Whole-Head Functional Near-Infrared Spectroscopy as an Ecological Monitoring Tool for Assessing Cortical Activity in Parkinson's Disease Patients at Different Stages.

Functional near-infrared spectroscopy (fNIRS) is increasingly employed as an ecological neuroimaging technique in assessing age-related chronic neurological disorders, such as Parkinson's disease (PD), mainly providing a cross-sectional characterization of clinical phenotypes in ecological settings. Current fNIRS studies in PD have investigated the effects of motor and non-motor impairment on cortical activity during gait and postural stability tasks, but no study has employed fNIRS as an ecological neuroimaging tool to assess PD at different stages. Therefore, in this work, we sought to investigate the cortical activity of PD patients during a motor grasping task and its relationship with both the staging of the pathology and its clinical variables. This study considered 39 PD patients (age 69.0 ± 7.64, 38 right-handed), subdivided into two groups at different stages by the Hoehn and Yahr (HY) scale: early PD (ePD; N = 13, HY = [1; 1.5]) and moderate PD (mPD; N = 26, HY = [2; 2.5; 3]). We employed a whole-head fNIRS system with 102 measurement channels to monitor brain activity. Group-level activation maps and region of interest (ROI) analysis were computed for ePD, mPD, and ePD vs. mPD contrasts. A ROI-based correlation analysis was also performed with respect to contrasted subject-level fNIRS data, focusing on age, a Cognitive Reserve Index questionnaire (CRIQ), disease duration, the Unified Parkinson's Disease Rating Scale (UPDRS), and performances in the Stroop Color and Word (SCW) test. We observed group differences in age, disease duration, and the UPDRS, while no significant differences were found for CRIQ or SCW scores. Group-level activation maps revealed that the ePD group presented higher activation in motor and occipital areas than the mPD group, while the inverse trend was found in frontal areas. Significant correlations with CRIQ, disease duration, the UPDRS, and the SCW were mostly found in non-motor areas. The results are in line with current fNIRS and functional and anatomical MRI scientific literature suggesting that non-motor areas-primarily the prefrontal cortex area-provide a compensation mechanism for PD motor impairment. fNIRS may serve as a viable support for the longitudinal assessment of therapeutic and rehabilitation procedures, and define new prodromal, low-cost, and ecological biomarkers of disease progression.

EXecutive-Functions Innovative Tool (EXIT 360°): A Usability and User Experience Study of an Original 360°-Based Assessment Instrument.

Over the last few decades, several studies have shown the feasibility, acceptability, and efficacy of VR-based instruments in the early evaluation of executive dysfunction (ED) in psychiatric and neurologic conditions. Due to the negative impact of ED in everyday functioning, identifying innovative strategies for evaluating ED allows clinicians to detect executive impairment early and minimize its effects. This work aimed to test the usability and user experience (UX) of EXecutive-functions Innovative Tool 360° (EXIT 360°), a 360°-based tool for assessing ED. Seventy-six healthy subjects underwent an evaluation that involved (1) usability assessment using System Usability Scale and (2) evaluation of UX using the ICT-Sense of Presence and UX Questionnaire. Results showed a satisfactory level of usability (mean = 75.9 ± 12.8), with good scores for usability and learnability. As regards UX, EXIT 360° showed an absence of negative effects (mean = 1.79 ± 0.95) and high scores in ecological validity (mean = 4.32 ± 0.54) and engagement (mean = 3.76 ± 0.56). Moreover, it obtained good scores in efficiency (mean = 1.84 ± 0.84), originality (mean = 2.49 ± 0.71), and attractiveness (mean = 1.93 ± 0.98). Interestingly, demographic characteristics and technological expertise had no impact on the performance (p > 0.05). Overall, EXIT 360° appeared to be a usable, learn-to-use, engaging, and creative tool with irrelevant negative effects. Further studies will be conducted to evaluate these aspects in the clinical population.

White matter alterations in early Parkinson's disease: role of motor symptom lateralization.

