A cultural training for the improvement of cognitive and affective Theory of Mind in people with Multiple Sclerosis: a pilot randomized controlled study

Theory of Mind (ToM), the ability to understand and attribute mental states to ourselves and others, could be impaired in Multiple Sclerosis (MS), a neurodegenerative disease affecting young adults. Considering that ToM is strictly connected to Quality of Life (QoL) in MS and that could enhance the social support network -which is particularly important for this population-, we aimed to design and implement a novel ToM rehabilitation training. To make the training as much ecological as possible, we have devised a protocol enhancing ToM through stimuli depicting real-world conditions (video-clips taken from cinema movies, literary fictions, and audio voices). We test training’s effect on both cognitive and affective components of ToM in a sample of 13 subjects, randomly assigned to the ToM training Group and to the Control Group. The following ToM tasks were administered: the Reading the Mind in the Eyes (RMET), the Strange Stories task, the Faux Pas Task and the False Belief First- and Second - Order Task (FB II and III order). We also administered a psycho-behavioral assessment through the Toronto Alexithymia Scale (TAS-20). Results show that our novel ToM training is useful in enhancing ToM abilities measured by the following tasks: the RMET (affective task, p = 0.015) and the FB II-order task (FB, cognitive task, p = 0.032). Our ToM training had also a significant effect on the total score of the TAS-20 Scale (p = 0.018) and on its “Difficulty Describing Feelings subscale” (p = 0.018), indicating a reduction of the alexithymia traits. Future works with larger samples could investigate the ToM training effectiveness in a more representative MS populations

How does prosodic deficit impact naïve listeners recognition of emotion? An analysis with speakers affected by Parkinson's disease

Abstract 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

Cardiac and Respiratory Influences on Intracranial and Neck Venous Flow, Estimated Using Real-Time Phase-Contrast MRI

The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck's venous flow, this aspect could not be studied using the conventional segmented PC-MRI since it reconstructs a single cardiac cycle. The advent of real-time PC-MRI has overcome these limitations. Using this technique, we measured the internal jugular veins and superior sagittal sinus flow rates in a group of 16 healthy subjects (12 females, median age of 23 years). Comparing forced-breathing and free-breathing, the average flow rate decreased and the respiratory modulation increased. The flow rate decrement may be due to a vasoreactive response to deep breathing. The respiratory modulation increment is due to the thoracic pump's greater effect during forced breathing compared to free breathing. These results showed that the breathing mode influences the average blood flow and its pulsations. Since effective drainage is fundamental for brain health, rehabilitative studies might use the current setup to investigate if respiratory exercises positively affect clinical variables and venous drainage

Non-Immersive Virtual Reality Telerehabilitation System Improves Postural Balance in People with Chronic Neurological Diseases

Background: People with chronic neurological diseases, such as Parkinson’s Disease (PD) and Multiple Sclerosis (MS), often present postural disorders and a high risk of falling. When difficulties in achieving outpatient rehabilitation services occur, a solution to guarantee the continuity of care may be telerehabilitation. This study intends to expand the scope of our previously published research on the impact of telerehabilitation on quality of life in an MS sample, testing the impact of this type of intervention in a larger sample of neurological patients also including PD individuals on postural balance. Methods: We included 60 participants with MS and 72 with PD. All enrolled subjects were randomized into two groups: 65 in the intervention group and 67 in the control group. Both treatments lasted 30–40 sessions (5 days/week, 6–8 weeks). Motor, cognitive, and participation outcomes were registered before and after the treatments. Results: All participants improved the outcomes at the end of the treatments. The study’s primary outcome (Mini-BESTest) registered a greater significant improvement in the telerehabilitation group than in the control group. Conclusions: Our results demonstrated that non-immersive virtual reality telerehabilitation is well tolerated and positively affects static and dynamic balance and gait in people with PD and MS

Theory of Mind in migraine and medication-overuse headache: A cross-sectional study

Theory of Mind (ToM) is the ability to predict and anticipate others' behaviors through the mental state attribution process. This study aims to investigate the ToM in patients with medication-overuse headache (MOH) and episodic migraine (EM) and to compare it with healthy controls (HC)

Neuroanatomical Correlates of Semantic Features of Narrative Speech in Semantic and Logopenic Variants of Primary Progressive Aphasia

