Michael Gaebler

WHITE MATTER INTEGRITY AND ITS RELATIONSHIP TO PTSD AND CHILDHOOD TRAUMA—A SYSTEMATIC REVIEW AND META-ANALYSIS

Recent reviews and meta‐analyses reported structural gray matter changes in patients suffering from adult‐onset posttraumatic stress disorder (PTSD) and in subjects with and without PTSD who experienced childhood trauma. However, it remains unclear if such structural changes are also affecting the white matter. The aim of this systematic review is to provide a comprehensive overview of all empirical investigations measuring white matter integrity in populations affected by PTSD and/or childhood trauma. To this end, results from different methodological approaches were included. Twenty‐five articles are reviewed of which 10 pertained to pediatric PTSD and the effects of childhood trauma measured during childhood, seven to the effects of childhood trauma measured during adulthood, and eight to adult‐onset PTSD. Overall, reductions in white matter volume were reported more often than increases in these populations. However, the heterogeneity of the exact locations indicates only a weak overlap across published studies. In addition, a meta‐analysis was carried out on seven whole‐brain diffusion tensor imaging (DTI) studies in adults. Significant clusters of both increases and decreases were identified in various structures, most notably the cingulum and the superior longitudinal fasciculus. Future research directions are discussed.

Heart rate variability and its neural correlates during emotional face processing in social anxiety disorder

The monitoring and regulation of ones own physiological reactions and cardioregulatory abnormalities are central to the aetiology and maintenance of social anxiety disorder (SAD). We therefore explored the neural correspondences of these heart rate alterations. 21 patients with SAD and 21 matched healthy controls (HCs) underwent 3T-fMRI scanning. Simultaneously, high-frequency heart rate variability (HF-HRV) was acquired during a short-term resting period and an implicit emotional face-matching task. Compared to HCs, patients with SAD reported increased self-focused attention while being less accurate in estimating their heartbeats. Physiologically, they showed less HF-HRV at rest and during task. Across groups, HF-HRV at rest correlated positively with activation in visual face-processing areas. The right caudate nucleus showed an interaction of group and cardioregulation: Activation in this region was positively correlated in patients with SAD but negatively in HCs. We conclude that cardioregulation is altered in SAD on the subjective, physiological, and brain level.

Stereoscopic depth increases intersubject correlations of brain networks

Three-dimensional movies presented via stereoscopic displays have become more popular in recent years aiming at a more engaging viewing experience. However, neurocognitive processes associated with the perception of stereoscopic depth in complex and dynamic visual stimuli remain understudied. Here, we investigate the influence of stereoscopic depth on both neurophysiology and subjective experience. Using multivariate statistical learning methods, we compare the brain activity of subjects when freely watching the same movies in 2D and in 3D. Subjective reports indicate that 3D movies are more strongly experienced than 2D movies. On the neural level, we observe significantly higher intersubject correlations of cortical networks when subjects are watching 3D movies relative to the same movies in 2D. We demonstrate that increases in intersubject correlations of brain networks can serve as neurophysiological marker for stereoscopic depth and for the strength of the viewing experience.

Aberrant Salience Is Related to Dysfunctional Self-Referential Processing in Psychosis

BACKGROUND A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis. We investigated the neural correlates of self-referential processing, aberrant salience attribution, and the relationship between these 2 measures across the psychosis continuum. METHODS Twenty-nine schizophrenia patients, 24 healthy individuals with subclinical delusional ideation, and 50 healthy individuals participated in this study. Aberrant salience was assessed behaviorally in terms of reaction times to task irrelevant cues. Participants performed a self-reference task during fMRI in which they had to apply neutral trait words to them or to a public figure. The correlation between self-referential processing and aberrant salience attribution was tested. RESULTS Schizophrenia patients displayed increased aberrant salience attribution compared with healthy controls and individuals with subclinical delusional ideation, while the latter exhibited intermediate aberrant salience scores. In the self-reference task, schizophrenia patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC), but individuals with subclinical delusional ideation did not differ from healthy controls. In schizophrenia patients, vmPFC activation correlated negatively with implicit aberrant salience attribution. CONCLUSIONS Higher aberrant salience attribution in schizophrenia patients is related to reduced vmPFC activation during self-referential judgments suggesting that aberrant relevance coding is reflected in decreased neural self-referential processing as well as in aberrant salience attribution.

Neural processing of negative emotional stimuli and the influence of age, sex and task-related characteristics

Negative emotional stimuli are particularly salient events that receive privileged access to neurocognitive resources. At the neural level, the processing of negative stimuli relies on a set of sensory, limbic, and prefrontal areas. However, controversies exist on how demographic and task-related characteristics modulate this brain pattern. Here, we used activation likelihood estimation (ALE) meta-analysis and replicator dynamics to investigate the processing of negative visual stimuli in healthy adults. Our findings endorse the central role of the amygdala. This result might reflect how this structure modulates perceptual and attentional mechanisms in response to emotional stimuli. Additionally, we characterize how the neural processing of negative visual stimuli is influenced by the demographic factors of age and sex as well as by task-related characteristics like stimulus type, emotion category, and task instruction, with the amygdala showing comparable engagement across different sexes, stimulus types, and task instructions. Our findings practically inform experimentation in the affective neurosciences but also suggest brain circuits for neurobiological investigations of affective symptomatology.

The Impact of Stimulus Valence and Emotion Regulation on Sustained Brain Activation: Task-Rest Switching in Emotion

Task-rest interactions, defined as the modulation of brain activation during fixation periods depending on the preceding stimulation and experimental manipulation, have been described repeatedly for different cognitively demanding tasks in various regions across the brain. However, task-rest interactions in emotive paradigms have received considerably less attention. In this study, we therefore investigated task-rest interactions evoked by the induction and instructed regulation of negative emotion. Whole-brain, functional MRI data were acquired from 55 healthy participants. Two-level general linear model statistics were computed to test for differences between conditions, separately for stimulation and for fixation periods, as well as for interactions between stimulation and fixation (task-rest interactions). Results showed that the regulation of negative emotion led to reverse task-rest interactions (decreased activation during stimulation but increased activation during fixation) in the amygdala as well as in visual cortex regions and to concordant task-rest interactions (increased activation during both, stimulation and fixation) in the dorsolateral prefrontal cortex as well as in a number of brain regions at the intersection of the default mode and the dorsal attention networks. Thus, this first whole-brain investigation of task-rest interactions following the induction and regulation of negative emotion identified a widespread specific modulation of brain activation in regions subserving emotion generation and regulation as well as regions implicated in attention and default mode.

Active vision varies across the cardiac cycle

Perception and cognition oscillate with fluctuating bodily states. For example, visual processing has been shown to change with alternating cardiac phases. Here, we study the heartbeat’s role for active information sampling—testing whether humans implicitly act upon their environment so that relevant signals appear during preferred cardiac phases. During the encoding period of a visual memory experiment, participants clicked through a set of emotional pictures to memorize them for a later recognition test. By self-paced key press, they actively prompted the onset of shortly (100-ms) presented pictures. Simultaneously recorded electrocardiograms allowed us to analyse the self-initiated picture onsets relative to the heartbeat. We find that self-initiated picture onsets vary across the cardiac cycle, showing an increase during cardiac systole, while memory performance was not affected by the heartbeat. We conclude that active information sampling integrates heart-related signals, thereby extending previous findings on the association between body-brain interactions and behaviour.

Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate

BACKGROUND Stress activates the central nervous, the autonomic nervous, and the endocrine system. This study aimed to (1) test the usability of salivary cortisone in a standardized psychosocial stressor, (2) create a comprehensive profile of hormonal responses to determine laboratory parameters with high discriminatory power, and (3) analyze their association with psychometric and autonomic stress measures. METHODS Healthy young men (18-35 years) completed either the Trier Social Stress Test (TSST) (n = 33) or a Placebo-TSST (n = 34). Blood and saliva were collected at 14 time points along with state-anxiety (STAI) and heart rate. Serum steroids (cortisol*, cortisone*, dehydroepiandrosterone-sulfate, androstenedione*, progesterone*, 17-hydroxyprogesterone*, testosterone, estradiol*, aldosterone*), salivary cortisol* and cortisone*, copeptin*, adrenocorticoptropic hormone*, corticosteroid-binding globulin, and salivary alpha-amylase* were analyzed. We used mixed-design ANOVAs to test group differences, receiver operator characteristic (ROC) curve analyses to assess the discriminatory power of each measure, and Spearman correlation analyses to probe the association between measures. RESULTS The largest area under the ROC curve was observed in salivary cortisone at 20 min after the end of the TSST (AUC = 0.909 ± 0.044, p < 0.0001). Significant time-by-group interactions were found in the parameters marked with * above, indicating stress-induced increases. The peak response of salivary cortisone was significantly associated with those of STAI (rho = 0.477, p = 0.016) and heart rate (rho = 0.699, p < 0.0001) in the TSST group. CONCLUSION Our study found salivary cortisone to be a stress biomarker with high discriminatory power and significant correlations with subjective and autonomic stress measures. Our results can inform future stress studies of sampling time for different laboratory parameters.

The age-dependent relationship between resting heart rate variability and functional brain connectivity

&NA; Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain – mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0 ± 4.2 years, 119 middle‐aged: 46.3 ± 6.2 years, 129 older: 66.9 ± 4.7 years), gray matter volume (GMV, voxel‐based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed‐based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV‐related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole‐brain functional connectivity analyses, we found an age‐dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed‐based functional connectivity analysis using the vmPFC cluster revealed an HRV‐related cortico‐cerebellar network in younger but not in middle‐aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain‐body interactions and their changes over the lifespan.

A functional connectome phenotyping dataset including cognitive state and personality measures

The dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a high-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.