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The extrastriate body area (EBA) is involved in perception of human bodies and nonfacial body parts, but its role in representing body identity is not clear. Here, we used on-line high-frequency repetitive transcranial magnetic stimulation (rTMS) to test the role of EBA in self-other distinction. In Experiments 1 and 2 we compared rTMS of right EBA with stimulation of left ventral premotor cortex (vPM), whereas in Experiment 3 we compared stimulation of right and left EBA. RTMS was applied during a hand laterality task in which self or others' hand images were presented in first- versus third-person view (Experiments 1 and 3), or while participants had to explicitly recognize their own hands (Experiment 2) presented in first- versus third-person view. Experiment 1 showed that right EBA stimulation selectively speeded judgments on others' hands, whereas no effect of left vPM stimulation was found. Experiment 2 did not reveal any effect of rTMS. Experiment 3 confirmed faster responses on others' hands while stimulating right EBA and also showed an advantage when judging self with respect to others' hands during stimulation of left EBA. These results would demonstrate that EBA responds to morphological features of human body contributing to identity processing.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity likely related to altered processing of sensory stimuli along the brain-gut axis. Previous neuroimaging studies demonstrated structural and functional alteration of several brain areas involved in bodily representation, e.g. the insula, in patients with IBS. By means of resting-state functional magnetic resonance imaging (rs-fMRI) we searched for alteration of functional connectivity within the network involved in self-bodily consciousness. We found significant inverse correlation between hypochondriasis assessed through a clinical questionnaire and connectivity between posterior cingulate cortex and left supramarginal gyrus, extending into the adjacent superior temporal gyrus. Moreover, we observed a significant and positive correlation between a clinical questionnaire assessing interoception and connectivity between left anterior ventral insula and two clusters located in supramarginal gyrus bilaterally.Our findings highlight an "abnormal network synchrony" reflecting functional alteration, in the absence of structural and micro-structural changes, which might represent a possible therapeutic target for Irritable Bowel Syndrome.

Chess involves the capacity to reason iteratively about potential intentional choices of an opponent and therefore involves high levels of explicit theory of mind [ToM] (i.e. ability to infer mental states of others) alongside clear, strategic rule-based decision-making. Functional magnetic resonance imaging was used on 12 healthy male novice chess players to identify cortical regions associated with chess, ToM and empathizing. The blood-oxygenation-level-dependent (BOLD) response for chess and empathizing tasks was extracted from each ToM region. Results showed neural overlap between ToM, chess and empathizing tasks in right-hemisphere temporo-parietal junction (TPJ) [BA40], left-hemisphere superior temporal gyrus [BA22] and posterior cingulate gyrus [BA23/31]. TPJ is suggested to underlie the capacity to reason iteratively about another's internal state in a range of tasks. Areas activated by ToM and empathy included right-hemisphere orbitofrontal cortex and bilateral middle temporal gyrus: areas that become active when there is need to inhibit one's own experience when considering the internal state of another and for visual evaluation of action rationality. Results support previous findings, that ToM recruits a neural network with each region sub-serving a supporting role depending on the nature of the task itself. In contrast, a network of cortical regions primarily located within right- and left-hemisphere medial-frontal and parietal cortex, outside the internal representational network, was selectively recruited during the chess task. We hypothesize that in our cohort of novice chess players the strategy was to employ an iterative thinking pattern which in part involved mentalizing processes and recruited core ToM-related regions., (Copyright © 2017. Published by Elsevier Ltd.)

Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We present evidence that all the available patients in these 3 familial cases are carrying the rare GRN gene exon 6 deletion g10325_10331delCTGCTGT (relative to nt 1 inNG_007886.1), alias Cys157LysfsX97. This mutation was previously described in 2 sporadic cases but was never associated with familial cases. Our patients demonstrate heterogeneous clinical phenotypes, such as the behavioral variant (bvFTD) in the affected men and the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) in the affected woman. Haploinsufficiency was revealed by both quantitative real-time PCR of the gene and protein analyses. These findings provide further support for a previously proposed role for the GRN gene in the genetic etiology of FTD and its phenotypic variability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Apathy is well described in neurodegenerative diseases characterized by motor disability; therefore, assessment of apathy avoiding possible confounding effects of motor impairments is necessary in neurological diseases. Recently, the Dimensional Apathy Scale (DAS) was developed to assess apathy as multifaceted construct, independent of physical disability. We developed the Italian version of the Dimensional Apathy Scale (I-DAS) and explored its psychometric properties in a sample of 309 healthy individuals. Participants also completed Apathy Evaluation Scale, Beck Depression Inventory-II and Addenbrooke's Cognitive Examination-Revised. The I-DAS showed high internal consistency, good convergent and divergent validity. The I-DAS had a three-factor structure, such as the original scale. The I-DAS scored was significantly correlated with individuals' education, but not with age or gender. We, therefore, computed correction factor for education and provided percentile distribution of the adjusted scores to identify individuals with high levels of apathy. The I-DAS showed good psychometric properties and can be a valid and reliable tool to assess multidimensional apathy.

