Ghrelin decreases sensitivity to negative feedback and increases prediction-error related caudate activity in humans, a randomized controlled trial.

The stomach-derived hormone ghrelin plays not only a role in feeding, starvation, and survival, but it has been suggested to also be involved in the stress response, in neuropsychiatric conditions, and in alcohol and drug use disorders. Mechanisms related to reward processing might mediate ghrelin's broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (n = 30), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants' task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (t = -2.448, p = 0.021), while reward sensitivity was unaltered (t = 0.8, p = 0.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis: t-values ≥ 4.21, p-values ≤ 0.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors.

Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Contributions of Polygenic Risk and Disease Status to Gray Matter Abnormalities in Major Depression.

BACKGROUND: Gray matter (GM) abnormalities in depression are potentially attributable to some combination of trait, state, and illness history factors. Here, we sought to determine the contributions of polygenic risk for depression, depressive disease status, and the interaction of these factors to these GM abnormalities. METHODS: We conducted a cross-sectional comparison using a 2 × 3 factorial design examining effects of polygenic risk for depression (lower vs. upper quartile) and depression status (never depressed, currently depressed, or remitted depression) on regional GM concentration and GM volume. Participants were a subset of magnetic resonance imaging-scanned UK Biobank participants comprising 2682 people (876 men, 1806 women) algorithmically matched on 16 potential confounders. RESULTS: In women but not men, we observed that elevated polygenic risk for depression was associated with reduced cerebellar GM volume. This deficit occurred in salience and dorsal attention network regions of the cerebellum and was associated with poorer performance on tests of attention and executive function but not fluid intelligence. Moreover, in women with current depression compared to both women with remitted depression and women who never had depression, we observed GM reductions in ventral and medial prefrontal, insular, and medial temporal regions. These state-related abnormalities remained when accounting for antidepressant medication status. CONCLUSIONS: Neuroanatomical deficits attributed broadly to major depression are more likely due to an aggregation of independent factors. Polygenic risk for depression accounted for cerebellar structural abnormalities that themselves accounted for cognitive deficits observed in this disorder. Medial and ventral prefrontal, insular, and temporal cortex deficits constituted a much larger proportion of the aggregate deficit and were attributable to the depressed state.

Efficient Brain Age Prediction from 3D MRI Volumes Using 2D Projections.

Using 3D CNNs on high-resolution medical volumes is very computationally demanding, especially for large datasets like UK Biobank, which aims to scan 100,000 subjects. Here, we demonstrate that using 2D CNNs on a few 2D projections (representing mean and standard deviation across axial, sagittal and coronal slices) of 3D volumes leads to reasonable test accuracy (mean absolute error of about 3.5 years) when predicting age from brain volumes. Using our approach, one training epoch with 20,324 subjects takes 20-50 s using a single GPU, which is two orders of magnitude faster than a small 3D CNN. This speedup is explained by the fact that 3D brain volumes contain a lot of redundant information, which can be efficiently compressed using 2D projections. These results are important for researchers who do not have access to expensive GPU hardware for 3D CNNs.

Towards a multilevel model of major depression: genes, immuno-metabolic function, and cortico-striatal signaling.

Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-level findings in major depressive disorder (MDD). Specifically, we connect recent genome-wide findings in MDD to metabolic and immunological disturbance in this disorder and then detail links between immunological abnormalities and dopaminergic signaling within cortico-striatal circuitry. Following this, we discuss implications of reduced dopaminergic tone for cortico-striatal signal conduction in MDD. Finally, we specify some of the flaws in the current model and propose ways forward for advancing multilevel formulations of MDD most efficiently.

A randomized controlled experimental medicine study of ghrelin in value-based decision making.

