating global cognitive functioning in children.

To retrospectively analyse a single-centre consecutive surgical series of patients with temporal lobe epilepsy (TLE) and negative MRI. To identify factors associated with postoperative seizure outcome among several presurgical, surgical and postsurgical variables. Clinical records of 866 patients who received temporal lobe resections and with a minimum follow-up of 12 months were retrospectively searched for MRI-negative cases. Anamnestic, clinical, neurophysiological, surgical, histopathological and postsurgical data were collected. Seizure outcome was categorised as favourable (Engel’s class I) and unfavourable (Engel’s classes II–IV). Uni- and multivariate statistical analysis was performed to identify variables having a significant association with seizure outcome. Forty-eight patients matched the inclusion criteria. 26 (54.1%) patients required invasive EEG evaluation with Stereo-electro-encephalography (SEEG) before surgery. Histological evaluation was unremarkable in 34 cases (70.8%), revealed focal cortical dysplasias in 13 cases and hippocampal sclerosis in 2. 28 (58.3%) patients were in Engel’s class I after a mean follow-up of 82 months (SD ± 74; range 12–252). Multivariate analysis indicated auditory aura, contralateral diffusion of the discharge at Video-EEG monitoring and use of 18F-FDG PET as variables independently associated with seizure outcome. Carefully selected patients with MRI-negative TLE can be good candidates for surgery. Surgery should be considered with caution in patients with clinical features of neocortical seizure onset and contralateral propagation of the discharge. Use of 18F-FDG PET may be helpful to improve SEEG and surgical strategies. The presented data help in optimising the selection of patients with MRI-negative TLE with good chances to benefit from surgery.

In everyday life, we continuously make decisions, assuming the risk by making choices on material possessions or our body. Bodily signals may support the decision-making process, informing us about possible outcomes. Sensibility for such internal bodily changes influences the way we perceive the environment, and it can boost the body-related stimuli processing. Thus, the question arises of whether the individual sensibility to interoceptive signals modulates decision-making in the presence of biological stimuli. To test this hypothesis, we administered 50 healthy subjects with the Balloon Analogue Risk Task, in which participants were required to inflate a virtual balloon, and a modified version of it, in which they inflated a virtual body. We found that interoceptive sensibility predicted risk-taking behaviour only in the presence of body-related stimuli. Our results provided new evidence on the role of interoceptive sensibility in complex cognitive functions, such as risk-taking behaviour, which impacts the way we act within our society.

The vestibular system plays a pivotal role in behavioural and physiological aspects of body representation. If on the one hand, the stimulation of the vestibular system in healthy subjects provokes body representation distortions, accompanied by a decrease of body temperature, on the other hand, in brain-damaged patients it transiently restores body representation disorders. So far, the physiological counterpart of such behavioural amelioration on patients has never been explored. Here we aimed at investigating body temperature variations following Caloric Vestibular Stimulation (CVS), in a patient affected by somatoparaphrenia who regained the sense of body part ownership after the stimulation. Results showed an increase in body temperature after CVS, which also correlated with the temporary restored sense of limb ownership. Our results support the idea that physiological signals are fundamental to maintain a coherent mental representation of the body.

In adult patients, Spinal Cord Injury (SCI) may influence the mental Body Representation (BR). Currently, there is no evidence on the modulation of SCI on BR during early stages of cognitive development. Here, we investigated BR in a 3-year-old child with complete SCI. The patient was administered with a specific battery assessing different BR components. We found evidence for putative classical neuropsychological dissociation between a preserved topological map with impaired semantic knowledge of the body. This finding sheds new light on the impact of SCI on BR in childhood, as well as on the level of interdependence between BR’s components..

The internal models of our body dimensions are prone to bias, but little evidence exists to explain how the motor system achieves fine-grained control despite these distortions. Previous work showed that the hand representation, assessed in a dynamic task (Proprioceptive Matching Task), was less distorted compared to that measured through a static body representation task (Localization Task), suggesting that either the hand representation was updated or the motor trajectory was adjusted during movement. The present study set out to shed light on this phenomenon by administering the Localization Task before and after either the Proprioceptive Matching Task or a control condition in a within-subjects design. Our results showed that hand map biases decreased during the Proprioceptive Matching Task, but that this increase in accuracy did not carry over to the Localization Task. In other words, more accurate performance in the dynamic body representation task does not reflect a change in how the hand is represented. Rather, it likely reflects a refinement of the motor trajectory, due to the integration of multisensory information, providing interesting insights into how the motor system partially overcomes biases in body representations.

Objectives: To estimate the frequency of prolonged grief disorder (PGD) in 90 primary caregivers of patients with dementia who live in the community dwelling in Milan and to identify the relationship between grief intensity (GI) and other caregiver variables; another aim was to clarify the role of the objective cognitive and functional impairment of the patients and the level of deterioration perceived by caregivers. Design: Cross-sectional study. Results: In all, 16.7% of caregivers had PGD. Caregiver variables increasing GI and the risk of developing PGD were burden, anxiety, and some sociodemographic features. The objective level of patient’s deterioration was irrelevant for PGD probability/GI, while the deterioration level perceived by the caregiver increased PGD probability and GI. Conclusions: Caregivers of patients with dementia may experience grief symptoms that are associated with low educational level, high level of burden and anxiety, and high perceived deterioration of their demented relatives’ cognitive and functional abilities.

