Tracking the impact of depression in a perspective-taking task

Research has identified impairments in Theory of Mind (ToM) abilities in depressed patients, particularly in relation to tasks involving empathetic responses and belief reasoning. We aimed to build on this research by exploring the relationship between depressed mood and cognitive ToM, specifically visual perspective-taking ability. High and low depressed participants were eye-tracked as they completed a perspective-taking task, in which they followed the instructions of a ‘director’ to move target objects (e.g. a “teapot with spots on”) around a grid, in the presence of a temporarily-ambiguous competitor object (e.g. a “teapot with stars on”). Importantly, some of the objects in the grid were occluded from the director’s (but not the participant’s) view. Results revealed no group-based difference in participants’ ability to use perspective cues to identify the target object. All participants were faster to select the target object when the competitor was only available to the participant, compared to when the competitor was mutually available to the participant and director. Eye-tracking measures supported this pattern, revealing that perspective directed participants’ visual search immediately upon hearing the ambiguous object’s name (e.g. “teapot”). We discuss how these results fit with previous studies that have shown a negative relationship between depression and ToM

Mood Modulates Auditory Laterality of Hemodynamic Mismatch Responses during Dichotic Listening

Hemodynamic mismatch responses can be elicited by deviant stimuli in a sequence of standard stimuli even during cognitive demanding tasks. Emotional context is known to modulate lateralized processing. Right-hemispheric negative emotion processing may bias attention to the right and enhance processing of right-ear stimuli. The present study examined the influence of induced mood on lateralized pre-attentive auditory processing of dichotic stimuli using functional magnetic resonance imaging (fMRI). Faces expressing emotions (sad/happy/neutral) were presented in a blocked design while a dichotic oddball sequence with consonant-vowel (CV) syllables in an event-related design was simultaneously administered. Twenty healthy participants were instructed to feel the emotion perceived on the images and to ignore the syllables. Deviant sounds reliably activated bilateral auditory cortices and confirmed attention effects by modulation of visual activity. Sad mood induction activated visual, limbic and right prefrontal areas. A lateralization effect of emotion-attention interaction was reflected in a stronger response to right-ear deviants in the right auditory cortex during sad mood. This imbalance of resources may be a neurophysiological correlate of laterality in sad mood and depression. Conceivably, the compensatory right-hemispheric enhancement of resources elicits increased ipsilateral processing

Excitation/inhibition balance in the aMCC influences resting state activity in the CEN

Introduction: Excitation/inhibition balance can be used as a predictor not only for the functional regional response in the task-based functional magnetic resonance imaging (fMRI) but also for functional connectivity (FC) strength measured within and between networks [1]. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns [2,3]. However, the results were inconsistent and they were mainly focused on the default mode network confirming that there is a need for more robust and extensive measurements. Therefore, we investigated whole brain associations between the main excitatory – Glu – and inhibitory neurotransmitter – GABA – with the FC of the anterior mid cingulate cortex (aMCC), a node of the salience network (SN), with a particular focus on regions of the central executive network (CEN). We additionally explored how these metabolites influence basic neuronal measurements such as fractional amplitude of low frequency fluctuations (fALFF). Methods: 106 subjects (age = 27.09 ± 6.72, 44 females) completed a research paradigm that included a resting-state fMRI and a magnetic resonance spectroscopy (MRS) session in 7T. An MRS voxel was placed in the aMCC, and Glu, GABA and Creatine (Cr) levels were acquired using a stimulated-echo acquisition mode (STEAM) sequence. A regression analysis was conducted in SPM8 between metabolites and aMCC voxel–seed FC maps with age, sex and grey matter ratio as covariates of nuisance. Additionally, the same regression analysis was performed for fALFF. Results are reported on FWE < 0.05 cluster level significance with an initial threshold of p < 0.001, uncorrected. Results: Glu/Cr and aMCC voxel FC showed a strong negative association in the left posterior frontal gyrus and several nodes of the visual cortex. A regionally converging positive correlation was found between fALFF and GABA/Cr in the left posterior frontal gyrus. Conclusions: Both GABA and Glu levels measured in the aMCC predict the strength and the basal activity of the posterior frontal gyrus, which is a node of the CEN

Excitation/inhibition balance in the aMCC influences resting state activity in the CEN

Introduction: Excitation/inhibition balance can be used as a predictor not only for the functional regional response in the task-based functional magnetic resonance imaging (fMRI) but also for functional connectivity (FC) strength measured within and between networks [1]. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns [2,3]. However, the results were inconsistent and they were mainly focused on the default mode network confirming that there is a need for more robust and extensive measurements. Therefore, we investigated whole brain associations between the main excitatory – Glu – and inhibitory neurotransmitter – GABA – with the FC of the anterior mid cingulate cortex (aMCC), a node of the salience network (SN), with a particular focus on regions of the central executive network (CEN). We additionally explored how these metabolites influence basic neuronal measurements such as fractional amplitude of low frequency fluctuations (fALFF). Methods: 106 subjects (age = 27.09 ± 6.72, 44 females) completed a research paradigm that included a resting-state fMRI and a magnetic resonance spectroscopy (MRS) session in 7T. An MRS voxel was placed in the aMCC, and Glu, GABA and Creatine (Cr) levels were acquired using a stimulated-echo acquisition mode (STEAM) sequence. A regression analysis was conducted in SPM8 between metabolites and aMCC voxel–seed FC maps with age, sex and grey matter ratio as covariates of nuisance. Additionally, the same regression analysis was performed for fALFF. Results are reported on FWE < 0.05 cluster level significance with an initial threshold of p < 0.001, uncorrected. Results: Glu/Cr and aMCC voxel FC showed a strong negative association in the left posterior frontal gyrus and several nodes of the visual cortex. A regionally converging positive correlation was found between fALFF and GABA/Cr in the left posterior frontal gyrus. Conclusions: Both GABA and Glu levels measured in the aMCC predict the strength and the basal activity of the posterior frontal gyrus, which is a node of the CEN

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

A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI’s network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate–glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic–creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength