Publications of Paolo Cardone
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See detailDisorders of Consciousness
Cardone, Paolo ULiege; Szymkowicz, Emilie ULiege

Scientific conference (2021, November 05)

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See detailThe nature of consciousness in anesthesia
Montupil, Javier ULiege; Martial, Charlotte ULiege; Gosseries, Olivia ULiege et al

E-print/Working paper (2021)

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See detailDepth of sedation with dexmedetomidine modulates cortical excitability non-linearly
Cardone, Paolo ULiege; Bodart, Olivier; Kirsch, Murielle et al

E-print/Working paper (2021)

Background Cortical excitability changes across conscious states, being higher in unconsciousness compared to normal wakefulness. Anaesthesia offers controlled manipulation to investigate conscious ... [more ▼]

Background Cortical excitability changes across conscious states, being higher in unconsciousness compared to normal wakefulness. Anaesthesia offers controlled manipulation to investigate conscious processes and underlying brain dynamics. Among commonly used anaesthetic agents, dexmedetomidine (DEX) effects are not completely known. In this study, we investigated cortical excitability as a function of DEX sedation depth.Methods Transcranial magnetic stimulation coupled with electroencephalography was recorded in 20 healthy subjects undergoing DEX sedation in four conditions (baseline, light sedation, deep sedation, recovery). Frontal and parietal cortices were stimulated using a neuronavigation system. Cortical excitability was inferred by slope, amplitude, positive and negative peak latencies of the first component (0-30 ms) of the TMS-evoked potential. Four Generalized Linear Mixed Models (GLMM) were used to test the effect of condition and brain region over cortical excitability.Results Dexmedetomidine modulated amplitude (P\<0.001), slope (P=0.0001) and positive peak (P=0.042), while the targeted brain region affected amplitude (P\<0.001), slope (P\<0.001), and negative peak (P=0.001). The interaction between dexmedetomidine and region had an effect over amplitude (P=0.004), and slope (P=0.009) such that cortical excitability was higher during all conditions where DEX was present as compared to the baseline.Conclusions Cortical excitability changes non-linearly as a function of the depth of DEX sedation, with a paradoxical non dose-dependent increase. The effect is region-specific, being present in the frontal but not in the parietal region. Future research should extend the current results with other anaesthetics to better understand the link between cortical excitability and depth of sedation.Competing Interest StatementVB declares that he has received a research grant from Orion Pharma and honoraria for consultancy from Medtronic for the past 6 years. PC, OB, MK, JS, AV, CM, JS, SW, RS, SL, MM \& OG declare that they have no conflict of interest. [less ▲]

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See detailPsycho-social factors associated with mental resilience in the Corona lockdown.
Veer, Ilya M.; Riepenhausen, Antje; Zerban, Matthias et al

in Translational Psychiatry (2021), 11(1), 67

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social ... [more ▼]

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics. [less ▲]

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See detailSleep slow waves generation and medial prefrontal microstructure in healthy older individuals
Van Egroo, Maxime ULiege; Chylinski, Daphné ULiege; Narbutas, Justinas ULiege et al

Conference (2020, September 22)

Introduction. Aging is associated with alterations in sleep-wake regulation that have been associated with changes in brain structural integrity. In particular, the ability to generate slow oscillations ... [more ▼]

Introduction. Aging is associated with alterations in sleep-wake regulation that have been associated with changes in brain structural integrity. In particular, the ability to generate slow oscillations during non-rapid eye movement (NREM) sleep decreases as early as in the 5th decade of life, predominantly over frontal regions. While previous investigations have identified macrostructural brain correlates of the age-related decrement in sleep slow waves generation, their relationships with brain tissue microstructure remain poorly understood. Methods. We recorded sleep under electroencephalography in 99 healthy older individuals (mean age = 59.6 ± 5.2 years; 66 women), and we quantified slow waves generation using the overnight cumulated power density in the delta band (0.5-4 Hz) during NREM sleep over the frontal Fz derivation. All participants also underwent 3T magnetic resonance imaging (MRI) scans to investigate tissue myelin content based on quantitative magnetization transfer (MT) saturation mapping, as well as diffusion-based metrics derived from neurite orientation dispersion and density imaging (NODDI) model. A region of interest covering bilateral medial prefrontal cortices was used to extract regional grey matter values. Results. We first observed that MT signal in the medial prefrontal cortex was positively associated with higher neurite orientation dispersion (r = .30, p = .003) and density (r = .22, p = .03), supposedly reflecting preserved microstructural integrity. Crucially, overnight NREM sleep slow waves generation was significantly related to higher prefrontal MT signal (r = .22, p = .03), but not to NODDI metrics (dispersion: r = .02, p = .85; density: r = .09, p = .36). Generalized linear mixed models adjusted for demographics and total sleep time confirmed these relationships, although as a statistical trend for MT signal (F1,93 = 3.64, p = .06). Discussion. Our findings suggest a positive association between tissue myelin content within medial prefrontal grey matter and generation of slow waves during NREM sleep in aging. Preserved prefrontal myelination may facilitate neuronal synchronization through enhanced cortico-cortical connections, resulting in higher power density in the slower frequency band. Given the existing link between sleep characteristics and age-related cognitive decline, these results may have implications for successful cognitive aging. Support: FNRS, ULiège, ARC17/21-09, FEDER, WBI, Clerdent Foundation, Leon Frédéricq Foundation [less ▲]