INTRODUCTION: Parkinson's disease (PD) is a motor disorder that initially presents with unilateral symptoms. Widespread white matter (WM) alterations have been reported since the early stages of the disease. The aim of this study was to investigate WM alterations in right-dominant and left-dominant symptom PD patients (RPD and LPD, respectively) with respect to healthy controls (HC) by diffusion-weighted magnetic resonance imaging (MRI). METHODS: Thirty-eight subjects participated in this study: 12 RPD (median H&Y [IQR] = 1.5 [1.1-2], median UPDRS III [IQR] = 23 [7.8-25]), 9 LPD (median H&Y [IQR] = 1.5 [1-2.5], median UPDRS III [IQR] = 17 [12-22]), and 17 HC. All the participants were scanned on a 1.5-T MRI scanner. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were computed for all the subjects. Tract-based spatial statistics (TBSS) was performed for each diffusion parameter, to test WM differences between RPD, LPD, and HC (ANCOVA design). Family-wise error (FWE) correction was performed and p values lower than 0.05 were considered significant. RESULTS: No significant FA and RD differences were observed between RPD, LPD, and HC. Significantly increased MD and AD were observed in RPD with respect to HC within widespread WM regions, bilaterally. Conversely, no significant WM alterations were detected in LPD. CONCLUSION: WM integrity was found to be significantly altered in RPD but not in LPD, suggesting that LPD profile may be associated to more favorable prognosis. Since clinical laterality onset may affect the extent of WM integrity changes, it should be taken into account in neuroimaging studies investigating PD.

Cognitive Reserve proxies can modulate motor and non-motor basal ganglia circuits in early Parkinson's Disease.

Parkinson's Disease (PD) is hallmarked by dysfunctional circuitry between the basal ganglia and dorsolateral-prefrontal cortex. Recently progress has been made in understanding factors contributing to differential susceptibility to pathology mitigating disease-related cognitive decline. Cognitive reserve, the brain processing resources accumulated throughout life while engaged in mentally stimulating activities, can play an important protective role in cognitive performance. We tested the hypothesis that Cognitive Reserve proxies may exert an impact on the basal ganglia and dorsolateral-prefrontal atrophy in early PD. Forty-five early patients with PD and 20 age-gender-matched healthy controls (HC) completed the Cognitive Reserve Index questionnaire to quantify Cognitive Reserve proxies by three indexes (CRI-Education, CRI-Working Activity, CRI-Leisure Time) and a structural MRI examination (3T). Morphometrical indexes for basal ganglia (bilateral putamen, caudate, pallidum volume) and dorsolateral-prefrontal cortex (cortical thickness) were computed. Significant differences between HC and PD were tested by direct comparisons in demographics, cognitive level, and cognitive reserve proxies indexes. Then two multiple regression analyses were performed to identify predictors of the basal ganglia and dorsolateral-prefrontal cortex structural integrity. Regression analysis revealed that basal ganglia volume was significantly predicted by CRI-Education (pFDR = 0.029), sex (pFDR = 0.029), and Total Intracranial Volume (pFDR < 0.001). Instead, the dorsolateral-prefrontal thickness was predicted by CRI-Leisure Time (pFDR = 0.030) and age (pFDR = 0.010). Cognitive Reserve proxies, especially education and leisure-time activities, can play a protective role on the structural integrity of the basal ganglia and dorsolateral-prefrontal cortex, respectively, critical regions hallmarking brain status of early phases of PD.

Efficacy of telerehabilitation with digital and robotic tools for the continuity of care of people with chronic neurological disorders: The TELENEURO@REHAB protocol for a randomized controlled trial.

Context: Chronic Neurological Disorders (CNDs) are among the leading causes of disability worldwide, and their contribution to the overall need for rehabilitation is increasing. Therefore, the identification of new digital solutions to ensure early and continuous care is mandatory. Objective: This protocol proposes to test the usability, acceptability, safety, and efficacy of Telerehabilitation (TR) protocols with digital and robotic tools in reducing the perceived level of disability in CNDs including Parkinson's Disease (PD), Multiple Sclerosis (MS), and post-stroke patients. Design Setting and Subjects: This single-blinded, multi-site, randomized, two-treatment arms controlled clinical trial will involve PD (N = 30), MS (N = 30), and post-stroke (N = 30). Each participant will be randomized (1:1) to the experimental group (20 sessions of motor telerehabilitation with digital and robotic tools) or the active control group (20 home-based motor rehabilitation sessions according to the usual care treatment). Primary and secondary outcome measures will be obtained at the baseline (T0), post-intervention (T1, 5 weeks after baseline), and at follow-up (T2, 2 months after treatment). Main Outcome Measures: a multifaceted evaluation including quality of life, motor, and clinical/functional measures will be conducted at each time-point of assessment. The primary outcome measures will be the change in the perceived level of disability as measured by the World Health Organization Disability Assessment Schedule 2.0. Conclusion: The implementation of TR protocols will enable a more targeted and effective response to the growing need for rehabilitation linked to CNDs, ensuring accessibility to rehabilitation services from the initial stages of the disease.

