A narrative review of the use of a cutting-edge virtual reality rehabilitation technology in neurological and neuropsychological rehabilitation.

BACKGROUND: Virtual reality (VR) interventions have been increasingly used in the rehabilitation of a wide range of neurological and neuropsychological dysfunctions. Findings of previous reviews showed positive and promising effects of VR-based interventions. However, they summarized findings on VR-based intervention carried out through different VR systems and tasks. OBJECTIVE: We carried out a narrative review with the aim of qualitatively synthesising the results of previous studies that used specific VR systems, i.e. the Khymeia -Virtual Reality Rehabilitation System, for treatment purposes. METHODS: We searched the literature in various databases (i.e. EMBASE, Web of Science, SCOPUS, PubMed and PubMed Central) for studies published until November 23, 2023. RESULTS: 30 studies were selected. The VRRS was used for neuromotor rehabilitation only in 13 studies, for cognitive rehabilitation in 11 studies, and for both neuromotor and cognitive rehabilitation in six studies. The study design was heterogeneous including 15 randomised controlled trials. CONCLUSION: After discussing each study according to the type of rehabilitation we concluded that the use and efficacy of VRRS rehabilitative intervention for increasing the neurological and neuropsychological functioning of patients are promising but more evidence is needed to make a comparison with conventional treatment. Future studies should also include long-term follow-up as well as cost-effectiveness analysis.

Grey-matter correlates of empathy in 4-Repeat Tauopathies.

Loss of empathy is an early and central symptom of frontotemporal lobar degeneration spectrum diseases. We aimed to investigate the topographical distribution of morphometric brain changes associated with empathy in Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS) patients. Twenty-seven participants with CBS and 31 with PSP were evaluated using Interpersonal Reactivity Index scales in correlation with gray matter atrophy using a voxel-based morphometry approach. Lower levels of empathy were associated with an increased atrophy in fronto-temporal cortical structures. At subcortical level, empathy scores were positively correlated with gray matter volume in the amygdala, hippocampus and the cerebellum. These findings allow to extend the traditional cortico-centric view of cognitive empathy to the cerebellar regions in patients with neurodegenerative disorders and suggest that the cerebellum may play a more prominent role in social cognition than previously appreciated.

Genuine Memory Deficits as Assessed by the Free and Cued Selective Reminding Test (FCSRT) in the Behavioural Variant of Frontotemporal Dementia. A Systematic Review and Meta-analysis Study.

The current diagnostic criteria for the behavioural variant of frontotemporal dementia (bvFTD) foresee a relative sparing of long-term memory. Although bvFTD patients were thought to report secondary memory deficits associated with prefrontal dysfunctions, some studies indicated the presence of a "genuine memory deficit" related to mesial temporal lobe dysfunctions. Among various neuropsychological tests, the Free and Cue Selective Reminding Test (FCSRT) has been recommended to distinguish genuine from apparent amnesia. We conducted a systematic review and a random effect Bayesian meta-analysis to evaluate the nature and severity of memory deficit in bvFTD. Our objective was to determine whether the existing literature offers evidence of genuine or apparent amnesia in patients with bvFTD, as assessed via the FCSRT. On 06/19/2021, we conducted a search across four databases (PMC, Scopus, Web of Science, and PubMed). We included all studies that evaluated memory performance using the FCSRT in patients with bvFTD, as long as they also included either cognitively unimpaired participants or AD groups. We tested publication bias through the Funnel plot and Egger's test. To assess the quality of studies, we used the Newcastle-Ottawa quality assessment scale adapted for cross-sectional studies. We included 16 studies in the meta-analysis. The results showed that bvFTD patients perform better than AD patients (pooled effects between 0.95 and 1.14), as their memory performance stands between AD and control groups (pooled effects between - 2.19 and - 1.25). Moreover, patients with bvFTD present both genuine and secondary memory disorders. As a major limitation of this study, due to our adoption of a rigorous methodology and stringent inclusion criteria, we ended up with just 16 studies. Nonetheless, our robust findings can contribute to the ongoing discussion on international consensus criteria for bvFTD and the selection of appropriate neuropsychological tools to facilitate the differential diagnosis between AD and bvFTD.