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See detailIncreased cortical excitability and reduced brain response propagation during attentional lapses
Cardone, Paolo ULiege; Van Egroo, Maxime ULiege; Chylinski, Daphné ULiege et al

E-print/Working paper (2020)

Modern lifestyle curtails sleep and increases nighttime work and leisure activities. This has a deleterious impact on vigilance and attention, exacerbating chances of committing attentional lapses, with ... [more ▼]

Modern lifestyle curtails sleep and increases nighttime work and leisure activities. This has a deleterious impact on vigilance and attention, exacerbating chances of committing attentional lapses, with potential dramatic outcomes. A full characterization of the brain mechanisms associated with lapses is still lacking. Here, we investigated the brain signature of attentional lapses and assessed whether cortical excitability and brain response propagation were modified during lapses and whether these modifications changed with aging. We compared electroencephalogram (EEG) responses to transcranial magnetic stimulation (TMS) during lapse and no-lapse periods while performing a continuous attentional/vigilance task at night, after usual bedtime. Data were collected in healthy younger (N=12; 18-30 y) and older individuals (N=12; 50- 70 y) of both sexes. Amplitude and slope of the first component of the TMS-Evoked Potential (TEP) and Response Scattering (ReSc) were used to assess cortical excitability and brain response propagation, respectively. In line with our predictions, TEP during lapses was characterized by larger amplitude and slope. We further found that ReSc over the cortical surface was lower during lapses. Importantly, cortical excitability increase and response propagation decrease during lapse did not significantly differ between age groups. These results demonstrate that attentional lapses are associated with transient increase of excitability, and decrease in response propagation and effective connectivity. This pattern is similar to what is observed during sleep, suggesting that lapses reflect a sleep-like phenomenon. These findings could contribute to develop models aimed to predicting and preventing lapses in real life situations. [less ▲]

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See detailIncreased cortical excitability but stable effective connectivity index during attentional lapses.
Cardone, Paolo ULiege; Van Egroo, Maxime ULiege; Chylinski, Daphné ULiege et al

in Sleep (2020)

Modern lifestyle curtails sleep and increases night-time work and leisure activities. This has a deleterious impact on vigilance and attention, exacerbating chances of committing attentional lapses, with ... [more ▼]

Modern lifestyle curtails sleep and increases night-time work and leisure activities. This has a deleterious impact on vigilance and attention, exacerbating chances of committing attentional lapses, with potential dramatic outcomes. Here, we investigated the brain signature of attentional lapses and assessed whether cortical excitability and brain response propagation were modified during lapses and whether these modifications changed with aging. We compared electroencephalogram (EEG) responses to transcranial magnetic stimulation (TMS) during lapse and no-lapse periods while performing a continuous attentional/vigilance task at night, after usual bedtime. Data were collected in healthy younger (N=12; 18-30 y) and older individuals (N=12; 50-70 y) of both sexes. The amplitude and slope of the first component of the TMS-Evoked Potential (TEP) were larger during lapses. In contrast, TMS response scattering over the cortical surface, as well as EEG response complexity, did not significantly vary between lapse and no-lapse periods. Importantly, despite qualitative differences, age did not significantly affect any of the TMS-EEG measures. These results demonstrate that attentional lapses are associated with a transient increase of cortical excitability. This initial change is not associated with detectable changes in subsequent effective connectivity - as indexed by response propagation - and are not markedly different between younger and older adults. These findings could contribute to develop models aimed to predicting and preventing lapses in real life situations. [less ▲]

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See detailCortical excitability transiently increases during attentional lapses - HBP
Cardone, Paolo ULiege; Gaggioni, Giulia ULiege; Van Egroo, Maxime ULiege et al

Poster (2020)

Introduction/Motivation: Cortical excitability is modulated both by conscious states, sleep homeostasis and circadian rhythm, following a nonlinear dynamic across the day1,2. It is low during wakefulness ... [more ▼]

