Sleep slow oscillations favour local cortical plasticity underlying the consolidation of reinforced procedural learning in human sleep

We investigated changes of slow-wave activity and sleep slow oscillations in the night following procedural learning boosted by reinforcement learning, and how these changes correlate with behavioural output. In the Task session, participants had to reach a visual target adapting cursor's movements to compensate an angular deviation introduced experimentally, while in the Control session no deviation was applied. The task was repeated at 13:00 hours, 17:00 hours and 23:00 hours before sleep, and at 08:00 hours after sleep. The deviation angle was set at 15° (13:00 hours and 17:00 hours) and increased to 45° (reinforcement) at 23:00 hours and 08:00 hours. Both for Task and Control nights, high-density electroencephalogram sleep recordings were carried out (23:30-19:30 hours). The Task night as compared with the Control night showed increases of: (a) slow-wave activity (absolute power) over the whole scalp; (b) slow-wave activity (relative power) in left centro-parietal areas; (c) sleep slow oscillations rate in sensorimotor and premotor areas; (d) amplitude of pre-down and up states in premotor regions, left sensorimotor and right parietal regions; (e) sigma crowning the up state in right parietal regions. After Task night, we found an improvement of task performance showing correlations with sleep slow oscillations rate in right premotor, sensorimotor and parietal regions. These findings suggest a key role of sleep slow oscillations in procedural memories consolidation. The diverse components of sleep slow oscillations selectively reflect the network activations related to the reinforced learning of a procedural visuomotor task. Indeed, areas specifically involved in the task stand out as those with a significant association between sleep slow oscillations rate and overnight improvement in task performance

A wearable system for stress detection through physiological data analysis

In the last years the impact of stress on the society has been increased, resulting in 77% of people that regularly experiences physical symptoms caused by stress with a negative impact on their personal and professional life, especially in aging working population. This paper aims to demonstrate the feasibility of detection and monitoring of stress, inducted by mental stress tests, through the analysis of physiological data collected by wearable sensors. In fact, the physiological features extracted from heart rate variability and galvanic skin response showed significant differences between stressed and not stressed people. Starting from the physiological data, the work provides also a cluster analysis based on Principal Components (PCs) able to showed a visual discrimination of stressed and relaxed groups. The developed system would support active ageing, monitoring and managing the level of stress in ageing workers and allowing them to reduce the burden of stress related to the workload on the basis of personalized interventions

Obese mice exposed to psychosocial stress display cardiac and hippocampal dysfunction associated with local brain-derived neurotrophic factor depletion

Introduction: Obesity and psychosocial stress (PS) co-exist in individuals of Western society. Nevertheless, how PS impacts cardiac and hippocampal phenotype in obese subjects is still unknown. Nor is it clear whether changes in local brain-derived neurotrophic factor (BDNF) account, at least in part, for myocardial and behavioral abnormalities in obese experiencing PS. Methods: In adult male WT mice, obesity was induced via a high-fat diet (HFD). The resident-intruder paradigm was superimposed to trigger PS. In vivo left ventricular (LV) performance was evaluated by echocardiography and pressure-volume loops. Behaviour was indagated by elevated plus maze (EPM) and Y-maze. LV myocardium was assayed for apoptosis, fibrosis, vessel density and oxidative stress. Hippocampus was analyzed for volume, neurogenesis, GABAergic markers and astrogliosis. Cardiac and hippocampal BDNF and TrkB levels were measured by ELISA and WB. We investigated the pathogenetic role played by BDNF signaling in additional cardiac-selective TrkB (cTrkB) KO mice. Findings: When combined, obesity and PS jeopardized LV performance, causing prominent apoptosis, fibrosis, oxidative stress and remodeling of the larger coronary branches, along with lower BDNF and TrkB levels. HFD/PS weakened LV function similarly in WT and cTrkB KO mice. The latter exhibited elevated LV ROS emission already at baseline. Obesity/PS augmented anxiety-like behaviour and impaired spatial memory. These changes were coupled to reduced hippocampal volume, neurogenesis, local BDNF and TrkB content and augmented astrogliosis. Interpretation: PS and obesity synergistically deteriorate myocardial structure and function by depleting cardiac BDNF/TrkB content, leading to augmented oxidative stress. This comorbidity triggers behavioral deficits and induces hippocampal remodeling, potentially via lower BDNF and TrkB levels. FUND: J.A. was in part supported by Rotary Foundation Global Study Scholarship. G.K. was supported by T32 National Institute of Health (NIH) training grant under award number 1T32AG058527. S.C. was funded by American Heart Association Career Development Award (19CDA34760185). G.A.R.C. was funded by NIH (K01HL133368-01). APB was funded by a Grant from the Friuli Venezia Giulia Region entitled: Heart failure as the Alzheimer disease of the heart; therapeutic and diagnostic opportunities . M.C. was supported by PRONAT project (CNR). N.P. was funded by NIH (R01 HL136918) and by the Magic-That-Matters fund (JHU). V.L. was in part supported by institutional funds from Scuola Superiore Sant\u27Anna (Pisa, Italy), by the TIM-Telecom Italia (WHITE Lab, Pisa, Italy), by a research grant from Pastificio Attilio Mastromauro Granoro s.r.l. (Corato, Italy) and in part by ETHERNA project (Prog. n. 161/16, Fondazione Pisa, Italy). Funding source had no such involvement in study design, in the collection, analysis, interpretation of data, in the writing of the report; and in the decision to submit the paper for publication