Pain assessment in autism: updating the ethical and methodological challenges through a state-of-the-art review.

Sensory features of autism include hypo- or hyper-reactivity to pain; however, previous studies on pain in autism lead to conflicting results. Here, we present the state of the art and the methodological challenges concerning pain perception in autism, focusing on studies that used standardized protocol as Quantitative Sensory Testing (QST) to measure perception. Despite there are still scant evidences found with the use of QST, they have challenged the presumed hyposensitivity to pain in autisms, which emerged from parents' reports. Both, peripheral and central mechanisms, have been found involved in typical features of perception in autism. Nonetheless, evidences with controlled protocols are still scarce, and even scarcer are studies focused on children. Overall, complex ethical challenges have to be overcome in order to collect subjective and objective measures from autistic children. With heterogeneous neurodevelopmental features, or intellectual disability, novel or modified protocols are needed.

The indirect effect of cognitive reserve on the relationship between age and cognition in pathological ageing: A cross-sectional retrospective study in an unselected and consecutively enrolled sample.

Cognitive reserve (CR) allows individuals to maintain cognitive functionality even in the presence of pathologies. The compensation hypothesis suggests that CR plays an indirect role between age and cognitive decline, contrasting the negative effect of ageing on cognition. We test this hypothesis in an unselected and consecutively enrolled sample of memory clinic attendees (n = 134) who completed the CR Index questionnaire and three neuropsychological tests assessing global cognition (MMSE, FAB, CDT). Participants were divided into two groups based on standard diagnostic criteria (DSM-5): those who were cognitively impaired (n = 92) and those who were preserved (n = 42). A principal component analysis was used to extract a composite measure of global cognitive functioning from the three neuropsychological tests, and mediation analysis was used to examine the relationship between CR, age and global cognitive functioning in the two groups. Results revealed that: (i) age had a significant direct negative effect on the global cognitive score in both groups; (ii) the three socio-behavioural proxies of CR together suppress the direct negative relationship between age and global cognitive score in cognitively impaired patients but not in cognitively preserved participants. This study confirms the association between CR, age and cognition and allows us to validate its role in a population with cognitive impairment and extend findings to a low-to-middle educated population. These results hold important implications for public health and wellness promotion, emphasising the beneficial role of maintaining healthy and active physical, cognitive and social lifestyles.

Visuo-Spatial Working Memory and Mathematical Skills in Children: A Network Analysis Study.

Visuo-spatial working memory is one of the main domain-general cognitive mechanisms underlying mathematical abilities and their development in children. However, if visuo-spatial working memory involves different processes and components, then the term 'mathematics' refers to a broad concept that includes multiple domains and skills. The aim of this present study was to investigate the relationship between different visuo-spatial working memory components and several mathematical abilities in a sample of third- to fifth-grade Italian children. To assess the relationships between different visuo-spatial working memory components and different mathematical abilities, we relied on Network Analysis (NA). Results indicate that some but not all visuo-spatial working memory components are associated with some mathematical abilities.

The Simple View of Reading in Children Acquiring a Regular Orthography (Italian): A Network Analysis Approach.

In the present study, we explored the unique contribution of reading accuracy, reading fluency and linguistic comprehension within the frame of Simple View of Reading (SVR). The experimental sample included 118 3rd to 5th grade children learning Italian, a language with a highly regular orthography. We adopted a flexible method of analysis, i.e., the Network Analysis (NA), particularly suited for exploring relations among different domains and where the direct relations between a set of intercorrelated variables is the main interest. Results indicated an independent and unique contribution of syntactic comprehension skills as well as reading fluency and reading accuracy in the comprehension of a written text. The decoding measures were not directly associated with non-verbal reasoning and the latter was not directly associated with reading comprehension but was strongly related to oral syntactic comprehension. Overall, the pattern of findings is broadly consistent with the predictions of SVR and underscores how, in an orthographically regular language, reading fluency and reading accuracy as well as oral comprehension skills directly influence reading comprehension. Data are discussed in a cross-linguistic perspective. Implications for education and rehabilitation are also presented.

