The effect of meninges on the electric fields in TES and TMS: Numerical modeling with adaptive mesh refinement

Background When modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges – dura, arachnoid, and pia mater – are often neglected due to high computational costs. Objective We investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model. Method We use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas ( and ) and for several distinct TES and TMS setups. Results Maximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (∼6%) decrease on average when the meninges are included. Conclusion Our results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online

Escitalopram enhances synchrony of brain responses during emotional narratives in patients with major depressive disorder

One-week treatment with escitalopram decreases amygdala responses to fearful facial expressions in depressed patients, but it remains unknown whether it also modulates processing of complex and freely processed emotional stimuli resembling daily life emotional situations. Inter-subject correlation (ISC) offers a means to track brain activity during complex, dynamic stimuli in a model-free manner. Twenty-nine treatment-seeking patients with major depressive disorder were randomized in a double-blind study design to receive either escitalopram or placebo for one week, after which functional magnetic resonance imaging (fMRI) was performed. During fMRI the participants listened to spoken emotional narratives. Level of ISC between the escitalopram and the placebo group was compared across all the narratives and separately for the episodes with positive and negative valence. Across all the narratives, the escitalopram group had higher ISC in the default mode network of the brain as well as in the fronto-temporal narrative processing regions, whereas lower ISC was seen in the middle temporal cortex, hippocampus and occipital cortex. Escitalopram increased ISC during positive parts of the narratives in the precuneus, medial prefrontal cortex, anterior cingulate and fronto-insular cortex, whereas there was no significant synchronization in brain responses to positive vs negative events in the placebo group. Increased ISC may imply improved emotional synchronization with others, particularly during observation of positive events. Further studies are needed to test whether this contributes to the later therapeutic effect of escitalopram.Peer reviewe

Short-term escitalopram treatment normalizes aberrant self-referential processing in major depressive disorder

Background: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. Methods: Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. Results: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. Limitations: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. Conclusion: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.Peer reviewe

Aberrant Cortical Integration in First-Episode Psychosis During Natural Audiovisual Processing

BACKGROUND: Functional magnetic resonance imaging studies of psychotic disorders have reported both hypoactivity and hyperactivity in numerous brain regions. In line with the dysconnection hypothesis, these regions include cortical integrative hub regions. However, most earlier studies focused on a single cognitive function at a time, assessed by delivering artificial stimuli to patients with chronic psychosis. Thus, it remains unresolved whether these findings are present already in early psychosis and whether they translate to real-life-like conditions that require multisensory processing and integration. METHODS: Scenes from the movie Alice in Wonderland (2010) were shown to 51 patients with first-episode psychosis (16 women) and 32 community-based control subjects (17 women) during 3T functional magnetic resonance imaging. We compared intersubject correlation, a measure of similarity of brain signal time courses in each voxel, between the groups. We also quantified the hubness as the number of connections each region has. RESULTS: Intersubject correlation was significantly lower in patients with first-episode psychosis than in control subjects in the medial and lateral prefrontal, cingulate, precuneal, and parietotemporal regions, including the default mode network. Regional magnitude of between-group difference in intersubject correlation was associated with the hubness. CONCLUSIONS: Our findings provide novel evidence for the dysconnection hypothesis by showing that during complex real-life-like stimulation, the most prominent functional alterations in psychotic disorders relate to integrative brain functions. Presence of such abnormalities in first-episode psychosis rules out long-term effects of illness or medication. These methods can be used in further studies to map widespread hub alterations in a single functional magnetic resonance imaging session and link them to potential downstream and upstream pathways.Peer reviewe

Affective Adaptation to Repeated SIT and MICT Protocols in Insulin-Resistant Subjects

Introduction The aim of this study was to investigate affective responses to repeated sessions of sprint interval training (SIT) in comparison with moderate-intensity continuous training (MICT) in insulin-resistant subjects.Methods Twenty-six insulin-resistant adults (age, 49 (4) yr; 10 women) were randomized into SIT (n = 13) or MICT (n = 13) groups. Subjects completed six supervised training sessions within 2 wk (SIT session, 4-6 x 30 s all-out cycling/4-min recovery; MICT session, 40-60 min at 60% peak work load). Perceived exertion, stress, and affective state were assessed with questionnaires before, during and after each training session.Results Perceived exertion, displeasure, and arousal were higher during the SIT compared with MICT sessions (all P 0.05).Conclusions The perceptual and affective responses are more negative both during and acutely after SIT compared with MICT in untrained insulin-resistant adults. These responses, however, show significant improvements already within six training sessions, indicating rapid positive affective and physiological adaptations to continual exercise training, both SIT and MICT. These findings suggest that even very intense SIT is mentally tolerable alternative for untrained people with insulin resistance