Oscillazione lenta del sonno ed apprendimento visuo-motorio: studio psicofisiologico mediante EEG ad alta densità

Il concetto di “Oscillazione Lenta del Sonno” (“Sleep Slow Oscillation” –SSO) è stato introdotto da Mircea Steriade (1993) mediante tecniche di registrazione intracellulare. La SSO è stata studiata attraverso approcci in computo ed in vivo sia nel modello animale che nell’uomo. Nell’uomo alcuni lavori hanno identificato le caratteristiche spazio-temporali dell'onda che corrispondono a specifici meccanismi molecolari: (i) picco negativo (downstate); (ii) picco positivo (upstate); (iii) Slope1 (sincronizzazione di apertura dei canali al potassio attività-dipendenti nel downstate); (iv) Slope2 (sincronizzazione dell’attività di scarica dei neuroni all’uscita dal downstate); (v) viaggio corticale, (Massimini et al. 2004, Menicucci et al. 2009, Piarulli et al. 2010). Recentemente alcuni lavori hanno posto l’attenzione su un'eccitazione (deflessione positiva) precedente al cosiddetto "silenzio elettrico" (downstate). Tale deflessione gioca un ruolo cruciale per tutta la dinamica dell'onda (esito e propagazione) in associazione con la "proneness" (massiva apertura dei canali al potassio in modo sincronizzato) alla bistabilità (Menicucci et al. 2013, Laurino et al. 2014). Oltre ad interessare alcune funzioni del sonno (downscaling sinaptico, incoscienza), la SSO rappresenta il comportamento cellulare e di network alla base del consolidamento delle memorie (Born e Rash, 2013). L’oscillazione lenta permette il replay della traccia mnestica inducendo interazioni cortico-ippocampali, mediate principalmente dall'attività dei fusi del sonno e dall’attività gamma sull’upstate. In sintesi, l’oscillazione lenta del sonno è un fenomeno complesso caratterizzato da origini, detezioni, caratteristiche morfologiche, dinamiche e da modulazioni di ritmi rapidi coalescenti con l’upstate. Queste caratteristiche rendono la SSO l’onda pivotale per i meccanismi dell’assenza di coscienza durante il sonno e per il consolidamento delle tracce mnestiche. Lo scopo di questa tesi sperimentale è modulare la plasticità loco-regionale mediante nuovi apprendimenti al fine di identificare le regioni “trigger” della SSO e di conseguenza anche il suo ruolo funzionale. In quest’ottica l’oscillazione lenta del sonno diventa “tout court” una finestra di osservazione elettiva per mappare i meccanismi di consolidamento dei nuovi engrammi mnestici durante il sonno. The concept of Sleep Slow Oscillation (SSO) was introduced by Mircea Steriade (1993) using intracellular recording techniques. SSO was studied adopting both in computo and in vivo techniques, and both in animal models and in humans. In humans, some works have identified the spatio-temporal characteristics of the wave, corresponding to specific molecular mechanisms: (i) negative peak (downstate); (ii) positive peak (upstate); (iii) Slope1 (potassium-channels opening synchronization); (iv) Slope2 (synchronization in firing activity of neuron exiting the downstate), and (v) cortical travel (Massimini et al. 2004, Menicucci et al. 2009 Piarulli et al. 2010). Some recent papers have focused on an excitation (positive deflction) preceding the so-called "electrical silence": this early peak is crucial to the whole dynamic of the wave (outcome and propagation) in association with the "proneness" (massive synchronized opening of potassium channels) to bistability (Menicucci et al. 2013, Laurino et al. 2014). Beside playing a role on some sleep functions (synaptic downscaling, unconsciousness), SSO represents the cellular and network mechanism at the basis of the consolidation of memories (Born and Rash, 2013). In fact, SSO allows the replay of the mnestic engram inducing cortico-hippocampal interactions, mostly mediated by the activity of sleep spindles and by gamma activity crowned upon the upstate. In summary, SSO is a complex phenomenon characterized by sources, detections, morphologies, dynamic modulations of rapid rhythms coalescing with the upstate. All these features make the SSO wave pivotal to the mechanisms of the absence of consciousness during sleep and for memory consolidation. The purpose of this thesis is to modulate the loco-regional plasticity via new learnings, in order to determine regions triggering SSO and its functional role. In this perspective, the SSO becomes "tout court" the most important observation window to map the mechanisms of consolidation of new memories during sleep

