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Objectives Neurocognitive disorders in Parkinson's disease (PD) are common and heterogeneous. The aim of this study was to use a data-driven method to describe different cognitive phenotypes in PD and to explore anxiety, depression, and motor disturbances across the different cognitive profiles. Method Latent profile analysis was applied to the neuropsychological performances of 65 patients with idiopathic PD assessed by means of a battery of tests that encompass measures of attention, memory, executive functions, social cognition, language, and visuospatial abilities. Results A three-cluster model produced the best solution: Cluster A (21.54%) included patients with intact cognition or with a relatively slight cognitive impairment in memory and executive functioning; Cluster B (53.85%) included patients with an intermediate level of cognitive impairment; and Cluster C (24.61%) included patients with the most severe cognitive impairment, with greater deficit compared to Cluster B in executive functioning, and, notably, in tasks with a predominantly posterior cortical basis (naming and visuospatial abilities). The three subgroups did not differ in terms of age, gender, disease duration, motor symptom severity or side of onset, levodopa equivalent daily dose, level of anxiety, or depression; however, patients from Cluster C showed greater impairment than patients from Cluster A in measures of everyday functioning. Conclusions We presented a qualitative description of three distinct cognitive phenotypes emerging from a sample of 65 PD patients. The three clusters seem to be related to daily functioning but are independent from the stage of disease, motor functioning, anxiety, and depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Starting from the early 2000s, paired associative stimulation (PAS) protocols have been used in humans to study brain connectivity in motor and sensory networks by exploiting the intrinsic properties of timing-dependent cortical plasticity. In the last 10 years, PAS have also been developed to investigate the plastic properties of complex cerebral systems, such as the frontal ones, with promising results. In the present work, we review the most recent advances of this technique, focusing on protocols targeting frontal cortices to investigate connectivity and its plastic properties, subtending high-order cognitive functions like memory, decision-making, attentional, or emotional processing. Overall, current evidence reveals that PAS can be effectively used to assess, enhance or depress physiological connectivity within frontal networks in a timing-dependent way, in turn modulating cognitive processing in healthy and pathological conditions.

Cognitive function impairment due to high altitude exposure has been reported with some contradictory results regarding the possible selective cognitive domain involvement. We prospectively evaluated in 36 lowlanders, exposed for 3 consecutive days to an altitude of 3,269 m, specific cognitive abilities (attention, processing speed, and decision-making) required to safely explore the mountains, as well as to work at altitude. We simultaneously monitored the physiological parameters. Our study provides evidence of a reduced processing speed in lowlanders when exposed to altitude in the first 24 h. There was a fairly quick recovery since this impairment was no more detectable after 36 h of exposure. There were no clinically relevant effects on decision-making, while psychomotor vigilance was unaffected at altitude except for individuals with poor sleep. Significant changes were seen in physiological parameters (increased heart rate and reduced peripheral oxygen saturation). Our results may have practical implications, suggesting that individuals should practice prudence with higher ascent when performing risky activities in the first 24–36 h, even at altitudes below 3,500 m, due to an impairment of the cognitive performance that could worsen and lead to accidents.

Introduction: Parkinson's Disease (PD) is characterized by motor and non-motor symptoms, among which deficits in social cognition might affect ~20% of patients. This study aims to evaluate the role of social cognitive abilities in the perceived impact of COVID-19 emergency, and the effects of lockdown measures on patients' social network and caregivers' burden.Methods: Fourteen PD patients performed a neuropsychological battery including sociocognitive tasks before the introduction of COVID-19 restrictive measures (i.e., social distancing and isolation). A structured interview through an online platform was performed in the last 2 weeks of the first lockdown phase to assess patients' health status, perception of COVID-19 emergency, changes in caregivers' burden, and patients' social isolation. Non-parametric analyses were performed to evaluate the association between social skills and patients' COVID-19 perception, as well as the effects of restrictive measures.Results: At baseline evaluation, half of the PD patients showed sociocognitive dysfunctions, mainly on mentalizing abilities. Patients with impaired social cognition skills showed a significantly lower concern on the possible effects of COVID-19 on their health. Caregiver burden and patients' social network remained stable during the lockdown.Conclusion: These preliminary results underline that PD sociocognitive dysfunctions might affect patients' abilities to estimate the effects of COVID-19 infection. However, the lack of a significant increase in caregivers' burden and social isolation suggests, in our sample, a good coping to COVID-19 emergency. Since COVID-19 pandemic can have direct and indirect severe consequences in patients with PD, the development of educational and preventive programs is recommended.