Right brain damaged patients sometimes deny that their left arm is paralysed or even claim to have just moved it. This condition is known as anosognosia for hemiplegia (AHP). Here, we used fMRI to study patients with and without AHP during the execution of a motor task. We found that the delusional belief of having moved was preceded by brain activation of the cortical regions that are implicated in motor control in the left intact hemisphere and in the spared motor regions of the right hemisphere; patients without anosognosia did not present with the same degree of activation. We conclude that the false belief of movement is associated with a combination of strategically placed brain lesions and the preceding residual neural activity of the fronto-parietal motor network. These findings provide evidence that the activity of motor cortices contributes to our beliefs about the state of our motor system.

Highlights • Left anodal galvanic vestibular stimulation increased tactile sensitivity. • No effects induced by sham stimulation or right anodal galvanic vestibular stimulation. • Even brief (100 ms) pulses of vestibular stimulation enhanced somatosensory detection. • Vestibular projections in the right hemisphere modulates somatosensory processing., The vestibular system has widespread interactions with other sensory modalities. Here we investigate whether vestibular stimulation modulates somatosensory function, by assessing the ability to detect faint tactile stimuli to the fingertips of the left and right hand with or without galvanic vestibular stimulation (GVS). We found that left anodal and right cathodal GVS, significantly enhanced sensitivity to mild shocks on either hand, without affecting response bias. There was no such effect with either right anodal and left cathodal GVS or sham stimulation. Further, the enhancement of somatosensory sensitivity following GVS does not strongly depend on the duration of GVS, or the interval between GVS and tactile stimulation. Vestibular inputs reach the somatosensory cortex, increasing the sensitivity of perceptual circuitry.

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by the progressive atrophy of both the first and the second motor neurons. Although the cognitive profile of ALS patients has already been defined by the occurrence of language dysfunctions and frontal deficit symptoms, it is less clear whether the degeneration of upper and lower motor neurons affects motor imagery abilities. Here, we directly investigated motor imagery in ALS patients by means of an established task that allows to examine the presence of the effects of the biomechanical constraints. Twenty-three ALS patients and 23 neurologically unimpaired participants have been administered with the (1) hand laterality task (HLT) in which participants were asked to judge the laterality of a rotated hand and the (2) mirror letter discrimination task (MLD) in which participants were asked to judge whether a rotated alphanumeric character was in its canonical or mirror-reversed form (i.e. control task). Results show that patients present the same pattern of performance as unimpaired participants at the MLD, while at the HLT, they present only partially with the effects of biomechanical constraints. Taken together, our findings provide evidences that motor imagery abilities, related to the mental simulation of an action, are affected by this progressive disease.

The vestibular system processes information about head movement and orientation. No unimodal vestibular cortex has been identified in the mammalian brain. Rather, vestibular inputs are combined with many other sensory signals in the cortex. This arrangement suggests that vestibular input could influence processing in other sensory modalities. Here we show that vestibular stimulation differentially modulates two submodalities of the somatosensory system, increasing sensitivity to tactile input, and independently reducing sensitivity to nociceptive input. These modulations of touch and pain can clearly be distinguished from supramodal attentional effects of vestibular stimulation, because they are bilateral and operate in different directions. Outside the artificial conditions of laboratory stimulation, the vestibular system codes movements of the head, indicating a new relation between the body and the external world. We suggest the vestibular system participates in a form of sensory signal management, changing the balance between the various sensory systems as the relation between the body and the external environment changes. This sensory rebalancing may be a crucial element in the brain's capacity to reorient towards novel or salient features in the environment.

We describe the clinical manifestations and the lesion patterns of five patients with somatoparaphrenia, the denial of ownership for a paralyzed limb, who showed the rare dissociation from anosognosia for hemiplegia. Similar cases have been only occasionally cited in the literature with scanty descriptions of their symptoms and no detailed anatomical assessment. All patients had extrapersonal and at least mild personal neglect. The lesions pattern was mainly subcortical, with a significant involvement of the right thalamus, the basal ganglia and the internal capsule. A formal comparison between the anatomical pattern previously associated with anosognosia in a study performed in 2005 by Berti and colleagues, and the lesion distribution of each patient clearly shows that our pure somatoparaphrenic patients had a sparing of most of the regions associated with anosognosia for hemiplegia. The behavioral dissociation between SP and anosognosia for hemiplegia, together with this new anatomical evidence, suggests that motor awareness is not sufficient to build up a sense of ownership and therefore these two cognitive abilities are at least in part functionally independent and qualitatively different.