Perioperative Heart-Brain Axis Protection in Obese Surgical Patients: the Nutrigenomic Approach

The number of obese patients undergoing cardiac and noncardiac surgery is rapidly increasing because they are more prone to concomitant diseases, such as diabetes, thrombosis, sleep-disordered breathing, cardiovascular and cerebrovascular diseases. Even if guidelines are already available to manage anesthesia and surgery of obese patients, the assessment of the perioperative morbidity and mortality from heart and brain disorders in morbidly obese surgical patients will be challenging in the next years. The present review will recapitulate the new mechanisms underlying the heart-brain axis (HBA) vulnerability during the perioperative period in healthy and morbidly obese patients. Finally, we will describe the nutrigenomics approach, an emerging noninvasive dietary tool, to maintain a healthy body weight and to minimize the HBA propensity to injury in obese individuals undergoing all types of surgery by personalized intake of plant compounds that may regulate the switch from health to disease in an epigenetic manner. Our review provides current insights into the mechanisms underlie HBA response in obese surgical patients and how they are modulated by epigenetically active food constituents

Long-term dietary intake of pasta enriched with barley (1–3) beta-d-glucan induces neovascularization-mediated cardioprotection against ischemia/reperfusion injury in mice

Background: The modulation of angiogenesis is known to be a strategy to increase heart resistance to ischemia/reperfusion (I/R). Whereas the angiogenic activity of barley (1- 3)beta-D-Glucan (BG) have been characterized in vitro, there are no clear experimental data demonstrating that chronic dietary intake and intestinal absorption of BG actually protects the heart against I/R. We tested whether long-term consumption of 3% w/v BG included in normal pasta would increase myocardial angiogenesis and render the heart of mice more resistant to I/R. Materials and methods: Healthy adult male C57BL/6 mice were fed for 5 weeks with a low-fat diet supplemented with pasta enriched with BG (3g/100mg) (BG, n=15) or regular pasta (control, n=15). Food intake, glucose tolerance test and cardiac function were weekly assessed. At fifth week of diet, anesthetized mice underwent to 30 min of cardiac ischemia followed by 60 min of reperfusion. The myocardial infarction was induced by ligation of the left anterior descending artery. The myocardial capillary density and infarct size/area at risk were assessed ex vivo. Myocardial Vascular Endothelial Growth Factor 165 (VEGF165) expression and anion superoxide (O2-) levels were measured respectively by western blot and dihydroethidium staining. To evaluate the paracrine activation of protective angiogenesis by BG, we measured the expression of VEGF165, a well known pro-angiogenic growth factor, in endothelial cells exposed for 7 days to 3% BG. Finally, we examined the expression of dectin-1, a receptor of BG, in both endothelial cells and cardiomyocytes. Results: At similar food intake, 3% w/v BG did not affect body weight, glucose metabolism and cardiac function of mice. At the end of reperfusion, BG mice survived 50±2% more than control (P<0.01). Infarct size/area at risk and myocardial O2- load were reduced respectively by 62±5% (P<0.001) and 35±4% (P<0.0001) in β-D-glucan mice. Myocardial capillary density and VEGF165 expression were increased respectively by 12±0.6% (P<0.05) and 47.6±1% (P<0.001) in BG group compared to control mice. In vitro, VEGF165 expression was significantly increased in BG-treated endothelial cells (P<0.001). Dectin-1 was expressed in endothelial cells, but not in cardiomyocytes. Conclusions: Long-term intake of BG-rich diet augments myocardial capillary density and reduces infarct size by sustained expression of VEGF165 in endothelial cells, which express dectin-1. Our findings suggest important potential health benefits of pasta-rich in BG and emphasize the need to develop BG-rich functional foods with protective activities for increasing heart resistance to I/R injury