L’obesità e il Disturbo da Uso di Sostanze (DUS) sono disturbi caratterizzati da ricadute croniche e dal desiderio incontrollabile di consumare la sostanza, o craving. La letteratura scientifica suggerisce che il craving può essere elicitato dall’esposizione ai cue e che le moderne tecniche non invasive di stimolazione cerebrale possono essere utilizzate per contrastarlo. Tuttavia, alcuni elementi che non sono stati sufficientemente esaminati dalla letteratura scientifica sull’argomento: (i) l’influenza di diversi fattori, interni ed esterni, sulle risposte neurali agli stimoli di cibo o droga; (ii) i meccanismi neurobiologici sottostanti gli interventi di stimolazione cerebrale non invasiva applicati all’obesità. Nella mia tesi propongo un’indagine sistematica di questi elementi mediante tecniche meta-analitiche e di functional Magnetic Resonance Imaging (fMRI), dimostrando che diversi fattori modulano le basi neurali del craving, e che la Stimolazione Magnetica Transcranica profonda (deep TMS) ad alta frequenza induce dei cambiamenti a livello dell’organizzazione funzionale cerebrale in un campione di pazienti obesi. Nell’introduzione generale (Capitolo 1), descrivo i circuiti neurali principali coinvolti nel craving per il cibo e per le sostanze, all’interno di una cornice teorica unitaria che considera l’influenza di diversi fattori interni ed esterni che modulano la risposta neurale ai cue, nell’obesità e nel DUS. Nel Capitolo 2, uso un nuovo toolbox basato su un algoritmo di clustering gerarchico (Clustering the Brain, CluB) combinandolo con il metodo Activation Likelihood Estimation, al fine di meta-analizzare 22 studi di neuroimmagine sull’influenza del peso (normopeso vs. obesi), della modalità sensoriale di presentazione del cue (visiva vs. gustativa) e della sazietà (a digiuno vs. sazietà) sulle risposte neurali agli stimoli di cibo. L’evidenza proveniente dagli effetti semplici e dalle interazioni fra questi fattori è stata interpretata in funzione delle principali teorie neurocognitive dell’obesità. Nel Capitolo 3 impiego lo stesso approccio metodologico per meta-analizzare 64 studi di neuroimmagine sull’influenza della severità della dipendenza (dipendenza da sostanze legali vs. illegali) e dello stato di trattamento (in cerca di trattamento vs. non in cerca) sulla reattività neurale agli stimoli visivi di droga in pazienti con DUS. L’evidenza proveniente dagli effetti semplici e dalle interazioni fra questi fattori è stata interpretata in funzione delle teorie più influenti circa l’effetto dello stato di trattamento e della disponibilità della sostanza sulle risposte neurali ai cue. Nell’Appendice A svolgo un’analisi approfondita dell’approccio meta-analitico impiegato nel Capitolo 2 e nel Capitolo 3, dimostrando che CluB può (i) estrarre in modo attendibile dei cluster di attivazioni coerenti a partire da un database di coordinate stereotassiche, e (ii) testare la specificità dei cluster nel contesto di disegni fattoriali che solitamente non possono essere implementati in studi meta-analitici. Nel Capitolo 4 valuto i cambiamenti neurofunzionali associati ad un trattamento di deep rTMS (target neuroanatomico: insula bilaterale e corteccia prefrontale) di 5 settimane per ridurre il craving per il cibo ed il peso corporeo in un campione di 17 pazienti obesi sottoposti a stimolazione ad alta frequenza (N=9) versus sham (N=8). In particolare, applico un nuovo metodo data-driven su dati provenienti da scansioni di resting-state fMRI per testare l’ipotesi che la stimolazione reale, rispetto alla stimolazione sham, può indurre cambiamenti plastici nell’organizzazione funzionale cerebrale di regioni implicate nel craving per il cibo. Concludo con il Capitolo 5, nel quale integro i miei risultati all’interno di una cornice teorica unitaria per i disordini della motivazione, discutendo le implicazioni per la ricerca di base e per la medicina traslazionale. Obesity and Substance Use Disorder (SUD) are chronic relapsing disorders characterized by pathological craving. Evidence suggests that craving can be prompted by the exposure to food or drug-related cues, and that current non-invasive brain stimulation techniques can be used to down-regulate craving. However, there is limited available information about (i) the influence of internal and external factors on the neural responses to food and drug cues, and (ii) on the neurobiological mechanisms beyond non-invasive brain stimulation applied to obesity.In my thesis, I provide a systematic meta-analytical and fMRI investigation of these issues, demonstrating that several internal and external factors modulate the neural correlates of craving in obesity and SUD, and that excitatory deep TMS induces plastic changes in the neurofunctional brain organization in sample of obese individuals. In the general introduction (Chapter 1), I describe the core neural networks involved in food and drug craving, within a unitary framework that accounts for the influence of several internal and external factors that modulate the neural responses to cues, in both obesity and SUD. In Chapter 2, I combine a novel toolbox based on hierarchical clustering algorithm (Clustering the Brain, CluB) with the Activation Likelihood Estimation method to meta- analyze 22 studies on the influence of weight-status (healthy-weight vs. obese), sensory modality of stimulus presentation (visual vs. gustatory), and satiety state (hungry vs. satiated) on the neural responses to food cues. In particular, evidence from such main and interaction effects are taken as a benchmark to test the validity of the main neurocognitive theories of overeating and obesity. In Chapter 3, I use the same method to meta-analyze 64 neuroimaging studies on the influence of addiction severity (addiction to legal vs. illegal substances) and treatment status (treatment-seeking vs. not-seeking treatment) on the neural drug cue-reactivity in SUD. Evidence from the main and interactive effects will be taken as a benchmark to discuss one of the most influential theories on the influence of treatment status and drug availability on the neural responses to drug cues. An in-depth analysis of the meta-analytical method employed in Chapter 2 and Chapter 3 is reported in Appendix A, where I describe two validation studies demonstrating that CluB can (i) reliably extract a set of spatially coherent clusters of activations from a database of stereotactic coordinates, and (ii) test for factor-specific clusters of convergent activation within designs that cannot be usually implemented in a meta-analytical study. In Chapter 4, I assess the neurofunctional changes associated with a 5-weeks deep rTMS treatment targeting the bilateral insular and prefrontal cortices to induce weight-loss and reducing food craving in a sample of 17 obese individuals undergoing excitatory (N=9) versus sham (N=8) stimulation. In particular, I apply a novel data-driven method on resting- state fMRI data to test that hypothesis that real, compared to sham, deep rTMS can induce plastic changes in the brain functional organization of key areas involved in food craving. Finally, I conclude with Chapter 5, where I integrate my findings into a unitary theoretical framework for the disorders of the motivation, discussing their implications for basic research and translational medicine.

Agire e modificare il mondo circostante attraverso le proprie intenzioni e azioni volontarie rappresenta una caratteristica essenziale della natura umana. Questa peculiare esperienza si accompagna tipicamente ad una sensazione implicita di controllo volontario sugli eventi esterni, denominata “senso di agentività”. A causa della natura elusiva e di difficile misurazione, che mal si concilia con un’indagine esplicita – diretta – delle sue caratteristiche, il senso di agentività e i meccanismi neurali che ne permettono l’origine nella mente umana rimangono ad oggi ancora poco esplorati e compresi. Nel corso delle ultime due decadi, nuove misure oggettive sono state introdotte per permettere lo studio del senso di agentività senza snaturarne la natura implicita. Fra queste, il cosiddetto “intentional binding effect”, si riferisce all’esperienza soggettivamente percepita di una compressione temporale fra un’azione svolta intenzionalmente prodotta e la conseguenza da essa generata. Dalla sua prima introduzione entro il panorama scientifico internazionale, l’intentional binding effect, unito ad i più moderni modelli cognitivi e computazionali del controllo cerebrale del movimento volontario, ha dato un nuovo slancio allo studio del senso di agentività. In aggiunta, l’introduzione di diverse tecniche strumentali - di neuroimmagine e neurostimolazione – offre oggi l’opportunità di indagare il senso di agentività personale – e i suoi correlati neurali – superando i limiti degli studi precedenti. Il presente progetto di dottorato ha pertanto avuto l’obiettivo di investigare le caratteristiche fondamentali – e i meccanismi neurali – del senso di agentività, utilizzando l’intentional binding effect come misura oggettiva, entro una serie di esperimenti condotti con tecniche meta-analitiche, di neuroimmagine e neurostimolazione, in diversi campioni di soggetti adulti sani e affetti da patologia del movimento. In particolare, il progetto ha avuto inizio con un’indagine meta-analitica della letteratura preesistente di neuroimmagine (capitolo 1) che ha permesso di caratterizzare lo stato dell’arte della ricerca dei correlati neurali del senso di agentività. In seguito, si è snodato attraverso l’indagine delle aree cerebrali che generano il senso di agentività mediante uno studio di risonanza magnetica funzionale con intentional binding effect in un campione di soggetti adulti sani (capitolo 2). Ha successivamente permesso di approfondire lo studio dei meccanismi neurali che generano il senso di agentività, mediante uno studio di stimolazione cerebrale invasiva mirato ad identificare il ruolo causale delle aree cerebrali implicate nel senso di agentività preventivamente evidenziate dallo studio di neuroimmagine (capitolo 3). Ha successivamente consentito di esplorare differenze e somiglianze dell’esperienza di agentività (e rispettivi correlati neurali) per diverse conseguenze generate dall’azione intensionalmente svolta, differenti per modalità sensoriale di presentazione (uditiva vs. visiva, capitolo 4). Si è infine concluso con l’indagine dell’esperienza soggettiva di agentività e meccanismi neurofunzionali ad essa associata entro un campione di pazienti adulti affetti da sindrome di Tourette, un disturbo neurologico del movimento volontario (capitolo 5). Insieme a nuove conoscenze di base relative alla percezione soggettiva del controllo volontario delle azioni e meccanismi neurali implicati, questo progetto di ricerca apre nuove frontiere per comprendere e trattare i disturbi del senso di agentività, ed offre diverse possibilità di sviluppo per nuove indagini cliniche ed empiriche (discusse entro il capitolo 6). Modifying the external world through our own voluntary actions is a fundamental aspect of human experience. In adult life, this experience also produces a peculiar feeling of controlling external events, called the “sense of agency.” Perhaps because of its elusive essence, both the subjective experience of agency and its neural correlates – although extensively investigated – remain poorly understood. Over the past decades, new objective measures have been developed to study the sense of agency (e.g., the intentional binding effect), together with new theories emerging from cognitive and computational neuroscience. Coupled with multi-modal neuroscientific techniques, these new methods and theories create a powerful set of tools for investigating the subjective experience of agency and overcoming the limits of previous studies. In this PhD project, I explored the sense of agency by taking advantage of the implicit index of the agency experience known as the intentional binding effect in a series of experiments with meta-analytical techniques, behavioral tasks, functional magnetic imaging, and non-invasive brain stimulation, in healthy and pathological populations. In particular, I first reviewed the state of the art of the investigation on the human sense of agency (chapter one, introduction and meta-analytical investigation). I then characterized the neurofunctional correlates of the sense of agency (chapter two, first functional magnetic resonance imaging (fMRI) study) and determined the consequences of modulating the key nodes of the resulting putative agency brain network on the behavior (chapter three, transcranial magnetic stimulation (TMS) study). I continued exploring the effects of modulating different features of the action-outcome on the behavior and cortical activity associated with the sense of agency (chapter four, second fMRI study). Finally, I completed my investigation exploring possible aberrant agency experiences and associated neurofunctional alterations in a clinical population affected by Gilles de la Tourette syndrome (chapter five, third fMRI study). As well as offering new insights into how we feel in control of our movements, this PhD thesis provides new chances for understanding and treating the disorders of the sense of agency and suggests a number of opportunities for future clinical and empirical works (chapter six, general discussion).