Exploring cognitive reserve's influence: unveiling the dynamics of digital telerehabilitation in Parkinson's Disease Resilience.

Telerehabilitation is emerging as a promising digital method for delivering rehabilitation to Parkinson's Disease (PD) patients, especially in the early stages to promote brain resilience. This study explores how cognitive reserve (CR), the brain's ability to withstand aging and disease, impacts the effectiveness of telerehabilitation. It specifically examines the influence of lifelong cognitive activities on the relationship between neural reserve and improved functional abilities following rehabilitation. In the study, 42 PD patients underwent a 4-month neuromotor telerehabilitation program. CR proxies were assessed using the Cognitive Reserve Index questionnaire (CRIq), brain changes via 3T-MRI, and functional response through changes in the 6-Minute Walk Distance (6MWD). Participants were divided into responders (n = 23) and non-responders (n = 19) based on their 6MWD improvement. A multiple regression model was run to test significant predictors of 6MWD after treatment in each group. The results revealed a significant correlation between 6MWD and CRIq scores, but only among responders. Notably, the CRIq Leisure-Time sub-index, along with baseline 6MWD, were predictors of post-treatment 6MWD. These findings highlight CR's role in enhancing the benefits of telerehabilitation on PD patients' neuromotor functions. Clinically, these results suggest that neurologists and clinicians should consider patients' lifestyles and cognitive engagement as important factors in predicting and enhancing the outcomes of telerehabilitation. The study underscores the potential of CR as both a predictor and booster of telerehabilitation's effects, advocating for a personalized approach to PD treatment that takes into account individual CR levels.

Long-lasting improvements in episodic memory among subjects with mild cognitive impairment who received transcranial direct current stimulation combined with cognitive treatment and telerehabilitation: a multicentre, randomized, active-controlled study.

Background: In recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI). Objective: The aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU). Results: An improvement in episodic memory was observed after the end of clinic-atDCS-VRRS (p < 0.001). We found no enhancement in episodic memory after clinic-ptDCS-VRRS or after clinic-TAU.Moreover, the combined treatment led to prolonged beneficial effects (clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-ptDCS-VRRS+Tele@H-VRRS: p = 0.047; clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-VRRS+Tele@H-VRRS: p = 0.06). Discussion: The present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation. Clinical trial registration: https://clinicaltrials.gov/study/NCT03486704?term=NCT03486704&rank=1, NCT03486704.

Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

Beyond the simplicity of theory of mind deficit in multiple sclerosis: from kinetic perception to socio-emotional abstraction and mentalizing.

BACKGROUND: Theory of Mind (ToM) processing in Multiple Sclerosis (MS) is still poorly understood due to the difficulty of most tasks in qualifying the mentalizing deficit net of cognitive load. METHODS: In this study, we administered the New False Belief Animation Task (NFBAT) to 50 MS and 33 healthy controls (HC) to investigate spontaneous mentalizing in ToM and goal-directed interactions. The global cognitive level was assessed by the Montreal Cognitive Assessment (MoCA). NFBAT appropriateness and intentionality scores were computed to investigate the ToM accuracy and intentionality attribution difficulties. NFBAT answers were qualitatively analyzed and categorized into kinetically and socially coherent/not coherent responses to test a low-level perceptual deficit. RESULTS: The main result showed dysfunctional mentalizing reasoning in MS compared to HC in the NFBAT Intentionality score in ToM conditions (p = 0.028, d = 0.501), while the two groups were equally proficient in mentalization accuracy. The Intentionality underperformance in MS was related to social low-level perceptual processing (ß =0.06, p < 0.001) and visuospatial functions (ß =0.05, p =0.002). A predictive role of memory and executive functions on NFBAT Intentionality scores was not observed. CONCLUSION: These results strengthen the hypothesis that ToM in MS is likely related to low-level social processing.

Psychometric Calibration of a Tool Based on 360 Degree Videos for the Assessment of Executive Functions.