Surgery is an effective treatment for drug resistant focal epilepsy. Predictors of seizure outcome have been extensively addressed in the general population but similar data on older patients are still lacking. The aim of this study is to evaluate effectiveness and safety of surgery for patients over 50 years and to investigate variables associated to seizure outcome.We performed a single center retrospective study including 50 patients over 50 years treated surgically for drug resistant focal epilepsy between 1997 and 2014. We analyzed the rate of success of seizure control, the association of several clinical variables with seizure outcome and the rate of surgery-related complications. We also investigated the impact of surgery on the patients' cognitive performances and mood profile.At last follow-up 78% of our patients were seizure-free, similar to patients younger than 50 years operated on in the same period (p=1). The rate of surgery-related complications was 10%, higher compared to younger patients (p0.0001). Pre-surgical daily seizure frequency (p=0.0040) and the histological diagnosis of LEAT (p=0.0233) were associated to a poorer seizure outcome. No significant differences were evidenced between pre- and postoperative neuropsychological profiles. A slight, not statistically significant improvement of the mood profile was observed postoperatively.Our results suggest that surgery is an effective treatment option also for older epileptic patients, although it is burdened by a higher surgical risk as compared to younger patients. The availability of predictors of outcome also for these patients may be helpful for pre-surgical counseling.

Neuropsychological assessment is critical in both diagnosis and prognosis of patients with epilepsy. Beyond electrophysiological and anatomical alterations, other factors including different ethnic-cultural and linguistic backgrounds might affect neuropsychological performance. Only a few studies considered migration and acculturation effects and they typically concerned nonclinical samples. The current study aimed at investigating the influence of ethnic background and time spent in Italy on a full neuropsychological battery administered to both Italian and foreign-born patients and at providing a brief interview for obtaining relevant information on each patient's transcultural and language-related history. Clinical reports from 43 foreign-born patients with drug-resistant epilepsy were collected from the archives of Milan Niguarda Hospital. Epileptogenic zone, age, education, profession, illness duration, seizure frequency, handedness, and gender were considered in selecting 43 Italian controls. Ethnicity (Italian/foreign-born) and years spent in Italy were analyzed as main predictors on 21 neuropsychological scales by means of General(ized) Linear Models. An additional analysis studied two composite scores of overall verbal and nonverbal abilities. Ethnicity significantly affected the following: the verbal overall score, Verbal Fluency, Naming, Token-test, Digit Span, Attentional Matrices, Trail-Making-Test, Line-Orientation-Test, and Raven matrices; no effects were found on the nonverbal overall score, Word Pairs Learning, Episodic Memory, reading accuracy, visual span, Bells test, Rey Figure, and face memory and recognition. No significant effects of years spent in Italy emerged. While years spent in Italy does not predict neuropsychological performance, linguistic background had a strong impact on it. With respect to Italian-speaking patients, those who were foreign-born showed large task-related variability, with an especially low performance on language-related tests. Hence, language tests should not be considered as valid measures of neuropsychological impairment in this population, not even in foreign-born patients with good Italian fluency. Clinicians should consider such asymmetries in order to improve the accuracy of neuropsychological assessment of foreign-born patients.

The vestibular system is unique among the senses because of the entirely multisensory nature of its cortical projections. Neuroanatomical and neuroimaging studies show that vestibular stimulation activates somatosensory areas, and particularly the so-called parieto-insular vestibular cortex (PIVC) in the monkey, while deactivating visual areas. Further, recent psychophysical studies showed that vestibular stimulation facilitates detection of electrocutaneous stimuli, suggesting a vestibular-somatosensory perceptual interaction. However, the functional mechanism underlying this perceptual facilitation remains unclear. We therefore recorded somatosensory potentials evoked by left median nerve stimulation, before and immediately after left cold caloric vestibular stimulation (CVS), in a small-scale study of eight healthy volunteers. CVS selectively enhanced the N80 component recorded over both ipsilateral and contralateral somatosensory areas, without significantly affecting earlier or later components. Interestingly, the N80 component has been localised to the parietal operculum, which includes the human homologue of the monkey PIVC, and is thus a prime neuroanatomical candidate for vestibular-somatosensory convergence. As a control, we measured visual evoked potentials to reversing checkerboard patterns and found no effects of vestibular stimulation. This rules out explanations based on indirect effects of vestibular modulations, such as general arousal or supramodal spatial attention. We believe our results provide the first clue linking brain structure to function for the interaction between vestibular and somatosensory systems.

When we reach out to grasp objects, vision plays a major role in the control of our movements. Nevertheless, other sensory modalities contribute to the fine-tuning of our actions. Even olfaction has been shown to play a role in the scaling of movements directed at objects. Much less is known about how auditory information might be used to program grasping movements. The aim of our study was to investigate how the sound of a target object affects the planning of grasping movements in normal right-handed subjects. We performed an experiment in which auditory information could be used to infer size of targets when the availability of visual information was varied from trial to trial. Classical kinematic parameters (such as grip aperture) were measured to evaluate the influence of auditory information. In addition, an optimal inference modeling was applied to the data. The scaling of grip aperture indicated that the introduction of sound allowed subjects to infer the size of the object when vision was not available. Moreover, auditory information affected grip aperture even when vision was available. Our findings suggest that the differences in the natural impact sounds of objects of different sizes being placed on a surface can be used to plan grasping movements.