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

Acquired Neglect Dyslexia is often associated with right-hemisphere brain damage and is mainly characterized by omissions and substitutions in reading single words. Martelli et al. proposed in 2011 that these two types of error are due to different mechanisms. Omissions should depend on neglect plus an oculomotor deficit, whilst substitutions on the difficulty with which the letters are perceptually segregated from each other (i.e., crowding phenomenon). In this study, we hypothesized that a deficit of focal attention could determine a pathological crowding effect, leading to imprecise letter identification and consequently substitution errors. In Experiment 1, three brain-damaged patients, suffering from peripheral dyslexia, mainly characterized by substitutions, underwent an assessment of error distribution in reading pseudowords and a T detection task as a function of cue size and timing, in order to measure focal attention. Each patient, when compared to a control group, showed a deficit in adjusting the attentional focus. In Experiment 2, a group of 17 right-brain-damaged patients were asked to perform the focal attention task and to read single words and pseudowords as a function of inter-letter spacing. The results allowed us to confirm a more general association between substitution-type reading errors and the performance in the focal attention task.

Nella presente tesi di dottorato, ho esplorato se fenomeni di apprendimento Hebbiano possano governare il funzionamento dei sistemi cross-modali e sensorimotori del cervello umano. A tal fine, durante il mio dottorato, ho sviluppato e testato due nuovi protocolli Paired Associative Stimulation (PAS), una classe di tecniche di stimolazione cerebrale non invasiva in cui una stimolazione sensoriale periferica viene ripetutamente accoppiata con un impulso di stimolazione magnetica transcranica (TMS) su un’area bersaglio al fine di indurre plasticità associativa Hebbiana. I due protocolli PAS presentati nella mia tesi mirano a due sistemi cerebrali sensoriali-motori con funzionamento a specchio (tactile mirror system e action observation network), sfruttando rispettivamente una via cross-corticale visuo-tattile (cross-modal PAS) e una visuo-motoria (mirror PAS). Nel primo capitolo del presente lavoro, dopo una breve introduzione al concetto di plasticità associativa Hebbiana, fornirò una revisione esaustiva dei protocolli PAS che mirano ai sistemi sensorimotori, proponendo una classificazione in tre macro-categorie (within-system, cross-systems e cortico-cortical), a seconda delle caratteristiche delle stimolazioni accoppiate. Nel secondo capitolo descriverò le principali proprietà del sistema dei neuroni specchio (MNS) considerando anche le sue proprietà cross-modali visuo-tattili ed i meccanismi di plasticità neuronale che sono stati ipotizzati alla base dello sviluppo dei neuroni specchio. Nel terzo capitolo, introdurrò il cross-modal PAS (cm-PAS), un nuovo cross-systems PAS sviluppato per sfruttare le proprietà visuo-tattili della corteccia somatosensoriale primaria, al fine di indurre plasticità associativa Hebbiana in tale regione sensoriale. In una serie di tre esperimenti, ho testo la dipendenza temporale (Esperimento 1), la specificità corticale (Esperimento 2) e visiva (Esperimento 3) del protocollo, misurando possibili cambiamenti nell'acuità tattile dei partecipanti. Nell'esperimento 3, ho valutato anche possibili cambiamenti neurofisiologici all'interno di S1, registrando i potenziali evocati somatosensoriali. Infine, in un quarto esperimento, la dipendenza temporale del cm-PAS è stata ulteriormente studiata, testando l'ipotesi che meccanismi anticipatori di tipo predittivo possano svolgere un ruolo centrale nell'efficacia del protocollo. Nel quarto capitolo introdurrò un secondo cross-systems PAS: il mirror PAS (m-PAS) che sfrutta le proprietà ‘mirror’ visuo-motorie del cervello umano. A differenza del cm-PAS, questo secondo protocollo sfrutta la natura associativa dell'integrazione visuo-motoria all'interno del MNS, mirando a indurre un nuovo, atipico, fenomeno di risonanza motoria attraverso apprendimento Hebbiano. In tre esperimenti ho testato la dipendenza temporale (Esperimento 1), la specificità visiva (Esperimento 2) e corticale (Esperimento 3) del protocollo registrando i potenziali evocati motori durante la visione di semplici movimenti (i.e., risonanza motoria). Inoltre, nel terzo esperimento, ho esplorato anche possibili effetti comportamentali dell’m-PAS, utilizzando un compito di compatibilità imitativa che sfrutta il fenomeno dell'imitazione automatica. Infine, nel capitolo conclusivo, discuterò i risultati teorici, metodologici e clinici e le prospettive future che derivano da questi due protocolli. In the present doctoral thesis, I have explored whether Hebbian learning may rule the functioning of cross-modal and sensory-motor networks of the human brain. To this aim, during my doctorate, I have developed and tested two novel Paired Associative Stimulation (PAS) protocols, a class of non-invasive brain stimulation techniques in which a peripheral, sensory, stimulation is repeatedly paired with a Transcranial Magnetic Stimulation (TMS) pulse to induce Hebbian associative plasticity. The two PAS protocols presented in my thesis target sensory-motor networks with mirror functioning, exploiting a visuo-tactile (cross-modal PAS), and a visuo-motor pathway (mirror PAS), respectively. In the first chapter of the present work, after a brief introduction to the concept of Hebbian associative plasticity, I will provide an exhaustive review of PAS protocols targeting sensory-motor systems, proposing a classification in three macro-categories: within-system, cross-systems, and cortico-cortical protocols, according to the characteristics of the paired stimulations. In the second chapter, I will describe the principal properties of the Mirror Neuron System (MNS) also considering its cross-modal (i.e., visuo-tactile) characteristics and the plastic mechanisms that are been hypothesize at the ground of the development of mirror neurons’ matching properties. In the third chapter, I will introduce the cross-modal PAS (cm-PAS), a novel cross-systems PAS developed to exploit the visuo-tactile mirroring properties of the primary somatosensory cortex (S1) to induce Hebbian associative plasticity in such primary sensory region. In a series of three experiments, timing dependency (Experiment 1), cortical (Experiment 2), and visual specificity (Experiment 3) of the protocol have been tested, by measuring changes in participants’ tactile acuity. In Experiment 3, also possible neurophysiological changes within S1 has been assessed, recording somatosensory-evoked potentials (SEP). Then, in a fourth experiment, cm-PAS timing dependency has been further investigated, testing the hypothesis that anticipatory, predictive-like, mechanisms within S1 may play a central role in the effectiveness of the protocol. In the fourth chapter, a second cross-systems PAS will be introduced: the mirror PAS (m-PAS) which exploits visuo-motor mirroring properties of the human brain. Differently from the cm-PAS, this second protocol targets visuo-motor integration within the MNS and aims at induce a novel, atypical, motor resonance phenomena (assessed recording motor-evoked potentials – MEPs) following Hebbian learning. In three experiments, timing dependency (Experiment 1), visual (Experiment 2), and cortical specificity (Experiment 3) of the protocol have been tested. Furthermore, in the third experiment, the behavioral effects of the m-PAS are explored, using an imitative compatibility task exploiting automatic imitation phenomenon. Finally, in the conclusive chapter, I will discuss theoretical, methodological, and clinical outcomes and future perspectives that arise from these two protocols and the related results.