Interoception collects all information coming from the body and is sustained by several brain areas such as insula and cingulate cortex. Here, we used resting-state functional magnetic resonance imaging to investigate functional connectivity (FC) of networks implied in interoception in patients with Illness anxiety disorders (IADs). We observed significantly reduced FC between the left extrastriate body area (EBA) and the paracentral lobule compared to healthy controls. Moreover, the correlation analysis between behavioural questionnaires and ROI to ROI FC showed that higher levels of illness anxiety were related to hyper-connectivity between EBA and amygdala and hippocampus. Scores on a questionnaire for interoceptive awareness were significantly correlated with higher FC between right hippocampus and nucleus accumbens bilaterally, and with higher connectivity between left anterior cingulate cortex (ACC) and left orbitofrontal cortex (OFC). Last, patients showed increased interoceptive awareness, measured by Self-Awareness Questionnaire (SAQ), and reduced capability in recognizing emotions, indicating inverse correlation between interoception and emotional awareness. Taken together our results suggested that, in absence of structural and micro-structural changes, patients with IADs show functional alteration in the neural network involved in the self-body representation; such functional alteration might be the target of possible treatments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Neuropsychiatric symptoms are common in multiple sclerosis (MS). Among these, apathy is relatively frequent but its relationships with cognitive dysfunctions have been poorly investigated., Objective: To explore cognitive correlates of apathy with or without depression ("pure apathy") in MS patients., Material and Method: Nondemented MS patients (n = 125), consecutively referred to the Multiple Sclerosis Center of Moscati Hospital, in Avellino, Italy, underwent the Apathy Evaluation Scale Self-Rated (AES-S), the Hamilton Depression Rating Scale (HDRS), and a comprehensive neuropsychological battery., Results: According to cut-off scores of AES-S (≥36), of HDRS (≥15) and criteria for diagnosis of apathy and major depression, the sample was divided into 4 subgroups: 49 patients without apathy or depression (A-D-), 20 patients with "pure" apathy (A+D-), 29 patients with depression only (A-D+), and 27 patients with apathy and depression (A+D+). Cognitive performance significantly differed in the 4 groups: in particular MS patients with apathy (A+D- and A+D+) performed significantly worse on executive tasks than patients without apathy, whereas patients with "pure" apathy (A+D-) performed significantly worse than patients without apathy only on executive tasks tapping cognitive control abilities., Conclusions: We found a significant relationship between apathy and dysexecutive defects in MS, consistent with the hypothesis that dysfunctions of prefrontal cortico-subcortical circuits contribute to specific neuropsychiatric syndromes in MS patients. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Together with stomatal conductance and root conductivity, the stem water reserve and transport systems could be regulatory mechanisms able to participate in the regulation of the plant water status. Lianas, such as Vitis spp., minimize the trunk support role, and stems have evolved to improve their ability in water transport. In this work, stems of 10 different Vitis species were studied in relation to their expected drought tolerance using reflectance spectroscopy. Spectra were measured before (T0) and after coloration with Sudan IV dye. The T0 spectral signature showed characteristic species features. The partial least squares (PLS) regression and the self-organizing map (SOM) neural network analysis were able to predict the expected drought tolerance score; thus, reflectance spectroscopy was demonstrated to be a useful technique for drought tolerance phenotyping. These methods could be applied for the preliminary selection of new rootstocks/cultivars. Wood composition variation appeared to be correlated with the water stress susceptibility. To clarify this relationship, the attention was focused on the wood hydrophobicity. Sudan IV is a microscopy dye traditionally used to underline suberin, waxes, and, in general, hydrophobic substances. Differences between rough and colored spectra evidenced the absorption band of Sudan IV with a maximum at 539 nm. The coloration intensity was used to develop a hydrophobicity index. The obtained values were correlated with the expected drought tolerance score. Therefore, hydrophobic compounds seem to play an important role in water use efficiency, and an hydrophobic barrier in the xylem tissue appears to be a protective mechanism against water stress.

Introduction: To report a single-institutional experience with the use of Superficial X-Ray Therapy (SXRT) for head and neck non-melanoma skin cancer (N-MSC) and to compare outcomes by prescribed fractionation schedules., Materials and Methods: The medical records of 597 patients with 1021 lesions (720 BCC, 242 SCC, 59 SCC in situ) treated with kilovoltage radiation from 1979-2013 were retrospectively reviewed. The majority of patients were treated according to 1 of 3 institutional protocols based on the discretion of the radiation oncologist: 1) 22 x 2.5 Gy; 2) 20 x 2.5 Gy; 3) 30 x 2.0 Gy. "T" stage at first presentation was as follows: Tis (59); T1 (765); T2 (175); T3 (6), T4 (9); Tx, (7). All patients were clinical N0 and M0 at presentation. Chi-square test was used to evaluate any potential association between variables. The Kaplan-Meier method was used to analyze survival with the Log Rank test used for comparison. A Cox Regression analysis was performed for multivariate analysis., Results: The median follow up was 44 months. No significant difference was observed among the 3 prescribed fractionation schemes (p = 0.78) in terms of RTOG toxicity. There were no failures among SCC in situ, 37 local failures (23 BCC, 14 SCC), 5 regional failures (all SCC) and 2 distant failures (both SCC). For BCC, the 5-year LC was 96% and the 10-year LC was 94%. For SCC the corresponding rates of local control were 92% and 87%, respectively (p = 0.03). The use of >2.0 Gy daily was significantly associated with improved LC on multivariate analysis (HR: 0.17; CI 95%: 0.05-0.59)., Conclusion: SXRT for N-MSC of the head and neck is well tolerated, achieves excellent local control, and should continue to be recommended in the management of this disease. Fractionation schedules using >2.0 Gy daily appear to be associated with improved LC.

