Alessandro Pingitore

Brain Responses to Emotional Stimuli During Breath Holding and Hypoxia: An Approach Based on the Independent Component Analysis

Voluntary breath holding represents a physiological model of hypoxia. It consists of two phases of oxygen saturation dynamics: an initial slow decrease (normoxic phase) followed by a rapid drop (hypoxic phase) during which transitory neurological symptoms as well as slight impairment of integrated cerebral functions, such as emotional processing, can occur. This study investigated how breath holding affects emotional processing. To this aim we characterized the modulation of event-related potentials (ERPs) evoked by emotional-laden pictures as a function of breath holding time course. We recorded ERPs during free breathing and breath holding performed in air by elite apnea divers. We modeled brain responses during free breathing with four independent components distributed over different brain areas derived by an approach based on the independent component analysis (ICASSO). We described ERP changes during breath holding by estimating amplitude scaling and time shifting of the same components (component adaptation analysis). Component 1 included the main EEG features of emotional processing, had a posterior localization and did not change during breath holding; component 2, localized over temporo-frontal regions, was present only in unpleasant stimuli responses and decreased during breath holding, with no differences between breath holding phases; component 3, localized on the fronto-central midline regions, showed phase-independent breath holding decreases; component 4, quite widespread but with frontal prevalence, decreased in parallel with the hypoxic trend. The spatial localization of these components was compatible with a set of processing modules that affects the automatic and intentional controls of attention. The reduction of unpleasant-related ERP components suggests that the evaluation of aversive and/or possibly dangerous situations might be altered during breath holding.

Thyroid and Heart Failure

n Th e editors present their book as the result of a collaborative eff ort at presenting a discussion on the relationship between thyroid and cardiac (dys)function. Th e book has been organized in four sections. Section one is a general introduction to the problem of heart failure with respect to thyroid function: (i) Heart failure: from epidemiology to pathophysiology; (ii) Neuroendocrine control of the cardiovascular system in heart failure; (iii) Cardiac morphology and function in mild hypothyroidism; (iv) Cardiovascular hemodynamics and work capacity in thyroid dysfunction. Section two explores the basic aspects of the thyroid hormone and cardiovascular systems in the normal and failing heart: (i) Mechanism of action of thyroid hormone on the cardiovascular system; (ii) Cardiac functional eff ects of 3-iodothyronamine, a new endogenous thyroid hormone derivative; (iii) Cardiac thyroid-hormone deiodinative pathways in ventricular hypertrophy and heart failure; (iv) Th yroid hormone receptor signaling in normal and failing heart; (v) Pharmacological eff ects of amiodarone and dronedarone on cardiac thyroid hormone receptors; (vi) Changes in thyroid hormone metabolism and gene expression in the failing heart: therapeutic implications; (vii) Th yroid-hormone-regulated cardiac metabolism in normal and failing heart; (viii) Cardiac myocyte and vascular remodeling in altered thyroid conditions; (ix) Th yroid hormone and ischemic myocardium. Section three examines the clinical aspects: (i) Th yroid and cardiovascular risk; (ii) Relationship between subclinical thyroid dysfunction, heart failure and mortality; (iii) Low triiodothyronine syndrome as a powerful predictor of death in heart failure; (iv) Th yroid, renal function and cardiac outcome; (v) Low triiodothyronine syndrome and depression in patients with chronic heart failure. Section four deals with the current and future therapeutic options for patients with thyroid and cardiac dysfunction: (i) Treatment options for primary thyroid disease in patients with heart failure; (ii) Synthetic thyroid hormone and thyroid hormone analogues for treatment of heart failure; (iii) Th yroid hormone supplementation for infants and children undergoing cardiopul monary bypass for cardiac surgery; (iv) New approaches for treating heart disease by modulating thyroid hormone signaling using gene therapy approaches. Th e scope of the book ranges from the cellular and subcellular mechanisms of thyroid-related cardiac disease to its clinical and epidemiological features.

Minimal changes of thyroid axis activity influence brain functions in young females affected by subclinical hypothyroidism

There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.

Heart Failure, Iodine Intake and Thyroid Hormones

Heart failure (HF) is a major public health problem in western countries. Experimental and clinical findings strongly support the concept that iodine and thyroid hormone (TH) have a fundamental role in cardiovascular homeostasis. Iodine is an essential component of the TH molecule. Biologically active triiodothyronine (T3) modulates cardiac contractility, heart rate, diastolic function and systemic vascular resistance through genomic- and nongenomic-mediated effects. The importance of THs in maintaining cardiovascular homeostasis is also deducible from data showing that mild forms of primary thyroid dysfunction, i.e., subclinical hypothyroidism and subclinical hyperthyroidism, significantly alter cardiovascular function and negatively affect the prognosis of cardiac patients. Dietary iodine deficiency still remains the leading cause of congenital hypothyroidism; hypothyroidism is also more prevalent and marked in adult persons consuming excessive amounts of iodine. Experimental studies in humans showed that a low thyroid state may alter cardiac histology, cardiomyocyte morphology and cardiac gene expression of structural and functional key proteins. Transformation from the fetal to the mature heart coincides with the rapid surge of TSH and T3 levels after birth. The re-activation of the fetal gene program observed during HF in adult life appears to be reversible when a normal thyroid hormone profile is restored. In patients with HF and low-T3 state, who received intravenous L-T3, cardiac output improved rapidly and systemic vascular resistance decreased; heart rate, BP and metabolic demand were unchanged.