In the early 2000s, a novel non-invasive brain stimulation protocol, the paired associative stimulation (PAS), was introduced, allowing to induce and investigate Hebbian associative plasticity within the humans' motor system, with patterns resembling spike-timing-dependent plasticity properties found in cellular models. Since this evidence, PAS efficacy has been proved in healthy, and to a lesser extent, in clinical populations. Recently, novel 'modified' protocols targeting sensorimotor and crossmodal networks appeared in the literature. In the present work, we have reviewed recent advances using these 'modified' PAS protocols targeting sensory and motor cortical networks. To better categorize them, we propose a novel classification according to the nature of the peripheral and cortical stimulations (i.e., within-system, cross-systems, and cortico-cortical PAS). For each protocol of the categories mentioned above, we describe and discuss their main features, how they have been used to study and promote brain plasticity, and their advantages and disadvantages. Overall, current evidence suggests that these novel non-invasive brain stimulation protocols represent very promising tools to study the plastic properties of humans' sensorimotor and crossmodal networks, both in the healthy and in the damaged central nervous system.

Mathematics, being a very ancient discipline, is usually seen as a formal subject that must be learned for school purposes, which is very far from creativity and fun. Also, mathematical skills are often considered a talent, so students are easily divided into gifted and not gifted, with a focus on speed and accuracy rather than encouraging the process of juggling between divergent and convergent thinking. In the present paper, we aimed at investigating the relationship between mathematical reasoning and different aspects of creative thinking, such as divergent and convergent creativity, aesthetic appreciation, and humor. To do so, 146 second and third graders in a primary school in Milan have been recruited and tested with mathematical and creative tasks. Correlational analyses showed significant positive relations between flexibility and originality dimensions of creativity and mathematical performance. Results are discussed by providing a theoretical framework about the relation between mathematics and creative skills.

The dual-route models of action distinguish between a semantic and a non-semantic visuo-motor route to execute different types of gestures. Despite the large amount of evidence in support to the model, some aspects are debated. One issue concerns the recruitment of the visuo-motor route to correctly execute meaningful gestures when the semantic route is damaged. Debated predictions of the dual-route model were investigated in a sample of 32 patients with left hemisphere stroke lesions compared to 27 healthy controls. Group analysis showed that patients were equally impaired on meaningful and meaningless gestures. Single-case analysis demonstrated that most cases were more impaired on meaningful than on meaningless gestures both when they are given in separate lists and when they are intermingled. Impaired performance on the imitation of meaningful gestures in both the separate and mixed list but spared performance on meaningless gestures in the separate list is against the hypothesis that the intact visuo-motor route compensates for damage to the semantic route. These results suggest that the damaged semantic route interferes with the visuo-motor route and prevents the processing of meaningful gestures along the visuo-motor route. Furthermore, an explorative analysis was conducted to investigate the relationship between gestures imitation and pantomime of object use on verbal command and between gestures imitation and performance on linguistic tasks. Although no significant correlation emerged, patients with moderate/severe impairment on the AAT performed significantly worse on meaningful, but not on meaningless gestures than patients with mild/minimal language impairment, suggesting that praxis and language systems are independent but dynamically interact.

Background: Comprehensive neuropsychological evaluations are often time-consuming and may not be suitable for every situation. Screening tests represent a useful tool to detect the altered status of cognitive functioning briefly. However, the majority of currently available tools show low to moderate ecological validity, limiting their capability to detect real-life impairments. Virtual Reality (VR) technology emerged as a possible solution as it can simulate everyday tasks maintaining a standard setting in almost any possible situation. Many VR-based cognitive tests are now present in the literature, but their psychometric properties are rarely assessed. Objective: The project has two objectives: achieving incremental evidence toward the feasibility of using 360° photos and videos in the neuropsychological assessment and creating a screening test for a valid and reliable clinical application. Methods: We are developing a new screening test (The 360° Mental Screening - MS-360°) that, instead of using computer-generated environments as scenarios, employs 360° photos and videos to generate an innovative, highly immersive VR environment. This media can simulate real-life situations in a photorealistic fashion, providing ecological stimuli and recording meaningful behavioral measures. The MS-360° uses videos recorded with an omnidirectional camera (Insta360 One X) as virtual environments, which can be administered wirelessly using a portable head-mounted display (Oculus Quest 2) and a 5GHzWi-Fi network. The test consists of a set of 360° videos including fourteen different scenarios: in each of these, the participant is asked to perform some ecological tasks aimed to elicit specific cognitive functions. We quantified the accuracy in each specific task as a measure of outcome. We are studying two groups at the current stage: patients reporting subjective cognitive impairment recruited from the CEMS Memory Center of Verona and healthy controls matched for age and education. We analyze differences and correlations between the score obtained at the MS-360° test and scores obtained in other established paper-and-pencil screening tests (e.g., MOCA, MMSE). We also analyze the user-experience, including usability and immersivity/presence measures. Results: Data collection is in due course. We expect that the MS-360° will show adequate user-experience rates as compared to similar technology. We also expect to find correlations between our test and the paper-and-pencil screening tests (range between |.5| and |.8|). Finally, we expect that the MS-360° will be able to distinguish patients’ and control’s performances. Conclusions: VR is emerging as a valid tool to design neuropsychological tests. However, the lack of proper validation studies limits the evidence for widespread use of this technology for a reliable assessment of cognitive functions. Moreover, the study of the ecological value of 360° scenarios compared to paper-and-pencil tests or computer graphic VR has the potential to unlock a new, easy-to-use, technological improvement.

Discriminating facial cues to trustworthiness is a fundamental social skill whose developmental origins are still debated. Prior investigations used computer-generated faces, which might fail to reflect infants' face processing expertise. Here, Event-Related Potentials (ERPs) were recorded in Caucasian adults (N = 20, 7 males, M age = 25.25 years) and 6-month-old infants (N = 21, 10 males) in response to variations in trustworthiness intensity expressed by morphed images of realistic female faces associated with explicit trustworthiness judgments (Study 1). Preferential looking behavior in response to the same faces was also investigated in infants (N = 27, 11 males) (Study 2). ERP results showed that both age groups distinguished subtle stimulus differences, and that interindividual variability in neural sensitivity to these differences were associated with infants' temperament. No signs of stimulus differentiation emerged from infants' looking behavior. These findings contribute to the understanding of the developmental origins of human sensitivity to social cues from faces by extending prior evidence to more ecological stimuli and by unraveling the mediating role of temperament.

