BREAKDOWN OF CAUSALITY AND CORTICAL DOWNSTATE WITHIN THE SLEEPING BRAIN

Theoretically, consciousness depends on the brain\u2019s ability to engage in complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). In a recent series of experiments the electroencephalographic response to a direct cortical stimulation in humans was recorded during wakefulness and non-rapid eyes movement sleep (NREM) by means of a combination of transcranial magnetic stimulation (TMS) and high-density electroencephalogram (hd-EEG). TMS/hd-EEG measurements showed that, while during wakefulness the brain is able to sustain long-range specific patterns of activation, during NREM sleep, when consciousness fades, this ability is lost: the thalamocortical system, despite being active and reactive, either breaks down in causally independent modules (producing a local slow wave), or it bursts into an explosive and non-specific response (producing a global EEG slow wave). We hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by TMS during deep sleep are due to bistability between periods of hyperpolarized down-state in cortical neurons, and periods of activation (up-state). In this condition, the inescapable occurrence of a silent, down-state after an initial activation could impair the ability of thalamocortical circuits to sustain long-range, differentiated patterns of activation, a theoretical requisite for consciousness. According to animal experiments the extracellular signature of the downstate is a transient suppression of high frequency (20Hz) oscillations \u2013 that is followed by a loss of both PLF and PLV, in spite of restored levels of neuronal activity. These results point to bistability as the underlying critical mechanism that prevents the emergence of complex interactions in human thalamocortical networks when consciousness is lost during NREM sleep. This finding is particularly relevant because a similar mechanism may play a role in other conditions where loss of consciousness is paralleled by the appearance of spontaneous (or TMS evoked) slow waves such as some kind of anesthesia and in brain injured subjects

Sleep-related epileptic behaviors and non-REM-related parasomnias: Insights from stereo-EEG

During the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique "in vivo" neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed

Global and local complexity of intracranial EEG decreases during NREM sleep

Key to understanding the neuronal basis of consciousness is the characterisation of the neural signatures of changes in level of consciousness during sleep. Here we analysed three measures of dynamical complexity on spontaneous depth electrode recordings from 10 epilepsy patients during wakeful rest and different stages of sleep: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability over time of the set of channels active above a threshold; (iii) synchrony coalition entropy, which measures the variability over time of the set of synchronous channels. When computed across sets of channels that are broadly distributed across multiple brain regions, all 3 measures decreased substantially in all participants during early-night non-rapid eye movement (NREM) sleep. This decrease was partially reversed during late-night NREM sleep, while the measures scored similar to wakeful rest during rapid eye movement (REM) sleep. This global pattern was in almost all cases mirrored at the local level by groups of channels located in a single region. In testing for differences between regions, we found elevated signal complexity in the frontal lobe. These differences could not be attributed solely to changes in spectral power between conditions. Our results provide further evidence that the level of consciousness correlates with neural dynamical complexity

Focal lesions induce large-scale percolation of sleep-like intracerebral activity in awake humans.

Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries

Stratification of unresponsive patients by an independently validated index of brain complexity.

OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior

Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients

peer reviewedUnresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness. © 2018, The Author(s)

Sleep as a model to understand neuroplasticity and recovery after stroke : observational, perturbational and interventional approaches

Our own experiences with disturbances to sleep demonstrate its crucial role in the recovery of cognitive functions. This importance is likely enhanced in the recovery from stroke; both in terms of its physiology and cognitive abilities. Decades of experimental research have highlighted which aspects and mechanisms of sleep are likely to underlie these forms of recovery. Conversely, damage to certain areas of the brain, as well as the indirect effects of stroke, may disrupt sleep. However, only limited research has been conducted which seeks to directly explore this bidirectional link between both the macro and micro-architecture of sleep and stroke. Here we describe a series of semi-independent approaches that aim to establish this link through observational, perturbational, and interventional experiments. Our primary aim is to describe the methodology for future clinical and translational research needed to delineate competing accounts of the current data. At the observational level we suggest the use of high-density EEG recording, combined analysis of macro and micro-architecture of sleep, detailed analysis of the stroke lesion, and sensitive measures of functional recovery. The perturbational approach attempts to find the causal links between sleep and stroke. We promote the use of transcranial magnetic stimulation combined with EEG to examine the cortical dynamics of the peri-infarct stroke area. Translational research should take this a step further using optogenetic techniques targeting more specific cell populations. The interventional approach focuses on how the same clinical and translational perturbational techniques can be adapted to influence long-term recovery of function

Stratification of unresponsive patients by an independently validated index of brain complexity

Objective: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness\u2014the Perturbational Complexity Index (PCI)\u2014in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). Methods: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). Results: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. Interpretation: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718\u2013729

Ethnobotanical remarks on Central and Southern Italy

<p>Abstract</p> <p>Background</p> <p>The present paper is a brief survey on the ethnobotanical works published by the Authors since 1981, concerning the research carried out in some southern and central Italian regions. Before Roman domination these territories were first inhabited by local people, while the southern areas were colonized by the Greeks. These different cultural contributions left certain traces, both in the toponyms and in the vernacular names of the plants and, more generally, in the culture as a whole.</p> <p>Methods</p> <p>Field data were collected through open interviews, mainly of farmers, shepherds and elderly people, born or living in these areas for a long time. Voucher specimens of collected plants are preserved in the respective herbaria of the Authors and in the herbarium of "Roma Tre" University. Important contributions have been made by several students native to the areas under consideration. A comparative analysis with local specific ethnobotanical literature was carried out.</p> <p>Results</p> <p>The paper reports several examples concerning human and veterinary popular medicine and in addition some anti-parasitic, nutraceutic, dye and miscellaneous uses are also described. Moreover vernacular names and toponyms are cited. Eight regions of central and southern Italy (particularly Latium, Abruzzo, Marche and Basilicata) were investigated and the data obtained are presented in 32 papers. Most of the species of ethnobotanical interest have been listed in Latium (368 species), Marche (274) and Abruzzo (203). The paper also highlights particularly interesting aspects or uses not previously described in the specific ethnobotanical literature.</p> <p>Conclusion</p> <p>Phyto-therapy in central and southern Italy is nowadays practised by a few elderly people who resort to medicinal plants only for mild complaints (on the contrary food uses are still commonly practised). Nowadays therapeutic uses, unlike in the past, are less closely or not at all linked to ritual aspects. Several plants deserve to be taken into consideration not only from the anthropological or cultural point of view, but also for further phyto-chemical investigation. Our studies, as well as those of other authors, try to provide an original picture of the local ethno-biodiversity.</p

The neural correlates of dreaming.

Consciousness never fades during waking. However, when awakened from sleep, we sometimes recall dreams and sometimes recall no experiences. Traditionally, dreaming has been identified with rapid eye-movement (REM) sleep, characterized by wake-like, globally 'activated', high-frequency electroencephalographic activity. However, dreaming also occurs in non-REM (NREM) sleep, characterized by prominent low-frequency activity. This challenges our understanding of the neural correlates of conscious experiences in sleep. Using high-density electroencephalography, we contrasted the presence and absence of dreaming in NREM and REM sleep. In both NREM and REM sleep, reports of dream experience were associated with local decreases in low-frequency activity in posterior cortical regions. High-frequency activity in these regions correlated with specific dream contents. Monitoring this posterior 'hot zone' in real time predicted whether an individual reported dreaming or the absence of dream experiences during NREM sleep, suggesting that it may constitute a core correlate of conscious experiences in sleep