Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.

OBJECTIVE: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults). METHODS: Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis. RESULTS: Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents. CONCLUSIONS: Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.

Making acute ischemic stroke thrombi visible in MRI imaging.

Knowledge of thrombus behavior and visualization on MRI in acute ischemic stroke is less than optimal. However, MRI sequences could be enhanced based on the typical T1 and T2 relaxation times of the target tissues, which mainly determine their signal intensities on imaging. We studied the relaxation times of a broad spectrum of clot analogs along with their image characteristics of three sequences analyzed: a T1-weighted turbo inversion-recovery sequence (T1w Turbo IR), a T1-weighted turbo spin echo with fat suppression (T1w TSE SPIR), and a T2-weighted 3D TSE with magnetization refocusing to remove T1 dependence (T2w TSE DRIVE). We compared their imaging behavior with the intensity values of normal brain tissue using the same imaging protocols as for clots. Each histological and biochemical clot component contributed to each of the relaxation times. Overall, histological composition correlated strongly with T1 times, and iron content, specifically, with T2 relaxation time. Using decision trees, fibrin content was selected as the primary biomarker for T1 relaxation times, inducing an increase. Up to four clot subgroups could be defined based on its distinctive T1 relaxation time. Clot signal intensity in the T1 and T2-weighted images varied significantly according to T1 and T2 relaxation times. Moreover, in comparison with normal brain tissue intensity values, T2w DRIVE images depict thrombi according to the principle of the more fibrin, the higher the intensity, and in T1w TSE, the more erythrocytes, the higher the intensity. These findings could facilitate improvements in MRI sequences for clot visualization and indicate that T2w DRIVE and T1w TSE sequences should depict the vast majority of acute ischemic stroke thrombi as more hyperintense than surrounding tissues.

2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas. / 2-Hydroxyglutarat als MR-spektroskopisch erfassbarer Prädiktor einer IDH-Mutation bei Gliomen.

The mutated enzyme isocitrate dehydrogenase (IDH) 1 and 2 has been detected in various tumor entities such as gliomas and can convert α-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG). This neuro-oncologically significant metabolic product can be detected by MR spectroscopy and is therefore suitable for noninvasive glioma classification and therapy monitoring.This paper provides an up-to-date overview of the methodology and relevance of 1H-MR spectroscopy (MRS) in the oncological primary and follow-up diagnosis of gliomas. The possibilities and limitations of this MR spectroscopic examination are evaluated on the basis of the available literature.By detecting 2-HG, MRS can in principle offer a noninvasive alternative to immunohistological analysis thus avoiding surgical intervention in some cases. However, in addition to an adapted and optimized examination protocol, the individual measurement conditions in the examination region are of decisive importance. Due to the inherently small signal of 2-HG, unfavorable measurement conditions can influence the reliability of detection. · MR spectroscopy enables the non-invasive detection of 2-hydroxyglutarate.. · The measurement of this metabolite allows the detection of an IDH mutation in gliomas.. · The choice of MR examination method is particularly important.. · Detection reliability is influenced by glioma size, necrotic tissue and the existing measurement conditions.. · Bauer J, Raum HN, Kugel H et al. 2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas. Fortschr Röntgenstr 2024; DOI 10.1055/a-2285-4923.

Cerebral MRI in a prospective cohort study on depression and atherosclerosis: the BiDirect sample, processing pipelines, and analysis tools.

BACKGROUND: The use of cerebral magnetic resonance imaging (MRI) in observational studies has increased exponentially in recent years, making it critical to provide details about the study sample, image processing, and extracted imaging markers to validate and replicate study results. This article reviews the cerebral MRI dataset from the now-completed BiDirect cohort study, as an update and extension of the feasibility report published after the first two examination time points. METHODS: We report the sample and flow of participants spanning four study sessions and twelve years. In addition, we provide details on the acquisition protocol; the processing pipelines, including standardization and quality control methods; and the analytical tools used and markers available. RESULTS: All data were collected from 2010 to 2021 at a single site in Münster, Germany, starting with a population of 2,257 participants at baseline in 3 different cohorts: a population-based cohort (n = 911 at baseline, 672 with MRI data), patients diagnosed with depression (n = 999, 736 with MRI data), and patients with manifest cardiovascular disease (n = 347, 52 with MRI data). During the study period, a total of 4,315 MRI sessions were performed, and over 535 participants underwent MRI at all 4 time points. CONCLUSIONS: Images were converted to Brain Imaging Data Structure (a standard for organizing and describing neuroimaging data) and analyzed using common tools, such as CAT12, FSL, Freesurfer, and BIANCA to extract imaging biomarkers. The BiDirect study comprises a thoroughly phenotyped study population with structural and functional MRI data. RELEVANCE STATEMENT: The BiDirect Study includes a population-based sample and two patient-based samples whose MRI data can help answer numerous neuropsychiatric and cardiovascular research questions. KEY POINTS: • The BiDirect study included characterized patient- and population-based cohorts with MRI data. • Data were standardized to Brain Imaging Data Structure and processed with commonly available software. • MRI data and markers are available upon request.