We describe the case of a bilingual patient with persistent symptoms largely, although not fully, consistent with those that are usually reported in Gerstmann’s syndrome. Twenty months after a spontaneous primary intracranial hemorrhage, the patient was evaluated with a series of neuropsychological tasks and underwent an MRI investigation based on Diffusion Tensor Imaging probabilistic tractography. The patient suffered from dysgraphia (difficulty in the access to the graphemic representation of letter forms), autotopoagnosia (difficulties in locating body parts on verbal command), right–left confusion (difficulties in localizing right and left side of symmetrical body parts), and number processing/calculation impairments (predominant difficulties on transcoding tasks). Probabilistic tractography revealed a relatively spared superior longitudinal fasciculus and severe damage to the subcortical white matter connecting the angular gyrus with other parietal regions, such as the intraparietal sulcus and the supramarginal gyrus. Within the framework of the contemporary cognitive accounts of Gerstmann’s syndrome, the case supports the assumption of an anatomical intraparietal disconnection more than a functional Grundstorung (core impairment).

OBJECTIVE: Expectations are known to be key determinants of placebo and nocebo phenomena. In previous studies, verbal suggestions to induce such expectations have mainly focused on the direction and magnitude of the effect, whereas little is known about the influence of temporal information. METHODS: Using an experimental placebo and nocebo design, we investigated whether information about the expected onset of a treatment effect modulates the start and time course of analgesic and hyperalgesic responses. Healthy volunteers (n = 166) in three placebo and three nocebo groups were informed that the application of an (inert) cream would reduce (placebo groups) or amplify pain (nocebo groups) after 5, 15, or 30 minutes. Two control groups were also included (natural history and no expectations). Participants' pain intensity rating of electrical stimuli administered before and 10, 20, and 35 minutes after cream application was obtained. RESULTS: Mixed-method analysis of variance showed a significant interaction between group and time (F(12,262) = 18.172, p < .001, pη2 = 0.454), suggesting that pain variations differed across time points and between groups. Post hoc comparisons revealed that the placebo and nocebo groups began to show a significantly larger change in perceived pain intensity than the no-expectancy control group at the expected time point (p < .05) but not earlier (p > .05). Once triggered, the analgesic effect remained constant over the course of the experiment, whereas the hyperalgesic effect increased over time. CONCLUSIONS: Our results indicate that temporal suggestions can shape expectancy-related treatment effects, which, if used systematically, could open up new ways to optimize treatment outcome.

Prism adaptation (PA) is used to investigate visuo-motor plasticity and to rehabilitate the syndrome of Unilateral Spatial Neglect (USN). After PA, participants show aftereffects (AEs), contralateral to the side of the optical displacement in several tasks. This study explored the features of these AEs, specifically the “egocentric” versus “allocentric, object-based”, reference frames involved, and their time course. In three experiments, healthy participants adapted to prismatic lenses inducing a horizontal displacement of the visual field. In Experiment #1, participants adapted to rightward displacing prisms. Four tasks were used requiring repeated pointings towards the participant's subjective egocentric straight-ahead, with the availability of proprioceptive or visual-proprioceptive signals, and, in some conditions, of an external allocentric visual frame (i.e., a rectangular paper sheet). Experiment #2 explored the role of the position of the allocentric frame, with AEs being tested by straight-ahead and frame bisection tasks, requiring pointing toward the external visual frame, placed in different positions of the working space. An egocentric visual proprioceptive task was administered after prism removal and after the execution of the allocentric tasks, to assess the effectiveness of the PA, as indexed by the AEs, and their persistence up to the end of the administration of the allocentric tasks. Experiment #3 differed from #2 in that participants adapted to leftward displacing lenses. Consistent with evidence from USN patients, in Experiment #1, in the egocentric tasks, AEs lasting up to 30 min after PA were found. In Experiment #2, AEs in “allocentric” tasks did not occur, regardless of frame position. Experiment #3 showed AEs in both the “egocentric” and the “allocentric” tasks, with the latter being minor in size. These findings illustrate that the spatial reference systems modulated by PA in extra-personal space primarily operate in spatial “egocentric” reference frames, with a comparatively minor and direction-specific role of “allocentric” frames.

Background: Research on placebo analgesia commonly focuses on the impact of information about direction (i.e., increase or decrease of pain) and magnitude of the expected analgesic effect, whereas temporal aspects of expectations have received little attention so far. In a recent study, using short-lasting, low-intensity stimuli, we demonstrated that placebo analgesia onset is influenced by temporal information. Here, we investigate whether the same effect of temporal suggestions can be found in longer lasting, high-intensity pain in a Cold Pressor Test (CPT). Methods: Fifty-three healthy volunteers were allocated to one of three groups. Participants were informed that the application of an (inert-)cream would reduce pain after 5 min (P5) or 30 min (P30). The third group was informed that the cream only had hydrating properties (NE). All participants completed the CPT at baseline and 10 (Test 10) and 35 min (Test 35) following cream application. Percentage change in exposure time (pain tolerance) from baseline to Test 10 (Δ10) and to Test 35 (Δ35) and changes in heart rate (HR) during CPT were compared between the three groups. Results: Δ10 was greater in P5 than in NE and P30, indicating that analgesia was only present in the group that was expecting an early onset of analgesia. Δ35 was greater in P5 and P30 compared to NE, reflecting a delayed onset of analgesia in P30 and maintained analgesia in P5. HR differences between groups were not significant. Conclusions: Our data suggest that ‘externally timing’ of placebo analgesia may be possible for prolonged types of pain. Significance: Research on placebo effects mainly focuses on the influence of information about direction (i.e., increase or decrease of pain) and magnitude (i.e., strong or weak) of the expected effect but ignores temporal aspects of expectations. In our study in healthy volunteers, the reported onset of placebo analgesia followed the temporal information provided. Such ‘external timing’ effects could not only aid the clinical use of placebo treatment (e.g., in open-label placebos) but also support the efficacy of active drugs.

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date.

Background Selective bilateral lesions of the parietal–occipital lobes can lead to an uncommon and incompletely understood clinical entity, Balint’ syndrome, which consists of simultanagnosia, oculomotor apraxia, optic ataxia and difficulty in perceiving distances between objects. Case presentation We herein report a rare presentation of Balint’s syndrome in a 65-year-old woman suffering from stroke and SARS-CoV2 infection. Conclusion During SARS-CoV2 pandemic, Italian physicians were forced to work with less instrumental diagnostic resources, relying on their clinical knowledge mostly. The aim of this case report is to highlight the importance of performing a precise neurological evaluation, particularly during these challenging times: it might avoid incorrect diagnosis and favour the discovery of rare clinical diseases.