Introduction/Motivation: Cortical excitability is modulated both by conscious states, sleep homeostasis and circadian rhythm, following a nonlinear dynamic across the day1,2. It is low during wakefulness and REM sleep, where subjects experience phenomenological states, and high in conditions such as NREM sleep and Disorders of Consciousness (DoC), where there is inappropriate or absent processing of external stimuli3,4. Cortical excitability increases across the day, peaking at night after habitual sleep time where behavioral impairments such as attentional lapses are more common. Previous researches demonstrated that, at night, lack of vigilance is connected with lower frontoparietal effective connectivity5. However, no study has investigated whether there is a transient increase of cortical excitability during attentional lapses per se. This would be in line with the idea that the brain is less efficient to engage in the ongoing task, acting similarly to an “unconscious state”. To test this hypothesis, we compared cortical excitability during normal awakening and attentional lapses. Methods: Data included in this analysis were retrospectively selected among 3 different studies including repeated assessment of cortical excitability using Transcranial Magnetic Stimulation (TMS) of the superior frontal gyrus coupled to high-density Electroencephalography (hdEEG). This region was selected because it is sensitive to sleep pressure1 and has been implicated both for motor and cognitive tasks6. To increase the likelihood of attention lapses, data was selected among nighttime sessions. Attention lapses were detected based on the performance to a continuous Compensatory Tracking Task (CTT) completed simultaneously to TMS-EEG recording. Volunteers with at least 25 lapses were included to reach a total sample of 26 healthy individuals in 2 age groups (young, N= 13, 18-30 y; old, N = 13, 50-69 y). As previously published1, cortical excitability was inferred from amplitude and slope of the first component of the TMS-evoked EEG potential (TEP; 0–30 ms post-TMS, Figure 1). Latencies of the negative and positive peaks of this evoked potential were also extracted. Statistics were run on SAS 9.4 with a Generalized Linear Mixed Model (GLMM) (for more details, description of Table 1). Results and Discussion: Cortical excitability showed a strong change from no-lapse to attention lapse. In particular, there was a significant increase of amplitude, with a smaller latency of the negative component and a bigger latency of the positive one, leading to an increase in slope (for more details, Table 1). These results suggest that there is a transient increase of cortical excitability during vigilance lapses pointing to an alteration of the brain function that could be similar to what is observed when sleep need is high compared to well-rested condition, or during states of altered consciousness (e.g. sleep). These results could constitute an epiphenomenon of the likelihood of transitions of conscious states or rather a sheer marker of errors. Alternatively, they could reflect a local sleep phenomenon over the target area. Future researches should validate the extent of this description and fathom its molecular mechanisms. [less ▲]

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See detailMental resilience in the Corona lockdown: First empirical insights from Europe
Veer, Ilya; Riepenhausen, Antje; Zerban, Matthias et al

E-print/Working paper (2020)

Background: The current Corona pandemic is not only a threat to physical health. First data from China and Europe indicate that symptoms of anxiety and depression and perceptions of stress rise ... [more ▼]

Background: The current Corona pandemic is not only a threat to physical health. First data from China and Europe indicate that symptoms of anxiety and depression and perceptions of stress rise significantly as a consequence of the pandemic. There are also anecdotal reports of increased domestic violence, divorce, and suicide rates. Hence, the Corona crisis is also a mental health crisis. There is urgent need for knowledge about factors that can protect mental health (resilience factors) in this world-wide crisis, which is different in nature from other crises that have so far been studied in resilience research. Methods: Potential resilience factors, exposure to Corona-specific and general stressors, as well as internalizing symptoms were assessed online in N=5000 adult Europeans. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results: Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience(p<0.001). The resilience factor PAS also mediated the positive association between perceived social support (PSS) and resilience (p<0.001). In comparison with other resilience factors, positive appraisal specifically of the consequences of the Corona crisis was the single strongest factor. Conclusions: This research identifies modifiable protective factors that can be targeted by public mental health efforts. Future work will have to identify potential group differences in the effectiveness of these resilience factors, for improved prevention planning [less ▲]

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See detailCortical excitability transiently increases during attentional lapses
Cardone, Paolo ULiege; Gaggioni, Giulia ULiege; Van Egroo, Maxime ULiege et al

Poster (2019)

It is well established that conscious state modulates cortical excitability, such that wakefulness has lower excitability compared to sleep. However, the impact of conscious content on cortical ... [more ▼]

It is well established that conscious state modulates cortical excitability, such that wakefulness has lower excitability compared to sleep. However, the impact of conscious content on cortical excitability has mostly been neglected in previous research: one can indeed be conscious without being truly aware of an external stimulus, for instance, during vigilance lapses. Here, we hypothesized that, during a vigilance lapse, the brain reacts to stimuli in a similar way to when it is unconscious. To test this hypothesis, cortical excitability was investigated while performing a continuous vigilance task (Compensatory Tracking Task, CTT) after prolonged wakefulness beyond habitual sleep time. Cortical excitability changes between periods with and without vigilance lapses were inferred from amplitude, slope and peak latencies of the first component of the TMS-evoked EEG potential (TEP; 0–30 ms post-TMS). During lapses vs. no-lapses, we found a significant amplitude increases of TEP and a concomitant significant increase in the latency of TEP positive peak. These results suggest that there is a transient change of cortical excitability during vigilance lapses, pointing to an alteration of the brain similar to the one observed during unconscious states, such as during sleep. Future research should investigate how these changes interfere with sensory processing and cognition and their molecular mechanisms. These findings provide new insight into the brain mechanisms underlying changes in consciousness content and in transient alteration of attention. [less ▲]

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