INTRODUCTION: Over the last decades, interactive technologies appeared a promising solution in the ecological evaluation of executive functioning. We have developed the EXecutive-functions Innovative Tool 360° (EXIT 360°), a new instrument that exploits 360° technologies to provide an ecologically valid assessment of executive functioning. AIM: This work wanted to evaluate the convergent validity of the EXIT 360°, comparing it with traditional neuropsychological tests (NPS) for executive functioning. METHODS: Seventy-seven healthy subjects underwent an evaluation that involved: (1) a paper-and-pencil neuropsychological assessment, (2) an EXIT 360° session, involving seven subtasks delivered by VR headset, and (3) a usability assessment. To evaluate convergent validity, statistical correlation analyses were performed between NPS and EXIT 360° scores. RESULTS: The data showed that participants had completed the whole task in about 8 min, with 88.3% obtaining a high total score (≥12). Regarding convergent validity, the data revealed a significant correlation between the EXIT 360° total score and all NPS. Furthermore, data showed a correlation between the EXIT 360° total reaction time and timed neuropsychological tests. Finally, the usability assessment showed a good score. CONCLUSION: This work appears as a first validation step towards considering the EXIT 360° as a standardized instrument that uses 360° technologies to conduct an ecologically valid assessment of executive functioning. Further studies will be necessary to evaluate the effectiveness of the EXIT 360° in discriminating between healthy control subjects and patients with executive dysfunctions.

System Integrated Digital Empowering and teleRehabilitation to promote patient Activation and well-Being in chronic disabilities: A usability and acceptability study.

Introduction: Telerehabilitation systems represent a promising way for the management of chronic disability, delivering technology-enabled rehabilitation outside the hospital setting. However, usability and acceptability assessment with users represents a critical starting point when using digital healthcare solutions. This study aims at evaluating the user experience with a Telerehabilitation system (SIDERA∧B) from the end-user side. Methods: SIDERA∧B consists of an asynchronous delivery of rehabilitation activities through multimedia digital contents and tele-monitoring of vital parameters with technological devices for individualized, home-based management of chronic conditions. Usability (with the System Usability Scale, SUS) and acceptability (using the Technology Acceptance Model, TAM - and The Service User Technology Acceptance Questionnaire, SUTAQ) data were analyzed from the dataset of the SIDERA∧B project (N = 112 patients with Chronic Heart Failure, Parkinson's Disease and Chronic Obstructive Pulmonary Disease). The possible influence of five external factors (i.e., technological expertise, education, sex, age, and level of disability) on TAM domains was tested using Spearman's Correlation analysis. Results: Results showed a satisfactory level of technological usability (SUS Median = 77.5) and good scores in usability and learnability SUS subdomains (mean scores > 2.5). Regarding technological acceptability, participants showed high scores (Median > 4) in "Behavioral Intention", "Perceived Usefulness", and "Perceived Ease of Use" TAM domains. Finally, results from the SUTAQ scale highlighted that the SIDERA∧B system obtained optimal scores in all domains, especially in "Increased accessibility," "Care personnel concerns," and "Satisfaction." Age (rho = -0.291, p = 0.002) and disability level (WHODAS Total score: rho = -0.218, p = 0.021) were the two external factors inversely associated with the Perceived Ease of Use. Discussion: The age of digital transformation requires everyone to understand, accept and master the changes affecting modern-day healthcare. The usability and acceptability of the SIDERA∧B system were high across all end-users, despite the medium-low level of the technological expertise of the sample. These findings support the efficiency and the suitability of these digital solutions in the modern digital age transition of rehabilitation from inside to outside the clinic.

Psychometric validation for a brand-new tool for the assessment of executive functions using 360° technology.

