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There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adul

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE = 0.037; right: d = -0.104, p FWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE < 0.001; right: d = -0.158, p FWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE = 0.006; right: d = 0.099, p FWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adol

Skill learning induces changes in estimates of gray matter volume (GMV) in the human brain, commonly detectable with magnetic resonance imaging (MRI). Rapid changes in GMV estimates while executing tasks may however confound between- and within-subject differences. Fluctuations in arterial blood flow are proposed to underlie this apparent task-related tissue plasticity. To test this hypothesis, we acquired multiple repetitions of structural T1-weighted and functional blood-oxygen level-dependent (BOLD) MRI measurements from 51 subjects performing a finger-tapping task (FTT; á 2 min) repeatedly for 30–60 min. Estimated GMV was decreased in motor regions during FTT compared with rest. Motor-related BOLD signal changes did not overlap nor correlate with GMV changes. Nearly simultaneous BOLD signals cannot fully explain task-induced changes in T1-weighted images. These sensitive and behavior-related GMV changes pose serious questions to reproducibility across studies, and morphological investigations during skill learning can also open new avenues on how to study rapid brain plasticity.

Background: Månsson et al., Biological Psychiatry, In press: Biomarkers of psychiatric treatment response remain elusive. Functional magnetic resonance imaging (fMRI) has shown promise, but low reliability has limited the utility of typical fMRI measures (e.g., average brain signal) as harbingers of treatment success. Notably, although historically considered a source of “noise,” temporal brain signal variability continues to gain momentum as a sensitive and reliable indicator of individual differences in neural efficacy, yet has not been examined in relation to psychiatric treatment outcomes. Methods: Forty-five patients with social anxiety disorder were scanned twice (11 weeks apart) using simple task-based and resting-state fMRI to capture moment-to-moment neural variability. After fMRI test-retest, patients underwent a 9-week cognitive-behavioral therapy. Multivariate modeling and reliability-based cross-validation were utilized to perform brain-based prediction of treatment outcomes. Results: Task-based brain signal variability was the strongest contributor in a treatment outcome prediction model (total r[ACTUAL,PREDICTED]=.77) - outperforming self-reports, resting-state neural variability, and standard mean-based measures of neural activity. Notably, task-based brain signal variability showed excellent test-retest reliability (intraclass correlation coefficient=.80), even with a task length less than 3 minutes long. Conclusions: Rather than a source of undesirable “noise”, moment-to-moment fMRI signal variability may instead serve as a highly reliable and efficient prognostic indicator of clinical outcome., Swedish Research Council (2018-06729, and 2016-02228); Swedish Brain Foundation (FO-2016-0106); Emmy Noether Programme grant from the German Research Foundation; Max Planck UCL Centre for Computational Psychiatry and Ageing Research in Berlin.

Background: Biomarkers of psychiatric treatment response remain elusive. Functional magnetic resonance imaging (fMRI) has shown promise, but low reliability has limited the utility of typical fMRI measures (e.g., average brain signal) as harbingers of treatment success. Notably, although historically considered a source of noise, temporal brain signal variability continues to gain momentum as a sensitive and reliable indicator of individual differences in neural efficacy, yet has not been examined in relation to psychiatric treatment outcomes. Methods: A total of 45 patients with social anxiety disorder were scanned twice (11 weeks apart) using simple task-based and resting-state fMRI to capture moment-to-moment neural variability. After fMRI test-retest, patients underwent a 9-week cognitive behavioral therapy. Multivariate modeling and reliability-based cross-validation were used to perform brain-based prediction of treatment outcomes. Results: Task-based brain signal variability was the strongest contributor in a treatment outcome prediction model (total rACTUAL,PREDICTED = 0.77), outperforming self-reports, resting-state neural variability, and standard mean-based measures of neural activity. Notably, task-based brain signal variability showed excellent test-retest reliability (intraclass correlation coefficient = 0.80), even with a task length less than 3 minutes long. Conclusions: Rather than a source of undesirable noise, moment-to-moment fMRI signal variability may instead serve as a highly reliable and efficient prognostic indicator of clinical outcome., This work was supported by the Swedish Research Council (Grant Nos. 2018-06729 and 2016-02228 [to KM and TF]) and the Swedish Brain Foundation (Grant No. FO-2016-0106 [to KM and TF]). DG and KM were supported partially by an Emmy Noether Programme grant from the German Research Foundation (to DG) and by the Max Planck UCL Centre for Computational Psychiatry and Ageing Research in Berlin.

The objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC). Whole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N = 227, aged 18–76 years old, male/female = 99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index and connectivity density index utilizing the convolutions of the cross-correlation histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately. With the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyri, posterior cingulate cortex (PCC), right insula and inferior parietal lobule of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: (1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; (2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; and (3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age. The proposed QDA framework can produce threshold-free and voxel-wise RFC metrics from R-fMRI data. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in, This work was supported by China Scholarship Council, Zhejiang Natural Science Foundation of China (No. LY18E070005), Key Research and Development Program of Zhejiang Province (No. 2020C03020), and Stockholm Regional ALF fund and the Joint China-Sweden Mobility program from the Swedish Foundation for International Cooperation Research and Higher Education (Dnr: 495 CH2019-8397).

To investigate the impact of adult age on the brain functional connectivity, whole-brain resting-state functional magnetic resonance imaging (R-fMRI) data were acquired on a 3T clinical MRI scanner in a cohort of 227, right-handed, native Swedish-speaking, healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). The dataset is mainly consisted of a younger (18-30 years old n=124, males/females=51/73) and elderly adult (n=76, 60-76 years old, males/females=35/41) subgroups. The dataset was analyzed using a new data-driven analysis (QDA) framework. With QDA two types of threshold-free voxel-wise resting-state functional connectivity (RFC) metrics were derived: the connectivity strength index (CSI) and connectivity density index (CDI), which can be utilized to assess the brain changes in functional connectivity associated with adult age. The dataset can also be useful as a reference to identify abnormal changes in brain functional connectivity resulted from neurodegenerative or neuropsychiatric disorders., This work was supported by China Scholarship Council, Zhejiang Natural Science Foundation of China (No. LY18E070005), Key Research and Development Program of Zhejiang Province (No. 2020C03020), and Stockholm Regional ALF fund.

Gender identity is a core aspect of self-identity and is usually congruent with birth-assigned sex and own body sex-perception. The neuronal circuits underlying gender identity are unknown, but greater awareness of transgenderism has sparked interest in studying these circuits. We did this by comparing brain activation and connectivity in transgender individuals (for whom gender identity and birth-assigned sex are incongruent) with that in cisgender controls (for whom they are congruent) when performing a body self-identification task during functional magnetic resonance imaging. Thirty transgender and 30 cisgender participants viewed images of their own bodies and bodies morphed in sex toward or opposite to birth-assigned sex, rating each image to the degree they identified with it. While controls identified with images of themselves, transgender individuals identified with images morphed opposite to their birth-assigned sex. After covarying out the effect of self-similarity ratings, both groups activated similar self- and body-processing systems when viewing bodies that aligned with their gender identity rather than birth-assigned sex. Additionally, transgender participants had greater limbic involvement when viewing ambiguous, androgynous images of themselves morphed toward their gender identity. These results shed light on underlying self-processing networks specific to gender identity and uncover additional involvement of emotional processing in transgender individuals.

Normal adult aging is associated with decline in some socioemotional abilities, such as the ability to recognize emotions in others, and age-related neurobiological processes may contribute to these deficits. There is increasing evidence that the neuropeptide oxytocin plays a key role in social cognition, including emotion recognition. The mechanisms through which oxytocin promotes emotion recognition are not well understood yet, and particularly in aging. In a randomized, double-blind, placebo-controlled within-subjects design, we investigated the extent to which a single dose of 40 IU of intranasal oxytocin facilitates emotion recognition in 40 younger (M = 24.90 yrs., SD = 2.97, 48% women) and 40 older (M = 69.70 yrs., SD = 2.99, 55% women) men and women. During two fMRI sessions, participants viewed dynamic positive and negative emotional displays. Preliminary analyses show that younger participants recognized positive and negative emotions more accurately than older participants (p < .001), with this behavioral effect not modulated by oxytocin. In the brain data, however, we found an age x treatment interaction in medial prefrontal cortex (xyz [14, 14, 6], p = .007) and superior temporal gyrus (xyz [53, 9, 2], p = .031). In particular, oxytocin (vs. placebo) reduced activity in these regions for older participants, while it enhanced activity in these regions for younger participants. In line with previous research, these findings support the notion that the effects of oxytocin vary by context and individual factors (e.g., social proficiency, age).