The semantic variant of a primary progressive aphasia (svPPA) is characterized by progressive disruption of semantic knowledge. This study aimed to compare the semantic features of words produced during a narrative speech in svPPA and the logopenic variant of PPA (lvPPA) and to explore their neuroanatomical correlates. Six patients with svPPA and sixteen with lvPPA underwent narrative speech tasks. For all the content words, a semantic depth index (SDI) was determined based on the taxonomic structure of a large lexical database. Study participants underwent an MRI examination. Cortical thickness measures were extracted according to the Desikan atlas. Correlations were computed between SDI and the thickness of cortical regions. Mean SDI was lower for svPPA than for lvPPA. Correlation analyses showed a positive association between the SDI and the cortical thickness of the bilateral temporal pole, parahippocampal and entorhinal cortices, and left middle and superior temporal cortices. Disruption of semantic knowledge observed in svPPA leads to the production of generic terms in narrative speech, and the SDI may be useful for quantifying the level of semantic impairment. The measure was associated with the cortical thickness of brain regions associated with semantic memory

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

BackgroundIn 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).ObjectiveThe 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).ResultsAn 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).DiscussionThe present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT03486704?term=NCT03486704&rank=1, NCT03486704

Measuring respiratory and cardiac influences on blood and cerebrospinal fluid flow with real-time MRI

Background. A link between various pathological conditions and blood and cerebrospinal fluid (CSF) flow alterations has been suggested by numerous studies.1 The blood and CSF dynamics are influenced by many factors, such as posture,2 heart beating, and thoracic pressure changes during respiration.2,3 The blood/CSF can be estimated using phase-contrast (PC) – magnetic resonance imaging (MRI). However, the clinical cardiac-gated cine PC-MRI requires several heartbeats to form the time-resolved flow images covering the entire cardiac cycle, not allowing to assess beat-by-beat variability differences and respiratory-driven flow changes. To overcome these limitations, we recently used a real-time (RT)-PC prototype for the study of blood and CSF flow rate modulations, showing low-frequency oscillations (Mayer waves).4 With the same MRI technique, in the current study we focused on assessing the cardiac and respiratory modulations on the blood and CSF flow rates, and the effects of different respiration modes. Methods. Thirty healthy volunteers (21 females, median age=26 years old, age range= 19-57 years old) were examined with a 3 T scanner. RT-PC sequences (Figure 1) allowed for a quantification of the flow rates of internal carotid arteries (ICAs), internal jugular veins (IJVs), and CSF at the first cervical level. The superior sagittal sinus (SSS) was also studied in 16 subjects.5 The flow rates were estimated with a temporal resolution of 58.5 ms for the blood, and 94 ms for the CSF. Each RT-PC lasted 60 seconds and was repeated three times: while the subject breathed with free (F) breathing, at a constant rate with a normal (PN) or forced (PD) strength. The systolic, diastolic and average flow rates and their power spectral densities were computed. High and very-high frequency peaks were identified on the spectra. Frequencies associated to the identified peaks were compared to the respiratory and cardiac frequencies estimated by a thoracic band and a pulse oximeter. The area under the spectra, normalized by the flow rate variance, was computed in the respiratory and cardiac frequency ranges (0.5 Hz-wide ranges, centered on the cardiac or breathing frequency peaks, respectively). Results. The frequencies associated with the spectral peaks were not significantly different compared to the respiratory and cardiac frequencies, for all regions and breathing modes. The average blood flow rate and the diastolic CSF peak progressively decreased from F to PN to PD breathing, the flow rate variance remained stable, and only the ICAs cross-sectional area decreased. The respiratory modulation increased with PD breathing compared with F and PN, while the cardiac modulations were less predominant for all the structures of interest. Conclusions. Using the RT-PC sequence we showed that the blood and CSF flow rates were modulated at the respiratory and cardiac frequencies. The observed reduced blood flow rate during forced breathing in the arteries and consequently in the extra and intracranial veins are suggestive of compensatory vasoconstriction in response to decreased CO2 blood concentration. Breathing modulation of flow rates was observed both in the extracranial and intracranial compartments, and it was greater during forced breathing than free breathing, due to the greater thoracic pump effect on the flow rates

Clinical and genetic characteristics of late-onset Huntington's disease in a large European cohort

