Palaeoenvironment, Settlement, and Land Use in the Late Neolithic—Bronze Age Site of Colombare di Negrar di Valpolicella (N Italy, On-Site)

Palynological and archaeobotanical analyses have been carried out as part of the interdisciplinary project of Colombare di Negrar, a prehistoric site in the Lessini Mountains (northern Italy). The palaeoenvironmental and economic reconstruction from the Late Neolithic to the beginning of the Early Bronze Age was based on 16 pollen samples and three samples of macroremains taken from two contiguous trenches. The landscape reconstruction shows the presence of natural clearings in the wood. Forest cover was characterised by oak wood, with Ulmus and Tilia. The intermediate morphology of size and exine of Tilia cordata/platyphyllos pollen may be regarded as the first palynological evidence of lime hybrids in palaeorecords. Hygrophilous trees and Vitis vinifera testify to the presence of riparian forests and moist soils. Among trees supplying fruits, in addition to the grapevine, hazelnut (Corylus avellana) and walnut (Juglans regia) were present. A mixed economy based on animal breeding and cultivation of cereals (Hordeum vulgare, Triticum monococcum, T. dicoccum, T. timopheevii) emerged from the data. The combined analysis of pollen and plant macroremains suggests that different activities were carried out simultaneously in Colombare and a relationship between natural resources and the socio-economic and cultural evolution of the territory

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power > 20 Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalamo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity. (C) 2015 The Authors. Published by Elsevier Inc.Peer reviewe

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naive patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach

Integrating Sleep and Alzheimer's Disease Pathophysiology: Hints for Sleep Disorders Management

Sleep represents an active phenomenon regulated by a highly integrated network of cortical and subcortical structures. This complex model results in disruptions at various levels during physiological aging and more deeply during neurodegenerative disorders, thus leading to different sleep alterations. In Alzheimer's disease (AD), sleep-wake abnormalities were described to occur even in the preclinical phase, thus suggesting they could be a possible AD biomarker. On the other hand, they also favor the progression of the disease. In this paper, we review current theories regarding sleep regulations and functions to highlight the pathophysiological mechanisms at the basis of the bidirectional relationship between sleep and AD. A better understanding of these complex interactions might also be useful to target both sleep disorder management and AD-related symptoms

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

INTRODUCTION During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive(Tononi and Massimini, 2008). Why is this? We hypothesized that the same neuronal mechanism that underlies sleep slow waves, that is bistability, between depolarized upstates and hyperpolarized downstate in cortical neurons (Steriade et al., 1993), may substantially impair information transmission within cortical networks. Specifically, we postulated that the inescapable occurrence of a silent, down-state after an initial activation couldbreak-off cortico-cortical causal interactions, thus impairing the ability of thalamocortical circuits to sustain long-range, deterministic patterns of activation, a theoretical requisite for consciousness(Tononi, 2008).Intracranial single-pulse electrical stimulation (SPES) and simultaneous stereotactic EEG (SEEG) recordings offer a unique opportunity to test this hypothesis. First, intracranial recordings allow a reliable detection of cortical down-states as a significant suppression of high frequency power above 20 Hz(Cash et al., 2009). Second, intracranial perturbations with SPES allow assessing cortico-cortical interactions from a causal perspective by calculating the phase locking factor (PLF)(Palva et al., 2005). METHODS We employedSPES and simultaneous stereotactic electroencephalography to compare cortico-cortical evoked potentials (CCEPs) recorded during wakefulness and NREM sleepin 8 epileptic patients undergoing intra-cerebral stimulations and recordings for clinical evaluation. The number of implanted electrodes (Figure 1) varied based on surgical requirements (max: 15 electrodes, 168 contacts). Stimulation trains (30 pulses, 0.2-1 Hz, 5mA) were delivered through one couple of adjacent contacts, while recordings of LFP were obtained from all other contacts (Figure 1). Preprocessing consisted in a median filtering to remove the artifact due to stimulation, abandpass filtering (0.5-300 Hz, Butterworth, 3rd order) and splitting of trials based on a digital trigger. Contacts showing spontaneous or evoked epileptic activity were removed from further analysis. Data analysis, consisting in time-frequency analysis (Wavelet, 3 cycles) and PLF, were performed using customized MATLAB scripts. RESULTS We observed that, while during wakefulness SPES triggers a widespread pattern of sustained causal effects (phase-locked activity), during NREM sleep the same initial activation induces a cortical downstate in its cortical targets – as reflected by a clear-cut suppression of high frequency (>20Hz) oscillations – that is followed by a break-off of PLF (~200 ms), in spite of restored levels of neuronal activity (Figure 2).These results were reproducible across contacts, significant across contacts at the single subject level (Wilcoxon ranksum test, p<0.05) and consistent at the population level (Wilcoxon ranksum test, p<0.05). Finally, significant correlations in each single subject showed (i) that, during NREM sleep, larger evoked slow waves corresponded to more pronounced suppressions of high frequencies and (ii) that earlier suppressions corresponded to an earlier dampening of PLF. CONCLUSIONS These results point to bistability as the underlying critical mechanism that prevents the emergence of complex interactions in human thalamocortical networks during NREM sleep. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions(Casali et al., 2013; Rosanova et al., 2012) where cortico-cortical communication and consciousness are impaired in spite of preserved neuronal activity