The neuropeptide oxytocin plays a prominent role in social and emotional cognition. Findings suggest that intranasal oxytocin administration facilitates emotion recognition in humans, but individual and contextual differences may have moderating effects. A major caveat in this line of work is its predominant focus on young males, which limits current knowledge and generalizability across gender. To uncover potential gender effects, the present study included 32 men (mean age 45.78, sd. 22.87) and 39 women (mean 47.87, sd. 22.59). Utilizing a randomized, double-blind, placebo-controlled, within-subjects design, participants self-administered a single-dose of 40 IUs intranasal oxytocin 40 minutes prior to completion of a dynamic emotion recognition task in the MRI scanning. The task paradigm used positive and negative stimuli from the Geneva Multimodal Emotion Portrayals Core Set. Preliminary analyses show that oxytocin induced dorsomedial prefrontal cortex (dmPFC) activity reductions during exposure to negative (relative to positive) stimuli in women, while dmPCF activity was increased under this condition in men. We observed no effect of sex in the behavioral data, however, the results show a similar trend as in brain data. We speculate that the effects of oxytocin on brain activity during emotion recognition may be related to emotion-regulatory and mentalization processes. The observed gender-differential modulatory role of oxytocin raises concern of a bias in the previous oxytocin literature on emotion recognition and associated brain activity by neglecting women in the examination. Next, we will determine the role of age effects on gender-bytreatment interactions, as well as consider modality of the emotion stimulus presentation.

The ability to understand how others are feeling is important for social interaction. Studies have reported large inter-individual variability in emotion recognition ability (ERA) in the general population, but the causes for such differences are not well understood. This study investigated neural response during emotion recognition in individuals with high and low ERA. Forty-nine young adults were selected for inclusion based on their performance during previous testing of ERA (e.g., Hovey et al., 2018, Soc Cogn Affect Neurosci, 13, 173-181). Neural response was determined using the blood-oxygen level-dependent (BOLD) signal in a 3-Tesla functional magnetic resonance imaging (fMRI) experiment. The participants were asked to judge which emotions (anger, fear, disgust, happiness, interest, pride, relief, sadness, and neutral expression) were demonstrated in brief clips (i.e. audio-only, video-only, and multimodal audio- video) using a forced-choice response format. Stimuli were taken from the GEMEP emotion portrayal database (Bänziger et al., 2009, Emotion, 9, 691-704). In neural response to emotional stimuli, individuals with high ERA, relative to low ERA, showed higher activation bilaterally in the supplementary motor area, and in the left postcentral gyrus. Results provide initial evidence that the ability to effectively recognize the emotions of others is related to motor and somatosensory neural responses. We speculate that these neural responses in individuals with improved skills in emotion recognition could be related to increased embodiment of emotion expressions during emotion perception.

This study presents findings about the effectiveness of two computerized training-programs for emotion recognition accuracy that were evaluated in a double-blind randomized controlled study with repeated measures design. Both trainings are effective in training emotion recognition accuracy. The trainings and results are presented in detail and practical implications are discussed.

The neuropeptide oxytocin plays a prominentrole in social and emotional cognition. Findings suggest that exogenous intranasal oxytocin administration facilitates emotion recognition in humans, but individual and contextual differences may have moderating effects. A major caveat in this line of work is that it is predominantly based on young males, which limits current knowledge and potential for generalizability across gender. To uncover potential gender effects, the present study included younger and older men and women. Utilizing a randomized, double-blind, placebo-controlled, within-subjects study design, we investigated the effects of a single-dose of 40 IUs intranasal oxytocin administration on emotion recognition of dynamic positive and negative stimuli in 32 men (mean age 45.78, sd. 22.87) and 39 women (mean 47.87, sd. 47.87), 40 minutes prior to MRI scanning. Preliminary analyses show that oxytocin induced brain activity reductions during exposure to negative (relative to positive) stimuli in women, while increasing brain activity in dorsomedial prefrontal cortex in men. We speculate that the effects of oxytocin on emotion recognition may possibly be related to emotion regulation and mentalization processes, and that oxytocin is related to potential sex-differences in these processes. The results also raise concern that previous oxytocin literature on emotion recognition may be biased as there appears to be gender-differential effects of oxytocin on brain activity across adulthood that have been underestimated. In the next stage of the present study, we will investigate the interaction effects among treatment, sex, age, and presentation modality.

