Human reasoning on social interactions in ecological contexts: insights from the theory of mind brain circuits.

Introduction: The relationship between neural social cognition patterns and performance on social cognition tasks in daily life is a topic of debate, with key consideration given to the extent to which theory of mind (ToM) brain circuits share properties reflecting everyday social functioning. To test the efficacy of ecological stimuli in eliciting brain activation within the ToM brain circuits, we adapted the Edinburgh Social Cognition test social scenarios, consisting of dynamic ecological contextually embedded social stimuli, to a fMRI paradigm. Methods: Forty-two adults (21 men, mean age ± SD = 34.19 years ±12.57) were enrolled and underwent an fMRI assessment which consisted of a ToM task using the Edinburgh Social Cognition test scenarios. We used the same stimuli to prompt implicit (movie viewing) and explicit (silent and two-choice answers) reasoning on cognitive and affective mental states. The fMRI analysis was based on the classical random effect analysis. Group inferences were complemented with supplemental analyses using overlap maps to assess inter-subject variability. Results: We found that explicit mentalizing reasoning yielded wide neural activations when two-choice answers were used. We also observed that the nature of ToM reasoning, that is, affective or cognitive, played a significant role in activating different neural circuits. Discussion: The ESCoT stimuli were particularly effective in evoking ToM core neural underpinnings and elicited executive frontal loops. Future work may employ the task in a clinical setting to investigate ToM network reorganization and plasticity.

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.

Eye movement desensitization and reprocessing for depressed individuals with multiple sclerosis: A pilot study.

BACKGROUND: Multiple studies have highlighted elevated rates of depression among individuals with Multiple Sclerosis (MS), with its associated symptoms posing a significant threat to overall well-being. Moreover, existing literature suggests a potential interconnection between depressive manifestations and the decline of physical functionalities in the context of MS. OBJECTIVE: to examine the viability of the Eye Movement Desensitization Reprocessing (EMDR) therapy protocol for the treatment of depressive disorders (DeprEND) for alleviating depression in individuals with MS. METHODS: We conducted a process-outcome study to examine the feasibilty and effectiveness DeprEND enrolling 13 individuals with MS and depressive symtpoms. Psychological and physical assessment pre-, post-intervention and 3-month follow-up were included. Pre- and post-magnetic resonance imaging (MRI) scans were conducted to analyze potential alterations in brain function. RESULTS: The EMDR DeprEND treatment showed a high level of adherence and feasibility. Significant reductions in depressive symptoms were found at post-intervention and at 3 months follow-up. No significant differences were observed in terms of physical symptoms. A significant modulation observed in parietal and premotor areas when examining negative valence stimuli post-treatment was found. CONCLUSION: for The EMDR DeprEND protocol may represent a feasible and cost-effective treatment for reducing depressive symptoms in MS patients and improving their mental well-being.

Unconsciousness or unresponsiveness in akinetic mutism? Insights from a multimodal longitudinal exploration.

The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour-based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology-based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients.

The impact of emotional valence and stimulus habituation on fMRI signal reliability during emotion generation.

