Neurocomputational mechanisms underlying fear-biased adaptation learning in changing environments.

Humans are able to adapt to the fast-changing world by estimating statistical regularities of the environment. Although fear can profoundly impact adaptive behaviors, the computational and neural mechanisms underlying this phenomenon remain elusive. Here, we conducted a behavioral experiment (n = 21) and a functional magnetic resonance imaging experiment (n = 37) with a novel cue-biased adaptation learning task, during which we simultaneously manipulated emotional valence (fearful/neutral expressions of the cue) and environmental volatility (frequent/infrequent reversals of reward probabilities). Across 2 experiments, computational modeling consistently revealed a higher learning rate for the environment with frequent versus infrequent reversals following neutral cues. In contrast, this flexible adjustment was absent in the environment with fearful cues, suggesting a suppressive role of fear in adaptation to environmental volatility. This suppressive effect was underpinned by activity of the ventral striatum, hippocampus, and dorsal anterior cingulate cortex (dACC) as well as increased functional connectivity between the dACC and temporal-parietal junction (TPJ) for fear with environmental volatility. Dynamic causal modeling identified that the driving effect was located in the TPJ and was associated with dACC activation, suggesting that the suppression of fear on adaptive behaviors occurs at the early stage of bottom-up processing. These findings provide a neuro-computational account of how fear interferes with adaptation to volatility during dynamic environments.

Inhibitory framing in hypersexual patients with Parkinson's disease. An fMRI pilot study.

Hypersexuality in medicated patients with PD is caused by an increased influence of motivational drive areas and a decreased influence of inhibitory control areas due to dopaminergic medication. In this pilot study, we test a newly developed paradigm investigating the influence of dopaminergic medication on brain activation elicited by sexual pictures with and without inhibitory contextual framing. Twenty PD patients with and without hypersexuality were examined with fMRI either OFF or ON standardized dopaminergic medication. The paradigm consisted of a priming phase where either a neutral context or an inhibitory context was presented. This priming phase was either followed by a sexual or a neutral target. Sexual, compared to neutral pictures resulted in a BOLD activation of various brain regions implicated in sexual processing. Hypersexual PD patients showed increased activity compared to PD controls in these regions. There was no relevant effect of medication between the two groups. The inhibitory context elicited less activation in inhibition-related areas in hypersexual PD, but had no influence on the perception of sexual cues. The paradigm partially worked: reactivity of motivational brain areas to sexual cues was increased in hypersexual PD and inhibitory contextual framing lead to decreased activation of inhibitory control areas in PD. We could not find a medication effect and the length of the inhibitory stimulus was not optimal to suppress reactivity to sexual cues. Our data provide new insights into the mechanisms of hypersexuality and warrant a replication with a greater cohort and an optimized stimulus length in the future.

Connectome-Based Predictive Modeling of Individual Anxiety.

Anxiety-related illnesses are highly prevalent in human society. Being able to identify neurobiological markers signaling high trait anxiety could aid the assessment of individuals with high risk for mental illness. Here, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity (rsFC) data to predict the degree of trait anxiety in 76 healthy participants. Using a computational "lesion" approach in CPM, we then examined the weights of the identified main brain areas as well as their connectivity. Results showed that the CPM successfully predicted individual anxiety based on whole-brain rsFC, especially the rsFC between limbic areas and prefrontal cortex. The prediction power of the model significantly decreased from simulated lesions of limbic areas, lesions of the connectivity within limbic areas, and lesions of the connectivity between limbic areas and prefrontal cortex. Importantly, this neural model generalized to an independent large sample (n = 501). These findings highlight important roles of the limbic system and prefrontal cortex in anxiety prediction. Our work provides evidence for the usefulness of connectome-based modeling in predicting individual personality differences and indicates its potential for identifying personality factors at risk for psychopathology.

Alexithymia and Cutaneous Disease Morbidity: A Systematic Review.

BACKGROUND: Alexithymia is a psychological construct that describes one's difficulty in understanding and describing their own emotions as well as differentiating feelings from bodily signals of arousal. In the general population, alexithymia's prevalence is approximately 10%. Alexithymia may act as a triggering factor for many medical and psychiatric disorders. In patients with physical disease, alexithymia's prevalence reaches up to 63%. Additionally, alexithymia is associated with worse outcomes and heightened psychosocial comorbidities. OBJECTIVE: This review continues where an earlier review (Willemsen, 2008) left off to (1) clarify alexithymia's prevalence in dermatology patients and (2) further investigate alexithymia's impact on disease burden, psychosocial comorbidities, and treatment. METHODS: Systematic searches on alexithymia and dermatologic conditions were conducted using PubMed, Embase, PsycInfo, and Web of Science databases from March 8, 2021, to March 12, 2021. Data from eligible publications, which were full-text, clinical studies published after September 1, 2008, and available in English, were extracted by two medical students and summarized. RESULTS: Despite a small number of publications (n = 37), data showed a markedly greater prevalence and severity of alexithymia in patients with alopecia, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic idiopathic urticaria, and primary focal hyperhidrosis compared to healthy controls. Further, data consistently demonstrate a complex interplay between alexithymia, disease burden, and psychosocial comorbidity. CONCLUSIONS: Identifying and addressing alexithymia in dermatology patients may improve treatment outcomes, associated comorbidities, and health-related quality of life.

