Impaired cognitive self-awareness mediates the association between alexithymia and excitation/inhibition balance in the pgACC.

BACKGROUND: Previous research showed that automatic emotion regulation is associated with activation of subcortical areas and subsequent feedforward processes to cortical areas. In contrast, cognitive awareness of emotions is mediated by negative feedback from cortical to subcortical areas. Pregenual anterior cingulate cortex (pgACC) is essential in the modulation of both affect and alexithymia. We considered the interplay between these two mechanisms in the pgACC and their relationship with alexithymia. METHOD: In 68 healthy participants (30 women, age = 26.15 ± 4.22) we tested associations of emotion processing and alexithymia with excitation/inhibition (E/I) balance represented as glutamate (Glu)/GABA in the pgACC measured via magnetic resonance spectroscopy in 7 T. RESULTS: Alexithymia was positively correlated with the Glu/GABA ratio (N = 41, p = 0.0393). Further, cognitive self-awareness showed an association with Glu/GABA (N = 52, p = 0.003), which was driven by a correlation with GABA. In contrast, emotion regulation was only correlated with glutamate levels in the pgACC (N = 49, p = 0.008). CONCLUSION: Our results corroborate the importance of the pgACC as a mediating region of alexithymia, reflected in an altered E/I balance. Furthermore, we could specify that this altered balance is linked to a GABA-related modulation of cognitive self-awareness of emotions.

Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants.

Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18 and 30 years (early adulthood) after ketamine or placebo infusion. Dissociative symptoms were generally increased only in the ketamine group post-infusion. Specifically, within the ketamine group, men reported significantly more depersonalization and amnestic symptoms than women. Furthermore, with rising age only men were less affected overall with respect to dissociative symptoms. This suggests a sex-specific protective effect of higher age which may be due to delayed brain maturation in men compared to women. We conclude that it is crucial to include sex and age in studies of drug effects in general and of ketamine-action in specific to tailor more efficient psychiatric treatments. Clinical Trial Registration: EU Clinical Trials Register (EudraCT), trial number: 2010-023414-31.

Functional connectivity changes following interpersonal reactivity.

Attachment experiences substantially influence emotional and cognitive development. Narratives comprising attachment-dependent content were proposed to modulate activation of cognitive-emotional schemata in listeners. We studied the effects after listening to prototypical attachment narratives on wellbeing and countertransference-reactions in 149 healthy participants. Neural correlates of these cognitive-emotional schema activations were investigated in a 7 Tesla rest-task-rest fMRI-study (23 healthy males) using functional connectivity (FC) analysis of the social approach network (seed regions: left and right Caudate Nucleus, CN). Reduced FC between left CN and bilateral dorsolateral prefrontal cortex (DLPFC) represented a general effect of prior auditory stimulation. After presentation of the insecure-dismissing narrative, FC between left CN and bilateral temporo-parietal junction, and right dorsal posterior Cingulum was reduced, compared to baseline. Post-narrative FC-patterns of insecure-dismissing and insecure-preoccupied narratives differed in strength between left CN and right DLPFC. Neural correlates of the moderating effect of individual attachment anxiety were represented in a reduced CN-DLPFC FC as a function of individual neediness-levels. These findings suggest specific neural processing of prolonged mood-changes and schema activation induced by attachment-specific speech patterns. Individual desire for interpersonal proximity was predicted by attachment anxiety and furthermore modulated FC of the social approach network in those exposed to such narratives.

Metabolic mapping reveals sex-dependent involvement of default mode and salience network in alexithymia.

Alexithymia, a personality construct marked by difficulties in processing one's emotions, has been linked to the altered activity in the anterior cingulate cortex (ACC). Although longitudinal studies reported sex differences in alexithymia, what mediates them is not known. To investigate sex-specific associations of alexithymia and neuronal markers, we mapped metabolites in four brain regions involved differentially in emotion processing using a point-resolved spectroscopy MRS sequence in 3 Tesla. Both sexes showed negative correlations between alexithymia and N-acetylaspartate (NAA) in pregenual ACC (pgACC). Women showed a robust negative correlation of the joint measure of glutamate and glutamine (Glx) to NAA in posterior cingulate cortex (PCC), whereas men showed a weak positive association of Glx to NAA in dorsal ACC (dACC). Our results suggest that lowered neuronal integrity in pgACC, a region of the default mode network (DMN), might primarily account for the general difficulties in emotional processing in alexithymia. Association of alexithymia in women extends to another region in the DMN-PCC, while in men a region in the salience network (SN) was involved. These observations could be representative of sex specific regulation strategies that include diminished internal evaluation of feelings in women and cognitive emotion suppression in men.