The alexithymic brain: the neural pathways linking alexithymia to physical disorders

Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala) and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT) was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The neural machinery in alexithymia is therefore activated more on the physiologic, motor-expressive level and less in the cognitive-experiential domains of the emotional response system. Affects may play an important role in alleviating intrinsic physiologic reactions and adapting to the environment. Deficient development of emotional neural structures may lead to hypersensitivity to bodily sensations and unhealthy behaviors, a possible mechanism linking alexithymia to psychosomatic disorders.     

Association between Ability Emotional Intelligence and Left Insula during Social Judgment of Facial Emotions

The human ability of identifying, processing and regulating emotions from social stimuli is generally referred as Emotional Intelligence (EI). Within EI, Ability EI identifies a performance measure assessing individual skills at perceiving, using, understanding and managing emotions. Previous models suggest that a brain “somatic marker circuitry” (SMC) sustains emotional sub-processes included in EI. Three primary brain regions are included: the amygdala, the insula and the ventromedial prefrontal cortex (vmPFC). Here, our aim was to investigate the relationship between Ability EI scores and SMC activity during social judgment of emotional faces. Sixty-three healthy subjects completed a test measuring Ability EI and underwent fMRI during a social decision task (i.e. approach or avoid) about emotional faces with different facial expressions. Imaging data revealed that EI scores are associated with left insula activity during social judgment of emotional faces as a function of facial expression. Specifically, higher EI scores are associated with greater left insula activity during social judgment of fearful faces but also with lower activity of this region during social judgment of angry faces. These findings indicate that the association between Ability EI and the SMC activity during social behavior is region- and emotion-specific.     

Racial Bias in Neural Empathic Responses to Pain

Recent studies have shown that perceiving the pain of others activates brain regions in the observer associated with both somatosensory and affective-motivational aspects of pain, principally involving regions of the anterior cingulate and anterior insula cortex. The degree of these empathic neural responses is modulated by racial bias, such that stronger neural activation is elicited by observing pain in people of the same racial group compared with people of another racial group. The aim of the present study was to examine whether a more general social group category, other than race, could similarly modulate neural empathic responses and perhaps account for the apparent racial bias reported in previous studies. Using a minimal group paradigm, we assigned participants to one of two mixed-race teams. We use the term race to refer to the Chinese or Caucasian appearance of faces and whether the ethnic group represented was the same or different from the appearance of the participant'' own face. Using fMRI, we measured neural empathic responses as participants observed members of their own group or other group, and members of their own race or other race, receiving either painful or non-painful touch. Participants showed clear group biases, with no significant effect of race, on behavioral measures of implicit (affective priming) and explicit group identification. Neural responses to observed pain in the anterior cingulate cortex, insula cortex, and somatosensory areas showed significantly greater activation when observing pain in own-race compared with other-race individuals, with no significant effect of minimal groups. These results suggest that racial bias in neural empathic responses is not influenced by minimal forms of group categorization, despite the clear association participants showed with in-group more than out-group members. We suggest that race may be an automatic and unconscious mechanism that drives the initial neural responses to observed pain in others.     

Alexithymia and the Processing of Emotional Facial Expressions (EFEs): Systematic Review, Unanswered Questions and Further Perspectives

Alexithymia is characterized by difficulties in identifying, differentiating and describing feelings. A high prevalence of alexithymia has often been observed in clinical disorders characterized by low social functioning. This review aims to assess the association between alexithymia and the ability to decode emotional facial expressions (EFEs) within clinical and healthy populations. More precisely, this review has four main objectives: (1) to assess if alexithymia is a better predictor of the ability to decode EFEs than the diagnosis of clinical disorder; (2) to assess the influence of comorbid factors (depression and anxiety disorder) on the ability to decode EFE; (3) to investigate if deficits in decoding EFEs are specific to some levels of processing or task types; (4) to investigate if the deficits are specific to particular EFEs. Twenty four studies (behavioural and neuroimaging) were identified through a computerized literature search of Psycinfo, PubMed, and Web of Science databases from 1990 to 2010. Data on methodology, clinical characteristics, and possible confounds were analyzed. The review revealed that: (1) alexithymia is associated with deficits in labelling EFEs among clinical disorders, (2) the level of depression and anxiety partially account for the decoding deficits, (3) alexithymia is associated with reduced perceptual abilities, and is likely to be associated with impaired semantic representations of emotional concepts, and (4) alexithymia is associated with neither specific EFEs nor a specific valence. These studies are discussed with respect to processes involved in the recognition of EFEs. Future directions for research on emotion perception are also discussed.     