BACKGROUNDThe stomach-derived hormone ghrelin stimulates appetite, but the ghrelin receptor is also expressed in brain circuits involved in motivation and reward. We examined ghrelin effects on decision making beyond food or drug reward using monetary rewards.METHODSThirty participants (50% women and 50% men) underwent 2 fMRI scans while receiving i.v. ghrelin or saline in a randomized counterbalanced order.RESULTSStriatal representations of reward anticipation were unaffected by ghrelin, while activity during anticipation of losses was attenuated. Temporal discounting rates of monetary reward were lower overall in the ghrelin condition, an effect driven by women. Discounting rates were inversely correlated with neural activity in a large cluster within the left parietal lobule that included the angular gyrus. Activity in an overlapping cluster was related to behavioral choices and was suppressed by ghrelin.CONCLUSIONThis is, to our knowledge, the first human study to extend the understanding of ghrelin's significance beyond the canonical feeding domain or in relation to addictive substances. Contrary to our hypothesis, we found that ghrelin did not affect sensitivity to monetary reward anticipation, but rather resulted in attenuated loss aversion and lower discounting rates for these rewards. Ghrelin may cause a motivational shift toward caloric reward rather than globally promoting the value of reward.TRIAL REGISTRATIONEudraCT 2018-004829-82.FUNDINGSwedish Research Council (2013-07434), Marcus and Marianne Wallenberg foundation (2014.0187) and National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism Intramural Research Program.

Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation.

Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.

A methodological checklist for fMRI drug cue reactivity studies: development and expert consensus.

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

Peripheral and central kynurenine pathway abnormalities in major depression.

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.

Affective context and its uncertainty drive momentary affective experience.

Affect fluctuates in a moment-to-moment fashion, reflecting the continuous relationship between the individual and the environment. Despite substantial research, there remain important open questions regarding how a stream of sensory input is dynamically represented in experienced affect. Here, approaching affect as a temporally dependent process, we show that momentary affect is shaped by a combination of the affective impact of stimuli (i.e., visual images for the current studies) and previously experienced affect. We also found that this temporal dependency is influenced by uncertainty of the affective context. Participants in each trial viewed sequentially presented images and subsequently reported their affective experience, which was modeled based on images' normative affect ratings and participants' previously reported affect. Study 1 showed that self-reported valence and arousal in a given trial is partly shaped by the affective impact of the given images and previously experienced affect. In Study 2, we manipulated context uncertainty by controlling occurrence probabilities for normatively pleasant and unpleasant images in separate blocks. Increasing context uncertainty (i.e., random occurrence of pleasant and unpleasant images) was associated with increased negative affect. In addition, the relative contribution of the most recent image to experienced pleasantness increased with increasing context uncertainty. Taken together, these findings provide clear behavioral evidence that momentary affect is a temporally dependent and continuous process, which reflects the affective impact of recent input variables and the previous internal state, and that this process is sensitive to the affective context and its uncertainty. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Altered resting-state functional connectome in major depressive disorder: a mega-analysis from the PsyMRI consortium.

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.psymri.com ). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

Investigating the Neural Correlates of the Affect Heuristic Using Functional Magnetic Resonance Imaging.

This study investigated the neural correlates of the so-called affect heuristic, which refers to the phenomenon whereby individuals tend to rely on affective states rather than rational deliberation of utility and probabilities during judgments of risk and utility of a given event or scenario. The study sought to explore whether there are shared regional activations during both judgments of relative risk and relative benefit of various scenarios, thus being a potential candidate of the affect heuristic. Using functional magnetic resonance imaging, we developed a novel risk perception task, based on a preexisting behavioral task assessing the affect heuristic. A whole-brain voxel-wise analysis of a sample of participants (n = 42) during the risk and benefit conditions revealed overlapping clusters in the left insula, left inferior frontal gyrus, and left medial frontal gyrus across conditions. Extraction of parameter estimates of these clusters revealed that activity of these regions during both tasks was inversely correlated with a behavioral measure assessing the inclination to use the affect heuristic. More activity in these areas during risk judgments reflect individuals' ability to disregard momentary affective impulses. The insula may be involved in integrating viscero-somatosensory information and forming a representation of the current emotional state of the body, whereas activity in the left inferior frontal gyrus and medial frontal gyrus indicates that executive processes may be involved in inhibiting the impulse of making judgments in favor of deliberate risk evaluations.

Psychophysiological and Neural Support for Enhanced Emotional Reactivity in Female Adolescents With Nonsuicidal Self-injury.

BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent in adolescent populations worldwide. Emotion dysregulation is believed to contribute to NSSI, but underlying mechanisms are less known. We combined psychophysiological and neural data with subjective self-report in close temporal proximity to examine the mechanisms underlying emotion processing in adolescents with NSSI relative to control adolescents without a psychiatric diagnosis. METHODS: Thirty female adolescents with NSSI and 30 age-matched female control subjects were included in this case-control study. Participants were presented with negative affective pictures during a functional magnetic resonance imaging scan. In a separate facial electromyography session, the same participants were shown positive and negative affective images and also provided ratings of valence and arousal. RESULTS: Participants with NSSI responded to affective images with greater positive (e.g., zygomatic) and greater negative (e.g., corrugator) reactivity. We found no differences in self-reported affect in response to the images. Analyses of the negative picture-viewing functional magnetic resonance imaging data showed a significant positive correlation between anterior insula response and the averaged electromyography magnitude in NSSI, but not in control subjects. CONCLUSIONS: Adolescents with NSSI show enhanced emotional reactivity that is associated with anterior insula responding, but no abnormalities in self-reported affect. This discrepancy between self-report and objective measures of emotional reactivity potentially indicates a suppression of the emotional reaction in adolescents with NSSI. Moreover, the current data suggest potential targets for novel therapeutic approaches that can be combined with existing clinical treatment, such as real-time electromyography-based biofeedback focusing on emotional awareness, labeling, and expressing emotional experiences.

Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females.

Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood-brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r = - 0.44, p = 0.002) and depression (r = - 0.50, p = 0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t(33) = 3.1, pFDR = 0.02) and right lateral orbitofrontal cortex (OFC; t(33) = 2.9, pFDR = 0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r = 0.28, p = 0.007) and left lateral OFC (r = 0.29, p = 0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.

Affective calculus: The construction of affect through information integration over time.

Humans receive a constant stream of input that potentially influence their affective experience. Despite intensive research on affect, it is still largely unknown how various sources of information are integrated into the single, unified affective features that accompany consciousness. Here, we aimed to investigate how a stream of evocative input we receive is dynamically represented in self-reported affect. In 4 experiments, participants viewed a number of sequentially presented images and reported their momentary affective experience on valence and arousal scales. The number and duration of images in a trial varied across studies. In Study 4, we also measured participants' physiological responses while they viewed images. We formulated and compared several models with respect to their capacity to predict self-reported affect based on normative image ratings, physiological measurements, and prior affective experience (measured in the previous trial). Our data best supported a model incorporating a temporally sensitive averaging mechanism for affective integration that assigns higher weights to affectively more potent and recently represented stimuli. Crucially, affective averaging of sensory information and prior affect accounted for distinct contributions to currently experienced affect. Taken together, the current study provides evidence that prior affect and integrated affective impact of stimuli partly shape currently experienced affect. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Tactile direction discrimination in humans after stroke.

Sensing movements across the skin surface is a complex task for the tactile sensory system, relying on sophisticated cortical processing. Functional MRI has shown that judgements of the direction of tactile stimuli moving across the skin are processed in distributed cortical areas in healthy humans. To further study which brain areas are important for tactile direction discrimination, we performed a lesion study, examining a group of patients with first-time stroke. We measured tactile direction discrimination in 44 patients, bilaterally on the dorsum of the hands and feet, within 2 weeks (acute), and again in 28 patients 3 months after stroke. The 3-month follow-up also included a structural MRI scan for lesion delineation. Fifty-nine healthy participants were examined for normative direction discrimination values. We found abnormal tactile direction discrimination in 29/44 patients in the acute phase, and in 21/28 3 months after stroke. Lesions that included the opercular parietal area 1 of the secondary somatosensory cortex, the dorsolateral prefrontal cortex or the insular cortex were always associated with abnormal tactile direction discrimination, consistent with previous functional MRI results. Abnormal tactile direction discrimination was also present with lesions including white matter and subcortical regions. We have thus delineated cortical, subcortical and white matter areas important for tactile direction discrimination function. The findings also suggest that tactile dysfunction is common following stroke.

Brain Changes Induced by Electroconvulsive Therapy Are Broadly Distributed.

BACKGROUND: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. METHODS: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. RESULTS: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = -.44, p < .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. CONCLUSIONS: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

Brain-based Classification of Negative Social Bias in Adolescents With Nonsuicidal Self-injury: Findings From Simulated Online Social Interaction.

BACKGROUND: Interpersonal stress and perceived rejection have been clinically observed as common triggers of nonsuicidal self-injury (NSSI), with self-injury behavior regulating both affective and social experiences. We investigated whether the subjective interpretation of social interaction in a simulated online environment might be biased in the NSSI group, and the brain mechanisms underlying the experience. METHODS: Thirty female adolescent patients with NSSI and thirty female age-matched controls were investigated in this case-control study. In our novel task that simulates interaction on current social media platforms, participants indicated whether they liked or disliked pictures of other players during a functional magnetic resonance imaging (fMRI) scan. Participants also viewed positive and negative feedback directed toward them by others. The task also assessed the subjective effects of the social interaction. Finally, subjects underwent a separate facial electromyography session, which measured facial expressions processing. OUTCOMES: Behaviorally, the NSSI group showed a negative bias in processing social feedback from others. A multi-voxel pattern analysis (MVPA) identified brain regions that robustly classified NSSI subjects and controls. Regions in which mutual activity contributed to the classification included dorsomedial prefrontal cortex and subgenual anterior cingulate cortex, a region implicated in mood control. In the NSSI group, multi-voxel classification scores correlated with behavioral sensitivity to negative feedback from others. Results remained significant after controlling for medication, symptoms of depression, and symptoms of borderline personality disorder. INTERPRETATION: This study identified behavioral and neural signatures of adolescents with NSSI during social interaction in a simulated social media environment. These findings highlight the importance of understanding social information processing in this clinical population and can potentially advance treatment approaches.

Touch aversion in patients with interpersonal traumatization.

BACKGROUND: Interpersonal touch is a key aspect of human interaction and a usually very comforting experience. For patients suffering from posttraumatic stress disorders (PTSD) caused by interpersonal traumatization, such touch is affectively ambiguous. METHODS: In two studies, we investigated the experience and neural processing of various types of interpersonal and impersonal touch in patients as compared with healthy controls. RESULTS: Patients strongly disliked show, interpersonal skin-to-skin stroking, while controls appreciated this kind of touch. No group differences were observed for ratings of impersonal touch. Similarly, the neural activation differed between groups for interpersonal, but not for impersonal touch. The interpersonal touch aversion in patients was accompanied by enhanced blood-oxygen-level-dependent response in the superior temporal gyrus and by a pronounced reduction of response in the hippocampus. This reduction was significantly correlated to symptoms of negative alterations and arousal within the patients. CONCLUSION: We interpret the hippocampal suppression as an attempt to control traumatic memories, evoked by interpersonal touch. This mechanism may maintain the aversion of interpersonal touch in patients with interpersonal trauma-related PTSD.

Functional Connectivity Between Extrastriate Body Area and Default Mode Network Predicts Depersonalization Symptoms in Major Depression: Findings From an A Priori Specified Multinetwork Comparison.

BACKGROUND: Depersonalization/derealization disorder is a dissociative disorder characterized by feelings of unreality and detachment from the self and surroundings. Depersonalization/derealization disorder is classified as a primary disorder, but depersonalization symptoms are frequently observed in mood and anxiety disorders. In the context of major depressive disorder (MDD), depersonalization symptoms are associated with greater depressive severity as indexed by treatment resistance, inpatient visits, and duration of depressive episodes. In the current investigation, we tested four network-based, neural-functional hypotheses of depersonalization in MDD. These hypotheses were framed in terms of functional relationships between 1) extrastriate body area and default mode network (DMN); 2) hippocampus and DMN; 3) medial prefrontal cortex and ventral striatum; and 4) posterior and anterior insular cortex. METHODS: We conducted functional magnetic resonance imaging during resting state on 28 female patients with MDD and 27 control subjects with no history of a psychiatric disorder. Functional connectivity between seed and target regions as specified by our network-level hypotheses was computed and correlated with scores on the Cambridge Depersonalization Scale. We used a conservative, unbiased bootstrapping procedure to test the significance of neural-behavioral correlations observed under each of the four models tested. RESULTS: Of the four neural-functional models of depersonalization symptoms tested, only the model proposing that reduced connectivity between the extrastriate body area and DMN predicts higher levels of depersonalization symptoms in MDD was confirmed. CONCLUSIONS: Our results indicate that depersonalization/derealization disorder symptoms in patients with depression are related to reduced functional connectivity between brain regions that are proposed to support processing of body-related (extrastriate body area) and autobiographical (DMN) information.