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Psicofisiologia dell'elaborazione emozionale e delle sue alterazioni: approcci innovativi e traslazionali
No full textLe emozioni sono una componente fondamentale dell’esperienza umana, e sono alterate in moltissimi disturbi psichiatrici. Nonostante ci sia ampio consenso riguardo al fatto che la disregolazione emotiva sia un fattore chiave in numerose psicopatologie, la ricerca sistematica su questo costrutto è stata piuttosto limitata. In questa tesi illustreremo l’approccio altamente interdisciplinare che abbiamo applicato allo studio dell’elaborazione emozionale con lo scopo di identificare possibili biomarker delle sue alterazioni, presenti anche a livello di tratto, che possano essere utilizzati per sviluppare protocolli di prevenzione specifici e rilevanti. Come prima cosa, abbiamo studiato la disregolazione emotiva per identificarne un completo profilo psicofisiologico e per delineare i diversi pattern neurali ad essa associati. Alti tratti di disregolazione emotiva si sono mostrati associati ad alterazioni della banda EEG Gamma in risposta a stimoli emozionali altamente ecologici, specie negativi. Un altro aspetto innovativo riguarda lo studio della connettività funzionale in resting state tramite localizzazione delle sorgenti derivata dall’EEG. Abbiamo riscontrato un’aumentata connettività del Ventral Attention Network, normalmente coinvolto nell’orientamento automatico dell’attenzione verso stimoli emotivamente salienti, nel gruppo ad alta disregolazione. Ciò suggerisce un’influenza pervasiva delle emozioni sulle dinamiche neurali dei network cerebrali in questo campione.
Abbiamo poi analizzato la psicopatia primaria, caratterizzata da alti livelli di distacco emotivo e da elaborazione deficitaria della paura. Tramite un paradigma di modulazione del riflesso di startle, un noto indice di reattività difensiva, combinato con la presentazione di materiale multisensoriale altamente ecologico, abbiamo mostrato come alti livelli di psicopatia primaria siano associati ad ampiezze del riflesso di startle inferiori rispetto a quanto rilevato nei controlli durante la presentazione di filmati che inducevano paura, in linea con la letteratura.
Considerando l’emozione come composta da fattori neurobiologici, input esterni ed interni, e da un output comportamentale, essa si può efficacemente suddividere in componenti singole sondabili anche in organismi semplici come Drosophila melanogaster, che possono essere studiati combinando strumenti neurofisiologici con paradigmi di ricerca psicofisiologici. Ci siamo quindi concentrati di nuovo sul riflesso di startle per vedere se, anche in questi organismi, potesse essere replicata la sua modulazione a seconda del contesto motivazionale (appetitivo, neutro o aversivo), un aspetto che per nostra conoscenza non era ancora stato verificato. Abbiamo adottato una metodologia elettrofisiologica per stimolare la via di trasmissione del giant fiber degli esemplari durante la loro esposizione a stimoli appetitivi, neutri e aversivi, e abbiamo registrato la risposta elettrica evocata. I risultati ottenuti indicano un coinvolgimento dell’arousal oltre che della valenza nella modulazione di questo indice in Drosophila. Questi risultati forniscono importanti contributi allo studio del riflesso di startle, che potrebbe essere ulteriormente studiato in linee di Drosophila specifiche e selezionate per rappresentare modelli genetici di alcuni disturbi psicologici come ansia o depressione.
Per concludere, questo lavoro rappresenta un contributo innovativo nel comprendere in modo più completo le alterazioni dell’elaborazione emozionale, e i risultati qui illustrati potrebbero essere utilizzati per creare interventi terapeutici ad hoc e per sviluppare strategie preventive che mirino all’insegnamento di strategie adattive di regolazione emozionale. Inoltre, la ricerca di base sugli animali, applicata in modo innovativo, ha fornito un ulteriore livello di analisi relativa all’elaborazione emozionale.Emotions are a core component of the human experience, and alterations in its processing are to be found in a multitude of psychiatric disorders. While there is wide consensus of the fact that emotion dysregulation is a core transdiagnostic factor for psychopathology, systematic research on this construct has been limited. In this thesis, we will illustrate the highly multilevel and interdisciplinary approach that we applied to the study of emotional processing with the aim to pinpoint possible biomarkers of its alterations, even at trait levels, which may be further used to develop specific and relevant preventive protocols. As a first step, we studied trait emotion dysregulation to comprehensively profile this condition from a psychophysiological perspective and to outline the different neural patterns associated with it. We showed that high emotion dysregulation levels, even if still not clinically relevant, are associated with alterations in EEG Gamma band activity in response to emotional ecological stimuli, especially negative ones. Another innovative step consisted in the study of resting state functional connectivity by means of EEG-derived source localization. We found an increased engagement of the Ventral Attention Network, a resting state network that is involved in the automatic orienting of attention towards emotionally salient stimuli, in the high dysregulation group compared with the low dysregulation group, suggesting a pervasive influence of emotion on brain network dynamics in this sample.
We then focused on primary psychopathy, which is mainly characterized by emotional detachment and impairments in the processing of fear-inducing stimuli. We relied on a startle reflex modulation paradigm, a well-known index of defensive reactivity, coupled with the presentation of highly ecological, multisensory material. Our results showed that high primary psychopathy was associated with lower startle amplitudes during the presentation of Fear clips compared with controls, in accordance with previous literature.
Considering that emotion is composed by neurobiological factors, external and internal inputs, and a behavioral output, it can be usefully broken into building blocks that can be readily investigated with basic research conducted on animals. Even simple organisms, such as Drosophila melanogaster, can indeed be studied by combining powerful neurophysiological tools and designs with psychophysiological research paradigms. We therefore implemented a startle reflex paradigm in D. melanogaster flies to assess whether the modulation of this index according to the motivational context (i.e., appetitive, neutral, or negative) could be replicated in these organisms, an aspect which to the extent of our knowledge had never been investigated before. We adopted a classical electrophysiological paradigm in which we electrically stimulated the giant fiber pathway while exposing the animals to appetitive, neutral, and aversive stimuli and recording the electrical evoked response. Our results point towards the involvement of arousal as well as valence in the modulation of this index in flies. These findings provide innovative insights in the study of the startle reflex, which could be implemented and further explored in select populations of D. melanogaster modeling certain psychological disorders, such as for example depression or anxiety.
In conclusion, this work represents an innovative contribution for a comprehensive understanding of alterations in emotional processing, and the findings here illustrated could be used to tailor treatment interventions and develop preventive strategies aiming to teach adaptive emotional management. Moreover, basic research on animals, applied in an innovative way, provided a novel level of analysis concerning emotional processing
Cardiac responses to emotional film clips in males with high vs low trait primary psychopathy
No full textVentral Attention Network Correlates With High Traits of Emotion Dysregulation in Community Women — A Resting-State EEG Study
Full text linkIn recent years, many studies have focused on resting-state brain activity, and especially on functional connectivity (FC), an approach that typically describes the statistical interdependence of activity in distant brain regions through specific networks. Our aim was to study the neurophysiological correlates of emotion dysregulation. Therefore, we expected that both the Default Mode Network (DMN), and the Ventral Attention Network (VAN) would have been involved. Indeed, the latter plays a role in the automatic orienting of attention towards biologically salient stimuli and includes key regions for emotion control and modulation. Starting from a community sample of 422 female students, we selected 25 women with high traits of emotion dysregulation (HD group) and 25 with low traits (LD group). They underwent a 64-channel EEG recording during a five-minute resting state with eyes open. Seed-based FC was computed on the EEG Alpha band (8–13 Hz) as a control band, and on EEG Gamma power (30–50 Hz) as the relevant measure. The power within each network and inter-network connectivity (Inter-NC) was also calculated. Analysis of the EEG Gamma band revealed, in the HD group, higher levels of Inter-NC between the VAN and all other resting-state networks as compared with the LD group, while no differences emerged in the Alpha band. Concerning correlations, Alpha power in the VAN was negatively correlated in the HD group with affective lability (ALS-18 questionnaire), both for total score (ρ = –0.52, p(FDR) < 0.01) and the Depression/Elation subscale) ρ = −0.45, p(FDR) < 0.05). Consistent with this, in the Gamma band, a positive correlation was found between VAN spectral power and the Depression/Elation subscale of ALS-18, again in the HD group only (ρ = 0.47, p(FDR) < 0.05). In conclusion, both resting state FC and network power in the VAN were found to be related to high emotion dysregulation, even in our non-clinical sample with high traits. Emotion dysregulation was characterized, in the EEG gamma band, by a VAN strongly connected to all other networks, a result that points, in women prone to emotion dysregulation, to a strong automatic orienting of attention towards their internal state, bodily sensations, and emotionally intense related thoughts
Case Report: High doses of Zolpidem and QT interval lengthening: Is there a relationship? A case series
