Ruolo dell'asse tiroideo nella modulazione di funzioni cognitive ed emotive: studio delle modificazioni neuropsicologiche, comportamentali e autonomiche in soggetti con ipotiroidismo subclinico

Lo scopo di questo lavoro di tesi è stato quello di valutare la modulazione svolta dall’asse tiroideo sull’assetto emotivo, sulle funzioni cognitive e sull’attività autonomica e comportamentale nell’uomo. A questo riguardo è stato utilizzato come modello sperimentale l’ipotiroidismo subclinico (SHYPO), una condizione preclinica caratterizzata esclusivamente da alterazioni del Thyroid Stimulating Hormone (TSH) e da normali valori plasmatici degli ormoni tiroidei. Per ogni soggetto studiato (SHYPO e eutiroidei) sono stati valutati, mediante scale psicometriche, l’assetto emotivo e le funzioni cognitive e, mediante EEG, ECG, respirogramma e resistenza cutanea, l’attività elettrica cerebrale e l’uscita neurovegetativa in condizioni di minima stimolazione sensoriale. Inoltre, al fine di evocare in modo riproducibile e maggiormente controllato una serie di risposte centrali e periferiche legate all’aumento del carico cognitivo e dello stress emotivo, i soggetti sono stati sottoposti a stimolazioni visive dinamiche (video clip) distinte per il contenuto cognitivo ed emotivo. Lo studio del ruolo dell'asse tiroideo nella modulazione di funzioni cognitive ed emotive è stato affrontato secondo un approccio integrato che ha previsto l’estrazione di un’ampia serie di misure dai segnali fisiologici acquisiti. A partire da questa caratterizzazione multiparametrica di ciascun soggetto, sono state portate a termine una serie di valutazioni volte ad evidenziare non solo le misure che sono significativamente associabili alla condizione SHYPO, ma anche le relazioni esistenti tra le misure effettuate e l’assetto ormonale individuale. Questa alterazione ormonale, sia in condizioni basali che in condizione di stimolazione, ha indotto pattern cognitivi, emotivi, neurovegetativi e comportamentali che distinguono i soggetti SHYPO dai controlli eutiroidei. I soggetti SHYPO hanno, infatti, presentato alcune performance cognitive migliori associate ad un incremento di un particolare tratto d’ansia non di natura clinica. Questo aspetto si associa ad una peculiare risposta autonomica e comportamentale in condizioni di stimolazione emotiva, con incremento delle frequenze rapide beta-gamma ed una loro maggiore frontalizzazione e lateralizzazione destra. I soggetti SHYPO esaminati, caratterizzati da giovane età, recente insorgenza di SHYPO e livello di TSH borderline, possano essere collocati sulla fase ascendente di un’ipotetica curva, in cui il peculiare assetto ormonale tende a migliorare alcune performance cognitive grazie agli effetti benefici del livello di eustress: ciò ricorda la curva di Yerkes-Dodson, che descrive la relazione tra livelli d’ansia e performace cognitiva. Da un punto di vista prettamente euristico si può ipotizzare che il perdurare di SHYPO, associato o meno a ulteriori incrementi dei livelli di TSH, possa condurre verso il passaggio nella fase discendente della curva, caratterizzata da quelle alterazioni emotive, cardiovascolari e comportamentali che si ritrovano in alcuni studi della letteratura SHYPO e nell’ipotiroidismo clinico. Dal punto di vista metodologico, questo studio, infine, si pone come ricerca pilota in cui un approccio psicofisiologico multiparametrico (stimolazione mediante strumenti audiovisivi, registrazione integrata di variabili neuropsicologiche, autonomiche e comportamentali) possa essere utilizzato in ambito clinico. L’importanza di quest’integrazione tra ricerca di base e clinica diventa rilevante nella presente condizione sperimentale per la quale ancora oggi in letteratura si discute se SHYPO sia da considerarsi una condizione patologica, e quindi da trattare, oppure uno stato con sintomatologia sottosoglia il cui trattamento si rende necessario dopo l’instaurarsi di una vera e propria ipofunzione tiroidea. Alla stessa stregua, in campo clinico (medico/psicologico) anche molte altre condizioni borderline, prive di manifestazioni cliniche definite, potrebbero, infine, beneficiare di un simile approccio integrato che contribuirebbe all’identificazione di indici predittivi di rischio di evoluzione patologica conclamata