Chemosensory anxiety cues enhance the perception of fearful faces - An fMRI study.

Recent evidence suggests that humans can communicate emotion via chemosensory signals. Olfactory cues signaling anxiety can bias the perception of ambiguous stimuli, but the underlying neurobiological mechanisms of this effect are currently unknown. Here, we investigated the brain responses to subtle changes in facial expressions in response to anxiety chemosensory cues. Ten healthy individuals donated their sweat in two situations: while anticipating an important oral examination (anxiety condition) and during physical exercise (control condition). Subsequently, 24 participants completed a parametrically morphed (neutral to fearful) emotion recognition task under exposure to the olfactory cues of anxiety and sports, in the fMRI scanner. Behaviorally, the participants rated more discernible fearful faces as more fearful and neutral faces as more neutral under exposure to the anxiety cues. For brain response, under exposure to the anxiety cues, increased fearfulness of the face corresponded to increased activity in the left insula and the left middle occipital gyrus extending into fusiform gyrus. Moreover, with higher subjective ratings of facial fearfulness, participants additionally showed increased activity in the left hippocampus. These results suggest that chemosensory anxiety cues facilitate processing of socially relevant fearful stimuli and boost memory retrieval due to enhanced emotional context.

Hormonal abnormalities in alexithymia.

Alexithymia is a personality trait characterized by difficulties in emotion recognition and regulation that is associated with deficits in social cognition. High alexithymia levels are considered a transdiagnostic risk factor for a range of psychiatric and medical conditions, including depression, anxiety, and autism. Hormones are known to affect social-emotional cognition and behavior in humans, including the neuropeptides oxytocin and vasopressin, the steroid hormones testosterone and estradiol, the stress hormone cortisol as well as thyroid hormones. However, few studies have investigated hormonal effects on alexithymia and on alexithymia-related impairments in emotion regulation and reactivity, stress response, and social cognition. Here, we provide a brief overview of the evidence linking alexithymia to abnormalities in hormone levels, particularly with regard to cortisol and oxytocin, for which most evidence exists, and to thyroid hormones. We address the current lack of research on the influence of sex hormones on alexithymia and alexithymia-related deficits, and lastly provide future directions for research on associations between hormonal abnormalities and deficits in emotion regulation and social cognition associated with alexithymia.

Perceptive and affective impairments in emotive eye-region processing in alexithymia.

Alexithymia is characterized by impairments in emotion processing, frequently linked to facial expressions of emotion. The eye-region conveys information necessary for emotion processing. It has been demonstrated that alexithymia is associated with reduced attention to the eyes, but little is known regarding the cognitive and electrophysiological mechanisms underlying emotive eye-region processing in alexithymia. Here, we recorded behavioral and electrophysiological responses of individuals with alexithymia (ALEX; n = 25) and individuals without alexithymia (NonALEX; n = 23) while they viewed intact and eyeless faces with angry and sad expressions during a dual-target rapid serial visual presentation task. Results showed different eye-region focuses and differentiating N1 responses between intact and eyeless faces to anger and sadness in NonALEX, but not in ALEX, suggesting deficient perceptual processing of the eye-region in alexithymia. Reduced eye-region focus and smaller differences in frontal alpha asymmetry in response to sadness between intact and eyeless faces were observed in ALEX than NonALEX, indicative of impaired affective processing of the eye-region in alexithymia. These findings highlight perceptual and affective abnormalities of emotive eye-region processing in alexithymia. Our results contribute to understanding the neuropsychopathology of alexithymia and alexithymia-related disorders.

Social-specific impairment of negative emotion perception in alexithymia.