The aim of this study is to clarify the specific role of the cerebellum during prism adaptation procedure (PAP), considering its involvement in early prism exposure (i.e., in the recalibration process) and in post-exposure phase (i.e., in the after-effect, related to spatial realignment). For this purpose we interfered with cerebellar activity by means of cathodal transcranial direct current stimulation (tDCS), while young healthy individuals were asked to perform a pointing task on a touch screen before, during and after wearing base-left prism glasses. The distance from the target dot in each trial (in terms of pixels) on horizontal and vertical axes was recorded and served as an index of accuracy. Results on horizontal axis, that was shifted by prism glasses, revealed that participants who received cathodal stimulation showed increased rightward deviation from the actual position of the target while wearing prisms and a larger leftward deviation from the target after prisms removal. Results on vertical axis, in which no shift was induced, revealed a general trend in the two groups to improve accuracy through the different phases of the task, and a trend, more visible in cathodal stimulated participants, to worsen accuracy from the first to the last movements in each phase. Data on horizontal axis allow to confirm that the cerebellum is involved in all stages of PAP, contributing to early strategic recalibration process, as well as to spatial realignment. On vertical axis, the improving performance across the different stages of the task and the worsening accuracy within each task phase can be ascribed, respectively, to a learning process and to the task-related fatigue., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Reliable and valid metamemory measures are needed to assess subjective memory complaints that can be distinct from objective memory performance. The Multifactorial Memory Questionnaire (MMQ) evaluates dimensions of subjective memory functioning such as frequency of memory problems (Ability), affect related to memory abilities (Contentment), and strategy use in everyday life (Strategy). To examine the psychometric properties of the Italian version of the MMQ, six hundred Italian healthy individuals (aged 25-91 years) completed MMQ, a questionnaire assessing metacognition (Cognitive Failures Questionnaire, CFQ) and two batteries assessing cognitive global status (Montreal Cognitive Assessment, MoCA; Mini Mental State Examination, MMSE). MMQ was easy to administer, acceptable, and had good test-retest reliability (r for the total MMQ score 0.95), and internal consistency (Cronbach's α for the total MMQ score = 0.83). An exploratory factor analysis provided a four-factor solution: "Ability" (α = 0.99), "Contentment" (α = 0.91), "External Strategies" (α = 0.85) and "Internal Strategies" (α = 0.78) factors. MMQ total score and MMQ-Ability factor score showed good convergent validity when compared to CFQ score (r rho ≥ 0.51), whereas MMQ total score and the four MMQ factors showed good divergent validity when compared to MoCA and MMSE score (r rho ≤ 0.27). Demographic variables significantly influenced MMQ total score and most subscale scores. From the derived linear equations, we computed correction factors for raw scores and percentile distribution of adjusted scores. The Italian version of MMQ is reliable and valid to assess dimensions of metamemory in adult and elderly subjects.

In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual-task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain-damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis"., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes.

Objective: The Clock Drawing Test (CDT) is widely used as a screening tool for discriminating cognitively normal individuals from patients with mild dementia. The aim of present study was to provide normative values for a 10-point quantitative scoring system proposed by Rouleau and colleagues (1992), including CDT total score and subscales score assessing representation of clock face (RC), layout of numbers (LN), and position of hands (PH), in a large sample of Italian healthy individuals., Method: Eight hundred and seventy-two Italian healthy participants (483 women; age range 20-94 years) with educational level from primary school to university underwent CDT and Mini Mental State Examination (MMSE)., Results: Multiple linear regression analysis revealed that age and education significantly influenced CDT total score and its subscale scores. Moreover, a significant effect of gender was found only in RC subscale. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-off values were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a weakly significant correlation between adjusted CDT total score and adjusted MMSE scores., Conclusions: The present study provided normative data for the Rouleau and colleagues version of CDT in an Italian sample, useful for clinical and research purposes.

Interoception is the basic process enabling evaluation of one's own bodily states. Several previous studies suggested that altered interoception might be related to disorders in the ability to perceive and express emotions, i.e., alexithymia, and to defects in perceiving and describing one's own health status, i.e., hypochondriasis. The main aim of the present study was to investigate the relationships between alexithymic trait and interoceptive abilities evaluated by the "Self-Awareness Questionnaire" (SAQ), a novel self-report tool for assessing interoceptive awareness. Two hundred and fifty healthy subjects completed the SAQ, the Toronto Alexithymia Scale-20 items (TAS-20), and a questionnaire to assess hypochondriasis, the Illness Attitude Scale (IAS). The SAQ showed a two-factor structure, with good internal consistency (Cronbach's alpha = 0.88). We observed significant direct correlations between SAQ, TAS-20 and two of its subscales, and the IAS. Regression analysis confirmed that the difficulty in identifying and expressing emotions is significantly related with awareness for one's own interoceptive feelings and with a tendency to misinterpret and amplify bodily sensations. From a clinical point of view, the assessment of interoceptive awareness by the SAQ could be pivotal in evaluating several psychopathological conditions, such as the somatoform disorders.

Battery for Visuospatial Abilities (BVA, known in Italy as TeRaDiC) has been developed to analyse putative basic skills involved in drawing and to plan and monitor outcomes after rehabilitation of visuoconstructional disorders. It encompasses eight tasks assessing both simple "perceptual" abilities, such as line length and line orientation judgments and complex "representational" abilities, such as mental rotation. The aim of present study was to provide normative values for BVA collected in a wide sample of healthy Italian subjects. Three hundred seventeen healthy Italian subjects (173 women and 144 men) of different age classes (age range, 40-95 years) and education level (from primary to university), with a normal score on Mini Mental State Examination, completed BVA/TeRaDiC. Multiple linear regression analysis revealed that age and education significantly influenced performance on most tests of the BVA/TeRaDiC; only line length judgment was not affected by educational level. Gender significantly affected line orientation judgment and mental rotation, with an advantage for males in both tests. From the derived linear equations, a correction grid for adjusting BVA/TeRaDiC raw scores was built. Using a non-parametric technique, inferential cut-off scores were determined and equivalent scores computed. The present study provided Italian normative data for the BVA/TeRaDiC useful for both clinical and research purposes.

Embodied cognition theories hold that cognitive processes are grounded in bodily states. Embodied processes in autism spectrum disorders (ASD) have classically been investigated in studies on imitation. Several observations suggested that unlike typical individuals who are able of copying the model's actions from the model's position, individuals with ASD tend to reenact the model's actions from their own egocentric perspective. Here, we performed two behavioral experiments to directly test the ability of ASD individuals to adopt another person's point of view. In Experiment 1, participants had to explicitly judge the left/right location of a target object in a scene from their own or the actor's point of view (visual perspective taking task). In Experiment 2, participants had to perform left/right judgments on front-facing or back-facing human body images (own body transformation task). Both tasks can be solved by mentally simulating one's own body motion to imagine oneself transforming into the position of another person (embodied simulation strategy), or by resorting to visual/spatial processes, such as mental object rotation (nonembodied strategy). Results of both experiments showed that individual with ASD solved the tasks mainly relying on a nonembodied strategy, whereas typical controls adopted an embodied strategy. Moreover, in the visual perspective taking task ASD participants had more difficulties than controls in inhibiting other-perspective when directed to keep one's own point of view. These findings suggested that, in social cognitive tasks, individuals with ASD do not resort to embodied simulation and have difficulties in cognitive control over self- and other-perspective., (© 2015 International Society for Autism Research, Wiley Periodicals, Inc.)

Background: Multiple sclerosis (MS) is frequently associated with depressive symptoms and major depression., Objective: We assessed psychometric properties of the Hamilton Depression Rating Scale (HDRS, 17-item version) for assessing depressive symptomatology in a sample of MS patients., Methods: Seventy patients (aged 43.3 ± 10.3 years) completed the HDRS and a thorough clinical and neuropsychological assessment, including diagnosis of major depression according to the established clinical criteria., Results: HDRS was easy to administer and acceptable, and showed fair internal consistency (Cronbach's alpha = 0.8). The HDRS showed good convergent validity with respect to neuropsychiatric inventory (NPI) subdomain of depression (r rho = .85) and good divergent validity with respect to remaining NPI subdomains (r rho < .30). Moreover, HDRS's total score correlated moderately with functional disability and apathetic symptomatology, and poorly with general cognitive status. Receiver operating characteristics curve analysis demonstrated that a cutoff >14.5 can identify clinically relevant depressive symptoms with good sensitivity (93 %) and specificity (97 %) with respect to the diagnosis of major depression. Such a cutoff identified clinically relevant depressive symptoms in 42 % of our MS sample, whereas 44.2 % patients met established clinical criteria for major depression., Conclusion: The HDRS can be considered as an easy, reliable, and valid tool to assess depressive symptomatology for clinical and research purposes in non-demented MS patients.

Introduction: Closing-in (CI) is a peculiar phenomenon consisting in the tendency to copy drawings close to or superimposed on a model. Recent findings showed that CI can be associated with frontal/executive dysfunctions, likely determining a failure in high-level monitoring of attention-action circuits. CI has been often observed in demented patients, but scarce data are available about CI in patients with Parkinson's disease (PD). In the present study, we detected occurrence of CI and investigated the cognitive processes associated to this phenomenon in a large sample of non-demented PD patients., Methods: We retrospectively analysed graphic reproductions in a copying task of 100 non-demented PD patients who had also completed cognitive, behavioural, and motor screening assessment., Results: CI phenomenon occurred in 50/100 non-demented PD patients (50%; 118/700 drawings). Among these patients, 46/50 patients copied drawings close to the model (near-CI), 2/50 patients superimposed their copy directly on the model (adherent-CI), whereas 2/50 patients showed both near-and adherent-CI. MANOVA showed that non-demented PD patients with CI showed more severe impairment on frontal/executive functions and visuo-constructional abilities than non-demented PD patients without CI. However, the logistic regression model revealed that occurrence of CI was significantly associated to lower scores on frontal/executive tasks only., Conclusion: CI can be found in a large proportion of non-demented PD patients, and it is related to frontal monitoring defects that could hamper inhibition of action and attention toward a model., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

Judgments on laterality of hand stimuli are faster and more accurate when dealing with one's own than others' hand, i.e. the self-advantage. This advantage seems to be related to activation of a sensorimotor mechanism while implicitly processing one's own hands, but not during explicit one's own hand recognition. Here, we specifically tested the influence of proprioceptive information on the self-hand advantage by manipulating participants' body posture during self and others' hand processing. In Experiment 1, right-handed healthy participants judged laterality of either self or others' hands, whereas in Experiment 2, an explicit recognition of one's own hands was required. In both experiments, the participants performed the task while holding their left or right arm flexed with their hand in direct contact with their chest ("flexed self-touch posture") or with their hand placed on a wooden smooth surface in correspondence with their chest ("flexed proprioceptive-only posture"). In an "extended control posture", both arms were extended and in contact with thighs. In Experiment 1 (hand laterality judgment), we confirmed the self-advantage and demonstrated that it was enhanced when the subjects judged left-hand stimuli at 270° orientation while keeping their left arm in the flexed proprioceptive-only posture. In Experiment 2 (explicit self-hand recognition), instead, we found an advantage for others' hand ("self-disadvantage") independently from posture manipulation. Thus, position-related proprioceptive information from left non-dominant arm can enhance sensorimotor one's own body representation selectively favouring implicit self-hands processing.

The Montreal Cognitive Assessment (MoCA) is a rapid screening battery, also including subtests to assess frontal functions such as set-shifting, abstraction and cognitive flexibility. MoCA seems to be useful to identify non-amnestic mild cognitive impairment (MCI) and subcortical dementia; it has high sensitivity and specificity in distinguishing MCI from mild Alzheimer's Disease. Previous studies revealed that certain items of MoCA may be culturally biased and highlighted the need for population-based norms for the MoCA. The aim of present study was to collect normative values in a sample of Italian healthy subjects. Four hundred and fifteen Italian healthy subjects (252 women and 163 men) of different ages (age range 21-95 years) and educational level (from primary to university) underwent MoCA and Mini Mental State Examination (MMSE). Multiple linear regression analysis revealed that age and education significantly influenced performance on MoCA. No significant effect of gender was found. From the derived linear equation, a correction grid for MoCA raw scores was built. Inferential cut-off score, estimated using a non-parametric technique, is 15.5 and equivalent scores were computed. Correlation analysis showed a significant but weak correlation between MoCA adjusted scores with MMSE adjusted scores (r = 0.43, p < 0.001). The present study provided normative data for the MoCA in an Italian population useful for both clinical and research purposes.