According to recent theories, drug addicted patients suffer of an impaired response inhibition and salience attribution (I-RISA) together with a perturbed connectivity between the nuclei accumbens (NAcs) and the orbito-prefrontal (oPFC) and dorsal prefrontal (dPFC) cortices, brain regions associated with motivation and cognitive control. To empirically test these assumptions, we evaluated the (neuro)psychological trait and the functional organization of the resting state brain networks associated with the NAcs in 18 former cocaine abusers (FCAs), while being in drug abstinence since 5 months. The psychological data were grouped into three empirical variables related with emotion regulation, emotion awareness and strategic and controlled behaviour. Comparison of the resting state patterns between the entire sample of FCAs and 19 controls revealed a reduction of functional connectivity between the NAcs and the dPFC and enhanced connectivity between the NAcs and the dorsal-striatum. In the 8 FCAs who relapsed into cocaine use after 3 months, the level of functional connectivity between the NAcs and dPFC was lower than the functional connectivity estimated in the group of patients that did not relapsed. Finally, in the entire sample of FCAs, the higher the connectivity between the NAc and the oPFC the lower was the level of strategic and controlled behaviour. Taken together, these results are compatible with models of the interactions between the NAcs, the dorsal striatum and frontal cortices in the I-RISA syndrome, showing that such interactions are particularly perturbed in patients at greater risk of relapse into cocaine abuse.

Homeostatic parameters, such as temperature, are related to body representation. In this study, we measured whether caloric vestibular stimulation (CVS) alters body temperature and tactile processing, and if in the direction predicted by a holistic body matrix representation. Skin temperature and tactile two-point discrimination (TPD) acuity were measured for both arms before, immediately after and with a delay from CVS. Participants were also administered a personality questionnaire and an anxiety inventory to rule out confounding factors. Two control experiments were planned to exclude casual variations. Our results show that temperature drops significantly in both arms after CVS. CVS also induces a bilateral improvement in tactile acuity (even though not immediately after but in the delayed condition). Finally, these effects are not due to learning, as demonstrated by the control experiment. In summary, our results suggest that vestibular stimulation updates body representation, supporting the evidence in favor of a body matrix.

Individuals with the peculiar disturbance of '. overcompleteness' experience an intense desire to amputate one of their healthy limbs, describing a sense of disownership for it (Body Integrity Identity Disorder - BIID). This condition is similar to somatoparaphrenia, the acquired delusion that one's own limb belongs to someone else. In ten individuals with BIID, we measured skin conductance response to noxious stimuli, delivered to the accepted and non-accepted limb, touching the body part or simulating the contact (stimuli approach the body without contacting it), hypothesizing that these individuals have responses like somatoparaphrenic patients, who previously showed reduced pain anticipation, when the threat was directed to the disowned limb. We found reduced anticipatory response to stimuli approaching, but not contacting, the unwanted limb. Conversely, stimuli contacting the non-accepted body-part, induced stronger SCR than those contacting the healthy parts, suggesting that feeling of ownership is critically related to a proper processing of incoming threats.

In this study, a series of tests exploring long-term verbal memory (the Short Story Test), attention (a modified version of Attentional Matrices and the Trail Making Test) and frontal functions (a modified version of the Frontal Assessment Battery) have been standardised on an Italian population of 283 children aged 5-14. Raw scores for each test have been adjusted for a series of variables (child's age, years of parents' education, handedness, gender) and transformed in equivalent scores enabling direct comparison across measures. This study was promoted by LICE (the Italian League Against Epilepsy) in order to provide Italian instruments standardised on the developmental age population and to study some of the most frequently impaired cognitive functions in epilepsy.

Neglect of contralesional stimuli and perseverative behavior on ipsilesional stimuli may co-occur on a target cancellation task. Our aim was to investigate whether the presence vs. absence of contralesional targets can modify perseveration on ipsilesional targets. We studied four right brain-damaged patients with left neglect and perseverative behavior on screening cancellation tasks. We compared their cancellation performance in two conditions: (i) targets equally distributed on both sides of space and (ii) targets confined to the right side. One patient showed no significant difference in perseveration between these two conditions; in contrast, three patients perseverated significantly more in condition (i) than in condition (ii). These results suggest that, at least in some patients, information from the ‘neglected’ targets is not completely lost, but rather it affects behavior in the ipsilesional side. The traditional dichotomy ‘bad space–good space’ would not apply here.

Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity.