There is little doubt that one of Simon’s key contributions throughout his scientific career - if not the main one - was rooting the notion of bounded rationality in cognitive psychology (Simon, 1976). He called his notion of bounded rationality in the cognitive psychology realm ‘cognitivism’ (Haugeland, 1978), an approach, also known as the ‘information-processing’ approach, which he contributed to affirming together with his colleague Allen Newell starting in the mid-1950s. According to cognitivism, cognition works through the internal (i.e. mental) manipulation of representations of the external environment accomplished through referential ‘symbols’ (e.g., Newell & Simon, 1972). Connecting Simon’s theory of cognition to his theory of rationality is the notion that cognition works in a way that is necessary and sufficient for intelligent behavior (what is known as the ‘physical symbol system hypothesis’, see Newell & Simon, 1976). The idea that results from integrating Simon’s view of cognition with his view of bounded rationality is that rationality is a “process and product of thought” (Simon, 1978) in which the internal bounds of reason (Simon, 1955) adapt to the external bounds of the environment (Simon, 1956) in a disembodied fashion. In this picture, in fact, there is no place for flesh and blood. Patokorpi (2008) has emphasized that there is an inner tension in Simon’s thought, as on the one hand he was a strong advocate for a realistic approach to the bounds of rationality while, on the other hand, he represented them through the ‘unbounded’ power of digital computation and the metaphor of computers. This inner tension, which did not simply concern Simon’s thought but an entire generation of cognitive scientists, would have huge consequences in the history of cognitive psychology. In the early 1990s, Newell and Simon’s physical symbol system hypothesis was questioned when the ‘embodied robots’ designed by Rodney Brooks proved able to simulate simple forms of intelligent behavior by externalizing most of cognition onto the physical properties of environments, thus dispensing with abstract symbolic processing (Brooks, 1991). This is just one instance from the recent history of cognitive science pointing to the fact that while bounded rationality remains a pivotal notion in behavioral economics and economic psychology, new theoretical views and massive experimental evidence in cognitive science have led to supersede cognitivism and its abstract representation of cognition (Wallace et al., 2007). Contemporary cognitive psychology emphasizes that cognition is ‘embodied’, as it constitutively depends on body states, on the morphological traits of the human body, and on the sensory-motor system (see, e.g., Wilson, 2002). As such, it can be said to introduce another ‘bound’ to human cognition, able to integrate the internal bounds represented by cognitive limitations and the external bounds of task environments: the human body. In this paper, we argue that, in so far as the human body represents a new bound for human cognition, it can also have an important role in the re-conceptualization of bounded rationality. Since the new approach of embodied cognition is so recent, it is still rather plural and variegated, and as such far from a stable synthesis (for reviews on the issue of conceptual pluralism in embodied cognition see the classic Wilson, 2002; for more recent reviews, see Gallese & Lakoff, 2005; Clark, 2008; Kiverstein & Clark, 2009). Without the pretension to be exhaustive, here is a list of classic books on the idea that the body is a constitutive part of cognition: Varela, Thompson, & Rosch (1991); Clancey (1997); Clark, (1997); Lakoff & Johnson (1999); Rowlands (1999); Shapiro (2004); Gallagher (2005); Pfeifer & Bongard (2006). As a matter of terminology, although different labels have been used to identify and distinguish different views of embodiment, we will refer to them all by means of the common synthetic label ‘embodied cognition’ (Calvo & Gomila, 2008; Shapiro, 2014).

We address existing controversies regarding neuroanatomical substrates of reading‐aloud processes according to the dual‐route processing models, in this particular instance in a series of 49 individuals with brain tumors who performed several reading tasks of real‐time neuropsychological testing during surgery (low‐ to high‐grade cerebral neoplasms involving the left hemisphere). We explored how reading abilities in individuals with brain tumors evolve during and after surgery for a brain tumor, and we studied the reading performance in a sample of 33 individuals in a 4‐month follow‐up after surgery. Impaired reading performance was seen pre‐surgery in 7 individuals with brain tumors, intra‐surgery in 18 individuals, at immediate post‐surgery testing in 26 individuals, and at follow‐up in 5 individuals. We classified their reading disorders according to operational criteria for either phonological or surface dyslexia. Neuroimaging results are discussed within the theoretical framework of the dual‐route model of reading. Lesion‐mask subtraction analyses revealed that areas selectively related with phonological dyslexia were located—along with the left hemisphere dorsal stream—in the Rolandic operculum, the inferior frontal gyrus, the precentral gyrus, the supramarginal gyrus, the insula (and/or the underlying external capsule), and parts of the superior longitudinal fasciculus, whereas lesions related to surface dyslexia involved the ventral stream, that is, the left middle and inferior temporal gyrus and parts of the left inferior longitudinal fasciculus., We explored how reading abilities in individuals with neurosurgical lesions evolve during and after surgery for a brain tumor, and we studied the reading performance in a sample of 33 individuals in a 4‐month follow‐up after surgery.

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

Il seguente lavoro di tesi indaga il senso di ownership e di agency in schizofrenia come modalità per approfondire i meccanismi di consapevolezza del sé in questi pazienti. Basandoci su studi precedenti che evidenziano disturbi del senso di agency e deficit di integrazione sensorimotoria, abbiamo condotto tre studi finalizzati ad esplorare il riconoscimento del proprio corpo servendoci di un’illusione corporea visuo-motoria, i.e., la Mirror Box illusion. Il paradigma è utile al fine di elicitare sensazioni di agency e ownership durante l’incorporazione illusoria di una mano aliena in movimento. Nell’Esperimento 1 è stato investigato l’effetto della congruenza temporale tra il feedback visivo (la mano di uno sperimentatore riflessa nello specchio) e il feedback propriocettivo (la mano del partecipante) sulle misure esplicite ed implicite dell’illusione (il questionario di embodiment e il compito di bisezione del braccio). I partecipanti sani presentano una modulazione significativa del senso di ownership, del senso di agency e dalla stima di bisezione in accordo col grado di congruenza visuo-motoria esperita durante l’illusione. Senso di agency e stima di bisezione non modulano invece nei pazienti. Abbiamo ipotizzato che due meccanismi potrebbero spiegare i risultati ottenuti nel gruppo di pazienti: una finestra di integrazione temporale visuo-propriocettiva ampia e/o un deficit a livello di copia efferente del comando motorio. Il secondo esperimento è stato pianificato al fine di dissociare il contributo relativo di ciascuno dei due meccanismi ipotizzati. Nell’Esperimento 2 i partecipanti dovevano eseguire movimenti attivi vs. passivi mentre un ritardo gradualmente maggiore veniva inserito tra l’input visivo e l’input propriocettivo tramite un’apposita apparecchiatura. Dalle analisi preliminari emerge un’alterata modulazione del senso di ownership nei pazienti, la quale sembra essere maggiormente dovuta ad un’aumentata finestra di integrazione sensoriale. Questo risultato potrebbe indicare che un’alterazione a livello di integrazione delle afferenze sensoriali potrebbe essere maggiormente implicata nell’alterazione del senso di ownership. Tale conclusione è tuttavia da considerarsi provvisoria data la scarsa numerosità del gruppo di pazienti. In ultimo, l’Esperimento 3 costituisce un’analisi esplorativa dei confini spaziali dell’illusione al fine di testare l’ipotesi relativa all’estrema malleabilità della rappresentazione corporea in schizofrenia. Basandosi su quest’ipotesi, è possibile che i pazienti siano maggiormente predisposti ad incorporare una mano aliena posizionata ad una distanza anatomicamente implausibile dal loro corpo. Abbiamo inizialmente condotto uno studio per verificare in che misura un’elevata discrepanza visuo-propriocettiva sia in grado di inibire il senso di ownership per la mano aliena in un gruppo di partecipanti sani. Utilizzando la stessa apparecchiatura dello studio precedente abbiamo ottenuto risultati solo parzialmente in accordo con l’ipotesi poichè il senso di ownership diminuisce a livello esplicito, ma non a livello implicito. Altro lavoro di ricerca basato su altre manipolazioni sperimentali potrebbe consentire di capire se i risultati ottenuti siano dovuti al compito utilizzato oppure ad una maggior sensibilità della valutazione soggettiva del senso di ownership a questo tipo di manipolazioni. In conclusione, il presente lavoro mostra che i deficit di integrazione visuo-motoria in schizofrenia non impattano solo sul senso di agency, ma anche sul riconoscimento del proprio corpo. Questi risultati espandono i risultati precedentemente osservati negli studi di Rubber Hand illusion, portando evidenza empirica rispetto al fatto che i disturbi di percezione corporea in schizofrenia potrebbero essere dipendenti da processi di integrazione sensorimotoria deficitari. The present thesis addresses the build-up of the senses of agency and ownership in schizophrenia, as a clue to understand the mechanisms of self-awareness in these patients. Based on previous literature highlighting disturbances of sense of agency and impairments in sensorimotor integration, we carried out a series of three studies aimed to explore self-body recognition by capitalizing on a visuomotor body illusion, i.e. the mirror box illusion. This paradigm was useful in order to elicit overt sensations of agency and ownership under condition of illusorily embodiment of a moving alien hand. In Experiment 1, the effect of temporal congruency between visual (experimenter’s hand reflected in the mirror) and the proprioceptive (participant’s hand) input on subjective and objective measures (namely, embodiment questionnaire and forearm bisection task) of the illusion was addressed in 36 healthy participants and 29 patients affected by schizophrenia. In healthy participants, sense of agency, sense of ownership and bisection performance modulate in accordance to the extent of visuo-proprioceptive synchrony. By contrast, the sense of agency and bisection performance did not significantly vary across conditions in patients. Such results indicate that impaired sensorimotor processes, as testified by previous work on self-attribution task, may explain the altered modulation of embodiment in the schizophrenia group. We hypothesized that two sensorimotor mechanisms might be implicated, namely a widened visuo-proprioceptive TBW and a disruption of efference-related signals. In order to help disentangling the role of these two mechanisms, the second experiment was designed. In Experiment 2, participants were asked to perform active vs. passive movements, while increasing time-lags between the visual and the proprioceptive input were introduced using a custom-made mirror box setting. A sample of 32 healthy controls and 18 patients with schizophrenia was recruited. Preliminary analyses show an altered modulation of the illusorily sense of ownership in patients, which is mostly accounted for by an enlarged visuo-proprioceptive temporal binding window. This result might indicate that an abnormal integration of afferent signals is strongly involved in the disruption of self-body ownership in schizophrenia. This conclusion, however, warrants caution given the small size of the patients group. Finally, Experiment 3 represents an exploratory study to test the hypothesis of abnormal malleability of body representation in schizophrenia derived from the literature on rubber hand illusion in schizophrenia. Based on this assumption, it could be expected that patients are abnormally prone to embody an alien hand positioned at an anatomically implausible distance from the body. In order to address this issue, we first sought to verify to what extent high spatial visuo-proprioceptive discrepancy can inhibit the sense of ownership for a moving alien hand in healthy people. Using the same mirror box setting previously mentioned, we obtained results that are only partially in agreement with the hypothesis, since illusory ownership deems to decreases only at a subjective, but not objective level. Further work, using a different experimental manipulation, might better address whether these results may be due to the task used or to the higher sensitivity of subjective assessment of body ownership to this kind of manipulation. In conclusion, the present work demonstrates that putatively impaired visuo-motor integration processes in schizophrenia do not only impact on the sense of agency, but also on the recognition of one’s own body. These findings expand previous work based on the rubber hand illusion, providing empirical evidence of the fact that disturbances of body perception in schizophrenia can be dependent on defective sensorimotor processes for action.