Long term intake of barley beta-D-glucan attenuates glucose intolerance, mood disorders and cognitive decline in high-fat diet-induced obese mice exposed to chronic psychosocial stress

High-fat diet (HFD)-induced obesity causes insulin resistance and increases vulnerability to chronic psychosocial stress-induced dysfunctions, including anxiety and mood disorders, cognitive decline and myocardial ischemia. The inhibition of class I histone deacetylases leads to metabolic homeostasis and dietary barley (1.3) beta-D-glucan (β-D-glucan), a water-soluble polysaccharide, increases levels of histone H4 acetylation. We tested whether the long-term intake of β-D-glucan prevents glucose intolerance, affective disorders and cognitive decline in stressed obese mice. 24 male mice C57BL/6 were fed three different diets for 18 wks: 1) standard diet (SD; 10% Kcal from fat; n=8), 2) HFD (58% Kcal from fat; n=8) or 3) HFD supplemented with 3% w/v β-D-glucan (HFD+BG; 58% Kcal from fat; n=8). From the 16th to the 18th wk all animals underwent to the resident-intruder stress test. Before and after chronic stress, the anxiety-related behaviour and the spatial working memory were evaluated by elevated plus-maze (PM; entries in open arms, %) and Y-maze test (YM; spontaneous alternation, %). At the end of the experiment, plasma brain derived neurotrophic factor (BDNF) and the hippocampal expression of tropomyosin-related kinase B (TrKB, the BDNF receptor) were evaluated because of their key role in energy balance and in the pathogenesis of affective and cognitive disorders. At the 16th wk, HFD’s body weight was increased compared to SD group (+36.6%, p<0.01), but the β-D-glucan supplementation prevented the HFD-induced weight gain. The glucose tolerance test area under the curve (AUC; 0–120 min) was higher in HFD than SD mice fasted (447.7 ± 55 vs 259.1 ± 23.4 mg/dL*min: p<0.001); although, it was lower (−25.8%, p<0.01) in the HFD+BG compared to HFD group. Compared to SD group, open arm activity at the16th week was lower in the HFD (−250%, p<0.001) than in the HFD+BG group (−55.5% p<0.05). After stress, the entries in open arms were absent in HFD mice and were further reduced (−75%, p<0.01) in SD animals, yet the open arm activity was unchanged in HFD+BG group. Spatial working memory after 16 wks. was similar in all groups, but after stress it was reduced only in HFD mice (−18.9%, p<0.01). Compared to SD, reduction of BDNF plasma levels was detected in HFD mice, but not in HFD+BG group (SD, 66 ± 22 pg/ml; HFD, 27 ± 11 pg/ml; HFD+BG, 78 ± 32 pg/ml, p<0.05). The hippocampal expression of TrKB in HFD+BG group was significantly higher than HFD mice (HFD+BG, 0.63 ± 0.13 a.u.; SD, 0.5± 0.1 a.u.; HFD, 0.44 ± 0.05 a.u., p<0.05). In conclusion, β-D-glucan intake attenuates glucose intolerance and improves the stress-induced response in obese mice through the upregulation of hippocampal BDNF/TrkB pathway. Our data provide a basis for developing a new nutraceutical approach for the protection against obesity/stress-related disorders

Barley (1,3)-β-d-Glucan Dietary Supplementation Prevents Cardiac Dysfunction in Obese Mice with Psychosocial Stress by Attenuating Myocardial Oxidative Stress

