Stéphanie Khalfa

Brain regions involved in the recognition of happiness and sadness in music

Here, we used functional magnetic resonance imaging to test for the lateralization of the brain regions specifically involved in the recognition of negatively and positively valenced musical emotions. The manipulation of two major musical features (mode and tempo), resulting in the variation of emotional perception along the happiness–sadness axis, was shown to principally involve subcortical and neocortical brain structures, which are known to intervene in emotion processing in other modalities. In particular, the minor mode (sad excerpts) involved the left orbito and mid-dorsolateral frontal cortex, which does not confirm the valence lateralization model. We also show that the recognition of emotions elicited by variations of the two perceptual determinants rely on both common (BA 9) and distinct neural mechanisms.

Dissociating Bottom-Up and Top-Down Mechanisms in the Cortico-Limbic System during Emotion Processing

The cortico-limbic system is critically involved in emotional responses and resulting adaptive behaviors. Within this circuit, complementary regions are believed to be involved in either the appraisal or the regulation of affective state. However, the respective contribution of these bottom-up and top-down mechanisms during emotion processing remains to be clarified. We used a new functional magnetic resonance imaging (fMRI) paradigm varying 3 parameters: emotional valence, emotional congruency, and allocation of attention, to distinguish the functional variation in activity and connectivity between amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Bottom-up appraisal of negative compared with positive stimuli led to a greater amygdala response and stronger functional interaction between amygdala and both dorsal ACC and DLPFC. Top-down resolution of emotional conflict was associated with increased activity within ACC and higher functional connectivity between this structure, and both the amygdala and DLPFC. Finally, increased top-down attentional control caused greater engagement of the DLPFC, accompanied by increased connectivity between DLPFC and dorsal ACC. This novel task provides an efficient tool for exploring bottom-up and top-down processes underlying emotion and may be particularly helpful for investigating the neurofunctional underpinnings of psychiatric disorders.

Evidence of lateralized anteromedial temporal structures involvement in musical emotion processing.

The right and left anteromedial temporal lobes have been shown to participate in emotion processing. The aim of the study was to further address their role in music emotion perception/recognition, and assessment by two emotional determinants, i.e., arousal (relaxing versus stimulating aspects) and valence (pleasantness degree). Epileptic patients with right or left anterior mesio-temporal resection (including the amygdala), and control subjects were presented with happy musical (chosen highly stimulating) or sad excerpts (chosen to be relaxing), that were either consonant (pleasant) or dissonant (unpleasant). The patients demonstrated an abnormal perception of dissonant music disregarding of the side of the resection; thereby confirming the role of the parahippocampal gyrus in the perception of unpleasantness. Moreover, the pleasantness of musical excerpts, in particular the happy consonant ones, was overestimated by patients with right temporal damage. In contrast, the arousal rating for happy consonant excerpts was reduced only in the group with left-resections. This modified perception of arousal might be related to the decreased ability of those patients to recognize happy and sad music. Indeed, both right and left temporal resections impaired sadness recognition, whereas happiness recognition was only reduced by the left-resections. The main result was that for the first time, the mesio-temporal structures were demonstrated to be asymmetrically involved in positive musical emotion recognition.

rTMS in fibromyalgia A randomized trial evaluating QoL and its brain metabolic substrate

Objective: This double-blind, randomized, placebo-controlled study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on quality of life (QoL) of patients with fibromyalgia, and its possible brain metabolic substrate. Methods: Thirty-eight patients were randomly assigned to receive high-frequency rTMS (n = 19) or sham stimulation (n = 19), applied to left primary motor cortex in 14 sessions over 10 weeks. Primary clinical outcomes were QoL changes at the end of week 11, measured using the Fibromyalgia Impact Questionnaire (FIQ). Secondary clinical outcomes were mental and physical QoL component measured using the 36-Item Short Form Health Survey (SF-36), but also pain, mood, and anxiety. Resting-state [18F]-fluorodeoxyglucose-PET metabolism was assessed at baseline, week 2, and week 11. Whole-brain voxel-based analysis was performed to study between-group metabolic changes over time. Results: At week 11, patients of the active rTMS group had greater QoL improvement in the FIQ (p = 0.032) and in the mental component of the SF-36 (p = 0.019) than the sham stimulation group. No significant impact was found for other clinical outcomes. Compared with the sham stimulation group, patients of the active rTMS group presented an increase in right medial temporal metabolism between baseline and week 11 (p < 0.001), which was correlated with FIQ and mental component SF-36 concomitant changes (r = −0.38, p = 0.043; r = 0.51, p = 0.009, respectively). QoL improvement involved mainly affective, emotional, and social dimensions. Conclusion: Our study shows that rTMS improves QoL of patients with fibromyalgia. This improvement is associated with a concomitant increase in right limbic metabolism, arguing for a neural substrate to the impact of rTMS on emotional dimensions involved in QoL. Classification of evidence: This study provides Class II evidence that rTMS compared with sham rTMS improves QoL in patients with fibromyalgia.

Childhood neglect predicts disorganization in schizophrenia through grey matter decrease in dorsolateral prefrontal cortex.