BACKGROUND: The emotional domain is often impaired across many neurological diseases, for this reason it represents a relevant target of rehabilitation interventions. Functional changes in neural activity related to treatment can be assessed with functional MRI (fMRI) using emotion-generation tasks in longitudinal settings. Previous studies demonstrated that within-subject fMRI signal reliability can be affected by several factors such as repetition suppression, type of task and brain anatomy. However, the differential role of repetition suppression and emotional valence of the stimuli on the fMRI signal reliability and reproducibility during an emotion-generation task involving the vision of emotional pictures is yet to be determined. METHODS: Sixty-two healthy subjects were enrolled and split into two groups: group A (21 subjects, test-retest reliability on same-day and with same-task-form), group B (30 subjects, test-retest reproducibility with 4-month-interval using two equivalent-parallel forms of the task). Test-retest reliability and reproducibility of fMRI responses and patterns were evaluated separately for positive and negative emotional valence conditions in both groups. The analyses were performed voxel-wise, using the general linear model (GLM), and via a region-of-interest (ROI)-based approach, by computing the intra-class correlation coefficient (ICC) on the obtained contrasts. RESULTS: The voxel-wise GLM test yielded no significant differences for both conditions in reliability and reproducibility analyses. As to the ROI-based approach, across all areas with significant main effects of the stimuli, the reliability, as measured with ICC, was poor (<0.4) for the positive condition and ranged from poor to excellent (0.4-0.75) for the negative condition. The ICC-based reproducibility analysis, related to the comparison of two different parallel forms, yielded similar results. DISCUSSION: The voxel-wise GLM analysis failed to capture the poor reliability of fMRI signal which was instead highlighted using the ROI-based ICC analysis. The latter showed higher signal reliability for negative valence stimuli with respect to positive ones. The implementation of two parallel forms allowed to exclude neural suppression as the predominant effect causing low signal reliability, which could be instead ascribed to the employment of different neural strategies to cope with emotional stimuli over time. This is an invaluable information for a better assessment of treatment and rehabilitation effects in longitudinal studies of emotional neural processing.

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.

Surface-based integration approach for fNIRS-fMRI reliability assessment.

INTRODUCTION: Studies integrating functional near-infrared spectroscopy (fNIRS) with functional MRI (fMRI) employ heterogeneous methods in defining common regions of interest in which similarities are assessed. Therefore, spatial agreement and temporal correlation may not be reproducible across studies. In the present work, we address this issue by proposing a novel method for integration and analysis of fNIRS and fMRI over the cortical surface. MATERIALS AND METHODS: Eighteen healthy volunteers (age mean±SD 30.55 ± 4.7, 7 males) performed a motor task during non-simultaneous fMRI and fNIRS acquisitions. First, fNIRS and fMRI data were integrated by projecting subject- and group-level source maps over the cortical surface mesh to define anatomically constrained functional ROIs (acfROI). Next, spatial agreement and temporal correlation were quantified as Dice Coefficient (DC) and Pearson's correlation coefficient between fNIRS-fMRI in the acfROIs. RESULTS: Subject-level results revealed moderate to substantial spatial agreement (DC range 0.43 - 0.64), confirmed at the group-level only for blood oxygenation level-dependent (BOLD) signal vs. HbO2 (0.44 - 0.69), while lack of agreement was found for BOLD vs. HbR in some instances (0.05 - 0.49). Subject-level temporal correlation was moderate to strong (0.79 - 0.85 for BOLD vs. HbO2 and -0.62 to -0.72 for BOLD vs. HbR), while an overall strong correlation was found for group-level results (0.95 - 0.98 for BOLD vs. HbO2 and -0.91 to -0.94 for BOLD vs. HbR). CONCLUSION: The proposed method directly compares fNIRS and fMRI by projecting individual source maps to the cortical surface. Our results indicate spatial and temporal correspondence between fNIRS and fMRI, and promotes the use of fNIRS when more ecological acquision settings are required, such as longitudinal monitoring of brain activity before and after rehabilitation.

Production of emotions conveyed by voice in Parkinson's disease: Association between variability of fundamental frequency and gray matter volumes of regions involved in emotional prosody.

