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Abstract Theory of Mind (ToM) is the ability to predict the behaviour of others by inferring their cognitive and affective states. The literature suggests that different neural substrates within the basal ganglia are involved in the affective (ventral striatum) and cognitive (dorsal striatum) components of ToM. We investigated ToM dysfunction in two different basal ganglia pathologies, Huntington’s disease (HD) and Parkinson’s disease (PD), in their early stages. Indeed, a different progression of neurodegeneration from the dorsal striatum to the ventral striatum is described in the two diseases. We also investigated whether there is a correlation between ToM and executive function. Twenty-one patients with HD, 21 with PD, and 22 healthy subjects (HS) were recruited. All participants completed a ToM assessment using the Yoni task, which assesses both cognitive and affective components at two levels of meta-representational difficulty (i.e. first-order items only require inferring the mental state of a person, while second-order items also require inferring the mental states of a person about others). The clinical groups also underwent a full neuropsychological assessment. In HD patients, both cognitive and affective ToM were equally impaired, whereas in PD patients, impairment of the cognitive component predominated. Specifically, compared to HS, HD patients scored lower on both inferential levels and on both cognitive and affective components, whereas PD patients scored lower than HS only on second-order and cognitive items. In the clinical groups, there was an imbalance between the cognitive and affective components, with higher accuracy on affective items. Performance on the Yoni task did not correlate with tests assessing executive functions. We suggest that the different pattern of ToM alteration in HD and PD may be a result of differential involvement of the ventral and dorsal striatum and that ToM abilities in these clinical populations are not directly supported by executive functioning.

The aim of the current study is to investigate the integrity of the Mirror Neurons (MN) network in normal aging, Mild Cognitive Impairment (MCI), and Alzheimer disease (AD). Although AD and MCI are considered \"cognitive\" diseases, there has been increasing recognition of a link between motor function and AD. More recently the embodied cognition hypothesis has also been developed: it postulates that a part of cognition results from the coupling between action and perception representations. MN represent a neuronal population which links perception, action, and cognition, therefore we decided to characterize MN functioning in neurodegenerative cognitive decline. Three matched groups of 16 subjects (normal elderly-NE, amnesic MCI with hippocampal atrophy and AD) were evaluated with a focused neuropsychological battery and an fMRI task specifically created to test MN: that comprised of an observation run, where subjects were shown movies of a right hand grasping different objects, and of a motor run, where subjects observed visual pictures of objects oriented to be grasped with the right hand. In NE subjects, the conjunction analysis (comparing fMRI activation during observation and execution), showed the activation of a bilateral fronto-parietal network in \"classical\" MN areas, and of the superior temporal gyrus (STG). The MCI group showed the activation of areas belonging to the same network, however, parietal areas were activated to a lesser extent and the STG was not activated, while the opposite was true for the right Broca's area. We did not observe any activation of the fronto-parietal network in AD participants. They did not perform as well as the NE subjects in all the neuropsychological tests (including tests of functions attributed to MN) whereas the MCI subjects were significantly different from the NE subjects only in episodic memory and semantic fluency. Here we show that the MN network is largely preserved in aging, while it appears involved following an anterior-posterior gradient in neurodegenerative decline. In AD, task performance decays and the MN network appears clearly deficient. The preservation of the anterior part of the MN network in MCI could possibly supplement the initial decay of the posterior part, preserving cognitive performance.

This study aimed to understand the impact of the prosodic deficit in Parkinson’s disease (PD) on the communicative effectiveness of vocal expression of emotion. Fourteen patients with PD and 13 healthy control subjects (HC) uttered the phrase “non è possible, non ora” (“It is not possible, not now”) six times reading different emotional narrations. Three experts evaluated the PD subjects’ vocal production in terms of their communicative effectiveness. The PD patients were divided into two groups: PD+ (with residual effectiveness) and PD− (with impaired effectiveness). The vocal productions were administered to 30 naïve listeners. They were requested to label the emotion they recognized and to make judgments about their communicative effectiveness. The PD speakers were perceived as less effective than the HC speakers in conveying emotions (especially fear and anger). The PD− group was the most impaired in the expression of emotion, suggesting that speech disorders impact differently at the same stage of the disease with varying degrees of severity.

