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Background: Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs). Methods: Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16–35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL's PALM for each task, covarying for age and sex (1000 permutations, thresholded at p < 0.05 FWE-corrected). Exploratory region of interest (ROI)-based analyses were also conducted. Results: ImObs and EA analyses included 164 and 174 participants, respectively (autism N = 56/59, SSD N = 50/56, TDC N = 58/59). EA and both lower- and higher-level social cognition scores differed across groups. While canonical social cognitive networks were activated, no significant whole-brain or ROI-based group-level differences in neural correlates for either task were detected. Transdiagnostically, neural activity during the EA task, but not the ImObs task, was associated with lower- and higher-level social cognitive performance. Limitations: Despite attempting to match our groups on age, sex, and race, significant group differences remained. Power to detect regional brain differences is also influenced by sample size and multiple comparisons in whole-brain analyses. Our findings may not generalize to autism and SSD individuals with co-occurring intellectual disabilities. Conclusions: The lack of whole-brain and ROI-based group-level differences identified and the dimensional EA brain-behavior relationship observed across our sample suggest that the EA task may be well-suited to target engagement in novel intervention testing. Our results also emphasize the potential utility of cross-condition approaches to better understand social cognition across autism and SSDs. [ABSTRACT FROM AUTHOR]

In 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs' waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 +/- 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (-13.9%; p < 0.0001) and mean HIT-6 score (-6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (-51.7%; p < 0.0001), pain intensity (-21.8%; p < 0.0001), headache duration (-18.1%; p = 0.0008)and HIT-6 score (-11.7%; p < 0.0001). Our data suggest that the effects of a "single shot" campaign are beneficial not only in a short-term perspective, but even in the longterm. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency,severity or duration of headache worsen should be promptly referred to the headache clinic.

Background: Research in the neurosciences has highlighted the importance of intersubjective relationships in promoting neuromental development of the child. Children's learning in early childhood occurs mainly in a dyadic context of an interaction with their parents: from this perspective, good dialogic parent–child communication is required to be promoted also through good educational practices. Dialogic Book-Sharing (DBS), a dialogic form of parent–child communication through the use of wordless picture books, provides a privileged 'intersubjective' space and is highly effective in promoting communication, language, attention, behavioural development and the parent–child relationship. DBS programme, successfully previously trialled in South Africa and the UK, will be applied for the first time in Italy for research purposes in Italian health, educational and maternal-child centres. Methods: A multicentre randomised controlled trial is being conducted to evaluate DBS parenting intervention for children aged between 14 and 20 months. Parent–child dyads are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, parents are trained in supportive book-sharing with their children by local staff of the centres. DBS intervention is carried out in small groups over a period of 4 weeks. Data are collected at baseline, post-intervention and at 6 months post-intervention with a questionnaire and video recording of parent–child interaction. Discussion: DBS programme in early childhood could enhance the educational resources offered by Italian health, educational and maternal-child centres, in support of child's development and parenting. DBS represents a strategic opportunity for bringing about positive effects, also in terms of prevention of socio-emotional and cognitive difficulties. As such it represents a promising response to the new social, health and educational needs of the post-COVID-19 pandemic era caused by the social isolation measures. Furthermore, the application of the DBS methodology is a way to promote the use of books, and thereby counteract the excessive use of technological devices already present in early childhood. Trial registration: The trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN11755019 Registered on 2 November 2023. This is version 1 of the protocol for the trial. [ABSTRACT FROM AUTHOR]

Background: The development of permanent disability in multiple sclerosis (MS) is highly variable among patients, and the exact mechanisms that contribute to this disability remain unknown.Methods: Following the idea that the brain has intrinsic network organization, we investigated changes of functional networks in MS patients to identify possible links between network reorganization and remission from clinical episodes in MS. Eighteen relapsing-remitting MS patients (RRMS) in their first clinical manifestation underwent resting-state functional MRI and again during remission. We used ten template networks, identified from independent component analysis, to compare changes in network coherence for each patient compared to those of 44 healthy controls from the Human Connectome Project test-retest dataset (two-sample t-test of pre-post differences). Combining a binomial test with Monte Carlo procedures, we tested four models of how functional coherence might change between the first clinical episode and remission: a network can change its coherence (a) with itself ("one-with-self"), (b) with another network ("one-with-other"), or (c) with a set of other networks ("one-with-many"), or (d) multiple networks can change their coherence with respect to one common network ("many-with-one").Results: We found evidence supporting two of these hypotheses: coherence decreased between the Executive Control Network and several other networks ("one-with-many" hypothesis), and a set of networks altered their coherence with the Cerebellar Network ("many-with-one" hypothesis).Conclusion: Given the unexpected commonality of the Cerebellar Network's altered coherence with other networks (a finding present in more than 70% of the patients, despite their clinical heterogeneity), we conclude that remission in MS may result from learning processes mediated by the Cerebellar Network. [ABSTRACT FROM AUTHOR]

Background : Sedentary behaviour among stroke inpatients may be due to high rates of depressive symptoms after stroke. Thus, efforts to address depressive symptoms among stroke inpatients are warranted to in turn lessen sedentary behaviour. Despite evidence that virtual reality (VR) is emerging as a method to help with depression, the use of VR to improve depression among inpatient stroke survivors has yet to be studied. In this paper, we report on the protocol investigating the feasibility of a VR entertainment system at improving depressive symptoms among stroke survivors receiving inpatient rehabilitation. Methods: In this single-blind randomized controlled trial, 30 inpatient stroke survivors from the rehabilitation unit at Kelowna General Hospital will be randomized to either (1) intervention: 3 times per week of VR entertainment for duration of inpatient rehabilitation or (2) control: usual care. Individuals will be included if they have a confirmed diagnosis of stroke, are 19 years of age or older, able to provide informed consent, have physician clearance to participate in the study (medically stable or fit), or are able to understand English. Outcome measures to address depressive symptoms (primary outcome), sedentary behaviour, motivation, anxiety, stress, and happiness (secondary outcome) will be administered at two timepoints: (1) baseline (T1) and (2) post-intervention (T2). Study analyses will consider study feasibility indicators and clinical (statistical) outcomes. Means and standard deviations (for continuous variables) and frequencies and proportions (for categorical variables) will be used to summarize the variables. Feasibility indicators will be dichotomized into either 'success' if they meet the a priori criteria, or 'revise' if they do not meet the criteria. Intervention effects post-intervention (T2) for the primary and secondary clinical outcomes will be estimated using linear regression including baseline (T1) controlling for age and sex. Discussion: The results of this trial will add to our understanding of depression and sedentary behaviour among individuals receiving inpatient stroke rehabilitation as well as the feasibility of a VR entertainment program to improve depressive symptoms, which will in turn may lessen sedentary behaviour in inpatient stroke survivors. Trial registration: ClinicalTrials.gov Identifier: NCT04011202. First posted July 8, 2019 (study postponed from March 2020 to July 2021 due to COVID-19). [ABSTRACT FROM AUTHOR]