OBJECTIVE: Parkinson's disease (PD) is associated with impairment in producing emotions conveyed by voice which could depend on motor limitations of the vocal apparatus and/or alterations in emotional processing. This study explores the relationship between the standard deviation of fundamental frequency (F0SD) of emotional speech and the volume of specific gray matter regions. METHOD: Fifteen PD patients and 15 healthy controls (HC) were asked to produce different emotions vocally elicited by reading short stories. For each vocal track, the F0SD was calculated as index of variability. All subjects underwent a structural magnetic resonance imaging and a voxel-based morphometry analysis. An ad hoc mask of brain regions implicated in emotional prosody was constructed to test the relationship between F0SD and the level of brain atrophy. RESULTS: PD patients showed lower F0SD values than HC in the expression of anger. Neuroimaging results showed brain atrophy in PD patients in a widespread bilateral network, including frontal areas, left cingulate cortex, parietal areas as well as occipital cortices. In the PD group, a positive correlation was observed between F0SD values of anger and volumes of the bilateral supramarginal gyrus, left thalamus, right inferior frontal gyrus, and amygdala. CONCLUSIONS: The lower F0SD values observed in PD patients in anger production are consistent with their lower ability to express anger effectively through voice compared to HC. Our data demonstrated the involvement of right-lateralized areas, such as the inferior frontal gyrus and amygdala, which are typically involved in emotional prosody. Disturbances in emotion processing might contribute to speech production deficits in PD, probably in addition to the motor impairment of the articulatory system. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

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.

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.

Embedding the Patient-Citizen Perspective into an Operational Framework for the Development and the Introduction of New Technologies in Rehabilitation Care: The Smart&Touch-ID Model.

To date, at least 2.41 billion people with Non-Communicable Diseases (NCDs) are in need of rehabilitation. Rehabilitation care through innovative technologies is the ideal candidate to reach all people with NCDs in need. To obtain these innovative solutions available in the public health system calls for a rigorous multidimensional evaluation that, with an articulated approach, is carried out through the Health Technology Assessment (HTA) methodology. In this context, the aim of the present paper is to illustrate how the Smart&TouchID (STID) model addresses the need to incorporate patients' evaluations into a multidimensional technology assessment framework by presenting a feasibility study of model application with regard to the rehabilitation experiences of people living with NCDs. After sketching out the STID model's vision and operational process, preliminary evidence on the experiences and attitudes of patients and citizens on rehabilitation care will be described and discussed, showing how they operate, enabling the co-design of technological solutions with a multi-stakeholder approach. Implications for public health are discussed including the view on the STID model as a tool to be integrated into public health governance strategies aimed at tuning the agenda-setting of innovation in rehabilitation care through a participatory methodology.

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.

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.

The impact of valproic acid treatment on weight gain in pediatric patients with epilepsy.

BACKGROUND: Valproic acid (VPA) is an antiepileptic drug, used for focal and generalized seizure. VPA treatment resulted in significant weight gain but there are no systematic data about the prevalence of this side effect. The aim of the study was to evaluate the weight gain of a pediatric population with epilepsy. METHODS: We enrolled 38 patients, 17 females and 21 males with a mean age of 8.2±4.4 years. We evaluated data about height, weight and BMI at beginning of treatment and at 24, 36 and 48 months of follow-up. RESULTS: There is a statistically significant difference between the percentile value of weight and BMI at baseline and at 36 and 48 months of follow-up (P<0.01) but there is not statistically significant difference between the percentile value of height (P=0.22 and P=0.18). CONCLUSIONS: We believe that a nutritional support should be guaranteed to the pediatric patients with epilepsy that begin the VPA therapy.

Neuroimaging Biomarkers Predicting the Efficacy of Multimodal Rehabilitative Intervention in the Alzheimer's Dementia Continuum Pathology.