Background/Objectives: The current meta-analysis looks at the effect of ethnicity on the connection between 5-HTTLPR SNPs and PTSD patients in all published genetic association studies. Techniques: In accordance with PRISMA principles, the literature was searched in PubMed, Scopus, and ScienceDirect. A consistent method was followed by two reviewers who independently chose publications for inclusion and extracted data. Using a random-effects model, a meta-analysis of the biallelic and triallelic studies was conducted in order to determine the pooled OR and the associated 95% CI. The impact estimates were corrected for minor study effects, including publication bias, using the trim-and-fill approach. Findings: After 17 studies were deemed eligible for inclusion, the overall sample size was 8838 controls and 2586 PTSD patients, as opposed to 627 and 3524 in the triallelic meta-analysis. The results of our meta-analysis and comprehensive review do not point to a direct main effect of the 5-HTTLPR polymorphisms on PTSD. Nonetheless, preliminary data suggest that ethnicity influences the association between 5-HTTLPR and PTSD. Conclusions: According to our findings, ethnicity—especially African ethnicity—has a major influence on the relationship between 5-HTTLPR and PTSD and needs to be taken into account as a crucial moderating factor in further studies.

•Voxel-wise GLM analysis failed to capture fMRI signal variability.•ROI-based ICC analysis differentiated fMRI signal reliability between stimuli.•Stimuli with negative emotional valence are more reliable than positive valence ones.•Emotional valence more than stimulus habituation impacts fMRI signal reliability. 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. 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. 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. 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. [Display omitted]

Despite recent interest in late-onset Huntington’s Disease (LoHD) phenotype, scarce evidence is available regarding it’s progression. This study aimed to investigate changes over time in clinical features in LoHD patients. This is a retrospective observational study on 99 LoHD (motor onset ≥60 years) and 854 patients with common-onset (CoHD, motor onset 30-59 years) from Enroll-HD PDS5, followed-up to 4 years. Linear mixed models were performed to evaluate differences between the two groups and the ‘time’ effect at three different timepoints: t0 (baseline), t1 and t2 (respectively, 2 and 4 years). Body Mass Index (BMI), Total UHDRS Functional Capacity (TFC) &Total Motor Score (TMS), Problem Behaviors Assessment (PBAs), MMSE and a short cognitive battery were examined at each timepoint. The results showed that 50.4% of CoHD patients were males, the mean age at baseline was 52.57±8.96 years, the mean CAGn on mutated allele was 43.50±2.47. LoHD patients were males in 41.4%; baseline mean age was 70.88±4.74 years, and mean CAGn was 40.83±1.31. In CoHD and LoHD, weight remained stable at t1 but significantly decreased at t2; motor performance significantly worsened at t1 and t2, and functionality scores lowered at both timepoints. Significant differences between groups emerged on many cognitive tasks, with LoHD showing less preserved cognitive status. Time effect emerged in most tests, with significant progressive worsening. At PBA-s, depression significantly reduced at t2 while apathy increased. No significant changes were detected in irritability and psychosis over time. In conclusion, the clinical progression of both groups is characterized by worsening in motor and cognitive performance and reduction in functionality over 2 and 4 years. Neuropsychiatric features follow different trajectories along HD course, deserving further exploration.

Huntington’s disease (HD) is a rare autosomal dominant neurodegenerative disorder. The onset is typically adult and the clinical profile includes movement disorders, cognitive deficits and behavioural changes. We examined sociodemographic, genetic and clinical characteristics of patients with negative family history of disease extracted from Enroll-HD PDS4. Out of the 5053 European Caucasian adult patients, 630 (12.50%) shared a missing/unknown inheritance status while 44.30% inherited HD from maternal and 43.20% from paternal side. The age of this group was 61.40±12.00; the sex ratio was exactly 50%. The age of onset was 53.78±11.96 and diagnosis was 4 years postponed (57.59±11.94); mean CAG triplets number in larger allele was 42.48±3.14. In 54.70% of subjects, the onset symptom was purely motor; mixed symptoms in 19.10%. Psychiatric onset was reported in 20.60% of patients while cognitive only in 5.40%. Psychiatric anamnesis included depression (pre-HD onset) in 26% of cases, suicidal ideation/behaviours in 25.40%. Alcohol abuse described in 8%. When sporadic HD cases appear, we can hypothesize parental intermediate allele transmission (tardive HD parent healthy until later age, or misdiagnosed). In a minority, adoption or non-paternity made HD not traceable. Further investigation of sociodemographic and clinical characteristics of this population is interesting as they carried on their own life until diagnosis unaware of HD, protected from a well-recognized major existential burden involving personal genetic risk, caregiving for affected family members, multiple losses. The role of life stressors in modulating aspects of disease is still unclear and may offer perspectives of psychobehavioral intervention.