Background and purpose Huntington's disease (HD) is an autosomal dominant condition caused by CAG-triplet repeat expansions. CAG-triplet repeat expansion is inversely correlated with age of onset in HD and largely determines the clinical features. The aim of this study was to examine the phenotypic and genotypic correlates of late-onset HD (LoHD) and to determine whether LoHD is a more benign expression of HD. Methods This was a retrospective observational study of 5053 White European HD patients from the ENROLL-HD database. Sociodemographic, genetic and phenotypic variables at baseline evaluation of subjects with LoHD, common-onset HD (CoHD) and young-onset HD (YoHD) were compared. LoHD subjects were compared with healthy subjects (HS) aged >= 60 years. Differences between the CoHD and LoHD groups were also explored in subjects with 41 CAG triplets, a repeat number in the lower pathological expansion range associated with wide variability in age at onset. Results Late-onset HD presented predominantly as motor-onset disease, with a lower prevalence of both psychiatric history and current symptomatology. Absent/unknown HD family history was significantly more common in the LoHD group (31.2%) than in the other groups. The LoHD group had more severe motor and cognitive deficits than the HS group. Subjects with LoHD and CoHD with 41 triplets in the larger allele were comparable with regard to cognitive impairment, but those with LoHD had more severe motor disorders, less problematic behaviors and more often an unknown HD family history. Conclusions It is likely that cognitive disorders and motor symptoms of LoHD are at least partly age-related and not a direct expression of the disease. In addition to CAG-triplet repeat expansion, future studies should investigate the role of other genetic and environmental factors in determining age of onset

NEUROSTRUCTURAL AND NEUROFUNCTIONAL SUBSTRATES OF EXECUTIVE DYSFUNCTION IN PARKINSON’S DISEASE: THE ROLE OF MOTOR LATERALIZATION AND COGNITIVE RESERVE

La disconnessione frontostriatale è considerata il correlato neurale della disfunzione esecutiva nei pazienti con malattia di Parkinson (MP), una patologia neurodegenerativa che si presenta nella fase iniziale come una sindrome clinica asimmetrica con sintomi predominanti nel lato destro o sinistro associati alla perdita neuronale nella sostanza grigia profonda dell'emisfero cerebrale controlaterale. Nella tesi, è stato indagato un particolare aspetto della disfunzione esecutiva nella MP espressa quando è richiesto di selezionare le parole nel contesto di alternative in competizione, cercando differenze in relazione all'insorgenza clinica dei sintomi motori. A livello neurostrutturale, sono state esplorate le alterazioni della sostanza grigia e bianca nelle sottopopolazioni di MP, verificando se la capacità di selezionare le parole è associata ad indici di integrità della materia sostanza grigia e bianca nelle sottopopolazioni di PD. Infine, a livello neurofunzionale, è stato esplorato se la connettività delle regioni cerebrali associate alla disfunzione esecutiva in MP è modulata dalla riserva cognitiva, un fattore di efficienza cognitiva dovuto ad esperienze di vita cognitivamente stimolanti che possono contribuire alla resilienza nel fronteggiare al meglio la neurodegenerazione. Le evidenze raccolte indicano che la lateralità di insorgenza dei sintomi motori e la riserva cognitiva dovrebbero essere prese in considerazione nella valutazione delle funzioni cognitive nei pazienti con MP.Frontostriatal disconnection is considered the neural correlate of executive dysfunction in patients with Parkinson’s disease (PD), a neurodegenerative pathology that exhibits at the initial phase as an asymmetric clinical syndrome with right or left sided predominant symptoms associated with neuronal loss in the deep grey matter of the contralateral cerebral hemisphere. In the current thesis, it was investigated a particular aspect of the executive dysfunction in PD expressed when it is required to select words in the context of competing alternatives, looking for differences according to the clinical onset of motor symptoms. At the neurostructural level, grey and white matter alterations were explored in PD subpopulations, testing if the ability to select words is associated with indices of grey and white matter integrity in PD subpopulations. Finally, at the neurofunctional level, it was explored if the connectivity of brain regions associated with the executive dysfunction in PD is modulated by the cognitive reserve, a factor of cognitive efficiency due to lifelong experiences that may contribute to the resilience against neurodegeneration. The evidence collected indicates that laterality of clinical motor symptom onset and cognitive reserve should be taken into account in the assessment of cognitive functions in patients with PD