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.

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.

Social cognition in Parkinson's disease and functional movement disorders.

INTRODUCTION: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. METHODS: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. RESULTS: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. DISCUSSION: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. CONCLUSION: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be.

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.

Elderly Onset of Functional Motor Disorders: Clinical Correlates from the Italian Registry.

BACKGROUND: Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. OBJECTIVE: To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables. METHODS: We recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics. RESULTS: Among the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48). CONCLUSIONS: These results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

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.

Neural correlates of empathy in mild cognitive impairment.

The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer's disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.

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.

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.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Background: Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes. Objective: To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR. Methods: Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies. Results: Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls. Conclusion: CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.

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).

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.

Self-assessment of empathy uncovers defective self-awareness in mild cognitive impairment.

OBJECTIVE: Self-assessment scales are broadly used to evaluate empathy in neurological patients, but it is conceivable that some discrepancy with caregiver evaluation may emerge as consequence of reduced self-awareness. The aim of the present study was to verify the presence of discrepancies in the self-assessment of empathy in subjects with mild cognitive impairment (MCI) and to explore their neural correlates. METHOD: Twenty MCI patients and 38 healthy controls (HCs) underwent the Interpersonal Reactivity Index (IRI), exploring the following four aspects of empathy: perspective taking (PT), fantasy, empathic concern, and personal distress. The questionnaire was administered in two modalities: self-administered, and administered to an informant, and the scores were compared. The correlation between discrepancies and regional cortical thickness was assessed. RESULTS: The self-administered version of IRI showed higher PT scores in MCI as compared to HC (p = .017), with no differences detected in the other subscales. The difference between the scores obtained in the self-administered and in the informant-administered IRI-PT was significantly higher in MCI than in HCs (p = .006). CONCLUSION: The self-assessment of empathy in subjects with MCI may be misleading because of a tendency toward an overestimation of the PT ability, typically considered as a cognitive component of empathy. Our results may reflect a particular aspect of reduced self-awareness in MCI subjects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Placebo and Nocebo Effects as Bayesian-Brain Phenomena: The Overlooked Role of Likelihood and Attention.

The Bayesian-brain framework applied to placebo responses and other mind-body interactions suggests that the effects on the body result from the interaction between priors, such as expectations and learning, and likelihood, such as somatosensorial information. Significant research in this area focuses on the role of the priors, but the relevance of the likelihood has been surprisingly overlooked. One way of manipulating the relevance of the likelihood is by paying attention to sensorial information. We suggest that attention can influence both precision and position (i.e., the relative distance from the priors) of the likelihood by focusing on specific components of the somatosensorial information. Two forms of attention seem particularly relevant in this framework: mindful attention and selective attention. Attention has the potential to be considered a "major player" in placebo/nocebo research, together with expectations and learning. In terms of application, relying on attentional strategies as "amplifiers" or "silencers" of sensorial information could lead to an active involvement of individuals in shaping their care process and health. In this contribution, we discuss the theoretical implications of these intuitions with the aim to provide a comprehensive framework that includes Bayesian brain, placebo/nocebo effects, and the role of attention in mind-body interactions.

Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters.

BACKGROUND: Cervical blood and cerebrospinal fluid (CSF) flow rates can be quantified with Phase-contrast (PC) MRI, which is routinely used for clinical studies. Previous MRI studies showed that venous and CSF flow alterations are linked to various pathological conditions. Since it is well known that, besides the heart beating, the thoracic pump influences the blood and CSF dynamics, we studied the effect of different respiration modes on blood and CSF flow rates using a real-time (RT)-PC prototype. METHODS: Thirty healthy volunteers were examined with a 3 T scanner. A RT-PC sequence was acquired at the first cervical level to quantify the flow rates of internal carotid arteries, internal jugular veins (IJVs) and CSF. Each RT-PC acquisition was repeated three times, while the subjects were asked to breathe in three different ways for 60 s each: freely (F), with a constant rate (PN) and with deep and constant respiration rate (PD). The average flow rates were computed, they were removed from the respective signals and integrated in the inspiratory and expiratory phases (differential volumes). Finally, the power spectral density was computed for each detrended flow rate. High- and very-high frequency peaks were identified on the spectra while their frequencies were compared to the respiratory and cardiac frequencies estimated using a thoracic belt and a pulse oximeter. The area under the spectra was computed in four 0.5 Hz-wide ranges, centered on the high-frequency peak, on very-high frequency peak and its 2nd and 3rd harmonics, and then they were normalized by the flow rate variance. The effect of breathing patterns on average flow rates, on systolic and diastolic peaks, and on the normalized power was tested. Finally, the differential volumes of inspiration were compared to those of expiration. RESULTS: The frequencies of the high- and very-high spectral peaks corresponded to the respiratory and cardiac frequencies. The average flow rate progressively decreased from F to PN to PD breathing, and the cardiac modulations were less predominant especially for the IJVs. The respiratory modulation increased with PD breathing. The average volumes displaced in the inspiratory phases were not significantly different from those of the expiratory one. CONCLUSIONS: The spectral analyses demonstrated higher respiratory modulations in PD compared to free breathing, even prevailing the cardiac modulation in the IJVs, showing an increment of the thoracic pump affecting the flow rate shape.

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

Background: 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). Methods: This study enrolled patients with MOH, patients with EM, and HC. ToM was assessed through the Theory of Mind Assessment Scale (ThOMAS), which includes four subscales: Scale A, I-Me, Scale B, Other-Self, Scale C, I-Other, and Scale D, Other-Me, through the Reading the Mind in the Eyes test (RMET), which measures complex emotion recognition, and through the Toronto Alexithymia Scale (TAS-20), which measures alexithymia. Concomitant psychiatric disturbances were evaluated through the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, and the Dissociative Experiences Scale-II. Results: The study involved 21 patients with EM, 22 patients with MOH, and 18 HC. In all the four subscales of the ThOMAS, there was a significant difference between HC, EM, and MOH patients: Scale A (p = 0.009), Scale B (p = 0.004), Scale C (p = 0.039), and Scale D (p = 0.008). In the RMET, MOH patients had worse performances than EM patients and HC (p = 0.039). MOH group exhibited higher levels of alexithymia when compared to the HC (p = 0.033) and higher levels of anxiety than HC (p = 0.001). Conclusion: MOH patients showed a subtle psychopathological pattern characterized by impaired social adaptation.