EXecutive-functions Innovative Tool 360° (EXIT 360°) is an original 360° instrument for an ecologically valid and multicomponent evaluation of executive functioning. This work aimed to test the diagnostic efficacy of EXIT 360° in distinguishing executive functioning between healthy controls (HC) and patients with Parkinson's Disease (PwPD), a neurodegenerative disease in which executive dysfunction is the best-defined cognitive impairment in the early stage. 36 PwPD and 44 HC underwent a one-session evaluation that involved (1) neuropsychological evaluation of executive functionality using traditional paper-and-pencil tests, (2) EXIT 360° session and (3) usability assessment. Our findings revealed that PwPD made significantly more errors in completing EXIT 360° and took longer to conclude the test. A significant correlation appeared between neuropsychological tests and EXIT 360° scores, supporting a good convergent validity. Classification analysis indicated the potential of the EXIT 360° for distinguishing between PwPD and HC in terms of executive functioning. Moreover, indices from EXIT 360° showed higher diagnostic accuracy in predicting PD group membership compared to traditional neuropsychological tests. Interestingly, EXIT 360° performance was not affected by technological usability issues. Overall, this study offers evidence that EXIT 360° can be considered an ecological tool highly sensitive to detect subtle executive deficits in PwPD since the initial phases of the disease.

Differential Roles of Neural Integrity, Physical Activity and Depression in Frailty: Sex-Related Differences.

The frailty sex paradox has recently gained attention. At all ages, females are more likely to be frail and show a more severe phenotype but have a higher survival rate compared to males. The main aim was to test sex-specific differences in frailty syndrome using a multimodal evaluation from clinical and imaging data to deepen the understanding of different underlying mechanisms involved in the two sexes, and thus understand the association with different risk factors. Ninety-six community-dwelling older adults were characterized by clinical underpinnings (Fried's frailty indicators: comorbidity, depression, global cognitive level, physical activity, autonomy), and neural integrity (T1-weighted brain 3T MRI). The frailty × sex interaction in clinical and neural profiles was tested. Additionally, frailty risk factors were identified in the two sexes separately. Results showed that fragility was associated with an increment of depressive symptomatology in females, while a decrement in physical activity was observed already in the pre-frail stage in males. Finally, different risk factors were observed in the two groups: significant frailty predictors were neural integrity and physical activity in males, and age and depression in females. These data support the starting hypothesis of at least partially different mechanisms involved in the frailty phenotype between men and women.

A digital health home intervention for people within the Alzheimer's disease continuum: results from the Ability-TelerehABILITation pilot randomized controlled trial.

PURPOSE: This study tested the efficacy of digital-health home intervention for people within the Alzheimer's disease (AD)-continuum. METHODS: Thirty people within the AD continuum were randomly assigned to a telerehabilitation (ABILITY; 6 males, Mage=78.2 ± 3.95) or treatment as usual (TAU; 8 males, Mage=77.13 ± 6.38), performing cognitive and physical activities at home for six weeks. The ABILITY intervention additionally included a digital platform enabling communication between the hospital and the patient's home. Efficiency, such as adherence, perceived fit of demands and skills, usability, and effectiveness measures, including neuropsychological level, neuropsychiatric symptoms, and autonomy in daily living, were collected before (T0), after the treatment (T1), and at the 1-year-follow-up (T2). RESULTS: The ABILITY program was efficient, with a higher adherence (81% vs. 62%), a higher perceived fit of demands and skills than TAU (p<.05), and a good level of technology usability. In terms of effectiveness, a treatment effect (ABILITY > TAU) emerged on the global cognitive level, especially in language, executive functions, and memory domains. Moreover, a treatment carry-over effect (1-year follow-up) was observed in global cognitive functions (especially language) (ABILITY > TAU), behavioral symptoms, and caregiver distress (TAU > ABILITY). CONCLUSIONS: Our preliminary findings suggest that ABILITY is a promising eHealth intervention to improve at-home treatment adherence and to preserve cognitive and behavioral abilities.

People in the Alzheimer's Disease continuum facing chronic cognitive disabilities represent an emergency for the healthcare system given the substantial need for long-term rehabilitation;This study evaluates a new model of rehabilitation in the continuity of care for people with cognitive disabilities, adopting an asynchronous approach;The asynchronous telerehabilitation model may be considered a new frontier for continuity of care, capable of answering the unmet need of scaling up rehabilitation services to the broad population.

The key role of depression and supramarginal gyrus in frailty: a cross-sectional study.