Since the early 1960s, human neuropsychology, the study of brain-behavior interrelations, mainly based on the analysis of their pathological variations, brought about by brain damage, has had a remarkable systematical development in Italy. All this started in Milan, with the neurologist Ennio de Renzi, and his collaborators (Luigi Vignolo, then Anna Basso, Pietro Faglioni, Hans Spinnler, François Boller, and, more autonomously, Edoardo Bisiach), in the Clinic of Nervous and Mental Diseases. Scientists of the "Milan group" investigated several neuropsychological deficits caused by focal hemispheric lesions in large series of left- and right-brain-damaged patients, and control participants, comparable for cultural and demographic variables. Standardized tests and advanced statistical methods were used, which also applied to the diagnosis and rehabilitation of aphasia. Subsequently, neuropsychology developed in Italy extensively, reaching high international reputation. Leading neuropsychologists have been the neurologists Guido Gainotti (Rome), and Franco Denes (Padua), the physicians and psychologists Luigi Pizzamiglio (Rome), and Carlo Umiltà (Parma, with fruitful interactions with the neurophysiologists Giovanni Berlucchi, Giacomo Rizzolatti, and Carlo Marzi, from the school of Giuseppe Moruzzi in Pisa) A second scientific generation of neuropsychologists has then developed in the 1970s, trained by the abovementioned scientists, further boosting and spreading high-level basic and applied research (diagnosis and rehabilitation of neuropsychological deficits of patients with brain damage or dysfunction throughout the life span, from childhood to the elderly). Available techniques include structural and functional imaging (CT, PET, SPET, MRI and fMRI Scans, DTI), electrophysiological recording (EEG, ERPs), non-invasive brain stimulation (TMS, tES), and their combined use.

Objective: Perseveration is the involuntary production of iterative responses. This study explored graphic perseverative errors in Alzheimer's disease and vascular dementia, to comprehend the neuropsychological correlates of this behavior., Method: We performed a retrospective analysis of graphic productions in 114 individuals with clinical diagnosis of Alzheimer's disease and in 63 individuals with clinical diagnosis of vascular dementia, who completed frontal-executive, visuo-spatial, visuo-constructional, and verbal memory tests. For assessing perseverative behavior, we considered recurrent perseverations (inappropriate re-drawing of a figure drawn in a previous trial) and continuous perseverations (inappropriate replication of the same figure or of its element within one trial) produced in a standard copying task., Results: Two or more graphic perseverative errors occurred in 66/114 individuals with Alzheimer's disease (57.9%) and in 31/63 individuals with vascular dementia (49.2%). Participants with moderate-to-severe dementia produced a significantly higher number of perseverations than individuals with mild dementia. Logistic regression revealed a significant relationship of graphic perseverations with frontal and visuo-constructive impairments, in both Alzheimer's disease and vascular dementia., Conclusions: Graphic perseverations are frequent in both Alzheimer's disease and vascular dementia. Frontal-executive defects can hamper inhibition of iterative graphic productions. Identification of graphic perseverations can be useful for detection and monitoring of frontal-executive impairments throughout the disease course in individuals with dementia.

Introduction: The tendency to reproduce figures close to or superimposed on the model in copying tasks, the so-called Closing-in (CI) phenomenon, has been rarely reported in individuals affected by Parkinson's disease and associated dementia (PD-D). We aimed to comprehend the genesis of CI in PD-D individuals by assessing whether reduction of attention/executive resources can increase the tendency to deviate toward the model., Method: Thirty PD-D individuals underwent a neuropsychological evaluation exploring visuo-spatial, visuo-constructional, executive and memory abilities. An experimental copying task was employed in single and in two dual task conditions to assess whether a (verbal) cognitive load can increase CI in these individuals, compared with a matched sample of healthy adults., Results: CI occurred in 19/30 (63.3%) PD-D individuals: 4 of them produced copies close to the model (near-CI), whereas 15 individuals also superimposed their copies on the model (adherent-CI) besides showing near-CI. Presence of CI in PD-D individuals was significantly correlated with executive dysfunction but not with general cognitive impairment. In the experimental copying task the tendency to deviate toward the model was strongly correlated with executive dysfunction, and significantly increased when PD-D individuals were engaged in dual-task compared with single task conditions. Some individuals attempted to counteract CI, but this trend significantly decreased in dual-task compared with the single task conditions. In healthy adults the drift toward the model was significantly smaller than in PD-D individuals; in dual-task conditions healthy adults only showed a significant decrease in their ability to compensate for this drift., Conclusions: In PD-D individuals the tendency to deviate toward a salient model is strongly enhanced by a concurrent cognitive load. Such preliminary findings would suggest a relationship between reduction of executive attentional resources and the genesis of CI in PD-D individuals.

Background: Apathy and depression are behavioral manifestations that may occur often in Alzheimer's disease (AD) patients. AD patients may also show Closing-in (CI) phenomenon, in graphic copying tasks. Recent evidence would suggest that apathetic symptoms are related to frontal dysfunctions in AD patients, whereas the cognitive bases of depressive symptoms in AD are still unclear. Recent studies demonstrated that frontal dysfunctions are also involved in the genesis of CI in AD patients., Objective: Since frontal dysfunctions are thought to be more strongly related to apathetic than depressive symptoms, here we tested the hypothesis that CI is significantly associated with apathy in AD patients., Methods: Forty-four AD patients were enrolled for this study. All patients completed a neuropsychological evaluation of visuo-spatial, frontal/executive, visuo-constructional, and memory skills. Moreover, graphic copying tasks were employed to detect CI, and behavioral scales to assess apathetic and depressive symptoms., Results: CI and apathetic and depressed symptoms occurred in more than half of the present AD sample, but regression models revealed that the number of CI was significantly related to apathy only. The number of CI was also significantly correlated with severity of apathetic but not of depressive symptoms., Conclusion: The present study demonstrated that CI and apathy are correlated with each other in mild to moderate AD, likely because they share common pathogenic mechanisms related to frontal/executive dysfunctions.