Una grande varietà di input sensoriali dal mondo e dal corpo, sono continuamente integrati nel cervello al fine di creare rappresentazioni mentali sovramodali e coerenti del nostro stesso corpo. La plasticità è una caratteristica fondamentale di tali rappresentazioni, che consente costanti cambiamenti adattativi nelle funzioni mentali e nel comportamento. Anche le rappresentazioni corporee possono cambiare in base all'esperienza e, soprattutto, possono essere temporaneamente modificate mediante protocolli sperimentali. Nel presente lavoro, eravamo interessati a valutare la plasticità della percezione metrica del corpo e l'effetto di cambiamenti temporanei in essa sull'elaborazione delle informazioni corporee e spaziali. A tale scopo, sono stati utilizzati due illusioni corporee: la Mirror Box Illusion (MB) e la Full-Body Illusion (FBI). Il meccanismo principale che spiega l'efficacia di queste procedure sperimentali è il processo di incorporazione di una parte del corpo aliena. Nell'esperimento 1 abbiamo usato un paradigma visuo-tattile di FBI per valutarne la fattibilità e la replicabilità con corpi di dimensioni diverse. Abbiamo confermato che è possibile indurre e replicare nello stesso partecipante l'incorporazione verso manichini di dimensioni standard o più grandi. Nell'esperimento 2 e 3 abbiamo studiato la rappresentazione metrica della gamba e la sua malleabilità. Abbiamo quindi misurato l'effetto dell'FBI indotto da diverse dimensioni corporee, su un compito di valutazione della distanza percepita tra due tocchi applicati alla gamba del partecipante. Abbiamo scoperto che l'esperienza soggettiva di incorporazione è accompagnata da un cambiamento nella percezione della metrica del corpo che va di pari passo con la dimensione delle gambe incarnate. Poiché abbiamo confermato che, in soggetti sani, la rappresentazione metrica del corpo può essere modulata, abbiamo affrontato una domanda simile in pazienti con emiplegia. Nell'esperimento 4, usando un compito di bisezione del corpo abbiamo osservato che pazienti emiparetici mostrano una distorsione prossimale nella rappresentazione metrica dell'arto interessato. Abbiamo, inoltre, scoperto che la bisezione si sposta verso il punto medio reale dopo una sessione di trattamento con MB, rispetto a un trattamento di controllo senza specchio. Nell'esperimento 5 abbiamo trovato una modulazione simile della metrica corporea che, in un gruppo di pazienti affetti da aprassia ideomotoria trattati con una versione modificata della MB, era accompagnata da un miglioramento della programmazione dei piani motori. Negli esperimenti 6 e 7 ci siamo concentrati maggiormente sulla relazione tra metrica del corpo e rappresentazione dello spazio. In primo luogo, abbiamo testato l'ipotesi che una rappresentazione del corpo alterata influenzasse la percezione delle proprie attività motorie immaginate. I risultati hanno mostrato che i partecipanti immaginavano di camminare più velocemente dopo essere stati esposti a una FBI con gambe più lunghe. Inoltre, abbiamo scoperto che l'incorporazione illusoria di gambe più lunghe può influenzare la stima delle distanze allocentriche nello spazio extra-personale. L'incorporazione di gambe più lunghe, da un lato, ha, infatti, ridotto la distanza percepita in metri, dall'altro, ha prodotto un aumento del numero di passi che i partecipanti immaginavano di dover percorrere tra gli stessi punti di riferimento. In conclusione, abbiamo confermato che è possibile manipolare la rappresentazione metrica del corpo, mediante illusioni corporee e che ciò influenza la nostra capacità di stimare le distanze nel mondo esterno sia in termini di raggiungibilità che di stima allocentrica della distanza. Tale plasticità della rappresentazione corporea e dell'interazione spazio-corpo fornisce importanti indizi per la comprensione della rappresentazione corporea e della sua riabilitazione nei pazienti neurologici. A large variety of sensory input from the world and the body, are continuously integrated in the brain in order to create supra-modal and coherent mental representations of our own body. Plasticity is a fundamental characteristic of the nervous systems, allowing constant adaptive changes in mental functions and behaviour. Thanks to this, even body representations can change according to experience and, crucially, they can be temporarily altered by means of experimental protocols. In the present work, we were interested in assessing the plasticity of the subjective metric of the body, and the effect of temporary changes in it on the processing of corporeal and spatial information. To this aim, two types of bodily illusion were used, i.e. the Mirror Box Illusion (MB) and the Full-Body Illusion (FBI), due to their known effects inducing strong modulations of body representation. The core mechanism accounting for the efficacy of these experimental procedures is likely to be the process of embodiment of an alien body part. In experiment 1 we used a visuotactile FBI-like paradigm to assess the feasibility and the replicability of the FBI for bodies of different sizes. Using this paradigm, we confirmed that it is possible to induce and replicate in the same participant, the embodiment towards mannequins of standard or bigger sizes. In experiment 2 and 3 we investigated body metric representation of the leg, and whether it can be plastically modulated by embodying mannequins of different sizes. To address this issue, we measured the effect of FBI induced by different body sizes, over a Body Distance Task (BDT), i.e. the assessment of the perceived distance between two touches applied to the participant’s leg. We found that the subjective experience of embodiment is also accompanied by a change in the perception of body metric that goes hand-in-hand with the current size of the embodied legs. Since we confirmed that, in healthy subjects, the metric representation of the body can be modulated, we addressed a similar question in patients with hemiplegia. In experiment 4, using a body bisection task we first observed that hemiparetic post-stroke patients show a proximal bias in the metric representation of their affected upper limb. Critically, we found that this bias shifts distally, towards the objective midpoint after a MB training session, compared to a control training without the mirror. In Experiment 5 we found a similar modulation of subjective body metric in a group of patients suffering from Ideomotor Apraxia, treated with a modified version of the MB setup, which was accompanied by an improvement in the programming of motor plans. In experiments 6 and 7 we focused more on the relationship between body metric and space representations. First, we tested the hypothesis that an altered body representation could modify the way in which individuals estimate their body affordances during a Motor Imagery Task. Our results showed that participants imagined walking faster after having been exposed to an illusion of longer legs. Furthermore, we found that the illusory embodiment of longer legs can affect the estimation of allocentric distances in extra-personal space. The embodiment of longer legs, on the one hand, reduced the perceived distance in meters, on the other hand, produced an enhancement of the number of steps that participants imagined they would have needed to walk between the same landmarks. In conclusion, we confirmed that it is possible to induce provisional modifications of the metric representation of the body, by means of body illusions. We showed that body representation is malleable to the point to shape our ability to estimate distances in the external world both in terms of reachability and allocentric distance estimation. Such plasticity of body representation and body-space interaction gives important clues for the understanding of body representation and its rehabilitation in neurological patients.