Body integrity identity disorder (BIID) is characterized by the overwhelming desire to amputate one or more healthy limbs or to be paraplegic. Recently, a neurological explanation of this condition has been proposed, in part on the basis of findings that the insular cortex might present structural anomalies in these individuals. While these studies focused on body representation, much less is known about emotional processing. Importantly, emotional impairments have been found in psychiatric disorders, and a psychiatric etiology is still a valid alternative to purely neurological accounts of BIID. In this study, we explored, by means of a computerized experiment, facial emotion recognition and emotional responses to disgusting images in seven individuals with BIID, taking into account their clinical features and investigating in detail disgust processing, strongly linked to insular functioning. We demonstrate that BIID is not characterized by a general emotional impairment; rather, there is a selectively reduced disgust response to violations of the body envelope. Taken together, our results support the need to explore this condition under an interdisciplinary perspective, taking into account also emotional connotations and the social modulation of body representation.

OBJECTIVE Representational neglect (RN) is a neuropsychological deficit mostly occurring after right brain damage affecting the mental imagery domain. Patients suffering from RN are unable to represent, describe, or explore the contralesional side of their mental images. Since its first description in 1978, RN has been explored using different theoretical frameworks and experimental paradigms. After 35 years, the nature of its behavioral and anatomical correlates is still unclear. METHOD We reviewed studies on RN published from 1978-2013 to systematize available knowledge and to shed light on future research directions. RESULTS The huge variety of tests used to diagnose RN reflects the different clinical features of the deficit, which can compromise space sectors and memory storage, depending on the stimulus to be imagined, even in a dissociated fashion. RN has been frequently described after parietal, temporal, and frontal right brain lesions, even though reliable group studies are scanty. CONCLUSION A number of priorities concerning RN were identified. Future studies might take into account several aspects of RN that are still poorly explored, starting from a more systematized investigation of RN using larger group studies. RESULTS might add pieces to the puzzle of spatial cognition and its neural basis in mental imagery, paving the way for tailored motor and cognitive rehabilitation programs.

Right brain damage patients may not complain of a left sided paralysis up to the point of denying it or even claiming of having just moved an otherwise paralyzed limb. This condition is known as anosognosia for hemiplegia (AHP). Recent behavioural experiments suggest that some residual intentionality might be preserved in patients with anosognosia and that the false belief of having moved originates from a failure to notice discrepancies between movement expectancies and the actual state of the motor system. This failure may be caused by a lack of afferent sensory information concerning the movement or alternatively by a direct dysfunction of the brain regions involved in actions' motor monitoring (i.e., the comparator system). Here we examined the effect of anodal transcranial direct current stimulation (tDCS) of the right premotor cortex in a patient with a bilateral lesion, involving predominantly the right hemisphere, and a dense unawareness for his left hemiplegia. During sham or anodal tDCS the patient was requested to judge his ability to perform simple motor actions (i) without actually executing the movement itself ("offline" condition) and after having performed a series of verbally cued finger opposition movements ("online" condition) with (i) eyes-closed or (ii) eyes-open. We found that anodal tDCS induces a significant remission of the false experience of movement only when the patient is requested to actually perform the movement with eyes open. Conversely, the patient's awareness does not improve in both the "offline" condition (in which the patient does not attempt to perform the movement) and in the "online" condition, when vision is precluded ("online" condition, eyes-closed). We conclude that the stimulation of the premotor cortex by tDCS activates brain regions involved in motor monitoring, temporary restoring the ability of the motor comparator system to correctly appreciate afferent information and build up a veridical motor awareness.

Neglect patients' performance during cancellation tasks is characterized by left sided omissions and, in many cases, by the production of inappropriate material of various kinds in the ipsilesional space, e.g. additional marks over already cancelled targets, marks drawn away from targets, scribbles, irrelevant drawings. It is unclear whether these behaviours, which have collectively been called perseverative, are functionally and anatomically connected and whether they correlate with the severity of neglect. Here we report a retrospective study on 33 right brain damaged patients with neglect after right hemisphere lesions in whom we measured the intensity of perseveration of the three following kinds: (1) 'additional marks' (AM) perseveration where patients cancelled a target with two or more well separated marks; (2) 'scribble' perseveration, where patients, instead of cancelling the target with a single pen stroke as required by the task, performed multiple pen strokes without breaking the pen-to-paper contact, with the final product being a scribble; (3) 'flying marks' (FM) perseveration where patients produced cancellation marks well away from the targets. We found that AM and FM perseveration correlated with neglect severity, while 'scribble' perseveration did not. The lesion-symptom mapping showed three separate anatomical areas in the right hemisphere: 'scribble' perseveration was associated with lesions of the orbitofrontal cortex and caudate nucleus; AM perseveration was associated with damage to the rolandic operculum, superior temporal gyrus and inferior frontal gyrus; FM perseveration was associated with damage to the dorsal premotor cortex and the temporal pole. Neglect severity followed damage to a region which grossly corresponds to the sum of the regions associated with AM and FM perseveration respectively. This complex behavioural and anatomical pattern is interpreted in terms of a three-factor model, in which AM perseveration is caused by a deficit of disengagement of attention from the right side (also causing omissions), FM perseveration is caused by directional hypokinesia (also causing left-side omissions), and 'scribble' perseveration is the consequence of a failure to inhibit an initiated motor act, which is completely separate (both anatomically and functionally) from the disorder inducing omissions. © 2013 Elsevier Ltd.