Erratum: Macchitella et al. Sleepiness, Neuropsychological Skills, and Scholastic Learning in Children. Brain Sci. 2020, 10, 529.

The author wishes to make an erratum to the published version of the paper [...].

Neuropsychological and socio-cognitive deficits in patients with obstructive sleep apnea.

Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive deficits. We investigated the cognitive and socio-cognitive profiles of patients with severe OSA, controlling for potentially relevant mediating variables (i.e. age, body-mass index, cognitive reserve and depression). Moreover, we studied the neuropsychological profile of a high-risk OSA phenotype characterized by severe OSA and severe nocturnal hypoxemia.Method: We assessed 29 previously untreated severe OSA patients with a mean age of 55.6 (± 9.9 years) and a mean apnea-hypopnea index (AHI) of 53.1 (± 17.4). A control group of 34 healthy participants was also enrolled. Participants completed an extensive neuropsychological battery that included social cognition, a relatively new investigation area among OSA patients.Data analysis: Data were analyzed with a Bayesian approach. Specifically, Bayesian ANCOVA was used to investigate whether the grouping variable could predict test performance. Age, body-mass index, cognitive reserve and state of depression were added as covariates to the null model to weight the effects of these potential confounding factors. Three groups were analyzed: healthy controls (H), OSA with severe apnea and severe nocturnal oxygen desaturation (D+), and OSA with severe apnea non-desaturators (D-). Performances on the various neuropsychological tests were treated as the dependent variables.Results: The results indicate that non-verbal reasoning, the theory of mind skills, and mental shifting ability were impaired in OSA patients. Patients with severe nocturnal hypoxemia underperformed compared to patients with the same severity of apnea but non-desaturators. Additionally, we observed a trend toward a worse performance among OSA desaturator patients in the following abilities: constructional ability, short term verbal memory, phonological fluency, and the ability to inhibit automatic and dominant responses.Conclusion: The data suggest a key role of hypoxemia in affecting cognitive functioning in OSA patients. Executive functions and the concomitant involvement of social cognition are particularly affected.

Sleepiness, Neuropsychological Skills, and Scholastic Learning in Children.

Excessive daytime sleepiness is a frequent condition among children and adolescents that may lead to several and significant daytime consequences, including impaired neurocognitive skills and scholastic performance. Here, we evaluated in one hundred and ninety-one unselected primary school children, the relationship between sleepiness and a wide range of cognitive and academic skills through a standardized neuropsychological test battery. In order to assess the statistical relationship, we performed a partial least squares path modelling, a non-parametrical approach which combined a model of paths between latent variables and the coefficients between indicators and dimensions. Results were validated through the bootstrap approach and suggest that sleepiness is not associated with all cognitive and scholastic abilities, but only with those relying on verbal abilities and complex cognitive functions (i.e., reading comprehension, oral/syntactic comprehension, spelling, and mathematic skills). Our data suggest the idea that sleepiness in children is associated mostly with "higher" (mainly verbal) cognitive function(s), while the visuospatial domain was not affected.

