The dynamic dimension of the emotional experience assessed during painful stimulation and in the resting-state using functional magnetic resonance imaging

Abstract

The PhD thesis aimed to characterize the dynamic or temporal dimension of the emotional experience assessed using functional magnetic resonance imaging (fMRI). Brain response to primary emotional stimuli and basal brain functional connectivity during a sustained resting-state have been analyzed using a dynamic approach in healthy subjects and in patients suffering from fibromyalgia and major depression (MDD), both disorders showing relevant abnormalities in the affective sphere. The technical advance recently incorporated to the field of fMRI data acquisition and analysis has made possible the dynamic study of the human emotional experience from a brain-system perspective. <br/><br/>Two different approaches were employed. The first approach (i) was intended to dynamically characterize brain responses in emotion circuits when specifically targeted by aversive painful stimulation, considered a primary elicitor of emotional responses, in healthy subjects and in the selected clinical populations. The second approach (ii) specifically aimed to dynamically characterize the "baseline" functional organization of distinct emotion-processing circuits in healthy subjects and in a core affective disorder such as major depression.<br/><br/>Four studies compose the PhD thesis. The first study assessed the existence of regional specialization within the right lateral aspect of the frontal cortex, important for the affective modulation of pain perception, on the basis of their response dynamics during mechanical painful stimulation in a group of healthy subjects. Three distinct locations were found with separate temporal courses of activation showing each of them a different contribution to the final experience of pain reported by the subject. In the second study, information concerning the actual brain response dynamics (time-courses of brain responses) to painful stimulation were used in a group of fibromyalgia patients (and in healthy subjects) to better characterize their overall subjective pain experience and the specific contribution of brain emotional processing abnormalities to such a clinical disorder. The dynamic analysis approach successfully identified relevant abnormalities in the patients' response to pain that would have not been possibly detected with a conventional model-based approach based on the fixed stimulus duration. The third study aimed to assess possible alterations in the baseline functional organization of the emotion-related brain networks during resting-state (stimulation free) conditions in a group of MDD patients, characterized by a continuous and severe negative affective state. Gray-matter abnormalities observed in MDD patients guided the functional connectivity study, which successfully captured major brain networks relevant to MDD physiopathology. Overall, the baseline functional disposition of the brain systems under study revealed functional connectivity disruptions (loss of coherence between fMRI signal fluctuations in distinct brain regions) affecting most of the networks, coinciding with the general hypo-functional state characterizing such patients. Specific functional connectivity enhancements were also found in regions integrating the basic threat response circuit, which may be associated with the sustained stress characterizing MDD patients. Finally, the fourth study aimed to characterize the temporal changes in the abnormal responses to aversive painful stimulation in MDD patients following one and eight weeks of antidepressant treatment observed within relevant emotion brain circuits, and the specific brain correlates of affect-related symptomatic improvement in such patients. The dynamic study successfully identified (i) the normalization of brain hyper-responses to painful stimulation in emotion-related systems in MDD patients, associated with their symptomatic improvement following antidepressant treatment (ii) brain imaging correlates of symptomatic improvement in specific clinical dimensions of interest (iii) baseline brain response measurements predicting clinical responders following 8 weeks of antidepressant treatment. All in all, the four studies presented in the PhD thesis constitute a step forward in the dynamic characterization of how the brain constructs emotion perception and sustained affective states in the context of both health and disease.