Background: About 40–50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. Methods: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together. Results: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). Conclusion: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI. [ABSTRACT FROM AUTHOR]

As the proportion of elderly in society increases, so do the number of older patients undergoing surgical procedures. This is concerning as exposure to anesthesia has been identified as a risk factor for Alzheimer's disease (AD). However, the causal relationship between clinical AD development and anesthesia remains conjectural. Preclinical studies have demonstrated that anesthesia, such as halothane, isoflurane, and sevoflurane, induces AD-like pathophysiological changes and cognitive impairments in transgenic mouse models of AD. Desflurane does not have these effects and is expected to have more potential for use in elderly patients, yet little is known about its effects, especially on non-cognitive functions, such as motor and emotional functions. Thus, we examined the postanesthetic effects of desflurane and sevoflurane on motor and emotional function in aged AppNL−G−F/NL−G−F (App-KI) mice. This is a recently developed transgenic mouse model of AD exhibiting amyloid β peptide (Aβ) amyloidosis and a neuroinflammatory response in an age-dependent manner without non-physiological amyloid precursor protein (APP) overexpression. Mice were subjected to a short behavioral test battery consisting of an elevated plus maze, a balance beam test, and a tail suspension test seven days after exposure to 8.0% desflurane for 6 h or 2.8% sevoflurane for 2 h. App-KI mice showed significant increments in the percentage of entry and time spent in open arms in the elevated plus maze, increments in the number of slips and latency to traverse for the balance beam test, increments in the limb clasping score, increments in immobile duration, and decrements in latency to first immobile episode for the tail suspension test compared to age-matched wild type (WT) controls. Desflurane- and sevoflurane-exposed App-KI mice showed a delayed decrement in the number of slips for each trial in the balance beam test, while air-treated App-KI mice rapidly improved their performance, and increased their clasping behavior in the tail suspension test. Furthermore, App-KI inhibited the change in membrane GluA3 following exposure to anesthetics in the cerebellum. These results suggest high validity of App-KI mice as an animal model of AD. [ABSTRACT FROM AUTHOR]

Background: The amyloid precursor protein (APP) is a transmembrane glycoprotein that undergoes alternative proteolytic processing. Its processing through the amyloidogenic pathway originates a large sAPPβ ectodomain fragment and the β-amyloid peptide, while non-amyloidogenic processing generates sAPPα and shorter non-fibrillar fragments. Hence, measuring sAPPα and sAPPβ has been proposed as a means to identify imbalances between the amyloidogenic/non-amyloidogenic pathways in the brain of Alzheimer's disease (AD) patients. However, to date, no consistent changes in these proteolytic fragments have been identified in either the brain or cerebrospinal fluid of AD individuals. Methods: In frontal cortex homogenates from AD patients (n = 7) and non-demented controls (NDC; n = 7), the expression of total APP mRNA and that of the APP isoforms generated by alternative splicing, APP695 and APP containing the Kunitz protease inhibitor (KPI), was analyzed by qRT-PCR using TaqMan and SYBR Green probes. The balance between the amyloidogenic/non-amyloidogenic pathways was examined in western blots estimating the sAPPα and sAPPβ fragments and their membrane-tethered C-terminal fragments CTFα and CTFβ. CHO-PS70 cells, stably over-expressing wild-type human APP, served to evaluate whether Aβ42 peptide treatment results in altered APP glycosylation. We determined the glycosylation pattern of sAPPα and sAPPβ in brain extracts and CHO-PS70 culture media by lectin-binding assays. Results: In the cortex of AD patients, we detected an increase in total APP mRNA relative to the controls, due to an increase in both the APP695 and APP-KPI variants. However, the sAPPα or sAPPβ protein levels remained unchanged, as did those of CTFα and CTFβ. We studied the glycosylation of the brain sAPPα and sAPPβ using lectins and pan-specific antibodies to discriminate between the fragments originated from neuronal APP695 and glial/KPI variants. Lectin binding identified differences in the glycosylation of sAPPβ species derived from the APP695 and APP-KPI variants, probably reflecting their distinct cellular origin. Moreover, the lectin-binding pattern differed in the sAPPα and sAPPβ originated from all the variants. Finally, when the lectin-binding pattern was compared between AD and NDC groups, significant differences were evident in sAPPα glycosylation. Lectin binding of the soluble sAPPα and sAPPβ from CHO-PS70 cells were also altered in cells treated with the Aβ peptide. Conclusion: Our analysis of the lectin binding to sAPPα and sAPPβ suggests that glycosylation dictates the proteolytic pathway for APP processing. Differences between the demented and controls indicate that changes in glycosylation may influence the generation of the different APP fragments and, consequently, the pathological progression of AD. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction plays a central role in the formation of neuroinflammation and oxidative stress, which are important factors contributing to the development of brain disease. Ample evidence suggests mitochondria are a promising target for neuroprotection. Recently, methods targeting mitochondria have been considered as potential approaches for treatment of brain disease through the inhibition of inflammation and oxidative injury. This review will discuss two widely studied approaches for the improvement of brain mitochondrial respiration, methylene blue (MB) and photobiomodulation (PBM). MB is a widely studied drug with potential beneficial effects in animal models of brain disease, as well as limited human studies. Similarly, PBM is a non-invasive treatment that promotes energy production and reduces both oxidative stress and inflammation, and has garnered increasing attention in recent years. MB and PBM have similar beneficial effects on mitochondrial function, oxidative damage, inflammation, and subsequent behavioral symptoms. However, the mechanisms underlying the energy enhancing, antioxidant, and anti-inflammatory effects of MB and PBM differ. This review will focus on mitochondrial dysfunction in several different brain diseases and the pathological improvements following MB and PBM treatment. [ABSTRACT FROM AUTHOR]