Environmental dependency (ED) phenomena, including utilization behavior and imitation behavior, are clinical manifestations typically observed in patients with the behavioral variant of fronto-temporal dementia (bvFTD), who may also show the closing-in (CI) phenomenon. Here, we explored the neuropsychological correlates of ED and CI in bvFTD, and the association of ED with CI to clarify the mechanisms underlying these clinical manifestations. Thirty-one bvFTD patients underwent a wide cognitive assessment in addition to special tasks to detect occurrence of CI and ED phenomena. Both ED and CI phenomena were present in more than half of the sample. Logistic regression analyses revealed that both ED and CI phenomena were significantly associated with poor scores on frontal neuropsychological tests. Although ED and CI often co-occurred, 3/12 patients with CI did not show ED, and 5/18 patients with ED did not show CI. A logistic regression model showed that the presence of ED was not significantly associated to CI. CI and ED are associated to progressive derangement of frontal functions in bvFTD. However, specific frontal dysfunctions might explain the occurrence of either phenomenon in isolation.

Background: Apathy is defined as lack of motivation affecting cognitive, emotional, and behavioral domains and is usually assessed by standardized scales, such as the Apathy Evaluation Scale (AES). Recently, apathy has been recognized as a frequent behavioral symptom in multiple sclerosis (MS)., Objective: To evaluate applicability and clinical-metric properties of AES in MS and the agreement between patients' and caregivers' evaluation of apathy., Materials and Methods: Seventy non-demented MS patients underwent a thorough clinical and neuropsychological assessment, including evaluation of apathy according to established clinical criteria. All patients also completed the self-report version of AES (AES-S)., Results: AES-S was easy to administer and acceptable, and showed fair internal consistency (Cronbach's alpha, α=0.87). The factorial analysis identified three factors, representing the cognitive dimension (α=0.87), a general aspect of apathy (α=0.84), and the behavioral-emotional aspects (α=0.74), respectively. The factors were significantly correlated with the total AES score (all rrho≥0.73, p<0.001). The total AES score showed fair convergent validity (rrho=0.38) and discriminant validity when compared to Expanded Disability Status Scale (rrho=0.38), Mini Mental State Examination (rrho=-0.17), and Hamilton Depression Rating Scale (rrho=0.37). Receiver-operating characteristic curve analysis demonstrated that a cutoff>35.5 can identify clinically significant apathy with good sensitivity (88%) and specificity (72%); such a cutoff identified apathy in 35.7% of our sample of non-demented MS patients. Total AES score was significantly correlated with reduced global cognitive efficiency and more severe frontal executive dysfunctions., Conclusion: AES-S can be considered as an easy and reliable tool to assess apathy in non-demented MS. The use of AES-S in non-demented MS patients is clinically important since apathy is relatively frequent and is correlated to more severe cognitive dysfunction., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Apathy is a behavioural disturbance occurring alone or in concomitance with depression in Parkinson's disease (PD). Here we present a validation study for the self-report version of the Apathy Evaluation Scale (AES-S), carried out in a sample of 60 non-demented, non-depressed untreated, drug-naïve, de novo PD patients; 20 patients of the sample (33.3%) were classified as apathetic according to current clinical criteria. All enrolled patients completed the AES-S and a neurological and cognitive assessment. Mean AES-S score was 34.43. AES-S did not show floor or ceiling effect. Cronbach's alpha was 0.872. Principal component analysis revealed three factors: the first (34.4% of the variance) represented constitutive aspects of the construct of apathy; the second (8.5% of the variance) represented a social dimension; the third factor (7.9% of the variance) represented a dimension related to insight. With respect to clinical criteria for apathy considered as the gold standard, receiver operating characteristics curve analysis showed that a cut-off of 36/37 has the maximum discrimination power. High sensitivity and negative predictive values were obtained with cut-off scores of 33/34 or lower; high specificity and positive predictive values were obtained with cut-off scores of 38/39 or higher. AES-S score correlated with scores on frontal tasks, but not on Beck Depression Inventory, Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale. The AES-S is a reliable and valid questionnaire for detecting apathy in PD. For screening purposes a 33/34 cut-off score is indicated, but a 38/39 cut-off score is necessary when a high specificity is desired.