Theory of Mind (ToM) is the ability to predict others’ behavior by inference of their mental states. The affective component (Aff-ToM) is responsible for understanding others’ emotions, while the cognitive component (Cogn-ToM) refers to the knowledge of others’ beliefs and intentions. We examined ToM abilities in patients with Huntington’s disease (HD) and Parkinson’s disease (PD) compared to healthy controls (HC). All 63 participants (HD (n=20) 55.65±12.86; PD (n=21) 72.00±5.98; HC (n=22) 61.82±12.25 years) were evaluated using the computerized Yoni task which assesses affective and cognitive ToM abilities. This task also contains control items balanced for the level of difficulty (1st and 2nd order). Only patients with mild-moderate cognitive impairment were included (MoCA: HD 17.58±5.90; PD 20.19±4.00). Compared to HC, HD patients performed worse on both Aff-ToM and Cog-ToM (1st and 2nd order), whereas PD scored lower than HC only on 2nd order Cog-ToM. No between-group differences were observed on control items. Within groups comparisons showed differences only on 2nd order items: for HC the accuracy in both Aff-ToM and Cog-ToM items was poorer than in the control items; for HD the accuracy on Cog-ToM was lower than Aff-ToM, which resulted both lower than control items; and for PD only Cog-ToM was lower than the control items. The good performance in control items confirms a specific ToM deficit in clinical groups. In both groups, the affective component is more preserved than the cognitive component suggesting that the affective dimension might be less sensitive to damage of the striatum and corticostriatal circuits.

In recent years, the potential usefulness of cognitive training procedures in normal aging and mild cognitive impairment (MCI) have received increased attention. The main aim of this study was to evaluate the efficacy of the face-to-face cognitive virtual reality rehabilitation system (VRRS) and to compare it to that of face-to-face cognitive treatment as usual for individuals with MCI. Moreover, we assessed the possibility of prolonging the effects of treatment with a telerehabilitation system. A total of 49 subjects with MCI were assigned to 1 of 3 study groups in a randomized controlled trial design: (a) those who received face-to-face cognitive VRRS (12 sessions of individualized cognitive rehabilitation over 4 weeks) followed by telerehabilitation (36 sessions of home-based cognitive VRRS training, three sessions for week); (b) those who received face-to-face cognitive VRRS followed by at-home unstructured cognitive stimulation (36 sessions of home-based unstructured cognitive stimulation, three sessions for week); and (c) those who received face-to-face cognitive treatment as usual (12 sessions of face-to-face cognitive treatment as usual). An improvement in memory, language and visuo-constructional abilities was observed after the end of face-to-face VRRS treatment compared to face-to-face treatment as usual. The application of home-based cognitive VRRS telerehabilitation seems to induce more maintenance of the obtained gains than home-based unstructured stimulation. The present study provides preliminary evidence in support of individualized VRRS treatment and telerehabilitation delivery for cognitive rehabilitation and should pave the way for future studies aiming at identifying optimal cognitive treatment protocols in subjects with MCI. www.ClinicalTrials.gov, identifier NCT03486704.

Huntington’s disease (HD) onset typically occurs in mid adulthood however, late onset phenotype with onset 60 years and over (LoHD) is recently gaining attention. We examined the baseline characteristics of 220 LoHD patients and their clinical, cognitive and behavioral correlates at two consecutive timepoints over 2 years. This is a retrospective observational study on 220 European LoHD patients from the Enroll-HD dataset with 2 consecutive annual follow-up visits. Linear models using repeated measures Anova were performed to investigate changes over time.LoHD patients were 114 Males (51.8%) and 106 Females (48.2%), their mean age at baseline visit (t0) was 70.0 ±5.0 years, with disease duration 6.34±3.89 years. Mean CAGn was respectively 40.75±1.29 in larger allele, and 18.19±2.86 in normal allele. In 18% of LoHD patients HD family history was not traceable. Body Mass index BMI, UHDRS Total functional Capacity TFC & Total Motor Score TMS, PBAs composite scores, MMSE and a cognitive battery restricted to the assessment of executive functions were reported at t0 and compared at t1 (375 ±61.01 days) and t2 (746.39±74.8 days). BMI remained stable at t1 and t2 , TMS significantly worsened at t2 and TFC was reduced of 0.80 point at t1 and 1.41 at t2. No significant cognitive changes over two years on MMSE, Phonological fluency and Symbol Digit Span Modalities Test, Trail Making Test and Stroop Interference Test. Lower scores detected at t2 for Categorial Fluency (animals), Stroop color reading and word reading.No significant changes were detected over two years in PBA-s composite scores rating depression/anxiety/suicidality, irritability and aggressivity, psychosis, apathy.LoHD phenotype clinical progression is characterized by significant reduction in daily functionality and worsening in motor symptoms over 2 years. In cognitive performance significant changes were detected only in few specific tasks, requiring further investigation.