In this work we aimed to identify neural predictors of the efficacy of multimodal rehabilitative interventions in AD-continuum patients in the attempt to identify ideal candidates to improve the treatment outcome. Subjects in the AD continuum who participated in a multimodal rehabilitative treatment were included in the analysis [n = 82, 38 Males, mean age = 76 ± 5.30, mean education years = 9.09 ± 3.81, Mini Mental State Examination (MMSE) mean score = 23.31 ± 3.81]. All subjects underwent an MRI acquisition (1.5T) at baseline (T0) and a neuropsychological evaluation before (T0) and after intervention (T1). All subjects underwent an intensive multimodal cognitive rehabilitation (8-10 weeks). The MMSE and Neuropsychiatric Inventory (NPI) scores were considered as the main cognitive and behavioral outcome measures, and Delta change scores (T1-T0) were categorized in Improved (ΔMMSE > 0; ΔNPI < 0) and Not Improved (ΔMMSE ≤ 0; ΔNPI ≥ 0). Logistic Regression (LR) and Random Forest classification models were performed including neural markers (Medial Temporal Brain; Posterior Brain (PB); Frontal Brain (FB), Subcortical Brain indexes), neuropsychological (MMSE, NPI, verbal fluencies), and demographical variables (sex, age, education) at baseline. More than 50% of patients showed a positive effect of the treatment (ΔMMSE > 0: 51%, ΔNPI < 0: 52%). LR model on ΔMMSE (Improved vs. Not Improved) indicate a predictive role for MMSE score (p = 0.003) and PB index (p = 0.005), especially the right PB (p = 0.002) at baseline. The Random Forest analysis correctly classified 77% of cognitively improved and not improved AD patients. Concerning the NPI, LR model on ΔNPI (Improved vs. Not Improved) showed a predictive role of sex (p = 0.002), NPI (p = 0.005), PB index (p = 0.006), and FB index (p = 0.039) at baseline. The Random Forest reported a classification accuracy of 86%. Our data indicate that cognitive and behavioral status alone are not sufficient to identify best responders to a multidomain rehabilitation treatment. Increased neural reserve, especially in the parietal areas, is also relevant for the compensatory mechanisms activated by rehabilitative treatment. These data are relevant to support clinical decision by identifying target patients with high probability of success after rehabilitative programs on cognitive and behavioral functioning.

Neuroplasticity and Motor Rehabilitation in Multiple Sclerosis: A Systematic Review on MRI Markers of Functional and Structural Changes.

Background: Motor rehabilitation is routinely used in clinical practice as an effective method to reduce progressive disability gain in multiple sclerosis (MS), but rehabilitation approaches are typically unstandardized, and only few studies have investigated the impact of rehabilitation on brain neuroplasticity. Objective: To summarize and critically analyze studies applying MRI markers of functional connectivity and structural changes to assess the effect of motor rehabilitation on brain neuroplasticity in MS. Methods: Literature search was performed using PubMed and EMBASE, selecting studies having as a subject motor rehabilitation and advanced MRI techniques investigating neuroplasticity in adult patients affected by MS. Results: Seventeen out of 798 papers were selected, of which 5 applied structural MRI (4 diffusion tensor imaging, 1 volumetric measurements), 7 applied functional fMRI (5 task-related fMRI, 2 resting-state fMRI) whereas the remaining 5 applied both structural and functional imaging. Discussion: The considerable data heterogeneity and the small sample sizes characterizing the studies limit interpretation and generalization of the results. Overall, motor rehabilitation promotes clinical improvement, paralleled by positive adaptive brain changes, whose features and extent depend upon different variables, including the type of rehabilitation approach. MRI markers of functional and structural connectivity should be implemented in studies testing the efficacy of motor rehabilitation. They allow for a better understanding of neuroplastic mechanisms underlying rehabilitation-mediated clinical achievements, facilitating the identification of rehabilitation strategies tailored to patients' needs and abilities.

SNAP-25 Single Nucleotide Polymorphisms, Brain Morphology and Intelligence in Children With Borderline Intellectual Functioning: A Mediation Analysis.