The discovery of mutations associated with familial forms of Alzheimer's disease (AD), has brought imperative insights into basic mechanisms of disease pathogenesis and progression and has allowed researchers to create animal models that assist in the elucidation of the molecular pathways and development of therapeutic interventions. Position 717 in the amyloid precursor protein (APP) is a hotspot for mutations associated with autosomal dominant AD (ADAD) and the valine to isoleucine amino acid substitution (V717I) at this position was among the first ADAD mutations identified, spearheading the formulation of the amyloid cascade hypothesis of AD pathogenesis. While this mutation is well described in multiple kindreds and has served as the basis for the generation of widely used animal models of disease, neuropathologic data on patients carrying this mutation are scarce. Here we present the detailed clinical and neuropathologic characterization of an APP V717I carrier, which reveals important novel insights into the phenotypic variability of ADAD cases. While age at onset, clinical presentation and widespread parenchymal beta-amyloid (Aβ) deposition are in line with previous reports, our case also shows widespread and severe cerebral amyloid angiopathy (CAA). This patient also presented with TDP-43 pathology in the hippocampus and amygdala, consistent with limbic predominant age-related TDP-43 proteinopathy (LATE). The APOE ε2/ε3 genotype may have been a major driver of the prominent vascular pathology seen in our case. These findings highlight the importance of neuropathologic examinations of genetically determined AD cases and demonstrate striking phenotypic variability in ADAD cases. [ABSTRACT FROM AUTHOR]

Background: Physician empathy has been associated with improved clinical outcomes and lower physician burnout. We evaluated whether forum theater (FT), a form of applied drama that allows participants to enter the performance and represent the actions associated with emotions, would foster empathy in medical students, and which underlying variables would be associated to empathy scores. Methods: Three classes totaling 488 fourth-year medical students participated in the study. Forum theater was used to explore difficult encounters with patients and family members: announcement of cancer, fall at home of an elderly person requiring hospitalization, appointment with a patient suffering from depression, announcement of diabetes in an adolescent. The first scene was played by actors in front of a group of students, then audience members were asked to enter the performance and, by taking over the role of the "physician-actor," to explore alternative interactions. All the students followed two sessions as actors and observers in random order and were randomly assigned to FT sessions after 36 or 56 weeks of clinical rotations. They completed the Jefferson Scale of Physician Empathy (JFSE) anonymously. Results: Students were 22.1 ± 1.5 years old (43% males). Empathy scores increased after each session: 102.0 ± 9.8 before the sessions, 106.3 ± 9.8 after session 1 and 107.8 ± 11.5 after session 2 (p < 0.05). In regression models, gender (F vs. M, + 3.0 ± 1.0, p < 0.001) and position in the session (actor vs. observer, + 2.1 ± 1.0, p < 0.05) were significant determinants of JFSE scores, whereas age, session theme, and duration of clinical rotation were not. Conclusion: Being an actor in forum theater was a valuable tool for enhancing empathy scores in medical students. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer's disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date.Main Body: ß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects.Conclusion: Early pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics. [ABSTRACT FROM AUTHOR]

Background: To investigate the impacts of carotid plaque and intima-media thickness (IMT) on future vascular events (VEs) in the patients with acute ischemic stroke.Methods: A total of 479 consecutive Korean patients with acute ischemic stroke were divided into 2 groups according to development of VEs; VE group (65.4 ± 10.9 years) vs no VE group (62.8 ± 13.2 years). VEs were defined as the development of recurrent stroke, coronary events, peripheral arterial disease, and death. Clinical, laboratory, and imaging findings were compared between the groups.Results: During 105.5 ± 29.0 months of follow up, VEs were developed in 142 patients (29.6%). In univariate analysis, VEs were significantly associated with age, gender, diabetes, renal function, lipid levels, left ventricular function, carotid plaque or IMT. In multivariate analysis, the presence of carotid plaque, diabetes, renal function and male gender were independent predictors of future VEs in the patients with ischemic stroke, but carotid IMT was not a predictor of future VEs. Event free survival was significantly lower in patients with carotid plaque than without carotid plaque on Kaplan-Meier analysis (log rank p < 0.001).Conclusion: The present study demonstrated that diabetes, impaired renal function, male gender, and the presence of carotid plaque rather than IMT were independent predictors of future VEs in Korean patients with acute ischemic stroke. Active medical management and careful monitoring for the development of recurrent VEs are strongly recommended in patients with acute ischemic stroke and carotid plaque. [ABSTRACT FROM AUTHOR]

Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth. [ABSTRACT FROM AUTHOR]

Background: Understanding and anticipating others' mental or emotional states relies on the processing of social cues, such as dynamic facial expressions. Individuals with high-functioning autism (HFA) may process these cues differently from individuals with typical development (TD) and purportedly use a 'mechanistic' rather than a 'mentalistic' approach, involving rule- and contingency-based interpretations of the stimuli. The study primarily aimed at examining whether the judgments of facial expressions made by individuals with TD and HFA would be similarly affected by the immediately preceding dynamic perceptual history of that face. A second aim was to explore possible differences in the mechanisms underpinning the perceptual judgments in the two groups. Methods: Twenty-two adults with HFA and with TD, matched for age, gender and IQ, were tested in three experiments in which dynamic, 'ecologically valid' offsets of happy and angry facial expressions were presented. Participants evaluated the expression depicted in the last frame of the video clip by using a 5-point scale ranging from slightly angry via neutral to slightly happy. Specific experimental manipulations prior to the final facial expression of the video clip allowed examining contributions of bottom-up mechanisms (sequential contrast/ context effects and representational momentum) and a top-down mechanism (emotional anticipation) to distortions in the perception of the final expression. Results: In experiment 1, the two groups showed a very similar perceptual bias for the final expression of joy-to-neutral and anger-to-neutral videos (overshoot bias). In experiment 2, a change in the actor's identity during the clip removed the bias in the TD group, but not in the HFA group. In experiment 3, neutral-to-joy/anger-to-neutral sequences generated an undershoot bias (opposite to the overshoot) in the TD group, whereas no bias was observed in the HFA group. Conclusions: We argue that in TD individuals the perceptual judgments of other's facial expressions were underpinned by an automatic emotional anticipation mechanism. In contrast, HFA individuals were primarily influenced by visual features, most notably the contrast between the start and end expressions, or pattern extrapolation. We critically discuss the proposition that automatic emotional anticipation may be induced by motor simulation of the perceived dynamic facial expressions and discuss its implications for autism. [ABSTRACT FROM AUTHOR]