The Neuropsychological Profile of Attention Deficits of Patients with Obstructive Sleep Apnea: An Update on the Daytime Attentional Impairment.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim to improve attention assessment, with a possible impact on clinical and medical-legal practices, in terms of which attention subdomains and parameters need consideration and which one is a high-risk OSA phenotype for attention dysfunctions. METHOD: For this purpose, we assessed 32 previously untreated OSA patients (26 men and 6 women) under 65 years of age (mean age 53.2 ± 7.3; mean education level 10.4 ± 3.4 years) suffering from moderate to severe sleep apnea and hypopnea (mean apnea-hypopnea index (AHI) 45.3 ± 22.9, range 16.1-69.6). A control group of 34 healthy participants matched with OSA patients for age, education level, and general cognitive functioning were also enrolled. The OSA patients and healthy participants were tested through an extensive computerized battery (Test of Attentional Performance, TAP) that evaluated intensive (i.e., alertness and vigilance) and selective (i.e., divided and selective) dimensions of attention and returned different outcome parameters (i.e., reaction time, stability of performance, and various types of errors). Data analysis: The data were analyzed by ANCOVA which compared the speed and accuracy performance of the OSA and control participants (cognitive reserve was treated as a covariate). The possible mechanisms underlying attention deficits in OSA patients were examined through correlation analysis among AHI, oxygenation parameters, sleepiness scores, and TAP outcomes and by comparing the following three phenotypes of patients: severe OSA and severe nocturnal desaturators (AHI++D+), severe OSA nondesaturators (AHI++D-), and moderate OSA nondesaturators (AHI+D-). RESULTS: The results suggest that the OSA patients manifest deficits in both intensive and selective attention processes and that reaction time (RT) alone is ineffective for detecting and characterizing their problems, for which error analysis and stability of performance also have to be considered. Patients with severe OSA and severe hypoxemia underperformed on alertness and vigilance attention subtests. CONCLUSIONS: The data suggest the importance of evaluating attention deficits among OSA patients through several parameters (including performance instability). Moreover, the data suggest a multifaceted mechanism underlying attention dysfunction in OSA patients.

Attention Deficits in Stroke Patients: The Role of Lesion Characteristics, Time from Stroke, and Concomitant Neuropsychological Deficits.

Attention impairments are frequent in stroke patients with important consequences on the rehabilitation outcomes and quality of life. The aim of the study was to perform a comprehensive assessment of selective and intensive attention processes in a large population of brain-damaged patients, evaluating the influence of the side and site of the brain lesion, the time from stroke, and the concomitant presence of aphasia or neglect. We assessed 204 patients with a first unilateral brain lesion and 42 healthy individuals with three subtests of the Test of Attentional Performance (TAP): Alertness, Go-No Go, and Divided Attention. 44.4% of patients had an impairment in both intensive and selective aspects of attention, 5.6% had deficits only in the intensive component, and 31.8% had deficits only in selective tasks. More than 80% of the patients fell below the cut-off point on at least one task. Patients with a right hemispheric lesion (RHL) were more impaired than patients with a left hemispheric lesion (LHL) especially in tonic and phasic alertness. Patients with total anterior infarcts (TACI) presented the worst profile compared to other stroke subtypes, with a difference between total and lacunar subtypes in the Alertness test, independent of the presence of warning. Patients in the chronic phase had shorter RTs than acute patients only in the Alertness test. In patients with LHL, the presence of aphasia was associated with a greater deficit in selective attention. In patients with RHL, the presence of unilateral neglect was associated with impaired alertness and selective attention. Attention deficits are common after a unilateral first stroke. In keeping with the hierarchical organization of attention functions, results confirm the important role of the right hemisphere for the intensive components of attention, also highlighting the involvement of left hemisphere functioning for the selective aspects, possibly indicating a role of its linguistic functions.

Waiting by mistake: symbolic representation of rewards modulates intertemporal choice in capuchin monkeys, preschool children and adult humans.