Association of hospitalization with structural brain alterations in patients with affective disorders over nine years.

Repeated hospitalizations are a characteristic of severe disease courses in patients with affective disorders (PAD). To elucidate how a hospitalization during a nine-year follow-up in PAD affects brain structure, a longitudinal case-control study (mean [SD] follow-up period 8.98 [2.20] years) was conducted using structural neuroimaging. We investigated PAD (N = 38) and healthy controls (N = 37) at two sites (University of Münster, Germany, Trinity College Dublin, Ireland). PAD were divided into two groups based on the experience of in-patient psychiatric treatment during follow-up. Since the Dublin-patients were outpatients at baseline, the re-hospitalization analysis was limited to the Münster site (N = 52). Voxel-based morphometry was employed to examine hippocampus, insula, dorsolateral prefrontal cortex and whole-brain gray matter in two models: (1) group (patients/controls)×time (baseline/follow-up) interaction; (2) group (hospitalized patients/not-hospitalized patients/controls)×time interaction. Patients lost significantly more whole-brain gray matter volume of superior temporal gyrus and temporal pole compared to HC (pFWE = 0.008). Patients hospitalized during follow-up lost significantly more insular volume than healthy controls (pFWE = 0.025) and more volume in their hippocampus compared to not-hospitalized patients (pFWE = 0.023), while patients without re-hospitalization did not differ from controls. These effects of hospitalization remained stable in a smaller sample excluding patients with bipolar disorder. PAD show gray matter volume decline in temporo-limbic regions over nine years. A hospitalization during follow-up comes with intensified gray matter volume decline in the insula and hippocampus. Since hospitalizations are a correlate of severity, this finding corroborates and extends the hypothesis that a severe course of disease has detrimental long-term effects on temporo-limbic brain structure in PAD.

Higher body weight-dependent neural activation during reward processing.

Obesity is associated with alterations in brain structure and function, particularly in areas related to reward processing. Although brain structural investigations have demonstrated a continuous association between higher body weight and reduced gray matter in well-powered samples, functional neuroimaging studies have typically only contrasted individuals from the normal weight and obese body mass index (BMI) ranges with modest sample sizes. It remains unclear, whether the commonly found hyperresponsiveness of the reward circuit can (a) be replicated in well-powered studies and (b) be found as a function of higher body weight even below the threshold of clinical obesity. 383 adults across the weight spectrum underwent functional magnetic resonance imaging during a common card-guessing paradigm simulating monetary reward. Multiple regression was used to investigate the association of BMI and neural activation in the reward circuit. In addition, a one-way ANOVA model comparing three weight groups (normal weight, overweight, obese) was calculated. Higher BMI was associated with higher reward response in the bilateral insula. This association could no longer be found when participants with obesity were excluded from the analysis. The ANOVA revealed higher activation in obese vs. lean, but no difference between lean and overweight participants. The overactivation of reward-related brain areas in obesity is a consistent finding that can be replicated in large samples. In contrast to brain structural aberrations associated with higher body weight, the neurofunctional underpinnings of reward processing in the insula appear to be more pronounced in the higher body weight range.

Treatment with the second-generation antipsychotic quetiapine is associated with increased subgenual ACC activation during reward processing in major depressive disorder.

BACKGROUND: The second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) - a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients. METHODS: Using the ACC as region of interest, an independent t-test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses. RESULTS: Left subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity. LIMITATIONS: Causal interpretation is limited due to cross-sectional findings. CONCLUSION: Elevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes.

Familial risk for major depression: differential white matter alterations in healthy and depressed participants.