Full text linkZolpidem is indicated in cases of severe insomnia in adults and, as for BDZs, its assumption should be limited to short periods under close medical supervision. Since several drugs cause corrected QT interval (QTc) elongation, the authors investigated whether high daily doses of Zolpidem could cause QTc elongation. The study was conducted in the Addiction Medicine Unit of the G.B. Rossi University Hospital in Verona. The data were collected from hospitalizations carried out between January 2015 and February 2020 and refer to a total of 74 patients, 38 males and 36 females, who were treated for detoxification from high doses of Zolpidem with the “Verona Detox Approach With Flumazenil.” One patient out of 74 had QTc elongation (479 ms). The patient was male and took a daily dose of 50 mg of Zolpidem; he did not take concomitant therapies that could cause QTc lengthening. He had no electrolyte alterations, no contemporary or previous intake of barbiturates, heroin, cocaine, THC, alcohol, NMDA or nicotine which could cause an elongation of the QTc interval. The present study highlights the low risk of QTc elongation due to high dosages of Zolpidem; however, if, on one hand, we can affirm that Zolpidem is a safe drug, on the other, the widespread use of high dosages of this drug for prolonged periods of time is problematic and worrying
Letter to editor, a comment to: Prevalence and concentrations of sedative-hypnotic drugs in blood of drivers involved in road traffic crashes in the Padova region of Italy − Not so easy to interpret
No full text[no abstract available
EEG Frontal Asymmetry in Dysthymia, Major Depressive Disorder and Euthymic Bipolar Disorder
Full text linkIn the last few decades, the incidence of mood disorders skyrocketed worldwide and has brought an increasing human and economic burden. Depending on the main symptoms and their evolution across time, they can be classified in several clinical subgroups. A few psychobiological indices have been extensively investigated as promising markers of mood disorders. Among these, frontal asymmetry measured at rest with quantitative EEG has represented the main available marker in recent years. Only a few studies so far attempted to distinguish the features and differences among diagnostic types of mood disorders by using this index. The present study measured frontal EEG asymmetry during a 5-min resting state in three samples of patients with bipolar disorder in a Euthymic phase (EBD, n = 17), major depressive disorder (MDD, n = 25) and persistent depressive disorder (PDD, n = 21), once termed dysthymia. We aimed to test the hypothesis that MDD and PDD lack the typical leftward asymmetry exhibited by normal as well as EBD patients, and that PDD shows greater clinical and neurophysiological impairments than MDD. Clinical scales revealed no symptoms in EBD, and significant larger anxiety and depression scores in PDD than in MDD patients. Relative beta (i.e., beta/alpha ratio) EEG asymmetry was measured from lateral frontal sites and results revealed the typical greater left than right frontal beta activity in EBD, as well as a lack of asymmetry in both MDD and PDD. The last two groups also had lower bilateral frontal beta activity in comparison with the EBD group. Results concerning group differences were interpreted by taking into account both the clinical and the neurophysiological domains
Alter Game: A Study Protocol on a Virtual “Serious Game” for Relapse Prevention in Patients With Gambling Disorder
Full text linkCognitive behavioral therapy (CBT) is the most successful protocol in gambling disorder (GD) treatment. However, it presents some weaknesses, especially concerning relapse prevention (RP). RP is one of the most important therapeutic steps, aiming at managing cravings and to avoid future relapse increasing perceived self-efficacy. Encouraging results come from the blending of psychotherapy and virtual reality (VR), containing gambling cues. The goal of Alter Game (approved by the Ethical Commission, Prot. No. 69346) is verifying the efficacy of an innovative psychological treatment for GD based on the integration of traditional CBT therapy and an immersive VR cue exposure therapy using a serious virtual game, which is a game designed for purposes other than entertainment. RP in virtual cue-exposure therapy allows pathological gamblers to manage the urge to gamble and to avoid relapse by becoming aware of which internal and external triggers are related to craving. We hypothesize that the integrated intervention will be more effective than simple CBT with regard to self-efficacy, craving, and gambling-related distortions. Four virtual ecological environments were developed, and a virtual app, Exludo, interfaced with a computerized multiparametric acquisition system for biofeedback, was created. A sample of about 60 patients aged between 18 and 65 with GD referring to the Addiction Medicine Unit of Verona (Rossi Hospital) will be recruited. Patients will be randomly assigned to the CBT group (16 CBT sessions) or the CBT + VR group (8 CBT sessions + 8 VR cue-exposure therapy sessions). The MCMI-III, the BIS-11, and the SOGS will be used to evaluate inclusion and exclusion criteria, while the Gambling Related Cognitions Scale and the Multidimensional Gambling Self-Efficacy Scale will be used to verify changes as a function of the treatment. Craving will be evaluated through VAS, and psychophysiological variables will be assessed through biofeedback. A pre-test/post-test experimental design with a 1-month follow-up will be conducted. This study will examine an innovative psychotherapeutic protocol for GD treatment, and it will help in identifying new virtual tools to increase the efficacy of traditional therapeutic approaches that could also be applied to treat other addictions