Objective: Obesity due to high fat intake and psychosocial stress (PSS) are major determinants of cardiovascular disease (CVD), particularly when combined. Long-term diets enriched with barley (1,3)-β- d-glucan (BBG), an inhibitor of the class I histone deacetylases and an antioxidant, increases post-ischemic survival rate in mice by promoting angiogenesis. However, the impact of a BBG-enriched diet on cardiac dysfunction due to conditions such as high-fat diet (HFD) and PSS, alone or in combination, is unknown. Here, we tested whether supplementing HFD-treated mice with BBG prevents HFD- or HFD/PSS induced cardiac dysfunction by attenuating myocardial oxidative stress. Methods: Controlmale C57BL/6 mice were fed with 3 different diets for 18 wks: 1) standard diet (SD; 10% kcal fromfat; n=9); 2) HFD (58%kcal from fat; n=9); or 3)HFD+3% BBG (HFD+BBG; 58% kcal from fat; n = 9). All mice were then subjected chronic PSS via a daily (10min) encounter with a male intruder (resident/intruder test, fromweek 16 to week 18). Cardiac function was evaluated by echocardiography before and after PSS, whereas left ventricle (LV) tissue was collected at study termination to assess reactive oxygen species (ROS) by emission electron paramagnetic resonance analysis. Results: At week 16, body weight was markedly higher in the HFD than in the SD group (+60.1%, P &lt; 0.001); however, BBG supplementation significantly prevented weight gain (−10% compared with HFD, P &lt; 0.05). The addition of PSS significantly worsened the LV dysfunction in HFD (LV ejection fraction (LVEF), −25%; LV fractional shortening (LVFS), −33% compared with SD (LVEF, −7%; LVFS, −10%) mice. Conversely, the LV function after PSS was significantly improved in HFD + BBG mice (LVEF, +7%; LVFS, +10%) when compared with basal values. HFD and PSS led a marked rise in LV ROS production, as compared with values found in the hearts of mice receiving SD (+76% P &lt; 0.001). However, this increment was significantly attenuated in HFD + BBG mice in which LV ROS emission rose only by 34%. Our study shows that a regular supplementation of 3% wt/vol BBG with diet prevents cardiac functional decay due to the combination of HFD and PSS, likely by countering HFD/PSS-induced myocardial ROS production. These findings may have preventative or therapeutic implications for all CVDs characterized by a cardiac, vascular, or both redox milieu

Obese Mice Exposed to Psychosocial Stress Display Cardiac and Hippocampal Impairment Associated With Local Brain-Derived Neurotrophic Factor Depletion

Introduction: Obesity and psychosocial stress (PS), two stigmata of Western society increasingly coexisting in the same individual, are risk factors for cardiovascular disease and cognitive deficits. However, the effects of PS on cardiac and hippocampal phenotype of obese subjects are still unknown. Furthermore, Brain-Derived Neurotrophic Factor (BDNF) can regulate the hippocampal and cardiac homeostasis; thus, its depletion may explain PS/obesity-induced dysfunction at both levels. Hypothesis: Obese mice exposed to PS display cardiac and hippocampal impairment associated to local BDNF depletion. Methods: Forty adult male C57BL6/J mice were subjected to: 1) normocaloric diet (ND) for 18 weeks (Control); 2) high-fat diet (HFD) for 18 weeks (Ob); 3) ND and resident-intruder paradigm (RIP) to trigger PS (PS); 4) HFD and RIP (Ob+PS). Left ventricular (LV) function was evaluated by pressure-volume loops. Spatial memory was assessed by Y-maze. LV ROS levels were measured by EPR. Myocardial apoptosis, fibrosis and vascular density were histologically evaluated. Hippocampus was assayed to evaluate volume, neurogenesis and synaptic plasticity. Tissue BDNF levels were measured by ELISA. Results: Preload recruitable stroke work and LV elastance, load-independent indexes of LV contractility, were impaired only in Ob+PS group (-44% and -41%, respectively, both p&lt;0.01 vs. Control). Moreover, combined regimen jeopardized also myocardial relaxation (tau), (p&lt;0.05 vs. Control), without affecting arterial elastance. Obesity/PS significantly increased LV oxidative stress, apoptosis and fibrosis, without changing vascular density, while halving cardiac BDNF (-48%, p&lt;0.01 vs. all groups). Spatial memory was compromised only in Ob+PS group (p&lt;0.05 vs. Control) consistent with reduced hippocampal volume (-27%, p&lt;0.05 vs. all groups), neurogenesis (-33%, p&lt;0.001 vs. Control), synaptic plasticity (-29%, p&lt;0.05 vs. Control) and local BDNF levels (-52%, p&lt;0.01 vs. Control; p&lt;0.05 vs. PS and Ob). Conclusions: PS triggers prominent myocardial and hippocampal dysfunction in obese mice. PS-challenged obese mice exhibit BDNF depletion in both remodeled tissues. Therefore, PS may jam heart-brain communication of obese mice though local BDNF exhaustion