Ongoing signals from one's own body (interoception) allow experience of self-feeling. In early studies interoception strictly referred to the awareness of visceral sensation but recent theories have expanded this concept to denote the ongoing status of the body. Here we asked left and right focal brain-damaged patients to answer questions about their interoceptive feelings, and correlated their responses to a quantitative measure of their lesions (voxel-based symptom-lesion mapping). By these means we could reveal that three key structures contribute to building up the feeling of self, namely insula (interoceptive modulator), amygdala (emotional modulator) and putamen (motor modulator). This brain network may be necessary for the integrity of self-feeling. A dysfunction of this network might impair perception of the inner body state, and also account for psychological disturbances, such as the somatic symptom disorders, in which individuals experience subjective symptoms suggesting physical illness or injury despite medical test results which are normal, and clinical examination do not disclose relevant medical conditions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Progressive prosopagnosia (PP) is a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people. Here we report a patient (G.S.) with PP, mainly related to a prominent deficit in recognition of familiar faces, without a semantic (cross-modal) impairment. An in-depth evaluation showed that his deficit extended to other classes of objects, both living and non-living. A follow-up neuropsychological assessment did not reveal substantial changes after about 1 year. Structural MRI showed predominant right temporal lobe atrophy. Diffusion tensor imaging was performed to elucidate structural connectivity of the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), the two major tracts that project through the core fusiform region to the anterior temporal and frontal cortices, respectively. Right ILF was markedly reduced in G.S., while left ILF and IFOFs were apparently preserved. These data are in favour of a crucial role of the neural circuit subserved by right ILF in the pathogenesis of PP., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Closing-in (CI) in visuo-constructional tasks occurs when a drawing is reproduced close to or superimposed on the original model. CI has been often observed in Alzheimer disease (AD) patients and only rarely investigated in patients with vascular dementia (VD). Recent studies suggested that CI in AD patients represents a default behavior released by frontal-executive impairments, but the cognitive mechanisms behind this phenomenon in VD patients have not been clarified. We aimed to ascertain whether the same mechanisms could determine CI in VD and in AD patients. For this purpose we explored whether CI is related to frontal-executive or visuospatial impairments in a prospective sample of AD and VD patients, and investigated whether CI can be induced by a secondary task in patients with either disease., Method: Sixty-three VD patients and 70 AD patients underwent a neuropsychological assessment of frontal-executive and visuospatial skills, and a copying drawings task for CI. Moreover, VD and AD patients without CI also performed a drawing copying task combined with a simple or a demanding verbal task., Results: In both VD and AD patients CI was related to frontal-executive impairments, with more severe forms of CI related to greater frontal-executive defects. In AD patients the tendency to deviate toward a salient model was significantly enhanced by reduction of cognitive resources, whereas VD could compensate for this tendency., Conclusions: CI is related to the tendency to deviate toward a salient model and can be released by frontal-executive impairments in demented patients, independently from clinical diagnosis., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Background and Purpose: Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non-demented Parkinson's disease (PD) outpatients., Methods: Amongst 115 patients, SubD was identified in 30 patients, major depression in 33; 36 patients were classified as non-depressed. Enrolled patients were administered tests and questionnaires validated in PD for assessing objective and subjective cognitive dysfunctions., Results: On objective cognitive measures SubD patients did not differ from non-depressed patients, whereas depressed patients achieved significantly lower scores than the other two groups. SubD and depressed patients reported more cognitive complaints than non-depressed patients., Conclusions: SubD is a non-motor aspect of PD that is not related to objective cognitive deficits but is associated with subjective cognitive complaints, thus impacting on patients' well-being., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

It has been repeatedly demonstrated that mentally performing an action and mentally transforming body-parts entail simulation of one's own body movements, consistent with predictions of embodied cognition theories. However, the involvement of embodied simulation in mental transformation of whole-body images is still disputed. Here, we assessed own body transformation in Parkinson's disease (PD) patients with symptoms most affecting the left or the right body side. PD patients were required to perform left-right judgments on front-facing or back-facing human figures, and a letter rotation task. Results demonstrated that PD patients were selectively impaired in judging the side of back-facing human figures corresponding to their own most affected side, but performed as well as healthy subjects on mental transformation of front-facing bodies and on letter rotation. These findings demonstrate a parallel impairment between motor and mental simulation mechanisms in PD patients, thus highlighting the specific contribution of embodied cognition to mental transformation of whole-body images., (Copyright © 2014. Published by Elsevier B.V.)

We investigated whether the extra-/introversion personality dimension can influence processing of others' eye gaze direction and emotional facial expression during a target detection task. On the basis of previous evidence showing that self-reported trait anxiety can affect gaze-cueing with emotional faces, we also verified whether trait anxiety can modulate the influence of intro-/extraversion on behavioral performance. Fearful, happy, angry or neutral faces, with either direct or averted gaze, were presented before the target appeared in spatial locations congruent or incongruent with stimuli's eye gaze direction. Results showed a significant influence of intra-/extraversion dimension on gaze-cueing effect for angry, happy, and neutral faces with averted gaze. Introverts did not show the gaze congruency effect when viewing angry expressions, but did so with happy and neutral faces; extraverts showed the opposite pattern. Importantly, the influence of intro-/extraversion on gaze-cueing was not mediated by trait anxiety. These findings demonstrated that personality differences can shape processing of interactions between relevant social signals.

Closing-in (CI) refers to copying drawings near to or superimposed on the original model, and is often observed in Alzheimer's disease (AD) patients. Contrasting hypotheses have been suggested to explain CI, but no prospective study has directly verified these interpretations. We evaluated the role of frontal/executive versus visuo-spatial impairments in a prospective sample of AD patients, and also explored whether different types of CI are related to specific neuropsychological tasks. We enrolled 64 AD patients who underwent copying tasks and an extensive neuropsychological assessment of visuo-spatial and visuo-constructional skills, frontal/executive abilities and anterograde memory. AD patients with CI showed more severe impairment on frontal/executive functions than AD patients without CI. Moreover, the tendency to produce copies superimposed on the model was selectively associated with poor inhibitory control for irrelevant responses. On this basis, we suggest that different CI phenomena could be ascribed to distinctive frontal/executive defects.

Asperger syndrome (AS) is a neurodevelopmental condition within the Autism Spectrum Disorders (ASD) characterized by specific difficulties in social interaction, communication and behavioural control. In recent years, it has been suggested that ASD is related to a dysfunction of action simulation processes, but studies employing imitation or action observation tasks provided mixed results. Here, we addressed action simulation processes in adolescents with AS by means of a motor imagery task, the classical hand laterality task (to decide whether a rotated hand image is left or right); mental rotation of letters was also evaluated. As a specific marker of action simulation in hand rotation, we assessed the so-called biomechanical effect, that is the advantage for judging hand pictures showing physically comfortable versus physically awkward positions. We found the biomechanical effect in typically-developing participants but not in participants with AS. Overall performance on both hand laterality and letter rotation tasks, instead, did not differ in the two groups. These findings demonstrated a specific alteration of motor imagery skills in AS. We suggest that impaired mental simulation and imitation of goal-less movements in ASD could be related to shared cognitive mechanisms.