Fractal Complexity in Spontaneous EEG Metastable-State Transitions: New Vistas on Integrated Neural Dynamics

Resting-state EEG signals undergo rapid transition processes (RTPs) that glue otherwise stationary epochs. We study the fractal properties of RTPs in space and time, supporting the hypothesis that the brain works at a critical state. We discuss how the global intermittent dynamics of collective excitations is linked to mentation, namely non-constrained non-task-oriented mental activity

Enhancing Qualities of Consciousness during Online Learning via Multisensory Interactions

Online-learning is a feasible alternative to in-person attendance during COVID-19 pan- demic. In this period, information technologies have allowed sharing experiences, but have also highlighted some limitations compared to traditional learning. Learning is strongly supported by some qualities of consciousness such as flow (intended as the optimal state of absorption and engagement activity) and sense of presence (feeling of exerting control, interacting with and get- ting immersed into real/virtual environments), behavioral, emotional, and cognitive engagement, together with the need for social interaction. During online learning, feelings of disconnection, social isolation, distractions, boredom, and lack of control exert a detrimental effect on the ability to reach the state of flow, the feeling of presence, the feeling of social involvement. Since online environments could prevent the rising of these learning–supporting variables, this article aims at describing the role of flow, presence, engagement, and social interactions during online sessions and at characterizing multisensory stimulations as a driver to cope with these issues. We argue that the use of augmented, mixed, or virtual reality can support the above-mentioned domains, and thus counteract the detrimental effects of physical distance. Such support could be further increased by enhancing multisensory stimulation modalities within augmented and virtual environme

Moving Auto-Correlation Window Approach for Heart Rate Estimation in Ballistocardiography Extracted by Mattress-Integrated Accelerometers

Continuous heart monitoring is essential for early detection and diagnosis of cardiovascular diseases, which are key factors for the evaluation of health status in the general population. Therefore, in the future, it will be increasingly important to develop unobtrusive and transparent cardiac monitoring technologies for the population. The possible approaches are the development of wearable technologies or the integration of sensors in daily-life objects. We developed a smart bed for monitoring cardiorespiratory functions during the night or in the case of continuous monitoring of bedridden patients. The mattress includes three accelerometers for the estimation of the ballistocardiogram (BCG). BCG signal is generated due to the vibrational activity of the body in response to the cardiac ejection of blood. BCG is a promising technique but is usually replaced by electrocardiogram due to the difficulty involved in detecting and processing the BCG signals. In this work, we describe a new algorithm for heart parameter extraction from the BCG signal, based on a moving auto-correlation sliding-window. We tested our method on a group of volunteers with the simultaneous co-registration of electrocardiogram (ECG) using a single-lead configuration. Comparisons with ECG reference signals indicated that the algorithm performed satisfactorily. The results presented demonstrate that valuable cardiac information can be obtained from the BCG signal extracted by low cost sensors integrated in the mattress. Thus, a continuous unobtrusive heart-monitoring through a smart bed is now feasible

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

Functional Structure of Spontaneous Sleep Slow Oscillation Activity in Humans

Background During non-rapid eye movement (NREM) sleep synchronous neural oscillations between neural silence (down state) and neural activity (up state) occur. Sleep Slow Oscillations (SSOs) events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. Methodology/Principal Findings We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. Conclusions/Significance This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices

Subjective Fear in Virtual Reality: A Linear Mixed-Effects Analysis of Skin Conductance

he investigation of the physiological and pathological processes involved in fear perception is complicated due to the difficulties in reliably eliciting and measuring the complex construct of fear. This study proposes a novel approach to induce and measure subjective fear and its physiological correlates combining virtual reality (VR) with a mixed-effects model based on skin conductance (SC). Specifically, we developed a new VR scenario applying specific guidelines derived from horror movies and video games. Such a VR environment was used to induce fear in eighteen volunteers in an experimental protocol, including two relaxation scenarios and a neutral virtual environment. The SC signal was acquired throughout the experiment, and after each virtual scenario, the emotional state and fear perception level were assessed using psychometric scales. We statistically evaluated the greatest sympathetic activation induced by the fearful scenario compared to the others, showing significant results for most SC-derived features. Finally, we developed a rigorous mixed-effects model to explain the perceived fear as a function of the SC features. Model-fitting results showed a significant relationship between the fear perception scores and a combination of features extracted from both fast- and slow-varying SC components, proposing a novel solution for a more objective fear assessme