Background The present study sought to clarify the relationship between empathy trait and attention responses to happy, angry, surprised, afraid, and sad facial expressions. As indices of attention, we recorded event-related potentials (ERP) and focused on N170 and late positive potential (LPP) components. Methods Twenty-two participants (12 males, 10 females) discriminated facial expressions (happy, angry, surprised, afraid, and sad) from emotionally neutral faces under an oddball paradigm. The empathy trait of participants was measured using the Interpersonal Reactivity Index (IRI, J Pers Soc Psychol 44:113-126, 1983). Results Participants with higher IRI scores showed: 1) more negative amplitude of N170 (140 to 200 ms) in the right posterior temporal area elicited by happy, angry, surprised, and afraid faces; 2) more positive amplitude of early LPP (300 to 600 ms) in the parietal area elicited in response to angry and afraid faces; and 3) more positive amplitude of late LPP (600 to 800 ms) in the frontal area elicited in response to happy, angry, surprised, afraid, and sad faces, compared to participants with lower IRI scores. Conclusions These results suggest that individuals with high empathy pay attention to various facial expressions more than those with low empathy, from very-early stage (reflected in N170) to late-stage (reflected in LPP) processing of faces. [ABSTRACT FROM AUTHOR]

Background Beyond cognitive decline, Alzheimer's disease (AD) is characterized by numerous neuropathological changes in the brain. Although animal models generally do not fully reflect the broad spectrum of disease-specific alterations, the APPSL mouse model is well known to display early plaque formation and to exhibit spatial learning and memory deficits. However, important neuropathological features, such as neuroinflammation and lipid peroxidation, and their progression over age, have not yet been described in this AD mouse model. Methods Hippocampal and neocortical tissues of APPSL mice at different ages were evaluated. One hemisphere from each mouse was examined for micro- and astrogliosis as well as concomitant plaque load. The other hemisphere was evaluated for lipid peroxidation (quantified by a thiobarbituric acid reactive substances (TBARS) assay), changes in Aβ abundance (Aβ38, Aβ40 and Aβ42 analyses), as well as determination of aggregated Aβ content (Amorfix A4 assay). Finally, correlation analyses were performed to illustrate the time-dependent correlation between neuroinflammation and Aβ load (soluble, insoluble, fibrils), or lipid peroxidation, respectively. Results As is consistent with previous findings, neuroinflammation starts early and shows strong progression over age in the APPSL mouse model. An analyses of concomitant Aβ load and plaque deposition revealed a similar progression, and high correlations between neuroinflammation markers and soluble or insoluble Aβ or fibrillar amyloid plaque loads were observed. Lipid peroxidation, as measured by TBARS levels, correlates well with neuroinflammation in the neocortex but not the hippocampus. The hippocampal lipid peroxidation correlated strongly with the increase of LOC positive fiber load, whereas neocortical TBARS levels were unrelated to amyloidosis. Conclusions These data illustrate for the first time the progression of major AD related neuropathological features other than plaque load in the APPSL mouse model. Specifically, we demonstrate that microgliosis and astrocytosis are prominent aspects of this AD mouse model. The strong correlation of neuroinflammation with amyloid burden and lipid peroxidation underlines the importance of these pathological factors for the development of AD. The new finding of a different relation of lipid peroxidation in the hippocampus and neocortical regions show that the model might contribute to the understanding of complex pathological mechanisms and their interplay in AD. [ABSTRACT FROM AUTHOR]

Background Acute ischemic stroke (AIS) has a biphasic effect on the peripheral immune system. The initial inflammatory response is followed by systemic immunosuppression, referred to as stroke-induced immunosuppression (SIIS), leading to severe complications in stroke patients. We aimed to identify an inflammatory marker that best represents this biphasic immunological response after AIS. Methods We investigated the alteration of CRP, WBC, neutrophil count, suPAR levels, CD4+ CD25high Tregs, CD64+ and CD177+ neutrophils and monocytes in 12 acute ischemic stroke patients free of infection within 6 hours and one week after the insult. As controls, 14 age-matched healthy individuals were included. Results CRP, WBC and neutrophil count values were comparable in stroke patients within 6 hours and controls, however, they were elevated in stroke one week after the insult. suPAR levels were higher in both stroke groups compared to controls. The prevalence of CD64+ neutrophils was higher in stroke patients within 6 hours than in controls and it decreased in stroke one week after the insult below the level in controls (5.95 [5.41-8.75] % vs. 32.38 [9.21-43.93] % vs. 4.06 [1.73-6.77] %, p < 0.05). Conclusions Our pilot study identified that the prevalence of CD64+ neutrophils may reflect a biphasic alteration of the immune response following AIS. Since its level decreases below baseline after one week of the CNS insult in stroke patients without infection, it might serve as a reliable candidate to identify the developing inflammatory response due to infection after stroke in the future. [ABSTRACT FROM AUTHOR]

Background The Stroke burden is increasing in many populations where health institutions may experience more patients. We wanted to examine whether incidence rates and absolute number of hospitalized stroke patients remained stable in Denmark during a 13 years period where exposure to major stroke risk factors decreased, changes in stroke treatment was implemented, and the age of the population increased. Methods The Danish National Patient Register was used to identify all subjects 25 years of age or above admitted with a first time stroke in Denmark from 1997-2009. Incidence rates (IRs) and age-adjusted Poisson regression analyses were used to examine trends in age-, genderand stroke subtype (ischaemic or unspecified). Results During the 13-year observation period there were 53.5 million person-years at risk (PY) and a total of 84,626 male and 84,705 female stroke patients were admitted to Danish hospitals. The IRs of hospitalized strokes per 1000 PY was 3.21 (95% confidence interval [CI] 3.16- 3.27) in 1997, 3.85 (95% CI 3.79-3.91) in 2003 and 3.22 (95% CI 3.16-3.28) in 2009, respectively. Incidence rate ratios of hospitalized stroke events adjusted for age in the period 2007-2009 compared to 1997-2000 were 0.89 (95% CI 0.87- 0.91) for men and 0.92 (95% CI 0.90-0.94) for women. The incidence of hospitalized unspecified strokes decreased from 1997 to 2009 whereas there was a steep rise in incidence for hospitalization with specified ischemic stroke during this period. Conclusion This study found a constant rate of stroke hospitalization in Denmark from 1997-2009. The overall rate of hospitalized strokes adjusted for age decreased during this period. [ABSTRACT FROM AUTHOR]