The lateralization of emotion processing is currently debated and may be further explored by examining facial expression recognition (FER) impairments in temporal lobe epilepsy (TLE). Furthermore, there is also debate in the literature whether FER deficits in individuals with TLE are more pronounced in the right than in the left hemisphere. Individuals with TLE were tested with an FER task designed to be more sensitive than those classically used to shed light on this issue. A total of 25 right- and 32 left-TLE patients, candidates for surgery, along with controls, underwent an FER task composed of stimuli shown not only at full-blown intensities (100 %), but also morphed to lower-intensity display levels (35 %, 50 %, and 75 %). The results showed that, as compared to controls, right-TLE patients showed deficits in the recognition of all emotional categories. Furthermore, when considering valence, right-TLE patients were impaired only in negative emotion recognition, but no deficits for positive emotions were highlighted in left-TLE patients. Finally, only the right-TLE patients’ impairment was found to be related to the age of epilepsy onset. Our work demonstrates that the FER deficits in TLE span multiple emotional categories and show manifestations dependent on the laterality of the epileptic focus. Taken together, our findings provide the strongest evidence for the right-hemisphere model, but they also partially support the valence model. We suggest that current models are not exhaustive at explaining emotional-processing cerebral control, and further that multistep models should be developed.

Background and Purpose: The mirror box (MB) was developed in the early 1990 s to relieve phantom limb sensations and chronic pain. Although its efficacy has been shown in several clinical populations, the mechanisms underpinning effects still have to be fully understood. Methods: 48 healthy subjects participated in 4 behavioral experiments where kinesthetic sensitivity of the hand inside the MB was tested during the observation of mirror-reflected finger movements, executed with the hand outside the MB. Results: We identified two effects on the hand hidden inside the MB: diminished kinesthetic sensitivity for passive movements, and the occurrence of unconscious, involuntary movements with the finger inside the box, suggesting reduced motor awareness. Such sensory-motor effects were somatotopically specific to the finger moved, were influenced by the contextual presence of the whole hand in the mirror, and occurred for both active and passive movements of the hand outside the MB. Conclusions: The present results suggest that the MB induce a somatotopically and contextually specific overriding of kinesthetic control by vision, compatible with a process of embodiment of the mirror-reflected hand image and provide novel clues to the understanding of the mechanisms underlying MB effects. © 2013 - IOS Press and the authors. All rights reserved.

As neuroinflammation is an early event in the pathogenesis of Alzheimer' s disease, new selective antiinflammatory drugs could lead to promising preventive strategies. We evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of CHF5074, a new microglial modulator, in a 12-week, double-blind, placebo-controlled, parallel groups, ascending dose study involving 96 MCI patients. Subjects were allocated into three successive study cohorts to receive ascending, titrated doses of CHF5074 (200, 400 or 600 mg/day) or placebo. Vital signs, cardiac safety, neuropsychological performance and safety clinical laboratory parameters were assessed on all subjects. Plasma samples were collected throughout the study for measuring drug concentrations, soluble CD40 ligand (sCD40L) and TNF-α. At the end of treatment, cerebrospinal fluid (CSF) samples were optionally collected after the last dose to measure drug levels, β- amyloid1-42 (Aβ42), tau, phospho-tau181, sCD40L and TNF-α. Ten patients did not complete the study: one in the placebo group (consent withdrawn), two in the 200-mg/day treatment group (consent withdrawn and unable to comply) and seven in the 400-mg/day treatment group (five AEs, one consent withdrawn and one unable to comply). The most frequent treatment-emergent adverse events were diarrhea, dizziness and back pain. There were no clinically significant treatmentrelated clinical laboratory, vital sign or ECG abnormalities. CHF5074 total body clearance depended by gender, age and glomerular filtration rate. CHF5074 CSF concentrations increased in a dose-dependent manner. At the end of treatment, mean sCD40L and TNF-α levels in CSF were found to be inversely related to the CHF5074 dose (p=0.037 and p=0.001, respectively). Plasma levels of sCD40L in the 600-mg/day group were significantly lower than those measured in the placebo group (p=0.010). No significant differences between treatment groups were found in neuropsychological tests but a positive dose-response trend was found on executive function in APOE4 carriers. This study shows that CHF5074 is well tolerated in MCI patients after a 12-week titrated treatment up to 600 mg/day and dose-dependently affects central nervous system biomarkers of neuroinflammation.