COMT val158met polymorphism and neural pain processing

A functional polymorphism (val158met) of the gene coding for Catechol-O-methyltransferase (COM) has been demonstrated to be related to processing of emotional stimuli. Also, this polymorphism has been found to be associated with pain regulation in healthy subjects. Therefore, we investigated a possible influence of this polymorphism on pain processing in healthy persons as well as in subjects with markedly reduced pain sensitivity in the context of Borderline Personality Disorder (BPD). Fifty females (25 patients with BPD and 25 healthy control participants) were included in this study. Genotype had a significant--though moderate--effect on pain sensitivity, but only in healthies. The number of val alleles was correlated with the BOLD response in several pain-processing brain regions, including dorsolateral prefrontal cortex, posterior parietal cortex, lateral globus pallidus, anterior and posterior insula. Within the subgroup of healthy participants, the number of val alleles was positively correlated with the BOLD response in posterior parietal, posterior cingulate, and dorsolateral prefrontal cortex. BPD patients revealed a positive correlation between the number of val alleles and BOLD signal in anterior and posterior insula. Thus, our data show that the val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people, this polymorphism was more related to cognitive aspects of pain processing, whereas BPD patients with reduced pain sensitivity showed an association with activity in brain regions related to affective pain processing.     

Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy

The degree to which perceptual awareness of threat stimuli and bodily states of arousal modulates neural activity associated with fear conditioning is unknown. We used functional magnetic neuroimaging (fMRI) to study healthy subjects and patients with peripheral autonomic denervation to examine how the expression of conditioning-related activity is modulated by stimulus awareness and autonomic arousal. In controls, enhanced amygdala activity was evident during conditioning to both "seen" (unmasked) and "unseen" (backward masked) stimuli, whereas insula activity was modulated by perceptual awareness of a threat stimulus. Absent peripheral autonomic arousal, in patients with autonomic denervation, was associated with decreased conditioning-related activity in insula and amygdala. The findings indicate that the expression of conditioning-related neural activity is modulated by both awareness and representations of bodily states of autonomic arousal.     

Brain responses to the acquired moral status of faces

We examined whether neural responses associated with judgments of socially relevant aspects of the human face extend to stimuli that acquire their significance through learning in a meaningful interactive context, specifically reciprocal cooperation. During fMRI, subjects made gender judgments on faces of people who had been introduced as fair (cooperators) or unfair (defector) players through repeated play of a sequential Prisoner's Dilemma game. To manipulate moral responsibility, players were introduced as either intentional or nonintentional agents. Our behavioral (likebility ratings and memory performance) as well as our imaging data confirm the saliency of social fairness for human interactions. Relative to neutral faces, faces of intentional cooperators engendered increased activity in left amygdala, bilateral insula, fusiform gyrus, STS, and reward-related areas. Our data indicate that rapid learning regarding the moral status of others is expressed in altered neural activity within a system associated with social cognition.     

Neural Correlates of Emotional Interference in Social Anxiety Disorder

Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients’ interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.     

Neural Responses to Smoking Stimuli Are Influenced by Smokers' Attitudes towards Their Own Smoking Behaviour

An important feature of addiction is the high drug craving that may promote the continuation of consumption. Environmental stimuli classically conditioned to drug-intake have a strong motivational power for addicts and can elicit craving. However, addicts differ in the attitudes towards their own consumption behavior: some are content with drug taking (consonant users) whereas others are discontent (dissonant users). Such differences may be important for clinical practice because the experience of dissonance might enhance the likelihood to consider treatment. This fMRI study investigated in smokers whether these different attitudes influence subjective and neural responses to smoking stimuli. Based on self-characterization, smokers were divided into consonant and dissonant smokers. These two groups were presented smoking stimuli and neutral stimuli. Former studies have suggested differences in the impact of smoking stimuli depending on the temporal stage of the smoking ritual they are associated with. Therefore, we used stimuli associated with the beginning (BEGIN-smoking-stimuli) and stimuli associated with the terminal stage (END-smoking-stimuli) of the smoking ritual as distinct stimulus categories. Stimulus ratings did not differ between both groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic responses (amygdala, hippocampus, insula) in dissonant compared to consonant smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced mesocortical responses (orbitofrontal cortex, subcallosal cortex) compared to consonant smokers. These results suggest that smoking stimuli with a high incentive value (BEGIN-smoking-stimuli) are more appetitive for dissonant than consonant smokers at least on the neural level. To the contrary, smoking stimuli with low incentive value (END-smoking-stimuli) seem to be less appetitive for dissonant smokers than consonant smokers. These differences might be one reason why dissonant smokers experience difficulties in translating their attitudes into an actual behavior change.     