Background Systolic dilation of the atherosclerotic carotid artery depends on several factors including arterial compliance and the haemodynamic environment. The purpose of this study was to quantify wall motion in stenotic carotid arteries and investigate any associations with the ultrasound greyscale plaque characteristics, the degree of stenosis, and the presence of cerebrovascular symptoms. Methods Variations in the lumen diameters of 61 stenotic carotid arteries (stenosis range 10%-95%) from 47 patients were measured before the proximal shoulder of the atherosclerotic plaque using ultrasound image sequences over several cardiac cycles. Absolute and percentage diameter changes from diastole to systole were calculated and their relationship to the degree of stenosis, greyscale plaque characteristics, and the presence of ipsilateral hemispheric symptoms were studied. Results The mean absolute diameter change from diastole to systole was 0.45 mm (s.d. 0.17), and the mean percentage diameter change was 6.9% (s.d. 3.1%). Absolute and percentage diameter changes did not have a statistically significant relationship to the degree of stenosis, greyscale plaque characteristics, or the presence of ipsilateral hemispheric symptoms (p > 0.05). Parameters significantly correlated with the presence of symptoms were the degree of stenosis (p = 0.01), plaque greyscale median (p = 0.02) and the plaque surface irregularity index (p = 0.02). Conclusions Our study confirmed the degree of stenosis, plaque greyscale median and our surface irregularity index were significant predictors of symptoms, but found no significant correlation between diameter changes of stenosed carotid arteries and the presence of ipsilateral hemispheric symptoms. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted therapy in patients with neurological disease is an attempt to improve function in a moderate to severe hemiparetic arm. A better understanding of cortical modifications after robot-assisted training could aid in refining rehabilitation therapy protocols for stroke patients. Modifications of cortical activity in healthy subjects were evaluated during voluntary active movement, passive robot-assisted motor movement, and motor imagery tasks performed under unimanual and bimanual protocols. Methods: Twenty-one channel electroencephalography (EEG) was recorded with a video EEG system in 8 subjects. The subjects performed robot-assisted tasks using the Bi-Manu Track robot-assisted arm trainer. The motor paradigm was executed during one-day experimental sessions under eleven unimanual and bimanual protocols of active, passive and imaged movements. The event-related-synchronization/desynchronization (ERS/ERD) approach to the EEG data was applied to investigate where movement-related decreases in alpha and beta power were localized. Results: Voluntary active unilateral hand movement was observed to significantly activate the contralateral side; however, bilateral activation was noted in all subjects on both the unilateral and bilateral active tasks, as well as desynchronization of alpha and beta brain oscillations during the passive robot-assisted motor tasks. During active-passive movement when the right hand drove the left one, there was predominant activation in the contralateral side. Conversely, when the left hand drove the right one, activation was bilateral, especially in the alpha range. Finally, significant contralateral EEG desynchronization was observed during the unilateral task and bilateral ERD during the bimanual task. Conclusions: This study suggests new perspectives for the assessment of patients with neurological disease. The findings may be relevant for defining a baseline for future studies investigating the neural correlates of behavioral changes after robot-assisted training in stroke patients. [ABSTRACT FROM AUTHOR]

Background The detection of early neuropsychological abnormalities as precursors of cognitive decline of vascular origin in patients with lacunar stroke is a subject of increasing interest. The objective of this study was to assess whether there were differences in the performance of a battery of neuropsychological tests in first-ever lacunar stroke patients with and without associated silent multiple lacunar infarctions found incidentally on the brain magnetic resonance imaging (MRI) scan. Methods A total of 72 consecutive patients with first-ever lacunar infarction were studied 1 month after stroke. All patients underwent a comprehensive neuropsychological evaluation, which included the California Verbal Learning Test (CVLT), Phonetic Verbal Fluency Test (PMR), Semantic Verbal Fluency Test (category "animals"), Digit Span Forward and Backward from the Wechsler Adult Intelligence Scale (WAIS-III), and Mini-Mental State Examination (MMSE). Results A total of 38 patients (52.7%) had silent multiple lacunar infarcts, with corona radiata as the most frequent topography (P < 0.023). White matter hyperintensities (leukoaraiosis) were observed in 81.1% of patients with silent multiple lacunar infarcts and in 50% with a single lacunar infarction (P < 0.007). Patients in both groups showed similar scores in the MMSE, but those with associated silent lacunar infarctions showed a poorer performance in the semantic fluency test (P < 0.008) and in short delayed verbal memory (P < 0.001). In both cases, however, leukoaraiosis was not statistically significant in multivariate linear regression models adjusted by confounding covariates. In these models, multiple silent lacunar infarctions and education were independent predictors of poor performance in the semantic fluency test and in short delayed verbal memory. Conclusions The presence of silent multiple lacunar infarctions documented on brain MRI scans in patients with first-ever lacunar stroke was associated with mild neuropsychological abnormalities, particularly in the performance of executive functions (semantic fluency) and short delayed verbal memory. According to these findings, in the initial stages of small vessel disease, mild neuropsychological abnormalities appear to be related to lacunes rather than to leukoaraiosis or perivascular hyperintensities of vascular cause. [ABSTRACT FROM AUTHOR]