In the Delay choice task subjects choose between a smaller immediate option and a larger delayed option. This paradigm, also known as intertemporal choice task, is frequently used to assess delay tolerance, interpreting a preference for the larger delayed option as willingness to wait. However, in the Delay choice task subjects face a dilemma between two preferred responses: "go for more" (i.e., selecting the larger, but delayed, option) vs. "go for sooner" (i.e., selecting the immediate, but smaller, option). When the options consist of visible food amounts, at least some of the choices of the larger delayed option might be due to a failure to inhibit a prepotent response towards the larger option rather than to a sustained delay tolerance. To disentangle this issue, we tested 10 capuchin monkeys, 101 preschool children, and 88 adult humans in a Delay choice task with food, low-symbolic tokens (objects that can be exchanged with food and have a one-to-one correspondence with food items), and high-symbolic tokens (objects that can be exchanged with food and have a one-to-many correspondence with food items). This allows evaluating how different methods of representing rewards modulate the relative contribution of the "go for more" and "go for sooner" responses. Consistently with the idea that choices for the delayed option are sometimes due to a failure at inhibiting the prepotent response for the larger quantity, we expected high-symbolic tokens to decrease the salience of the larger option, thus reducing "go for more" responses. In fact, previous findings have shown that inhibiting prepotent responses for quantity is easier when the problem is framed in a symbolic context. Overall, opting for the larger delayed option in the visible-food version of the Delay choice task seems to partially result from an impulsive preference for quantity, rather than from a sustained delay tolerance. In capuchins and children high-symbolic stimuli decreased the individual's preference for the larger reward by distancing from its appetitive features. Conversely, the sophisticated symbolic skills of adult humans prevented the distancing effect of high-symbolic stimuli in this population, although this result may be due to methodological differences between adult humans and the other two populations under study. Our data extend the knowledge concerning the influence of symbols on both human and non-human primate behavior and add a new element to the interpretation of the Delay choice task. Since high-symbolic stimuli decrease the individual's preference for the larger reward by eliminating those choices due to prepotent responses towards the larger quantity, they allow to better discriminate responses based on genuine delay aversion. Thus, these findings invite greater caution in interpreting the results obtained with the visible-food version of the Delay choice task, which may overestimate delay tolerance.

How capuchin monkeys (Cebus apella) behaviorally cope with increasing delay in a self-control task.

Displacement activities are behavior patterns apparently irrelevant to the situation in which they are performed that facilitate transitions between behavioral states. Scratching is one of the most commonly described displacement activities in primates and is related to frustration and anxiety. In chimpanzees scratching during cognitive tasks increases with task difficulty. We analyzed behavioral data obtained from video clips on nine capuchin monkeys tested in a delay choice task, a potentially stressful self-control task where subjects choose between a small immediate and a large delayed option. Scratching, response latency, and motor impulsivity scored during the delay decreased across sessions, as capuchins became indifferent between options, whereas the bias for choosing the option placed on one side of the apparatus increased. Capuchins might have found the delay choice task less stressful over time because they shifted from slower discriminatory responses in the earlier sessions to more 'automatic', faster responses in the later sessions. However, it cannot be excluded that they habituated over time to the contingencies of the task. In contrast with previous data on chimpanzees, handedness in scratching behavior or preferential scratching on one side of the body did not emerge, but further studies are needed to corroborate this finding.

Delay choice versus delay maintenance: different measures of delayed gratification in capuchin monkeys (Cebus apella).

Delaying gratification involves 2 components: (1) delay choice (selecting a delayed reward over an immediate one) and (2) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). Two tasks most commonly have explored these components in primates: the intertemporal choice task and the accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance on the intertemporal choice task and the accumulation task of capuchin monkeys (Cebus apella) belonging to 2 study populations. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support for the hypothesis that these tasks provide equivalent measures of delay of gratification.

[Quality sharing between the national health service and citizens: a diagnostic and therapeutic planning experience at the "S. Maria" Hospital in Terni]. / La qualità condivisa fra servizio sanitario nazionale e cittadini: Esperienza di un percorso diagnostico terapeutico nell'azienda ospedaliera "S. Maria" di Terni.

The Diagnostic and Therapeutic Programs are instruments of clinical management. The authors report on their experience with the construction of a Diagnostic and Therapeutic Program in the field of breast cancer. This is the result of collaboration between the Breast Unit, an administrative team and a computer team at the "S. Maria" Hospital in Terni. The implementation of the guidelines in the hospital setting makes it possible to systematise the clinical activities, to quantify the economic impact for each disease, and to plan any changes in the use of resources. The application of this method, moreover, makes it possible to develop a common language between medical and nursing staff which can be easily understood by the patients and to inform patients adequately with regard to the diagnostic and therapeutic program they will have to comply with for their respective conditions.