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Physical inactivity is a leading modifiable risk factor for cardiovascular and cerebrovascular disease, cognitive dysfunction, and global mortality. Regular exercise might mitigate age-related declines in cardiovascular and cerebrovascular function. In this study, we hypothesize that a 6-month aerobic exercise intervention will lead to a decrease in cerebrovascular resistance index (CVRi) and to an increase in cerebral blood flow (CBF) and cerebrovascular conductance index (CVCi) during two submaximal exercise workloads (40% VO

ObjectiveTo test the hypothesis that aerobic exercise is associated with improvements in cognition and cerebrovascular regulation, we enrolled 206 healthy low-active middle-aged and older adults (mean ± SD age 65.9 ± 6.4 years) in a supervised 6-month aerobic exercise intervention and assessed them before and after the intervention.MethodsThe study is a quasi-experimental single group pre/postintervention study. Neuropsychological tests were used to assess cognition before and after the intervention. Transcranial Doppler ultrasound was used to measure cerebral blood flow velocity. Cerebrovascular regulation was assessed at rest, during euoxic hypercapnia, and in response to submaximal exercise. Multiple linear regression was used to examine the association between changes in cognition and changes in cerebrovascular function.ResultsThe intervention was associated with improvements in some cognitive domains, cardiorespiratory fitness, and cerebrovascular regulation. Changes in executive functions were negatively associated with changes in cerebrovascular resistance index (CVRi) during submaximal exercise (β = −0.205,p= 0.013), while fluency improvements were positively associated with changes in CVRi during hypercapnia (β = 0.106,p =0.03).ConclusionThe 6-month aerobic exercise intervention was associated with improvements in some cognitive domains and cerebrovascular regulation. Secondary analyses showed a novel association between changes in cognition and changes in cerebrovascular regulation during euoxic hypercapnia and in response to submaximal exercise.

To determine the relationship between sleep spindle characteristics (density, power and frequency), executive functioning and cognitive decline in older adults, we studied a convenience subsample of healthy middle-aged and older participants of the Brain in Motion study. Participants underwent a single night of unattended in-home polysomnography with neurocognitive testing carried out shortly afterwards. Spectral analysis of the EEG was performed to derive spindle characteristics in both central and frontal derivations during non-rapid eye movement (NREM) Stage 2 and 3. Multiple linear regressions were used to examine associations between spindle characteristics and cognitive outcomes, with age, body mass index (BMI), periodic limb movements index (PLMI) and apnea hypopnea index (AHI) as covariates. NREM Stage 2 total spindle density was significantly associated with executive functioning (central: β = .363, p = .016; frontal: β = .408, p = .004). NREM Stage 2 fast spindle density was associated with executive functioning (central: β = .351, p = .022; frontal: β = .380, p = .009) and Montreal Cognitive Assessment score (MoCA, central: β = .285, p = .037; frontal: β = .279, p = .032). NREM Stage 2 spindle frequency was also associated with MoCA score (central: β = .337, p = .013). Greater spindle density and fast spindle density were associated with better executive functioning and less cognitive decline in our study population. Our cross-sectional design cannot infer causality. Longitudinal studies will be required to assess the ability of spindle characteristics to predict future cognitive status.

To investigate the relative importance of isolated thoracic perfusion (ITP) in the multidisciplinary palliative treatment of progressive malignant pleural mesothelioma (MPM) patients.Fifty-two MPM patients with progressive disease after systemic chemotherapy with cisplatin and pemetrexed were submitted to 112 ITP using mitomycin C (25 mg/m2) and cisplatin (70 mg/m2) between 2000 and 2017. Isolation of the chest was achieved by insertion of stop-flow balloon catheters via femoral or iliac access. Primary endpoints were adverse events, tumor response rate, progression-free survival (PFS) and overall survival (OS) from initial ITP.Median interval-time from MPM diagnosis was 9 months. There were no perfusion-related postoperative deaths. The main procedure-related complication was persistent leakage of lymphatic fluid from the incision in less than 10% of ITP. No severe perfusion-related toxicity was reported, with grade 3 haematological toxicity and platinum-induced neurotoxicity in less than 8% of the patients. Following initial ITP, overall tumor response rate was 25%, median PFS was 7 months (IQR 5-10.5), and median OS was 16 months (IQR 12.5-21). After the last ITP, 14 patients received further therapies, including targeted therapy with cetuximab or bevacizumab. Non-epithelioid histology, stage III, and ECOG performance status 3 pre-ITP were prognostic factors with a significant influence on OS. Median OS, calculated from the diagnosis of MPM, was 26.5 months (IQR 22.5-28).ITP is safe, tolerable, and useful but its inclusion in the multidisciplinary palliative treatment of progressive MPM patients should be investigated in a larger multicentre controlled study.

The human ability to vicariously share someone else's emotions (i.e., emotional empathy) relies on an extended neural network including regions in the anterior cingulate and insular cortex. Here, we tested the hypothesis that good sleep quality is associated with increased activation in the brain areas underlying emotional empathy. To this aim, we assessed subjective sleep quality in a large sample of healthy young volunteers, and asked participants to complete a computerized emotional empathy task. Then, we asked 16 participants to complete the same task while undergoing functional Magnetic Resonance Imaging (fMRI). After confirming the behavioral relationship between quality of sleep and emotional empathy in the large sample, we conducted a Region of Interest (ROI) analysis on selected ROIs involved in emotional empathy, and measured Blood Oxygen Level Dependent (BOLD) signal change in participants who performed the emotional empathy task in the MRI scanner; additionally, we assessed how the BOLD signal in different brain areas temporally correlated with performance throughout the task (i.e., task-based functional connectivity). We found increased BOLD signal change in a selective region within the left insula for individuals with better subjective sleep quality. These findings provide the very first evidence that individuals' sleep quality relates to emotional empathic responses through increased neural activation of a specific area within the insular cortex.

Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision. Among the 41 patients, 22 (53.7%) patients exhibited a wild-type BRAF genotype, 11 of which were not eligible for immunotherapy. The first treatment resulted in a 97.5% response-rate in the full cohort and a 100% response-rate in the 22 wild-type BRAF patients. MST was 18 months in the full sample, 20 months for the 22 wild-type BRAF patients and 21 months for the 11 wild-type BRAF patients not eligible for immunotherapy. Melphalan hypoxic perfusion is a potentially effective treatment for patients with pelvic melanoma loco regional metastases that requires confirmation in a larger multicenter study.

Trait neuroticism is suggested to be related to measures of volume and function of the hippocampus, a brain structure located in the medial temporal lobe that is critical for human navigation and orientation. In this study, we assessed whether measures of trait neuroticism and self-concept are correlated with the human ability to orient by means of cognitive maps (i.e. mental representations of an environment that include landmarks and their spatial relationships). After controlling for gender differences, which are well-known in spatial orientation abilities, we found that measures of neuroticism (i.e. negative affect, emotional stability) and self-concept (i.e. self-esteem) were correlated with individual differences in the rate at which cognitive maps were formed; the same measures were generally unrelated to the ability to make use of cognitive maps, as well as the ability to orient using visual path integration. The relationships (and lack thereof) between personality traits and the spatial orientation skills, as reported in the present study, are consistent with specific neural correlates underlying these factors, and may have important implications for treatment of disorders related to them.

Aging is associated with decline in white matter (WM) microstructure, decreased cognitive functioning, and increased risk of Alzheimer’s disease and related dementias . Recent research has identified aerobic physical exercise as a promising intervention for increasing white matter microstructure in aging, with the aim of increasing cognitive abilities, and protecting against neurodegenerative processes . However, the degree to which white matter microstructure can be protected or improved with exercise remains incompletely understood. Here, a sub-group of 25 healthy, sedentary participants (aged 57 to 86 years; M = 67.1; SD = 7.9; 11 female, 14 male) from the larger Brain in Motion Study (Tyndall et al ., 2013) underwent diffusion tensor imaging (DTI) before and after a six-month aerobic exercise intervention. DTI data were analysed with FSL’s Tract-Based Spatial Statistics (TBSS) to determine whether WM microstructure improved, as defined by increased fractional anisotropy (FA) and/or decreased mean diffusivity (MD), after the aerobic exercise intervention. Neither FA nor MD of the cerebral WM were significantly correlated with either age or cardiovascular fitness at baseline. Whole-brain WM mean FA decreased over the intervention while mean MD showed no significant change. Longitudinal TBSS analyses revealed decreased FA in the left uncinate fasciculus , left anterior corona radiata , left inferior fronto-occipital fasciculus, and left anterior thalamic radiation. MD increased in the left forceps major, left inferior longitudinal fasciculus , and left superior longitudinal fasciculus . Results indicate that six months of aerobic exercise in healthy, sedentary older adults was not associated with improvements in FA or MD measures of cerebral WM microstructure.

The aim of this study is to evaluate the empathic ability and its functional brain correlates in post-traumatic stress disorder subjects (PTSD). Seven PTSD subjects and ten healthy controls, all present in the L'Aquila area during the earthquake of the April 2009, underwent fMRI during which they performed a modified version of the Multifaceted Empathy Test. PTSD patients showed impairments in implicit and explicit emotional empathy, but not in cognitive empathy. Brain responses during cognitive empathy showed an increased activation in patients compared to controls in the right medial frontal gyrus and the left inferior frontal gyrus. During implicit emotional empathy responses patients with PTSD, compared to controls, exhibited greater neural activity in the left pallidum and right insula; instead the control group showed an increased activation in right inferior frontal gyrus. Finally, in the explicit emotional empathy responses the PTSD group showed a reduced neural activity in the left insula and the left inferior frontal gyrus. The behavioral deficit limited to the emotional empathy dimension, accompanied by different patterns of activation in empathy related brain structures, represent a first piece of evidence of a dissociation between emotional and cognitive empathy in PTSD patients. The present findings support the idea that empathy is a multidimensional process, with different facets depending on distinct anatomical substrates.

Previous studies have shown that sleep loss has a detrimental effect on the ability of the individuals to process emotional information. In this study, we tested the hypothesis that this negative effect extends to the ability of experiencing emotions while observing other individuals, i.e. emotional empathy. To test this hypothesis, we assessed emotional empathy in 37 healthy volunteers who were assigned randomly to one of three experimental groups: one group was tested before and after a night of total sleep deprivation (sleep deprivation group), a second group was tested before and after a usual night of sleep spent at home (sleep group) and the third group was tested twice during the same day (day group). Emotional empathy was assessed by using two parallel versions of a computerized test measuring direct (i.e. explicit evaluation of empathic concern) and indirect (i.e. the observer's reported physiological arousal) emotional empathy. The results revealed that the post measurements of both direct and indirect emotional empathy of participants in the sleep deprivation group were significantly lower than those of the sleep and day groups; post measurement scores of participants in the day and sleep groups did not differ significantly for either direct or indirect emotional empathy. These data are consistent with previous studies showing the negative effect of sleep deprivation on the processing of emotional information, and extend these effects to emotional empathy. The findings reported in our study are relevant to healthy individuals with poor sleep habits, as well as clinical populations suffering from sleep disturbances.