Psychosocial trauma during childhood is associated with schizophrenia vulnerability. The pattern of grey matter decrease is similar to brain alterations seen in schizophrenia. Our objective was to explore the links between childhood trauma, brain morphology and schizophrenia symptoms.

Relationship between emotional experience and resilience: An fMRI study in fire-fighters

Resilience refers to the capacity to cope effectively in stressful situations or adversity. It may involve the ability to experience emotions matching the demands of environmental circumstances. The brain mechanisms underlying resilience remain unclear. In this study, we aim to investigate the relationship between the neural basis of emotional experience and resilience. Thirty-six fire-fighters were included. They performed an fMRI script-driven paradigm comprising relaxing and trauma-related scripts to evaluate the cerebral substrate of emotional experience (p<0.05, FDR-corrected). Correlations were examined between fMRI activations and the resilience DRS15 scale (p<0.05). Resilience was positively correlated with the right amygdala and left orbitofrontal activations when performing the contrast of trauma vs. relaxing script. The present study provides neural data on the mechanisms underlying resilience and their relationship with emotional reactivity, suggesting that appropriate emotional response in stressful situations is essential for coping with aversive events in daily life.

Effect of trait anxiety on prefrontal control mechanisms during emotional conflict.

Converging evidence points to a link between anxiety proneness and altered emotional functioning, including threat‐related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task‐related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high‐order control, characterized by insufficient ACC‐LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders. Hum Brain Mapp 36:2207–2214, 2015.

Acute stress disorder modifies cerebral activity of amygdala and prefrontal cortex.

The diagnosis constraint of acute stress disorder (ASD), consisting of testing individuals in the month following trauma exposure, limits research on the very early and initial stage of the disease. In this regard, this work aims to explore the cerebral mechanism of ASD in a population of fire-fighters before and after trauma exposure. Thirty-six healthy non-traumatized male fire-fighters were explored by an fMRI emotional face-matching task to evaluate the cerebral substrate of emotional recognition. During the two years of the follow-up, two subjects were traumatized, and thus retested, as were 10 non-traumatized subjects among the initial non-exposed ones. In comparison to non-exposed subjects, fire-fighters with ASD had enhanced amygdala, orbitofrontal, and dorsolateral prefrontal BOLD responses to fearful and angry faces (p < .05, FDR-corrected). These results shed new light on the cerebral mechanism associated with ASD. We observed for the first time the existence of an altered fear processing pathway in ASD that is mediated by amygdala and prefrontal cortex hyperactivity, which might be at the core of the disorder.

A case-control study of skin conductance biofeedback on seizure frequency and emotion regulation in drug-resistant temporal lobe epilepsy

This study investigates the physiological basis of effects of skin conductance biofeedback on anxiety disorders, depressive disorders and stress in drug-resistant temporal lobe epilepsy (TLE). This method presents an interest in seizure reduction and improvement in psychiatric comorbidities frequently associated with TLE. Our goal was to better understand the impact of biofeedback on seizure control and on emotional regulation. Fifteen patients with TLE were treated with 12 skin conductance biofeedback sessions and compared with 15 control TLE patients on a waiting list. They were evaluated in terms of seizure frequency, clinical evaluations of anxiety and depression and skin conductance responses (SCR) to five emotions: fear, disgust, sadness, happiness and peacefulness induced by short films. Biofeedback training significantly reduced seizure frequency with a mean reduction of -47.42% in the biofeedback group, while the control group did not differ at the two time measures. A significant improvement was found for depression and trait-anxiety in the biofeedback group but not in the control group. There were no differences on SCR on any emotion after biofeedback treatment. A correlation was found between mean change in SCR over the biofeedback treatment and the reduction of seizure frequency, but not between SCR changes and scores on psychiatric comorbidities. These results show independent effect of biofeedback on mood and seizure control. Improvements in anxiety and depressive symptoms were not related to SCR, whereas improved seizure control was, suggesting differential mechanisms underlying these two phenomena.

Bilateral Alternating Auditory Stimulations Facilitate Fear Extinction and Retrieval

Disruption of fear conditioning, its extinction and its retrieval are at the core of posttraumatic stress disorder (PTSD). Such deficits, especially fear extinction delay, disappear after alternating bilateral stimulations (BLS) during eye movement desensitization and reprocessing (EMDR) therapy. An animal model of fear recovery, based on auditory cued fear conditioning and extinction learning, recently showed that BLS facilitate fear extinction and fear extinction retrieval. Our goal was to determine if these previous results found in animals can be reproduced in humans. Twenty-two healthy participants took part in a classical fear conditioning, extinction, and extinction recall paradigm. Behavioral responses (fear expectations) as well as psychophysiological measures (skin conductance responses, SCRs) were recorded. The results showed a significant fear expectation decrease during fear extinction with BLS. Additionally, SCR for fear extinction retrieval were significantly lower with BLS. Our results demonstrate the importance of BLS to reduce negative emotions, and provide a successful model to further explore the neural mechanisms underlying the sole BLS effect in the EMDR.