One of the most intriguing frontiers of current neuroscientific research is represented by the investigation of the possible neural substrates of morality. The assumption is that in humans an innate moral sense would exist. If this is true, with no doubt it should be regulated by specific brain mechanisms selected over the course of evolution, as they would promote our species' survival. In the last decade, an increasing number of studies have been carried out to explore the neural bases of human morality. The aim of this paper is to present a comprehensive review of the data regarding the neurobiological origin of the moral sense, through a Medline search of English-language articles from 1980 to February 2012. The available findings would suggest that there might be a main integrative centre for the innate morality, in particular the ventromedial prefrontal cortex, with its multiple connections with the limbic lobe, thalamus and brainstem. The subjective moral sense would be the result of an integration of multiple automatic responses, mainly associated with social emotions and interpretation of others' behaviours and intentions. Since converging observations outline how lesions of the proposed neural networks may underlie some personality changes and criminal behaviours, the implications of the studies in this field encompass many areas of the scientific domain. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia. Methods/design: The NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30-80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010. Discussion: Previous studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer's disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was administered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the autonomic reactions and body weight changes following thromboembolic stroke in rats. Wistar rats were subjected to right-sided focal cerebral ischemia by thromboembolic middle cerebral artery occlusion (MCAO), and fluorescein isothiocyanate (FITC)-albumin was administered to characterize blood brain barrier (BBB) impairment. Results show that heart rate (HR) increased significantly and mean arterial pressure (MAP) decreased during MCAO.

Background: The anterior insula cortex is considered to be both the structural and functional link between experience, affect, and behaviour. Magnetic resonance imaging (MRI) studies have shown changes in anterior insula gray matter volume (GMV) in psychosis, bipolar, depression and anxiety disorders in older patients, but few studies have investigated insula GMV changes in young people. This study examined the relationship between anterior insula GMV, clinical symptom severity and neuropsychological performance in a heterogeneous cohort of young people presenting for mental health care. Methods: Participants with a primary diagnosis of depression (n = 43), bipolar disorder (n = 38), psychosis (n = 32), anxiety disorder (n = 12) or healthy controls (n = 39) underwent structural MRI scanning, and volumetric segmentation of the bilateral anterior insula cortex was performed using the FreeSurfer application. Statistical analysis examined the linear and quadratic correlations between anterior insula GMV and participants' performance in a battery of clinical and neuropsychological assessments.Results: Compared to healthy participants, patients had significantly reduced GMV in the left anterior insula (t = 2.05, p = .042) which correlated with reduced performance on a neuropsychological task of attentional set-shifting (ρ = .32, p = .016). Changes in right anterior insula GMV was correlated with increased symptom severity (r = .29, p = .006) and more positive symptoms (r = .32, p = .002).Conclusions: By using the novel approach of examining a heterogeneous cohort of young depression, anxiety, bipolar and psychosis patients together, this study has demonstrated that insula GMV changes are associated with neurocognitive deficits and clinical symptoms in such young patients. [ABSTRACT FROM AUTHOR]

Alzheimer Disease (AD) is the most common neurodegenerative disorder worldwide, and account for 60% to 70% of all cases of progressive cognitive impairment in elderly patients. At the microscopic level distinctive features of AD are neurons and synapses degeneration, together with extensive amounts of senile plaques and neurofibrillars tangles. The degenerative process probably starts 20-30 years before the clinical onset of the disease. Senile plaques are composed of a central core of amyloid β peptide, Aβ, derived from the metabolism of the larger amyloid precursor protein, APP, which is expressed not only in the brain, but even in non neuronal tissues. More than 30 years ago, some studies reported that human platelets express APP and all the enzymatic activities necessary to process this protein through the same pathways described in the brain. Since then a large number of evidence has been accumulated to suggest that platelets may be a good peripheral model to study the metabolism of APP, and the pathophysiology of the onset of AD. In this review, we will summarize the current knowledge on the involvement of platelets in Alzheimer Disease. Although platelets are generally accepted as a suitable model for AD, the current scientific interest on this model is very high, because many concepts still remain debated and controversial. At the same time, however, these still unsolved divergences mirror a difficulty to establish constant parameters to better defined the role of platelets in AD. [ABSTRACT FROM AUTHOR]

Background: Dysphagia is a major complication in hemispheric as well as brainstem stroke patients causing aspiration pneumonia and increased mortality. Little is known about the recovery from dysphagia after stroke. The aim of the present study was to determine the different patterns of cortical swallowing processing in patients with hemispheric and brainstem stroke with and without dysphagia in the early subacute phase. Methods: We measured brain activity by mean of whole-head MEG in 37 patients with different stroke localisation 8.2 +/- 4.8 days after stroke to study changes in cortical activation during self-paced swallowing. An age matched group of healthy subjects served as controls. Data were analyzed by means of synthetic aperture magnetometry and group analyses were performed using a permutation test. Results: Our results demonstrate strong bilateral reduction of cortical swallowing activation in dysphagic patients with hemispheric stroke. In hemispheric stroke without dysphagia, bilateral activation was found. In the small group of patients with brainstem stroke we observed a reduction of cortical activation and a right hemispheric lateralization. Conclusion: Bulbar central pattern generators coordinate the pharyngeal swallowing phase. The observed right hemispheric lateralization in brainstem stroke can therefore be interpreted as acute cortical compensation of subcortically caused dysphagia. The reduction of activation in brainstem stroke patients and dysphagic patients with cortical stroke could be explained in terms of diaschisis. [ABSTRACT FROM AUTHOR]