The neurobiology of sexual preference is often discussed in terms of cerebral sex dimorphism. Yet, our knowledge about possible cerebral differences between homosexual men (HoM), heterosexual men (HeM) and heterosexual women (HeW) are extremely limited. In the present MRI study, we addressed this issue investigating measures of cerebral anatomy and function, which were previously reported to show sex difference. Specifically, we asked whether there were any signs of sex atypical cerebral dimorphism among HoM, if these were widely distributed (providing substrate for more general 'female' behavioral characteristics among HoM), or restricted to networks involved in self-referential sexual arousal. Cortical thickness (Cth), surface area (SA), subcortical structural volumes, and resting state functional connectivity were compared between 30 (HoM), 35 (HeM) and 38 (HeW). HoM displayed a significantly thicker anterior cingulate cortex (ACC), precuneus, and the left occipito-temporal cortex compared to both control groups. These differences seemed coordinated, since HoM also displayed stronger cortico-cortical covariations between these regions. Furthermore, functional connections within the default mode network, which mediates self- referential processing, and includes the ACC and precuneus were significantly weaker in HoM than HeM and HeW, whereas their functional connectivity between the thalamus and hypothalamus (important nodes for sexual behavior) was stronger. In addition to these singular features, HoM displayed 'female' characteristics, with a similar Cth in the left superior parietal and cuneus cortices as HeW, but different from HeM. These data suggest both singular and sex atypical features and motivate further investigations of cerebral midline structures in relation to male homosexuality.

White matter changes (WMC) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMC labor intensive and prone to subjective bias. We present a fast, fully automated method for WMC segmentation using a cascade of reduced support vector machines (SVMs) with active learning. Data of 102 subjects was used in this study. Two MRI sequences (T1-weighted and FLAIR) and masks of manually outlined WMC from each subject were used for the image analysis. The segmentation framework comprises pre-processing, classification (training and core segmentation) and post-processing. After pre-processing, the model was trained on two subjects and tested on the remaining 100 subjects. The effectiveness and robustness of the classification was assessed using the receiver operating curve technique. The cascade of SVMs segmentation framework outputted accurate results with high sensitivity (90%) and specificity (99.5%) values, with the manually outlined WMC as reference. An algorithm for the segmentation of WMC is proposed. This is a completely competitive and fast automatic segmentation framework, capable of using different input sequences, without changes or restrictions of the image analysis algorithm., QC 20121217

Normal adult aging is associated with a decline in socioemotional abilities, and underlying these deficits are age-related neurobiological processes. There is increasing evidence that the neuropeptide oxytocin plays a key role in social cognition, specifically in the ability to recognize emotions. In a randomized, double-blind, placebo controlled within-subjects design, we investigated the extent to which a single dose of 40 IU of intranasal oxytocin facilitates neural recruitment in younger and older adults during negative compared to positive dynamic multimodal expressions. Based on the literature, several regions of interest were selected prior analyses: insula, amygdala, caudate head, fusiform gyrus, superior temporal gyrus, medial prefrontal cortex, medial orbitofrontal cortex, ventral medial prefrontal cortex, and dorsomedial prefrontal cortex. Behavioral data showed that younger adults outperformed older adults. and higher accuracy scores were observed during the PL condition compared to the OT condition. This was further qualified by the brain data, where OT induced brain activity reductions in the fusiform gyrus, dorsomedial prefrontal cortex, and medial orbitofrontal cortex in response to negative compared to positive expressions. Both age groups showed hypoactivity in most regions of interest during auditory stimuli compared to visual and multimodal stimuli. In line with previous research, these findings suggest that the effects of oxytocin may vary due to context, social proficiency, and individual factors (i.e. age). Future studies should target how age, presentation modality, and oxytocin interact.