Prosopagnosia is a disorder leading to difficulties in recognizing faces. However, recent evidence suggests that individuals with congenital prosopagnosia can achieve considerable accuracy when they have to recognize their own faces (self-face advantage). Yet, whether this advantage is face-specific or not is still unclear. Here, we aimed to investigate whether individuals with congenital prosopagnosia show a self-advantage also in recognizing other self body-parts and, if so, whether the advantage for the body parts differs from the one characterizing the self-face. Eight individuals with congenital prosopagnosia and 22 controls underwent a delayed matching task in which they were required to recognize faces, hands, and feet belonging to the self or to others. Controls showed a similar self-advantage for all the stimuli tested; by contrast, individuals with congenital prosopagnosia showed a larger self-advantage with faces compared to hands and feet, mainly driven by their deficit with others’ faces. In both groups the self-advantages for the different body parts were strongly and significantly correlated. Our data suggest that the self-face advantage showed by individuals with congenital prosopagnosia is not face-specific and that the same mechanism could be responsible for both the self-face and self body-part advantages.

Background Post-stroke depression (PSD) is among the most frequent neuropsychiatric consequences of stroke, negatively affecting the patient's functional recovery and the quality of life. While pharmacological therapy has limited efficacy and important side effects, new appropriate treatments based on specific physiological mechanisms for PSD remain to be developed. Non-invasive brain stimulation (NIBS) techniques, modulating brain plasticity, might offer valid, alternative strategies. Methods We systematically searched four databases: MEDLINE, PsycARTICLES, PsycINFO and Web of Science, up to December 2017, using definite keywords, to identify studies on TMS and tDCS treatment for PSD. Results Seven studies met the inclusion criteria and the results indicate that both tDCS and rTMS are safe and have very low side effects. The reported positive results, suggesting that these methods can be considered effective therapeutic options, are questionable, and a general statement about their efficacy for PSD is premature due to small sample sizes, heterogeneous methodologies, lack of uniform diagnostic criteria, and divergent data. Limitations The selected articles suffer lack of information about quality of life and daily living performance measures; in addition, the number of randomized controlled trials is small. Conclusion (s) The aim of this review was to analyze current research in the clinical use of noninvasive brain stimulation (NIBS) in PSD treatment in order to verify whether there are alternative perspectives in the treatment of PSD. Given the present evidence, future research is needed to address methodological limitations and evaluate the long-term efficacy of these methods, alone and in combination with pharmacological treatment.

Individuals with pure alexia often have visual field defects such as right homonymous hemianopia. Relatively few attempts have been made to develop criteria to differentiate pure alexia from hemianopic alexia. In this Commentary we provide concrete suggestions to distinguish the two disorders. We also report on additional assessments with two previously reported cases for whom the diagnosis of pure alexia was called into question and an alternative proposal was offered that the reading deficits were instead due to hemianopia. We show that the results of clinical and neuropsychological tests do not support the account that the reading impairment was caused by the visual field defect. In particular, for both cases, the right homonymous hemianopia was not complete, and a split-field reading task demonstrated an inability also to read words presented in the intact left visual field. In conclusion, pure alexics may indeed show fairly modest word-length effects; however, the presence of right homonymous hemianopia and a non-extreme gradient of reading speed alone are not sufficient grounds to put in doubt the diagnosis. We propose that a fuller clinical and neuropsychological examination taking into account the possible confounding effects of the visual field defects will help to distinguish pure alexia from hemianopic alexia.

Prism adaptation (PA) is a technique that induces a temporary change of the alignment between different reference frames. This technique has been shown to reduce many signs of unilateral spatial neglect (USN). Two procedures of prism adaptation have been used. In concurrent exposure participants can see their arm and hand during the movement trajectory, and during terminal exposure, participants can see only the most distal few centimetres. Because the two exposures elicit different proportions of visual and proprioceptive realignment, they could present different rehabilitation efficacies. We compared these procedures in 12 USN patients and 12 healthy participants who performed one session of PA with concurrent exposure and one session with terminal exposure. We compared the effects of the two exposure types on sensorimotor outcomes (visual subjective straight ahead, proprioceptive subjective straight ahead, open loop pointing, and error correction during exposure) and neglect outcomes. We found no significant differences in the effects of the two exposure types on sensorimotor performance of patients and controls, nor on patients’ neuropsychological outcomes. Compared with controls, USN patients showed a significant rightward bias in visual subjective straight ahead pre-adaptation, a slower rate of error correction during prism exposure, and some evidence that visual and proprioceptive shift could be influenced by their neglect. Based on these results, we recommend that prism adaptation be conducted with concurrent exposure for easiness of execution.

Emotional empathy plays a crucial role in social intra-species and inter-species interactions. However the role of interspecies interactions and of some personality components was underestimated. The present research explored electrophysiological correlates of affective processing in relation to emotionally valenced human-human (HH) and human-animal (HA) interactions. Further, we explored the link between such cortical responses and personality empathic profile as measured by the Balanced Emotional Empathy Scale (BEES) and the Interpersonal Reactivity Index (IRI). Both HH and HA interactions was associated to a significant increase of N300 and P300 deflections in response to positive and negative compared with neutral interactions. However, whereas N300 was mainly influenced by stimuli valence and was frontally distributed, P300 seemed to be mainly modulated by the stimuli attentional relevance and showed even a posterior distribution. Finally, a significant association was found between emotional empathy trait (BEES) and N300 amplitude. Results are discussed in light of the significance of empathic traits in mediating species-specific and speciesaspecific relationships.