Visual illusions have been used to explore implicit perception in neglect. Previous studies have highlighted differences between length and surface illusion perception in neglect, but much less is known about depth illusion perception. In the Ponzo illusion (a classic depth illusion), two converging oblique lines modulate the perceived length of two horizontal lines. In the current study, we presented modified versions of the Ponzo illusion in which only one of the converging oblique lines was presented (alternatively the right or the left one). This manipulation allowed us to explore (1) how acute patients with neglect process depth illusions, and (2) whether awareness of both converging lines is necessary for the full effect of the illusion. To examine these questions, we had participants (i.e. healthy controls, patients with neglect and right brain-damaged patients) to make a perceptual judgment regarding the perceived length of the upper versus lower horizontal line within the Ponzo frame in four conditions: (1) the classic Ponzo illusion, (2) a “modified left” Ponzo illusion with a single oblique line on the left, (3) a “modified right” Ponzo illusion with a single oblique line on the right and (4) a control condition with parallel lines. The results indicated that all participants perceived the canonical Ponzo illusion and the modified right illusion. Critically, patients with neglect did not perceive the modified left illusion. In addition, for neglect patients, there was no difference in the strength of the perceived illusion when comparing the canonical illusion with the modified right illusion. Importantly, single case analysis revealed a high degree of variability in the neglect group that seemed to be linked with the amount of damage to occipital areas. Overall our results indicate that: (1) the classic Ponzo illusion might be perceived in neglect patients based solely on perception of the right side of the stimulus configuration, and (2) differences between types of illusions (i.e. depth vs. length), and variability between patients suggest that caution is needed when utilizing these kinds of illusions to assess implicit processing in neglect.

Both real action control and execution and motor imagery abilities require knowledge of the spatial location of body parts, in other words efference copy information and feedbacks from the sensory system (Frith et al., 2000, Philos. Trans. R. Soc. Lond. B. Biol. Sci., 355, 1771). Spinal cord injuries induce severe motor disability, due to a damage of the descending motor pathways (Cramer et al., 2007, Exp. Brain. Res., 177, 233). Patients' motor imagery competences are variably reported as either normal or defective (Decety & Boisson, 1990, Eur. Arch. Psychiatry Clin. Neurosci., 240, 39; Lacourse et al., 1999, Behav. Brain Sci., 104, 73). We explored biomechanical constraint effects in Spinal Cord Injury (SCI) patients, as they are considered the most reliable indexes of motor imagery abilities (Parsons, 1987b, Cogn. Psychol., 19, 178). Sixteen spinal cord injuries patients and 16 neurologically unimpaired subjects have been administered with (1) the Hand Laterality Task (HLT), in which subjects were asked to judge the laterality of a rotated hand; and (2) the Mirror Letter Discrimination Task (MLD), in which subjects were asked to judge if a rotated character was in its correct upright position or mirror-reversed form. Our patients did not present the effect of stimulus orientation, neither did they show any effect related to biomechanical constraints. Based on these data, the hypothesis is that SCI patients' performance may be ascribed to the use of a different strategy to solve the tasks, based on memory rather than on mental rotation.

In the present study, we showed that a representational disorder for words can dissociate from both representational neglect for objects and neglect dyslexia. This study involved 14 brain-damaged patients with left unilateral spatial neglect and a group of normal subjects. Patients were divided into four groups based on presence of left neglect dyslexia and representational neglect for non-verbal material, as evaluated by the Clock Drawing test. The patients were presented with bisection tasks for words and lines. The word bisection tasks (with words of five and seven letters) comprised the following: (1) representational bisection: the experimenter pronounced a word and then asked the patient to name the letter in the middle position; (2) visual bisection: same as (1) with stimuli presented visually; and (3) motor bisection: the patient was asked to cross out the letter in the middle position. The standard line bisection task was presented using lines of different length. Consistent with the literature, long lines were bisected to the right and short lines, rendered comparable in length to the words of the word bisection test, deviated to the left (crossover effect). Both patients and controls showed the same leftward bias on words in the visual and motor bisection conditions. A significant difference emerged between the groups only in the case of the representational bisection task, whereas the group exhibiting neglect dyslexia associated with representational neglect for objects showed a significant rightward bias, while the other three patient groups and the controls showed a leftward bisection bias. Neither the presence of neglect alone nor the presence of visual neglect dyslexia was sufficient to produce a specific disorder in mental imagery. These results demonstrate a specific representational neglect for words independent of both representational neglect and neglect dyslexia.

We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, theBAD-respondersshowed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that theBAD-respondershad larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.

We studied the linguistic profile and neurolinguistic organization of a 14-year-old adolescent (EB) who underwent a left hemispherectomy at the age of 2.5 years. After initial aphasia, his language skills recovered within 2 years, with the exception of some word finding problems. Over the years, the neuropsychological assessments showed that EB's language was near-to-normal, with the exception of lexical competence, which lagged slightly behind for both auditory and written language. Moreover, EB's accuracy and speed in both reading and writing words and non-words were within the normal range, whereas difficulties emerged in reading loan words and in tasks with homophones. EB's functional magnetic resonance imaging (fMRI) patterns for several linguistic and metalinguistic tasks were similar to those observed in the dominant hemisphere of controls, suggesting that his language network conforms to a left-like linguistic neural blueprint. However, a stronger frontal recruitment suggests that linguistic tasks are more demanding for him. Finally, no specific reading activation was found in EB's occipitotemporal region, a finding consistent with the surface dyslexia-like behavioral pattern of the patient. While a lone right hemisphere may not be sufficient to guarantee full blown linguistic competences after early hemispherectomy, EB's behavioral and fMRI patterns suggest that his lone right hemisphere followed a left-like blueprint of the linguistic network.