Polysubstance Use Patterns Among High Dose Benzodiazepine Users: A Latent Class Analysis and Differences Between Male and Female Use
Full text linkBenzodiazepines (BZDs) represent one of the most widely used groups of pharmaceuticals, but if used for long periods of time they are associated with dependence and an increased risk of harmful effects. High-dose (HD) BZD dependence is a specific substance use disorder associated with a poor quality of life. It is especially important to pinpoint differences in HD BZD addict subgroups in order to tailor treatment to the individual's specific needs, also considering possible comorbidities with other substance use disorders. We conducted a study to evaluate HD BZD dependence (converted doses to diazepam equivalents, mg) in an Italian sample of 1,354 participants. We also investigated if and to which extent participants co-used other substances (alcohol, tobacco, cannabis/cannabinoids, cocaine, and heroin). We then performed latent class analysis (LCA) to identify the use patterns of these substances, finding three classes: participants in Class 1 (4.3% of the sample) had the highest probability of also using cocaine and alcohol (Polysubstance BZD users); Class 2 comprised subjects with the highest probability of being former heroin, cocaine, THC, and alcohol users (Former polysubstance BZD users); Class 3 represented mono-dependence BZD users (78.5% of the sample) and was the most prevalent among women, while young men were most prevalent in Class 1. The present study underlines different characteristics in HD BZD users both concerning other addictions and sex, and also highlights the need for a stricter control of BZD use, ranging from prescriptions to sales
Comparison of Slides and Video Clips as Different Methods for Inducing Emotions: An Electroencephalographic Alpha Modulation Study
Full text linkFilms, compared with emotional static pictures, represent true-to-life dynamic stimuli that are both ecological and effective in inducing an emotional response given the involvement of multimodal stimulation (i.e., visual and auditory systems). We hypothesized that a direct comparison between the two methods would have shown greater efficacy of movies, compared to standardized slides, in eliciting emotions at both subjective and neurophysiological levels. To this end, we compared these two methods of emotional stimulation in a group of 40 young adults (20 females). Electroencephalographic (EEG) Alpha rhythm (8–12 Hz) was recorded from 64 scalp sites while participants watched (in counterbalanced order across participants) two separate blocks of 45 slides and 45 clips. Each block included three groups of 15 validated stimuli classified as Erotic, Neutral and Fear content. Greater self-perceived arousal was found after the presentation of Fear and Erotic video clips compared with the same slide categories. sLORETA analysis showed a different lateralization pattern: slides induced decreased Alpha power (greater activation) in the left secondary visual area (Brodmann Area, BA, 18) to Erotic and Fear compared with the Neutral stimuli. Instead, video clips elicited reduced Alpha in the homologous right secondary visual area (BA 18) again to both Erotic and Fear contents compared with Neutral ones. Comparison of emotional stimuli showed smaller Alpha power to Erotic than to Fear stimuli in the left precuneus/posterior cingulate cortex (BA 7/31) for the slide condition, and in the left superior parietal lobule (BA 7) for the clip condition. This result matched the parallel analysis of the overlapped Mu rhythm (corresponding to the upper Alpha band) and can be interpreted as Mu/Alpha EEG suppression elicited by greater motor action tendency to Erotic (approach motivation) compared to Fear (withdrawal motivation) stimuli. Correlation analysis found lower Alpha in the left middle temporal gyrus (BA 21) associated with greater pleasantness to Erotic slides (r(38) = –0.62, p = 0.009), whereas lower Alpha in the right supramarginal/angular gyrus (BA 40/39) was associated with greater pleasantness to Neutral clips (r(38) = –0.69, p = 0.012). Results point to stronger emotion elicitation of movies vs. slides, but also to a specific involvement of the two hemispheres during emotional processing of slides vs. video clips, with a shift from the left to the right associative visual areas
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