Background: The age-related decrease in reserve and resistance to stressors is recognized as frailty, one of the most significant challenges identified in recent years. Despite a well-acknowledged association of frailty with cognitive impairment, depression, and gray matter morphology, no clear data are available regarding the nature of this relationship. This cross-sectional study aims to disentangle the role of the behavioral, neuropsychological, and neural components as predictors or moderators of frailty. Methods: Ninety-six older adults (mean age = 75.49 ± 6.62) were consecutively enrolled and underwent a clinical and MRI (3 T) evaluation to assess frailty, physical activity, global cognitive level, depression, wellbeing, autonomy in daily living, cortical thickness, and subcortical volumes. Results: Results showed a full mediation of depression on the link between cortical thickness and frailty, while the cognitive level showed no significant mediating role. In particular, left supramarginal thickness had a predicting role on depression, that in turn impacted frailty occurrence. Finally, handgrip weakness was an early key indicator of frailty in this study's cohort. Conclusion: These data substantiate the role of depression in mediating the link between neural integrity of the supramarginal gyrus and frailty. In the complexity of frailty, handgrip weakness seems to be an early key indicator. These results are relevant for the design of rehabilitation interventions aimed at reversing the frail condition.

A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia (MAINSTREAM): A Study Protocol.

Primary Progressive Aphasia (PPA) is a syndrome due to different neurodegenerative disorders selectively disrupting language functions. PPA specialist care is underdeveloped. There are very few specialists (neurologists, psychiatrists, neuropsychologists, and speech therapists) and few hospital- or community-based services dedicated to the diagnosis and continuing care of people with PPA. Currently, healthcare systems struggle to provide adequate coverage of care that is too often fragmented, uncoordinated, and unresponsive to the needs of people with PPA and their families. Recently, attention has been gained by non-invasive brain stimulation techniques that allow a personalized treatment approach, such as transcranial Direct Current Stimulation (tDCS). The MAINSTREAM trial looks forward to introducing and evaluating therapeutic innovations such as tDCS coupled with language therapy in rehabilitation settings. A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM (ID: 3430931) was registered in the clinicaltrials.gov database (identifier: NCT05730023) on 15 February 2023.

Standardization and normative data of the 48-item Yoni short version for the assessment of theory of mind in typical and atypical conditions.

Introduction: The Yoni task is a computerized tool assessing first-and second-order affective and cognitive Theory of Mind (ToM), accounting for the multidimensional and multi-level mentalizing features. The Italian Yoni task has been validated and standardized in its 98-item version, and a 48-item short version has been proposed for a quick digital evaluation of ToM in clinical contexts. Methods: The present study aimed to test the Yoni-48's convergent validity, correlating the tool score with the Reading the Mind in the Eyes test (ET) and Gender Test (GT), its items discrimination ability through the Classical Test Theory, and Rash model, its reliability by evaluating the internal consistency (McDonald's ω, Cronbach's α, Guttman's λ 2, and Guttman's λ 6) and Spearman-Brown ϱSP split-half analysis, and to provide standardization and normative data in the Italian population. Results: Results suggested a good convergent validity with a statistically significant association with ET (p < 0.001), while a null correlation was observed with GT (p = 0.947). The Classical Test Theory and Rash model confirmed a good discrimination ability of the Yoni-48's second-order affective and cognitive ToM items, while weaker discrimination capacity was registered for the first-order ToM items. The inter-item reliability was optimal for clinical purposes (ω, α, λ 2, λ 6 ≥ 0.90). Also, the split-half reliability was high (Spearman-Brown ϱSP = 0.90). For standardization, age and education were revealed as significant predictors of Yoni accuracy scores, except for the first-order ToM score. Instead, age was the only predictor of Yoni's response speed score. The Italian normative data showed a high Yoni accuracy in healthy adults (mean accuracy = 0.85) and speed (mean response time = 0.92). Finally, both accuracy and response time level was balanced between the affective and cognitive components of ToM. Discussion: This study supports the psychometric properties of the Yoni-48 and provides normative data for the Italian population. Further studies are needed to test the suitability of this short version for profiling the social cognition neurocognitive phenotype.

A Psychometric Tool for Evaluating Executive Functions in Parkinson's Disease.