Can reading others' emotional states be shaped by expertise? We assessed processing of emotional facial expressions in professional actors trained either to voluntary activate mimicry to reproduce character's emotions (as foreseen by the "Mimic Method"), or to infer others' inner states from reading the emotional context (as foreseen by "Stanislavski Method"). In explicit recognition of facial expressions (Experiment 1), the two experimental groups differed from each other and from a control group with no acting experience: the Mimic group was more accurate, whereas the Stanislavski group was slower. Neither acting experience, instead, influenced implicit processing of emotional faces (Experiment 2). We argue that expertise can selectively influence explicit recognition of others' facial expressions, depending on the kind of "emotional expertise".

Closing-in (CI) is the tendency to act very close to the model in tasks such as drawing, 3D construction, gesture imitation, or writing. Closing-in is observed in degenerative and focal brain diseases, but also in normally developing children. In the present paper, three experiments were conducted to evaluate whether CI can be triggered during a copying task in normal young adults by increasing stimulus complexity and attentional load. Participants were required to copy complex lines in one of three conditions: without interfering activities (baseline), during counting, or during execution of a 2-back short-term memory task. In Experiment 1, participants were required to reproduce horizontally aligned stimuli, starting from a dot placed below each stimulus and proceeding from left to right; in Experiment 2, stimuli were again horizontally aligned, but the starting dot was placed above each stimulus, and writing proceeded from right to left; in Experiment 3, stimuli were aligned vertically and copying proceeded in upward direction. Results from all experiments showed that when normal young adults are engaged in an attentional-demanding concurrent activity, they tend to approach to the model, whereas the effect of stimulus complexity disappeared with unusual writing direction (Experiments 2 and 3). These findings demonstrate that even in normal young adults, a reduction in available attentional resources can release an attraction toward the model.

The theory of mind (ToM) is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the present study was to explore the neuropsychological correlates of cognitive and affective ToM in patients affected by essential tremor (ET). Thirty consecutive ET outpatients and 30 healthy age-, sex- and education-matched control subjects underwent tasks assessing short-term memory, verbal learning and executive functions, as well as tasks assessing "cognitive" and "affective" ToM; questionnaires evaluating behavioral disorders and quality of life were also administered. Although the two groups did not differ on demographic variables, ET patients scored worse on memory tasks, and showed more apathy and worse quality of life than controls. After covarying for mnestic, behavioral and quality of life scores, ET patients achieved significantly lower scores than controls on task assessing cognitive ToM, whereas no difference was found between the two groups on task assessing affective ToM. In ET, "Cognitive" ToM was significantly associated with frontal tasks, whereas "Affective" ToM was not correlated with cognitive, behavioral or quality of life scales. Our results indicate that cognitive aspects of ToM may be selectively impaired in ET. Possible underlying neural mechanisms of the deficits are discussed.

We report the case of a man affected by Parkinson's disease who developed an unusual, severe, repetitive behavior characterized by an irrepressible need to drum and beat percussion instruments following to the introduction of pramipexole. This compulsive behavior was not associated to a pattern of chronic inappropriate overuse of dopaminergic medication or other psychiatric symptoms. Sharing many features with other repetitive behaviors, compulsive drumming might be considered a distinct manifestation of punding in Parkinson's disease.

Apathy is defined as a lack of motivation and has been reported to be common in Alzheimer's disease (AD) and Parkinson's disease (PD). To explore the neuropsychological correlates of apathy in patients with PD related dementia (PDD) and AD and to identify the specific cognitive profile of apathy in the two forms of neurodegenerative disease, 61 non-depressed patients (29 PDD and 32 AD) were selected. Out of these, 29 patients (47.5%) were detected as apathetic (14 PDD-A+ and 15 AD-A+), and 32 patients as non-apathetic (15 PDD-A- and 17 AD-A-). All patients underwent cognitive tasks tapping memory, visuospatial and executive functions, behavioral rating scales and Clinical Judgment for Apathy Syndrome (CJ-AS), an inventory developed to measure severity of apathy. The four subgroups differed significantly on memory and frontal tasks. The PDD-A+ performed significantly worse than PDD-A- on frontal tasks. The AD-A+ had poorer performance than AD-A- on frontal tasks. Last, PDD-A+ achieved significantly higher scores than AD-A+ on memory tasks. The four groups differed significantly on CJ-AS and behavioral rating scales.The results showed that apathetic patients with both forms of dementia showed a common neuropsychological and behavioral picture, characterized by defects on frontal tasks, thus strongly supporting the existence of an 'apathetic syndrome', characterized by specific cognitive and psychological symptoms.

Apathy has been defined as lack of motivation. It has been traditionally considered as a symptom of psychiatric disorders, such as major depression and schizophrenia, but more recently it has been recognized as a specific neuropsychiatric syndrome associated with neurodegenerative such as Parkinson's disease (PD). As a consequence the reported prevalence of apathy in PD ranges from 13.9% to 70%; the mean prevalence is 35%. Prevalence of "pure apathy" (i.e., of apathy without comorbid depression and dementia) seems to be substantially lower, from 3 to 47.9%. High levels of apathy in PD are associated with decreased daily function, specific cognitive deficits and increased stress for families. Although neuroimaging studies do not provide a unique anatomic pattern, several data suggest that the ventromedial prefrontal cortex and the basal ganglia connected through frontal-subcortical circuits, are particularly involved in the genesis of apathy. At present, there are no approved medications for the treatment of apathy in and no proof of efficacy exists for any drug in current use. Further studies and innovative pharmacologic approaches are thus needed to ameliorate our understanding and treatment of apathy in PD.