Borderline intellectual functioning (BIF) is a multifactorial condition in which both genetic and environmental factors are likely to contribute to the clinical outcome. Abnormal cortical development and lower IQ scores were shown to be correlated in BIF children, but the genetic components of this condition and their possible connection with intelligence and brain morphology have never been investigated in BIF. The synaptosomal-associated protein of 25 kD (SNAP-25) is involved in synaptic plasticity, neural maturation, and neurotransmission, affecting intellectual functioning. We investigated SNAP-25 polymorphisms in BIF and correlated such polymorphisms with intelligence and cortical thickness, using socioeconomic status and environmental stress as covariates as a good proxy of the variables that determine intellectual abilities. Thirty-three children with a diagnosis of BIF were enrolled in the study. SNAP-25 polymorphisms rs363050, rs363039, rs363043, rs3746544, and rs1051312 were analyzed by genotyping; cortical thickness was studied by MRI; intelligence was measured using the WISC-III/IV subscales; environmental stressors playing a role in neuropsychiatric development were considered as covariate factors. Results showed that BIF children carrying the rs363043(T) minor allele represented by (CT + TT) genotypes were characterized by lower performance Perceptual Reasoning Index and lower full-scale IQ scores (p = 0.04) compared to those carrying the (CC) genotype. This association was correlated with a reduced thickness of the left inferior parietal cortex (direct effect = 0.44) and of the left supramarginal gyrus (direct effect = 0.56). These results suggest a link between SNAP-25 polymorphism and intelligence with the mediation role of brain morphological features in children with BIF.

A New Perspective on the Role of Self-Confidence and Confidence in the Evaluation and Rehabilitation of Children With Adverse Life Experience and Borderline Intellectual Functioning: A Preliminary Study.

The borderline intellectual functioning (BIF) is a neurodevelopmental condition characterized by a borderline intelligence quotient (range 70-85) with difficulties in cognitive and social domains. Children with BIF often live in adverse conditions and show academic and behavioral difficulties. Rehabilitation programs for these children focus mainly on cognitive aspects, sometimes with the aid of new technologies that are able to engage and motivate. In this framework, the affective development of children with BIF and its possible role both in the difficulties they manifest and in the rehabilitation is still poorly investigated. In this work, we investigate the characteristics of the internal working models of these children by applying the separation anxiety test, using both the classical and a new coding system to identify the specific features of the attachment representation. Results delineate a profile characterized by low self-confidence and high separation anxiety, with a tendency to somatization. In the light of these results, we suggest that this attachment profile has an impact on the therapeutic relationships and on the efficacy in the use of technological devices. We propose a new perspective in which the interpersonal relationship with the psychologist and the support of the self-confidence of children are crucial to treating cognitive and behavioral difficulties in children with BIF. Only in this case, the use of new technologies and tools may be effective in promoting the greatest possible benefit from therapeutic interventions.

How Do We Motorically Resonate in Aging? A Compensatory Role of Prefrontal Cortex.

Aging is the major risk factor for chronic age-related neurological diseases such as neurodegenerative disorders and neurovascular injuries. Exploiting the multimodal nature of the Mirror Neuron System (MNS), rehabilitative interventions have been proposed based on motor-resonance mechanisms in recent years. Despite the considerable evidence of the MNS' functionality in young adults, further investigation of the action-observation matching system is required in aging, where well-known structural and functional brain changes occur. Twenty-one healthy young adults (mean age 26.66y) and 19 healthy elderly participants (mean age 71.47y) underwent a single MRI evaluation including a T1-3D high-resolution and functional MRI (fMRI) with mirror task. Morphological and functional BOLD data were derived from MRI images to highlight cortical activations associated with the task; to detect differences between the two groups (Young, Elderly) in the two MRI indexes (BOLD and thickness z-scores) using mixed factorial ANOVA (Group∗Index analyses); and to investigate the presence of different cortical lateralization of the BOLD signal in the two groups. In the entire sample, the activation of a bilateral MNS fronto-parietal network was highlighted. The mixed ANOVA (pFDR-corr < 0.05) revealed significant interactions between BOLD signal and cortical thickness in left dorsal premotor cortex, right ventral premotor and prefrontal cortices. A different cortical lateralization of the BOLD signal in frontal lobe activity between groups was also found. Data herein reported suggest that age-related cortical thinning of the MNS is coupled with increased interhemispheric symmetry along with premotor and prefrontal cortex recruitment. These physiological changes of MNS resemble the aging of the motor and cognitive neural systems, suggesting specific but also common aging and compensatory mechanisms.