The fear of spiders: perceptual features assessed in augmented reality

BackgroundPersons with specific phobias typically generalize the dangerousness of the phobic animal to all members of its species, possibly as a result of malfunctioning brain circuitry normally providing quick and dirty identification of evolutionary-relevant stimuli. An objective assessment of which perceptual features make an animal more or less scary to phobic and non-phobic people would help overcome the limitations of the few studies available so far, based on self-reports.ObjectiveTo achieve this aim, we built an augmented reality setting where volunteers with different levels of fear of spiders were asked to make holographic spiders that look either dangerous or harmless. To reach this goal, a computerized interface allowed participants to modify the spider’s perceptual features (hairiness, body/leg size, and locomotion) in real time.ResultsOn average, the dangerous spiders were made hairy, thick, and moving according to spider-like locomotion; coherently, the harmless spiders were made hairless, slim, and moving according to a butterfly-like locomotion. However, these averaged preferences could not fully describe the complex relationship between perceptual preferences with each other and with arachnophobia symptoms. An example of a key finding revealed by cluster analysis is the similarity in perceptual preferences among participants with little or no fear of spiders, whereas participants with more arachnophobia symptoms expressed more varying preferences.ConclusionPerceptual preferences toward the spider’s features were behaviorally assessed through an observational study, objectively confirming a generalization effect characterizing spider-fearful participants. These results advance our knowledge of phobic preferences and could be used to improve the acceptability of exposure therapies

Systematic Review of Studies on Subliminal Exposure to Phobic Stimuli : Integrating Therapeutic Models for Specific Phobias

We systematically review 26 papers investigating subjective, behavioral, and psychophysiological correlates of subliminal exposure to phobic stimuli in phobic patients. Stimulations were found to elicit: (1) cardiac defense responses, (2) specific brain activations of both subcortical (e.g., amygdala) and cortical structures, (3) skin conductance reactions, only when stimuli lasted >20 ms and were administered with intertrial interval >20 s. While not inducing the distress caused by current (supraliminal) exposure therapies, exposure to subliminal phobic stimuli still results in successful extinction of both psychophysiological and behavioral correlates: however, it hardly improves subjective fear. We integrate those results with recent bifactorial models of emotional regulation, proposing a new form of exposure therapy whose effectiveness and acceptability should be maximized by a preliminary subliminal stimulation. Systematic Review Registration: identifier [CRD42021129234]

Mind-body relationships in elite apnea divers during breath holding: a study of autonomic responses to acute hypoxemia

The mental control of ventilation with all associated phenomena, from relaxation to modulation of emotions, from cardiovascular to metabolic adaptations, constitutes a psychophysiological condition characterizing voluntary breath-holding (BH). BH induces several autonomic responses, involving both autonomic cardiovascular and cutaneous pathways, whose characterization is the main aim of this study. Electrocardiogram and skin conductance (SC) recordings were collected from 14 elite divers during three conditions: free breathing (FB), normoxic phase of BH (NPBH) and hypoxic phase of BH (HPBH). Thus, we compared a set of features describing signal dynamics between the three experimental conditions: from heart rate variability (HRV) features (in time and frequency-domains and by using nonlinear methods) to rate and shape of spontaneous SC responses (SCRs). The main result of the study rises by applying a Factor Analysis to the subset of features significantly changed in the two BH phases. Indeed, the Factor Analysis allowed to uncover the structure of latent factors which modeled the autonomic response: a factor describing the autonomic balance (AB), one the information increase rate (IIR), and a latter the central nervous system driver (CNSD). The BH did not disrupt the FB factorial structure, and only few features moved among factors. Factor Analysis indicates that during BH (1) only the SC described the emotional output, (2) the sympathetic tone on heart did not change, (3) the dynamics of interbeats intervals showed an increase of long-range correlation that anticipates the HPBH, followed by a drop to a random behavior. In conclusion, data show that the autonomic control on heart rate and SC are differentially modulated during BH, which could be related to a more pronounced effect on emotional control induced by the mental training to BH