Motor imagery (M.I.) is a mental state in which real movements are evoked without overt actions. There is some behavioural evidence that M.I. declines with ageing. The neurofunctional correlates of these changes have been investigated only in two studies, but none of the these studies has measured explicit correlations between behavioural variables and the brain response, nor the correlation of M.I. and motor execution (M.E.) of the same acts in ageing. In this paper, we report a behavioural and functional magnetic resonance imaging (fMRI) experiment that aimed to address this issue. Twenty-four young subjects (27 ± 5.6 years) and twenty-four elderly subjects (60 ± 4.6 years) performed two block-design fMRI tasks requiring actual movement (M.E.) or the mental rehearsal (M.I.) of finger movements. Participants also underwent a behavioural mental chronometry test in which the temporal correlations between M.I. and M.E. were measured. We found significant neurofunctional and behavioural differences between the elderly subjects and the young subjects during the M.E. and the M.I. tasks: for the M.E. task, the elderly subjects showed increased activation in frontal and prefrontal (pre-SMA) cortices as if M.E. had become more cognitively demanding; during the M.I. task, the elderly over-recruited occipito-temporo-parietal areas, suggesting that they may also use a visual imagery strategy. We also found between-group behavioural differences in the mental chronometry task: M.I. and M.E. were highly correlated in the young participants but not in the elderly participants. The temporal discrepancy between M.I. and M.E. in the elderly subjects correlated with the brain regions that showed increased activation in the occipital lobe in the fMRI. The same index was correlated with the premotor regions in the younger subjects. These observations show that healthy elderly individuals have decreased or qualitatively different M.I. compared to younger subjects.

We describe the case of a patient with late onset fronto-temporal dementia (FTD), who presented with typical personality changes, but also perseverative and confabulatory behaviors while performing the Rey-Osterrieth Complex Figure Test. We hypothesize that the progressive atrophy of orbitobasal, medial, and dorsolateral frontal cortices may give rise to both confabulations and perseverations in the non-verbal domain. In agreement with previous studies, reporting atypical profiles, this case report underlines the clinical heterogeneity of FTD. Authors declare that they have no conflicts of interest.

Our aim was to investigate the caregiver burden by means of scales to quantify the perceived burden, and the anxiety and depression levels.Seventy-seven caregivers of patients with Alzheimer disease or other kinds of dementia (19 males and 58 females) admitted to the Alzheimer Evaluation Unit of Milan Niguarda Ca'Granda Hospital, were enrolled and filled in Caregiver Burden Inventory (CBI) and the short form of the Anxiety and Depression scale (AD-R). The statistical analysis demonstrates that caregiver with relatives affected by more severe cognitive impairment (patients) show significant levels of burden and anxiety.The most relevant burden dimensions are: Time-Dependence Burden, Developmental Burden and Physical Burden. Time-Dependence Burden and Social Burden significantly correlate with cognitive (p = 0.01, p = 0.05) and functional rates of patients (p = 0.01, p = 0.05), whereas Developmental Burden only correlates with cognitive rates (p = 0.01). The more prolonged patients' disease the higher the caregivers'anxiety level (p0.05). There is nota significant correlation between the Developmental Burden, Physical Burden and Depression, observed in the caregivers' sample, and the cognitive and functional state of patients.Alzheimer disease caregivers need an increase of their personal time anda specific intervention aimed to reduce the perceived feeling of social isolation, the physical distress and the anxious and depressive symptoms.

Caloric vestibular stimulation (CVS) is a physiological technique demonstrated to transiently improve hemianaesthesia in right brain-damaged patients (Bottini et al. in Exp Brain Res 99(1):164-169, 1994, Nature 376:778-781, 1995, Neurology 65(8):1278-1283, 2005). Recent studies suggest that these effects are based on the anatomical overlapping between vestibular and tactile projections (Bottini et al. in Nature 376:778-781, 1995) in the human brain. However, much less is known about behavioural effects of this manipulation on normal subjects. We aimed to explore tactile perception during left ear CVS in normal subjects. We administered seventeen right-handed normal subjects with different types of tactile stimuli (above and below threshold) during left ear CVS. To further ensure standardized procedure, tactile stimulation was delivered through a tool-developed ad hoc for the experiment. The experiment was divided in 3 conditions: (1) Baseline, (2) PostCVS and (3) Delayed CVS. We found a main effect of stimulus type (F ((2,32)) = 907.712; P = 0.000) and condition (F ((2,32)) = 55.505; P = 0.000). Moreover, post hoc comparisons revealed that below threshold stimuli are most affected by CVS (t ((16)) = -11.213; P = 0.000). Left ear CVS modulates tactile perception also in normal subjects. Moreover, this modulation seems to be selective for below threshold stimuli and not caused by attentive processes. A multisensory phenomenon is possibly the best explanation for this interaction between touch and vestibular systems, corroborated also by the anatomical evidence and by the previous knowledge about interaction with the environment.

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.