Alexithymia has been characterized as an impaired ability of emotion processing and regulation. The definition of alexithymia does not include a social component. However, there is some evidence that social cognition may be compromised in individuals with alexithymia. Hence, emotional impairments associated with alexithymia may extend to socially relevant information. Here, we recorded electrophysiological responses of individuals meeting the clinically relevant cutoff for alexithymia (ALEX; n = 24) and individuals without alexithymia (NonALEX; n = 23) while they viewed affective scenes that varied on the dimensions of sociality and emotional valence during a rapid serial visual presentation task. We found that ALEX exhibited lower accuracy and larger N2 than NonALEX in the perception of social negative scenes. Source reconstruction revealed that the group difference in N2 was localized at the dorsal anterior cingulate cortex. Irrespective of emotional valence, ALEX showed stronger alpha power than NonALEX in social but not non-social conditions. Our findings support the hypothesis of social processing being selectively affected by alexithymia, especially for stimuli with negative valence. Electrophysiological evidence suggests altered deployment of attentional resources in the perception of social-specific emotional information in alexithymia. This work sheds light on the neuropsychopathology of alexithymia and alexithymia-related disorders.

Understanding the relationship between apathy, cognition and functional outcome in schizophrenia: The significance of an ecological assessment.

In recent years there has been an increasing interest in understanding the role apathy plays in mediating the relationship between cognitive impairment and functional outcome. In general, most studies measure cognition with traditional cognitive tests that give explicit instructions and guide the participants toward generating a response. However, given that apathy is defined by a decrease in self-initiated behavior, it is crucial to evaluate cognition with ecological tasks that do not explicitly direct the patient´s motivation to generate behaviors to assess the actual effect. This study investigated whether an ecological cognitive assessment (the Jansari Executive Function Assessment, JEF©) would uniquely contribute to the relationship between cognition, apathy, and functional outcome in schizophrenia. The Apathy Evaluation Scale (AES), neuropsychological tests and the JEF© were administered to 20 patients with schizophrenia. Hierarchical multiple regression and mediation analysis were performed to test the associations between the variables of interest. Results showed that JEF© explained a significant portion of the variance in AES (25%). In addition, apathy explained 36% of the variance in functional outcome. However, AES did not mediate between cognition and functional outcome. Our results highlight the importance of assessing cognition with tasks that require integration of cognitive functions needed for real life demands.

Deficient auditory emotion processing but intact emotional multisensory integration in alexithymia.

Alexithymia has been associated with emotion recognition deficits in both auditory and visual domains. Although emotions are inherently multimodal in daily life, little is known regarding abnormalities of emotional multisensory integration (eMSI) in relation to alexithymia. Here, we employed an emotional Stroop-like audiovisual task while recording event-related potentials (ERPs) in individuals with high alexithymia levels (HA) and low alexithymia levels (LA). During the task, participants had to indicate whether a voice was spoken in a sad or angry prosody while ignoring the simultaneously presented static face which could be either emotionally congruent or incongruent to the human voice. We found that HA performed worse and showed higher P2 amplitudes than LA independent of emotion congruency. Furthermore, difficulties in identifying and describing feelings were positively correlated with the P2 component, and P2 correlated negatively with behavioral performance. Bayesian statistics showed no group differences in eMSI and classical integration-related ERP components (N1 and N2). Although individuals with alexithymia indeed showed deficits in auditory emotion recognition as indexed by decreased performance and higher P2 amplitudes, the present findings suggest an intact capacity to integrate emotional information from multiple channels in alexithymia. Our work provides valuable insights into the relationship between alexithymia and neuropsychological mechanisms of emotional multisensory integration.

Brain structure changes associated with sexual orientation.

Biological sex differences in brain function and structure are reliably associated with several cortico-subcortical brain regions. While sexual orientation (hetero- versus homosexuality) has been similarly linked to functional differences in several phylogenetically-old brain areas, the research on morphological brain phenotypes associated with sexual orientation is far from conclusive. We examined potential cerebral structural differences linked to sexual orientation in a group of 74 participants, including 37 men (21 homosexual) and 37 women (19 homosexual) using voxel-based morphometry (VBM). Gray matter volumes (GMV) were compared with respect to sexual orientation and biological sex across the entire sample using full factorial designs controlling for total intracranial volume, age, handedness, and education. We observed a significant effect of sexual orientation for the thalamus and precentral gyrus, with more GMV in heterosexual versus homosexual individuals, and for the putamen, with more GMV in homosexual + than heterosexual individuals. We found significant interactions between biological sex and sexual orientation, indicating that the significant effect for the putamen cluster was driven by homosexual women, whereas heterosexual women had increased precentral gyrus GMV. Heterosexual men exhibited more GMV in the thalamus than homosexual men. This study shows that sexual orientation is reflected in brain structure characteristics and that these differ between the sexes. The results emphasize the need to include or control for potential effects of participants' sexual orientation in neuroimaging studies. Furthermore, our findings provide important new insights into the brain morphology underlying sexual orientation and likely have important implications for understanding brain functions and behavior.