Childhood Emotional Maltreatment Severity Is Associated with Dorsal Medial Prefrontal Cortex Responsivity to Social Exclusion in Young Adults

Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.     

Self-Recognition of One's Own Fall Recruits the Genuine Bodily Crisis-Related Brain Activity

While bipedalism is a fundamental evolutionary adaptation thought to be essential for the development of the human brain, the erect body is always an inch or two away from falling. Although the neural mechanism for automatically detecting one''s own body instability is an important consideration, there have thus far been few functional neuroimaging studies because of the restrictions placed on participants'' movements. Here, we used functional magnetic resonance imaging to investigate the neural substrate underlying whole body instability, based on the self-recognition paradigm that uses video stimuli consisting of one''s own and others'' whole bodies depicted in stable and unstable states. Analyses revealed significant activity in the regions which would be activated during genuine unstable bodily states: The right parieto-insular vestibular cortex, inferior frontal junction, posterior insula and parabrachial nucleus. We argue that these right-lateralized cortical and brainstem regions mediate vestibular information processing for detection of vestibular anomalies, defensive motor responding in which the necessary motor responses are automatically prepared/simulated to protect one''s own body, and sympathetic activity as a form of alarm response during whole body instability.     

Emotional and social behaviors elicited by electrical stimulation of the insula in the macaque monkey

Evidence from a large number of brain imaging studies has shown that, in humans, the insula, and especially its anterior part, is involved in emotions and emotion recognition. Typically, however, these studies revealed that, besides the insula, a variety of other cortical and subcortical areas are also active. Brain imaging studies are correlative in nature, and, as such, they cannot give indications about the necessary contribution of the different centers involved in emotions. In the present study, we aimed to define more clearly the role of the insula in emotional and social behavior of the monkey by stimulating it electrically. Using this technique, one may determine whether direct activation of the insula can produce specific emotional or social behaviors and exactly which parts of this structure are responsible for these behaviors. The results showed that two emotional behaviors, a basic one (disgust) and a social one (affiliative state), were easily elicited by electrical stimulation of specific parts of the insula. Both behaviors were characterized by specific motor and vegetative responses and by a dramatic change in the monkey's responsiveness to external stimuli.     

The obese brain athlete: self-regulation of the anterior insula in adiposity

The anterior insular cortex (AIC) is involved in emotional processes and gustatory functions which can be examined by imaging techniques. Such imaging studies showed increased activation in the insula in response to food stimuli as well as a differential activation in lean and obese people. Additionally, studies investigating lean subjects established the voluntary regulation of the insula by a real-time functional magnetic resonance imaging-brain computer interface (rtfMRI-BCI) approach. In this exploratory study, 11 lean and 10 obese healthy, male participants were investigated in a rtfMRI-BCI protocol. During the training sessions, all obese participants were able to regulate the activity of the AIC voluntarily, while four lean participants were not able to regulate at all. In successful regulators, functional connectivity during regulation vs. relaxation between the AIC and all other regions of the brain was determined by a seed voxel approach. Lean in comparison to obese regulators showed stronger connectivity in cingular and temporal cortices during regulation. We conclude, that obese people possess an improved capacity to self-regulate the anterior insula, a brain system tightly related to bodily awareness and gustatory functions.     

Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception

The insula, particularly its posterior portion, is often regarded as a primary cortex for pain. However, this interpretation is largely based on reverse inference, and a specific involvement of the insula in pain has never been demonstrated. Taking advantage of the high spatiotemporal resolution of direct intracerebral recordings, we investigated whether the human insula exhibits local field potentials (LFPs) specific for pain. Forty-seven insular sites were investigated. Participants received brief stimuli belonging to four different modalities (nociceptive, vibrotactile, auditory, and visual). Both nociceptive stimuli and non-nociceptive vibrotactile, auditory, and visual stimuli elicited consistent LFPs in the posterior and anterior insula, with matching spatial distributions. Furthermore, a blind source separation procedure showed that nociceptive LFPs are largely explained by multimodal neural activity also contributing to non-nociceptive LFPs. By revealing that LFPs elicited by nociceptive stimuli reflect activity unrelated to nociception and pain, our results confute the widespread assumption that these brain responses are a signature for pain perception and its modulation.     

Neural responses to facial and vocal expressions of fear and disgust.

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington''s disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus.     