A single dose of mirtazapine attenuates neural responses to self-referential processing

Increased self-focus is a core factor in the psychopathology of depression. Cortical midline structures (CMS) are implicated in the neurobiology of self, depression and antidepressant treatment response. Mirtazapine, an antidepressant that increases serotonin and norepinephrine release, enhances processing of positive and attenuates processing of negative emotional information in healthy volunteers after a single dose. These early changes, which are opposite to the negative information bias in depression, may be important for the therapeutic effect of mirtazapine. It nevertheless remains unresolved whether/how mirtazapine specifically influences processing of self-referential emotional information. Half of the healthy volunteers (n=15/30) received a single dose of mirtazapine, in an open-label design, two hours before functional magnetic resonance imaging (fMRI), and the other half was scanned as a control group without medication. During fMRI the participants categorized positive and negative self-referential adjectives. Mirtazapine attenuated responses to self-referential processing in the medial prefrontal cortex and the anterior cingulate cortex. Mirtazapine further decreased responses to positive self-referential processing in the posterior cingulate cortex and parietal cortex. These decreased responses of the CMS suggest that mirtazapine may rapidly improve the ability of the CMS to down-regulate self-referential processing. In depressed patients, this could lead to decreased self-focus and rumination, contributing to the antidepressant effect.Peer reviewe

Decoding brain basis of laughter and crying in natural scenes

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66–77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others’ bonding and distress signals

Neurons in the human amygdala encode face identity, but not gaze direction

The amygdala is important for face processing, and direction of eye gaze is one of the most socially salient facial signals. Recording from over 200 neurons in the amygdala of neurosurgical patients, we found robust encoding of the identity of neutral-expression faces, but not of their direction of gaze. Processing of gaze direction may rely on a predominantly cortical network rather than the amygdala

Escitalopram enhances synchrony of brain responses during emotional narratives in patients with major depressive disorder

One-week treatment with escitalopram decreases amygdala responses to fearful facial expressions in depressed patients, but it remains unknown whether it also modulates processing of complex and freely processed emotional stimuli resembling daily life emotional situations. Inter-subject correlation (ISC) offers a means to track brain activity during complex, dynamic stimuli in a model-free manner.& nbsp; Twenty-nine treatment-seeking patients with major depressive disorder were randomized in a double-blind study design to receive either escitalopram or placebo for one week, after which functional magnetic resonance imaging (fMRI) was performed. During fMRI the participants listened to spoken emotional narratives. Level of ISC between the escitalopram and the placebo group was compared across all the narratives and separately for the episodes with positive and negative valence.& nbsp; & nbsp;Across all the narratives, the escitalopram group had higher ISC in the default mode network of the brain as well as in the fronto-temporal narrative processing regions, whereas lower ISC was seen in the middle temporal cortex, hippocampus and occipital cortex. Escitalopram increased ISC during positive parts of the narratives in the precuneus, medial prefrontal cortex, anterior cingulate and fronto-insular cortex, whereas there was no significant synchronization in brain responses to positive vs negative events in the placebo group. Increased ISC may imply improved emotional synchronization with others, particularly during observation of positive events. Further studies are needed to test whether this contributes to the later therapeutic effect of escitalopram

Cross-cultural similarity in relationship-specific social touching

Many species use touching for reinforcing social structures, and particularly, non-human primates use social grooming for managing their social networks. However, it is still unclear how social touch contributes to the maintenance and reinforcement of human social networks. Human studies in Western cultures suggest that the body locations where touch is allowed are associated with the strength of the emotional bond between the person touched and the toucher. However, it is unknown to what extent this relationship is culturally universal and generalizes to non-Western cultures. Here, we compared relationship-specific, bodily touch allowance maps across one Western (N = 386, UK) and one East Asian (N = 255, Japan) country. In both cultures, the strength of the emotional bond was linearly associated with permissible touch area. However, Western participants experienced social touching as more pleasurable than Asian participants. These results indicate a similarity of emotional bonding via social touch between East Asian and Western cultures