Effects of exogenous testosterone application on network connectivity within emotion regulation systems.

Studies with steroid hormones underlined the vital role of testosterone on social-emotional processing. However, there is still a lack of studies investigating whether testosterone modulates network connectivity during resting-state. Here, we tested how the exogenous application of testosterone would affect functional connectivity between regions implicated in emotion regulation. In total, 96 male participants underwent resting-state fMRI scanning. Before the measurement, half of the subjects received 5 g TestimTM gel (containing 50 mg testosterone) and the other half a corresponding amount of placebo gel. Seeds for the connectivity analysis were meta-analytically defined. First, all regions associated with emotion regulation were chosen via Neurosynth (data driven). Among those, specific seeds were selected and categorized based on the neural model of emotion regulation by Etkin and colleagues (Etkin et al., 2015) (theory-guided). Resting-state connectivity analysis revealed decreased connectivity between the right DLPFC and the right amygdala as well as between the VMPFC and the left IPL for the testosterone group compared to the placebo group. A complementary dynamic causal modeling (DCM) analysis on findings from the resting-state connectivity analysis underlined a bidirectional coupling which was decreased close to zero by testosterone administration. Our results demonstrate that testosterone administration disrupts resting-state connectivity within fronto-subcortical and fronto-parietal circuits. The findings suggest that even without a specific task (e.g. challenge, reward processing) testosterone modulates brain networks important for social-emotional processing.

The Multifaceted Nature of Alexithymia - A Neuroscientific Perspective.

Neuroscientific studies have mostly employed the 20-item Toronto Alexithymia Scale (TAS-20; Bagby et al., 1994a) for the assessment of alexithymia, a self-report scale that assesses the alexithymia facets difficulty identifying feelings, difficulty describing feelings, and externally oriented thinking. These facets can be considered to capture difficulties in the cognitive processing of emotions associated with alexithymia. However, Nemiah and Sifneos' original conceptualization of alexithymia included also an affective component, a lack of imaginative capacities, which cannot be assessed using the TAS-20. Aiming to capture the entire alexithymia construct, the Bermond-Vorst Alexithymia Questionnaire (BVAQ; Vorst and Bermond, 2001) was developed, a self-report scale which assesses two affective facets (difficulty fantasizing and difficulty emotionalizing) in addition to three cognitive facets. Based on these facets, an affective and a cognitive dimension of alexithymia can be distinguished. By now, several neuroscientific studies have investigated the neural signatures of the different facets and dimensions of alexithymia. Here, I provide an overview of the history of the alexithymia facets and dimensions and review findings provided by functional and structural magnetic resonance imaging (MRI) studies that differentiated between the alexithymia facets and/or its affective and cognitive dimensions. I then provide a synopsis of the current neuroscientific evidence for dissociable substrates of alexithymia facets and dimensions. Finally, the scientific value and clinical implications of these findings are discussed.

Structure of the alexithymic brain: A parametric coordinate-based meta-analysis.

Alexithymia refers to deficiencies in identifying and expressing emotions. This might be related to changes in structural brain volumes, but its neuroanatomical basis remains uncertain as studies have shown heterogeneous findings. Therefore, we conducted a parametric coordinate-based meta-analysis. We identified seventeen structural neuroimaging studies (including a total of 2586 individuals with different levels of alexithymia) investigating the association between gray matter volume and alexithymia. Volumes of the left insula, left amygdala, orbital frontal cortex and striatum were consistently smaller in people with high levels of alexithymia. These areas are important for emotion perception and emotional experience. Smaller volumes in these areas might lead to deficiencies in appropriately identifying and expressing emotions. These findings provide the first quantitative integration of results pertaining to the structural neuroanatomical basis of alexithymia.

Impulsive aggression and response inhibition in attention-deficit/hyperactivity disorder and disruptive behavioral disorders: Findings from a systematic review.

BACKGROUND: Although impulsive aggression (IA) and dysfunctional response inhibition (RI) are hallmarks of attention-deficit/hyperactivity disorder (ADHD) and disrupted behavioral disorders (DBDs), little is known about their shared and distinct deviant neural mechanisms. AIMS AND METHODS: Here, we selectively reviewed s/fMRI ADHD and DBD studies to identify disorder-specific and shared IA and RI aberrant neural mechanisms. RESULTS: In ADHD, deviant prefrontal and cingulate functional activity was associated with increased IA. Structural alterations were most pronounced in the cingulate cortex. Subjects with DBDs showed marked cortico-subcortical dysfunctions. ADHD and DBDs share similar cortico-limbic structural and functional alterations. RI deficits in ADHD highlighted hypoactivity in the dorso/ventro-lateral PFC, insula, and striatum, while the paralimbic system was primarily dysfunctional in DBDs. Across disorders, extensively altered cortico-limbic dysfunctions underlie IA, while RI was mostly associated with aberrant prefrontal activity. CONCLUSION: Control network deficits were evidenced across clinical phenotypes in IA and RI. Dysfunctions at any level within these cortico-subcortical projections lead to deficient cognitive-affective control by ascribing emotional salience to otherwise irrelevant stimuli. The clinical implications of these findings are discussed.

Neuroanatomical and Neuropsychological Markers of Amnestic MCI: A Three-Year Longitudinal Study in Individuals Unaware of Cognitive Decline.

Structural brain changes underlying mild cognitive impairment (MCI) have been well-researched, but most previous studies required subjective cognitive complaints (SCC) as a diagnostic criterion, diagnosed MCI based on a single screening test or lacked analyses in relation to neuropsychological impairment. This longitudinal voxel-based morphometry study aimed to overcome these limitations: The relationship between regional gray matter (GM) atrophy and behavioral performance was investigated over the course of 3 years in individuals unaware of cognitive decline, identified as amnestic MCI based on an extensive neuropsychological test battery. Region of interest analyses revealed GM atrophy in the left amygdala, hippocampus, and parahippocampus in MCI individuals compared to normally aging participants, which was specifically related to verbal memory impairment and evident already at the first measurement point. These findings demonstrate that GM atrophy is detectable in individuals with amnestic MCI despite unawareness of beginning cognitive decline. Thus, individuals with GM atrophy in regions associated with verbal memory impairment do not necessarily need to experience SCC before meeting neuropsychological criteria for MCI. These results have important implications for future research and diagnostic procedures of MCI.

Predicting Stability of Mild Cognitive Impairment (MCI): Findings of a Community Based Sample.

BACKGROUND: Mild Cognitive Impairment (MCI) is a risk factor for Alzheimer's disease (AD) and other forms of dementia. However, much heterogeneity concerning neuropsychological measures, prevalence and progression rates impedes distinct diagnosis and treatment implications. OBJECTIVE: Aim of the present study was the identification of specific tests providing a high certainty for stable MCI and factors that precipitate instability of MCI in a community based sample examined at three measurement points. METHOD: 130 participants were tested annually with an extensive test battery including measures of memory, language, executive functions, intelligence and dementia screening tests. Exclusion criteria at baseline comprised, severe cognitive deficits (e.g. diagnosis of dementia, psychiatric or neurological disease). Possible predictors for stability or instability of MCI-diagnosis were analyzed using Regression and Receiver Operating Characteristic (ROC) curve analysis. Age, IQ and APOE status were tested for moderating effects on the interaction of test performances and group membership. RESULTS: A high prevalence of MCI (49%) was observed at baseline with a reversion rate of 18% after two years. Stability of MCI was related to performances in four measures (VLMT: delayed recall, CERAD: recall drawings, CERAD: Boston Naming Test, Benton Visual Retention Test: number of mistakes). Conversion to MCI is associated with language functions. Reversion to 'normal' was primarily predicted by single domain impairment. There was no significant influence of demographic, medical or genetic variables. CONCLUSION: The results highlight the role of repeated measurements for a reliable identification of functional neuropsychological predictors and better diagnostic reliability. In cases of high uncertainty close monitoring over time is needed in order of estimating outcome.

Neural correlates of alexithymia: a meta-analysis of emotion processing studies.

Alexithymia is a personality trait characterized by difficulties in the experience and cognitive processing of emotions. It is considered a risk factor for a range of psychiatric and neurological disorders. Functional neuroimaging studies investigating the neural correlates of alexithymia have reported inconsistent results. To integrate previous findings, we conducted a parametric coordinate-based meta-analysis including fifteen neuroimaging studies on emotion processing in alexithymia. During the processing of negative emotional stimuli, alexithymia was associated with a diminished response of the amygdala, suggesting decreased attention to such stimuli. Negative stimuli additionally elicited decreased activation in supplementary motor and premotor brain areas and in the dorsomedial prefrontal cortex, possibly underlying poor empathic abilities and difficulties in emotion regulation associated with alexithymia. Positive stimuli elicited decreased activation in the right insula and precuneus, suggesting reduced emotional awareness in alexithymia regarding positive affect. Independent of valence, higher (presumably compensatory) activation was found in the dorsal anterior cingulate possibly indicating increased cognitive demand. These results suggest valence-specific as well as valence-independent effects of alexithymia on the neural processing of emotions.