Recently, there has been an increasing interest in using 360° virtual-reality video for an ecologically valid assessment of executive functioning in the neurologic population. In this framework, we have developed the EXecutive-functions Innovative Tool (EXIT 360°), an original 360°-based instrument for a multicomponent, ecologically valid evaluation of executive functioning in Parkinson's Disease (PD). This work aimed to test the usability and user experience of EXIT 360° in patients with PD (PwPD). Twenty-seven PwPD and twenty-seven healthy controls underwent an evaluation that involved: (1) usability assessment by the System Usability Scale and (2) evaluation of user experience using the ICT-Sense of Presence and User Experience Questionnaire. Results showed a satisfactory level of usability for patients (mean = 76.94 ± 9.18) and controls (mean = 80 ± 11.22), with good scores for usability and learnability. Regarding user experience, patients provided a positive overall impression of the tool, evaluating it as attractive, enjoyable, activating, and funny. Moreover, EXIT 360° showed good pragmatic (e.g., efficient, fast, clear) and hedonic quality (e.g., exciting, interesting, and creative). Finally, PwPD considered EXIT 360° as an original tool with high ecological validity (mean = 4.29 ± 0.61), spatial presence (mean = 3.11 ± 0.83) and engagement (mean = 3.43 ± 0.54) without relevant adverse effects. Technological expertise had no impact on performance. Overall, EXIT 360° appeared to be a usable, easy-to-learn, engaging, and innovative instrument for PD. Further studies will be conducted to deepen its efficacy in distinguishing between healthy subjects and patients with executive dysfunctions.

Affective Theory of Mind as a residual ability to preserve mentalizing in amnestic Mild Cognitive Impairment: A 12-months longitudinal study.

Introduction: Theory of Mind (ToM) decline has been outlined in people with amnestic Mild Cognitive Impairment (aMCI), but evidence from longitudinal studies is lacking. This longitudinal study aims to investigate changes in cognitive and affective ToM performance in an aMCI sample (n = 28; 14 females, mean age = 76.54 ± 4.35). Method: Participants underwent two steps of neurocognitive evaluation, at the baseline (T1) and 12-month follow-up (T2), to obtain their global cognitive level and both affective (Reading the Mind in the Eyes test, ET) and cognitive (Strange Stories, SS) ToM profile. Then, participants were categorized into two groups based on ToM changes: people who worsened (ETΔ < 0; SSΔ < 0) and people who did not (ETΔ≥0; SSΔ≥0) at follow-up. Differences between groups in cognitive functions and ToM profiles at baseline have been investigated. Results: Our results showed that 46% of subjects worsened in affective (ET) and 28% in cognitive (SS) ToM at follow-up. People who worsened in ET reported a statistically significantly higher performance in ET at baseline (p = 0.002) but not at follow-up than people who did not worsen. In contrast, subjects who worsened in SS showed a lower Immediate Free Recall (IFR, p = 0.026) and Delayed Free Recall (DFR, p = 0.028) score of the Free and Cued Selective Reminding test at baseline and at follow-up, a lower ET (p = 0.020) baseline score, a lower SS and MMSE level at follow-up than people who not worsened. About 71% of MCI subjects showed the same trend of evolution of the Mini-Mental State Examination and SS. Variables that significantly differed between groups have been inserted in a stepwise logistic regression to pilot explore predictors of affective and cognitive ToM evolution. Logistic regression showed ET at baseline (p = 0.015) as the only significant predictor of affective ToM evolution (R2 = 0.450), while both ET (p = 0.044) and memory performance (p = 0.045) at baseline significantly predicted cognitive ToM evolution (R2 = 0.746). Discussion: In conclusion, our results support the role of affective ToM as a residual mentalizing ability in preserving the mentalizing level in people with aMCI.

Available Virtual Reality-Based Tools for Executive Functions: A Systematic Review.

Introduction: Executive dysfunctions constitute a significant public health problem: their high impact on everyday life makes it a priority to identify early strategies for evaluating and rehabilitating these disorders in a real-life context. The ecological limitation of traditional neuropsychological tests and several difficulties in administering tests or training in real-life scenarios have paved the way to use Virtual Reality-based tools to evaluate and rehabilitate Executive Functions (EFs) in real-life. Objective: This work aims to conduct a systematic review to provide a detailed description of the VR-based tools currently developed for the evaluation and rehabilitation of EFs. Methods: We systematically searched for original manuscripts regarding VR tools and EFs by looking for titles and abstracts in the PubMed, Scopus, PsycInfo, and Web of Science databases up to November 2021 that contained the following keywords "Virtual Reality" AND "Executive function*." Results and Conclusion: We analyzed 301 articles, of which 100 were included. Our work shows that available VR-based tools appear promising solutions for an ecological assessment and treatment of EFs in healthy subjects and several clinical populations.