Background: This review analyses and summarises the recent advances in understanding the neurobiology of violence and empathy, taxonomical issues on defining personality disorders characterised by disregard for social norms, evidence for efficacy of different treatment modalities and ethical implications in defining 'at-risk' individuals for preventive interventions. Methods: PubMed was searched with the keywords 'antisocial personality disorder', 'dissocial personality disorder' and 'psychopathy'. The search was limited to articles published in English over the last 10 years (1999 to 2009) Results: Both diagnostic manuals used in modern psychiatry, the Diagnostic and Statistical Manual published by the American Psychiatric Association and the International Classification of Diseases published by the World Health Organization, identify a personality disorder sharing similar traits. It is termed antisocial personality disorder in the diagnostic and statistical manual and dissocial personality disorder in the International Classification of Diseases. However, some authors query the ability of the existing manuals to identify a special category termed 'psychopathy', which in their opinion deserves special attention. On treatment-related issues, many psychological and behavioural therapies have shown success rates ranging from 25% to 62% in different cohorts. Multisystemic therapy and cognitive behaviour therapy have been proven efficacious in many trials. There is no substantial evidence for the efficacy of pharmacological therapy. Currently, the emphasis is on early identification and prevention of antisocial behaviour despite the ethical implications of defining at-risk children. Conclusions: Further research is needed in the areas of neuroendocrinological associations of violent behaviour, taxonomic existence of psychopathy and efficacy of treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Stem cells or immune cells targeting the central nervous system (CNS) bear significant promises for patients affected by CNS disorders. Brain or spinal cord delivery of therapeutic cells is limited by the blood-brain barrier (BBB) which remains one of the recognized rate-limiting steps. Osmotic BBB disruption (BBBD) has been shown to improve small molecule chemotherapy for brain tumors, but successful delivery of cells in conjunction with BBBD has never been reported. We have used a clinically relevant model (pig) of BBBD to attempt brain delivery of TALL-104, a human leukemic T cell line. TALL-104 cells are potent tumor killers and have demonstrated potential for systemic tumor therapy. The pig model used is analogous to the clinical BBBD procedure. Cells were injected in the carotid artery after labeling with the MRI T1 contrast agent GdHPDO3A. Contrast CT scans were used to quantify BBBD and MRI was used to detect Gd++-loaded cells in the brain. Transcranial Doppler was used to monitor cerebral blood flow. EEG recordings were used to detect seizures. Immunocytochemical detection (Cresyl Violet, anti-human CD8 for TALL-104, Evans Blue for BBB damage, GFAP and NEUN) was performed. Results: At the concentration used TALL-104 cells were tolerated. Incomplete BBBD did not allow cell entry into the brain. MRI scans at 24 and 48 hours post-injection allowed visualization of topographically segregated cells in the hemisphere that underwent successful BBBD. Perivascular location of TALL-104 was confirmed in the BBBD hemisphere by Cresyl violet and CD8 immunocytochemistry. No significant alteration in CBF or EEG activity was recorded during cell injections. Conclusions: Our data show that targeted CNS cell therapy requires blood-brain barrier disruption. MRI-detectable cytotoxic anti-neoplastic cells can be forced to transverse the BBB and accumulate in the perivascular space. The virtual absence of toxicity, the high anti-tumor activity of TALL-104, and the clinical feasibility of human osmotic BBBD suggest that this approach may be adopted to treat brain or spinal cord tumors. In addition, BBBD may favor CNS entry of other cells that normally lack CNS tropism. [ABSTRACT FROM AUTHOR]

Background: Visual hallucinations are commonly seen in various neurological and psychiatric disorders including schizophrenia. Current models of visual processing and studies in diseases including Parkinsons Disease and Lewy Body Dementia propose that Acetylcholine (Ach) plays a pivotal role in our ability to accurately interpret visual stimuli. Depletion of Ach is thought to be associated with visual hallucination generation. AchEI's have been used in the targeted treatment of visual hallucinations in dementia and Parkinson's Disease patients. In Schizophrenia, it is thought that a similar Ach depletion leads to visual hallucinations and may provide a target for drug treatment Case Presentation: We present a case of a patient with Schizophrenia presenting with treatment resistant and significantly distressing visual hallucinations. After optimising treatment for schizophrenia we used Rivastigmine, an AchEI, as an adjunct to treat her symptoms successfully. Conclusions: This case is the first to illustrate this novel use of an AchEI in the targeted treatment of visual hallucinations in a patient with Schizophrenia. Targeted therapy of this kind can be considered in challenging cases although more evidence is required in this field. [ABSTRACT FROM AUTHOR]

Background: Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh) depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition. Methods: A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia. Results: No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group. Discussion: Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly. Conclusions: We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed. [ABSTRACT FROM AUTHOR]