情绪模仿的神经生理机制：从镜像神经系统到神经网络

情绪模仿是指观察者对表达者传递出的非言语情绪信号进行模仿,进而表现出一致的表情与行为.以往关于情绪模仿的神经机制着重强调镜像神经系统的作用,然而随着研究成果越来越丰富,研究者们发现仅仅是镜像神经系统不足以解释情绪模仿的发生过程.梳理以往实证研究可以发现,情绪模仿是包括镜像神经系统、情绪系统、运动系统以及与社会认知相关脑区在内的脑网络共同作用的结果,该网络同时受到内分泌系统的调节.本文首先基于过往研究对情绪模仿的神经生理基础进行总结,然后介绍新近的神经网络概念模型,试图解释情绪信息从表达者传递至观察者完成模仿的神经路径,为情绪模仿的神经生理机制提供较为完整的框架,并在此基础上指出未来可能的研究方向.     

Early specialization for voice and emotion processing in the infant brain

Human voices play a fundamental role in social communication, and areas of the adult "social brain" show specialization for processing voices and their emotional content (superior temporal sulcus, inferior prefrontal cortex, premotor cortical regions, amygdala, and insula). However, it is unclear when this specialization develops. Functional magnetic resonance (fMRI) studies suggest that the infant temporal cortex does not differentiate speech from music or backward speech, but a prior study with functional near-infrared spectroscopy revealed preferential activation for human voices in 7-month-olds, in a more posterior location of the temporal cortex than in adults. However, the brain networks involved in processing nonspeech human vocalizations in early development are still unknown. To address this issue, in the present fMRI study, 3- to 7-month-olds were presented with adult nonspeech vocalizations (emotionally neutral, emotionally positive, and emotionally negative) and nonvocal environmental sounds. Infants displayed significant differential activation in the anterior portion of the temporal cortex, similarly to adults. Moreover, sad vocalizations modulated the activity of brain regions involved in processing affective stimuli such as the orbitofrontal cortex and insula. These results suggest remarkably early functional specialization for processing human voice and negative emotions.     

Identifying distinct components in the cerebral treatment of visual sexual information through functional neuroimaging

For now several years, the growing developement of neuroimaging techniques such as Positron Emission Tomography (PET) or functional Magnetic Resonance Imaging (fMRI) allowed a better understanding of neural processes involved in human emotions and goal-directed behaviors. In particular, several studies are now available on the neural correlates of male sexual arousal. A neurobehavioral model of neural processes involved in sexual arousal has been proposed (Redouté et al., 2000) comprising: i) a cognitive component; ii) an emotional component; iii) a motivational component and iv) an autonomic component. Among other regions, several cerebral areas have been found to be linked to: 1) the cognitive component which comprises: i) the orbitofrontal cortex involved in attentional processes directed toward the target and the superior parietal lobules; ii) the inferior parietal lobules involved in motor imagery processes; 2) the motivational component which involves the caudal part of the anterior cingulate cortex, related to motor preparation processes; 3) the autonomic component: concurrent measures of cerebral activations by functional neuroimaging and of erectile response by penile plethysmography allow the demonstration of the involvement of the hypothalamus, the insula, and the rostral part of the anterior cingulate cortex in this component.     

How everyday sounds can trigger strong emotions: ASMR,misophonia and the feeling of wellbeing

We propose that synesthetic cross-activation between the primary auditory cortex and the anatomically adjacent insula may help explain two puzzling conditions—autonomous sensory meridian response (ASMR) and misophonia—in which quotidian sounds involuntarily trigger strong emotional responses. In ASMR the sounds engender relaxation, while in misophonia they trigger an aversive response. The insula both plays an important role in autonomic nervous system control and integrates multiple interoceptive maps representing the physiological state of the body to substantiate a dynamic representation of emotional wellbeing. We propose that in ASMR cross-activation of the map for affective (sensual) touch leads to an increase in subjective wellbeing and parasympathetic activity. Conversely, in misophonia the effect of the cross-activation is to decrease emotional wellbeing and increase sympathetic activity. Our hypothesis also illuminates the connection between hearing and wellbeing more broadly and helps explain why so many people experience decreased wellbeing from modern urban soundscapes.     

A right hemispheric prefrontal system for cognitive time measurement

Despite a growing body of neuroimaging data, little consensus has been reached regarding the neural correlates of temporal processing in humans. This paper presents a reanalysis of two previously published neuroimaging experiments, which used two different cognitive timing tasks and examined both sub- and supra-second intervals. By processing these data in an identical manner, this reanalysis allows valid comparison and contrasting across studies. Conjunction of these studies using inclusive masking reveals shared activity in right hemispheric dorsolateral and ventrolateral prefrontal cortex and anterior insula, supporting a general-purpose system for cognitive time measurement in the right hemispheric prefrontal cortex. Consideration of the patterns of activity in each dataset with respect to the others, and taking task characteristics into account, provides insight into the possible role of dorsolateral prefrontal cortex in working memory and of posterior parietal cortex and anterior cingulate in attentional processing during cognitive time measurement tasks.