Palaeoenvironment, Settlement, and Land Use in the Late Neolithic&mdash;Bronze Age Site of Colombare di Negrar di Valpolicella (N Italy, On-Site)

Palynological and archaeobotanical analyses have been carried out as part of the interdisciplinary project of Colombare di Negrar, a prehistoric site in the Lessini Mountains (northern Italy). The palaeoenvironmental and economic reconstruction from the Late Neolithic to the beginning of the Early Bronze Age was based on 16 pollen samples and three samples of macroremains taken from two contiguous trenches. The landscape reconstruction shows the presence of natural clearings in the wood. Forest cover was characterised by oak wood, with Ulmus and Tilia. The intermediate morphology of size and exine of Tilia cordata/platyphyllos pollen may be regarded as the first palynological evidence of lime hybrids in palaeorecords. Hygrophilous trees and Vitis vinifera testify to the presence of riparian forests and moist soils. Among trees supplying fruits, in addition to the grapevine, hazelnut (Corylus avellana) and walnut (Juglans regia) were present. A mixed economy based on animal breeding and cultivation of cereals (Hordeum vulgare, Triticum monococcum, T. dicoccum, T. timopheevii) emerged from the data. The combined analysis of pollen and plant macroremains suggests that different activities were carried out simultaneously in Colombare and a relationship between natural resources and the socio-economic and cultural evolution of the territory

Behavioural and emotional profiles of children and adolescents with disorders of arousal.

Disorders of arousals are common sleep disorders characterized by complex motor behaviours that arise episodically out of slow-wave sleep. Psychological distress has long been associated with disorders of arousal, but this link remains controversial, especially in children and adolescents. The aim of this multi-centre study was to characterize behavioural and emotional problems in a sample of children/adolescents with disorders of arousal, and to explore their relationship with the severity of nocturnal episodes. The parents of 41 children/adolescents with a diagnosis of disorders of arousal (11.5 ± 3.3 years old, 61% males) and of a group of 41 age- and gender-matched control participants filled in the Child Behavior Checklist, along with the Sleep Disturbance Scale for Children and the Paris Arousal Disorders Severity Scale. Multilevel t-tests revealed significantly higher total scores and sub-scores of the Child Behavior Checklist for the patient group compared with the control group. Thirty-four percent of the patients obtained pathological total scores, and 12% of them borderline scores. The severity of emotional/behavioural problems in the patient group was positively correlated with the severity of the nocturnal episodes. Interestingly, children/adolescents with disorders of arousal also obtained higher excessive daytime sleepiness and insomnia symptoms sub-scores at the Sleep Disturbance Scale for Children. These results confirmed the hypothesis that behavioural/emotional problems are surprisingly common in children/adolescents with disorders of arousal. Further studies are warranted to investigate the causal relationship between pathological manifestations, subtler sleep abnormalities, and diurnal emotional/behavioural problems in children/adolescents with disorders of arousal

Psychobiological personality traits of children and adolescents with disorders of arousal

Disorders of arousal (DOA) are Non-Rem Sleep (NREM) parasomnias that emerge from incomplete arousal out of deep sleep and lead to a broad variety of emotional and motor behaviours. Increasing evidence supports the hypothesis that specific psychopathological traits contribute to the multifactorial origin of these phenomena. The aim of the current multicenter study was to compare the personality profile of children and adolescents with and without DOA using the Junior Temperament and Character Inventory (JTCI). We enrolled 36 patients with a diagnosis of DOA (mean age of 11 ± 3 years, 64% males), and 36 healthy age and gender matched control subjects (mean age of 11.2 ± 3.6, years, 67% males). Their parents completed the Paris Arousal Disorder Severity Scale (PADSS), the Sleep Disturbance Scale for Children (SDSC) and the JTCI. Patients with DOA reached significantly higher levels compared to their control group in total PADSS (p &lt;.0001) and in total SDSC (p &lt; 0.0001). They also displayed higher scores in novelty seeking (p = 0.005), harm avoidance (p = 0.01), self-transcendence (p = 0.006) JTCI subscales, and lower scores on the self- directedness subscale (p = 0.004). Our pediatric sample with DOA exhibited specific psychobiological personality traits compared to age and gender matched subjects without DOA. These results shed light on new possible etiopathogenetic mechanisms, as TCI traits have been linked to specific genetic variants and brain circuits, like the reward system. Prospective studies are required to assess the effect of targeted psychological/psychiatric treatment on DOA symptomatology