Background: Postural balance is an important rehabilitation outcome, and screening stroke patients for confidence in postural balance during rehabilitation and before hospital discharge is recommended. Early supported discharge could improve postural balance self-confidence. This study aimed to investigate associations between patient self-confidence in postural balance and observer-assessed postural balance and anxiety during the first year after stroke. Whether very early supported discharge (VESD) affects self-confidence in postural balance compared with standard discharge was also evaluated.Methods: A longitudinal trial for with data extracted from a randomized controlled study of 140 adults with confirmed stroke was conducted. The experimental group received VESD. The control group was discharged according to the standard routine. Postural balance was assessed with Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and Falls Efficacy Scale. Anxiety was assessed with the Hospital Anxiety and Depression Scale. Spearman's rank correlation coefficient (rho) was used to test associations between independent variables. The Wilcoxon signed-rank test was used to examine differences over time. A single test, according to Eid, Gollwitzer, and Schmidt, was used to test temporal differences in correlation.Results: The correlation between self-confidence in postural balance and observer-assessed postural balance was 0.62-0.78 in the first year after stroke. The correlation between self-confidence and anxiety was 0.22-0.41 in the first year after stroke. Correlations did not differ by group affiliation at any time point when the postural balance was assessed with BBS. The intervention group had a significantly higher correlation (r = - 0.709) than the control group (r = - 0.416) when postural balance was assessed with the TUG test 1 month after discharge. There were no significant differences in correlations between confidence in postural balance and anxiety between the two groups at any time point.Conclusions: Patients with mild stroke can accurately assess their confidence in performing daily activities without falling. VESD does not substantially affect the correlation between self-confidence in postural balance and observer assessed postural balance and is safe to use as an alternative to standard discharge. Assessment of self-confidence can provide important information for rehabilitation planning and supporting the physical activity of patients after discharge.Trial Registration: Clinical Trials.gov: NCT01622205 . Registered 19 June 2012 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Mutations in amyloid precursor protein ( APP ), presenilin 1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) cause autosomal dominant forms of Alzheimer disease (ADAD). More than 280 pathogenic mutations have been reported in APP , PSEN1 , and PSEN2. However, understanding of the basic biological mechanisms that drive the disease are limited. The Dominantly Inherited Alzheimer Network (DIAN) is an international observational study of APP , PSEN1 , and PSEN2 mutation carriers with the goal of determining the sequence of changes in presymptomatic mutation carriers who are destined to develop Alzheimer disease. Results: We generated a library of 98 dermal fibroblast lines from 42 ADAD families enrolled in DIAN. We have reprogrammed a subset of the DIAN fibroblast lines into patient-specific induced pluripotent stem cell (iPSC) lines. These cells were thoroughly characterized for pluripotency markers. Conclusions: This library represents a comprehensive resource that can be used for disease modeling and the development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: The human mirror neuron system exists in adults, and even in children. However, a significant, unanswered question in the literature concerns age differences in the effect of visual orientation of human body movements. The observation of actions performed by others is known to activate populations of neural cells called mirror neuron system. Moreover, the power of mu rhythms (8–13 Hz) in the EEG is known to decrease while performing and observing human movements. Therefore, the mu rhythm could be related to the activity of the mirror neuron system. This study investigated the effects of the visual perspective on electroencephalography responses to hand actions in two age groups. Methods: The participants were 28 elementary school students and 26 university students. Videos of the two hands operating switches were used as stimuli. The electroencephalogram mu rhythm (8–13 Hz) was measured during stimuli presentation as an index of mirror neuron system activity. Results: Adult participants showed significant mirror neuron system activation under both conditions, although no effect of visual perspectives was observed. On the other hand, children only reacted to egocentric stimuli and not to the others. Conclusions: These findings confirmed the suggested differences in the activity of the mirror neuron system between different age groups. The demonstration that brain activities related to mirroring change during development could help explain previous findings in the literature. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is the most common psychiatric complication after a stroke. The most frequently used antidepressants are selective serotonin receptor inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), however, these exhibit a series of side effects. Traditional Chinese medicine has been used to treat PSD with few side effects. The aim of this study is to evaluate the efficacy and safety of Jiedu Tongluo granules for treating PSD with qi deficiency and blood stasis syndrome.Methods: The planned study is a double-blind, randomized, placebo-controlled pilot trial. Eighty participants will be randomly assigned to receive either treatment or placebo. The treatment group will receive Jiedu Tongluo granules (JDTLG) with conventional treatment, and the placebo group will receive placebo with conventional treatment for 8 weeks. The primary outcome is the effectiveness of JDTLG on depression after 8 weeks treatment, which is defined as a decrease of 50% or more in 17-item Hamilton Depression Scale (HAMD-17) score or clinical recovery (score < 7). Secondary outcomes are improvement in neurological function, degree of independence, activities of daily living, and TCM syndrome at each visit, which will be measured with National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and TCM scale, respectively. Interleukin (IL)-6, IL-8, and small-molecule metabolites will be monitored to explore the mechanism of action of JDTLG on PSD. Safety measures include vital signs, results of electrocardiography, laboratory index (full blood count, kidney and liver function tests) and adverse events.Discussion: The purpose of this trial is to evaluate the therapeutic effects and safety of JDTLG in individuals with PSD with concomitant qi deficiency and blood stasis syndrome. If successful, the outcome of this trial will provide a viable treatment option for PSD patients.Trial Registration: ClinicalTrials.gov ID: NCT03147053 . Registered on 27 April 2017. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in whether anesthetic agents affect the risk or progression of Alzheimer's disease (AD). To mitigate many of the methodological issues encountered in human retrospective cohort studies we have used a transgenic model of AD to investigate the effect of propofol on AD pathology. Methods: Six month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic AD mice and control mice were exposed to 3 doses of propofol (200 mg/kg) or vehicle, delivered at monthly intervals. Results: There was no difference in the extent of β-amyloid (Aβ) immunolabeled plaque deposition in APP/PS1 mice in vehicle versus propofol treatment groups. We also detected no difference in plaque-associated synapse loss in APP/PS1 mice following repeat propofol exposure relative to vehicle. Western blotting indicated that there was no difference in post-synaptic density protein 95, synaptophysin or glutamic acid decarboxylase 65/67 expression in control or APP/PS1 mice subjected to repeat propofol treatment relative to vehicle. Conclusions: These data suggest that repeat propofol anesthesia may not exacerbate plaque deposition or associated synapse loss in AD. Interestingly, this data also provides some of the first evidence suggesting that repeat propofol exposure in adult wild-type mice does not result in robust long-term alterations in the levels of key excitatory and inhibitory synaptic markers. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health and can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). Using such approaches, some researchers have explored the relationship between CVR and cognition; here we systematically review this work.Results: We extracted information pertaining to: (1) study location and design, participant characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2 (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive assessment, (5) CVR values, and outcomes of statistical analyses with cognitive tests. Five studies assessed participants with cognitive impairment compared to controls, one studied patients with multiple sclerosis with or without cognitive impairment compared to controls, one examined patients with moyamoya disease with or without cognitive impairment, two investigated patients with Type 2 diabetes mellitus (T2DM), and one was a cross-sectional study with younger and older healthy adults. Cognition was typically probed using the MMSE and tests of executive function, while a number of vasodilatory techniques were employed.Conclusion: CVR was associated with cognition in six of ten studies, but heterogeneity of study samples, designs and vasodilatory methods may have a role in the inconsistent findings. We make recommendations for future research that includes use of a multi-domain cognitive assessment and standardised hypercapnic challenge with MRI. [ABSTRACT FROM AUTHOR]

Background: Some alterations of the lipoprotein profile have been associated with cerebrovascular disease. Recently, it has been suggested that cerebrovascular disease might play a role in the pathogenesis of both vascular dementia (VD) and Alzheimer's disease (AD). Nevertheless, the possible association of dyslipidemias with VD or AD is still a controversial issue.Methods: We investigated the lipoprotein profile in 100 older patients with vascular dementia (VD; no degrees: 60) or Late Onset Alzheimer's Disease (LOAD; no degrees: 40). The patients were compared with 54 community dwelling non-demented older controls.Results: After adjustment for functional status, blood sedimentation rate, and serum albumin levels, no differences in lipoprotein profile emerged between the three groups, with the exception of HDL-C that was lower in VD compared with controls. Low HDL-C (< 45 mg/dL) was associated with VD (O.R.: 6.52, C.I. 95%: 1.42-30.70 vs controls, and 4.31, C.I. 95%: 0.93-19.82 vs LOAD), after multivariate adjustment. No differences in plasma lipid levels emerged between the three groups after stratification for apo E4 genotype.Conclusions: In this cross-sectional study low HDL-C levels are associated with VD, but not with LOAD, in a sample of older subjects. [ABSTRACT FROM AUTHOR]