BACKGROUND: Major depressive disorder (MDD) has been associated with alterations in brain white matter (WM) microstructure. However, diffusion tensor imaging studies in biological relatives have presented contradicting results on WM alterations and their potential as biomarkers for vulnerability or resilience. To shed more light on associations between WM microstructure and resilience to familial risk, analyses including both healthy and depressed relatives of MDD patients are needed. METHODS: In a 2 (MDD v. healthy controls, HC) × 2 (familial risk yes v. no) design, we investigated fractional anisotropy (FA) via tract-based spatial statistics in a large well-characterised adult sample (N = 528), with additional controls for childhood maltreatment, a potentially confounding proxy for environmental risk. RESULTS: Analyses revealed a significant main effect of diagnosis on FA in the forceps minor and the left superior longitudinal fasciculus (ptfce-FWE = 0.009). Furthermore, a significant interaction of diagnosis with familial risk emerged (ptfce-FWE = 0.036) Post-hoc pairwise comparisons showed significantly higher FA, mainly in the forceps minor and right inferior fronto-occipital fasciculus, in HC with as compared to HC without familial risk (ptfce-FWE < 0.001), whereas familial risk played no role in MDD patients (ptfce-FWE = 0.797). Adding childhood maltreatment as a covariate, the interaction effect remained stable. CONCLUSIONS: We found widespread increased FA in HC with familial risk for MDD as compared to a HC low-risk sample. The significant effect of risk on FA was present only in HC, but not in the MDD sample. These alterations might reflect compensatory neural mechanisms in healthy adults at risk for MDD potentially associated with resilience.

Practical Aspects of novel MRI Techniques in Neuroradiology: Part 2 - Acceleration Methods and Implications for Individual Regions. / Praktische Aspekte neuerer MRT-Techniken in der Neuroradiologie: Teil 2 ­ Beschleunigungsverfahren und Regionen-spezifische Implikationen.

BACKGROUND: Recently introduced MRI techniques facilitate accelerated examinations or increased resolution with the same duration. Further techniques offer homogeneous image quality in regions with anatomical transitions. The question arises whether and how these techniques can be adopted for routine diagnostic imaging. METHODS: Narrative review with an educational focus based on current literature research and practical experiences of different professions involved (physicians, MRI technologists/radiographers, physics/biomedical engineering). Different hardware manufacturers are considered. RESULTS AND CONCLUSIONS: Compressed sensing and simultaneous multi-slice imaging are novel acceleration techniques with different yet complimentary applications. They do not suffer from classical signal-to-noise-ratio penalties. Combining 3 D and acceleration techniques facilitates new broader examination protocols, particularly for clinical brain imaging. In further regions of the nervous systems mainly specific applications appear to benefit from recent technological improvements. KEY POINTS: · New acceleration techniques allow for faster or higher resolution examinations.. · New brain imaging approaches have evolved, including more universal examination protocols.. · Other regions of the nervous system are dominated by targeted applications of recently introduced MRI techniques.. CITATION FORMAT: · Sundermann B, Billebaut B, Bauer J et al. Practical Aspects of novel MRI Techniques in Neuroradiology: Part 2 - Acceleration Methods and Implications for Individual Regions. Fortschr Röntgenstr 2022; 194: 1195 - 1203.

Practical Aspects of novel MRI Techniques in Neuroradiology: Part 1-3D Acquisitions, Dixon Techniques and Artefact Reduction. / Praktische Aspekte neuerer MRT-Techniken in der Neuroradiologie: Teil 1­3D, Dixon-Techniken und Artefaktreduktion.

BACKGROUND: Recently introduced MRI techniques offer improved image quality and facilitate examinations of patients even when artefacts are expected. They pave the way for novel diagnostic imaging strategies in neuroradiology. These methods include improved 3D imaging, movement and metal artefact reduction techniques as well as Dixon techniques. METHODS: Narrative review with an educational focus based on current literature research and practical experiences of different professions involved (physicians, MRI technologists/radiographers, physics/biomedical engineering). Different hardware manufacturers are considered. RESULTS AND CONCLUSIONS: 3D FLAIR is an example of a versatile 3D Turbo Spin Echo sequence with broad applicability in routine brain protocols. It facilitates detection of smaller lesions and more precise measurements for follow-up imaging. It also offers high sensitivity for extracerebral lesions. 3D techniques are increasingly adopted for imaging arterial vessel walls, cerebrospinal fluid spaces and peripheral nerves. Improved hybrid-radial acquisitions are available for movement artefact reduction in a broad application spectrum. Novel susceptibility artefact reduction techniques for targeted application supplement previously established metal artefact reduction sequences. Most of these techniques can be further adapted to achieve the desired diagnostic performances. Dixon techniques allow for homogeneous fat suppression in transition areas and calculation of different image contrasts based on a single acquisition. KEY POINTS: · 3D FLAIR can replace 2 D FLAIR for most brain imaging applications and can be a cornerstone of more precise and more widely applicable protocols.. · Further 3D TSE sequences are increasingly replacing 2D TSE sequences for specific applications.. · Improvement of artefact reduction techniques increase the potential for effective diagnostic MRI exams despite movement or near metal implants.. · Dixon techniques facilitate homogeneous fat suppression and simultaneous acquisition of multiple contrasts.. CITATION FORMAT: · Sundermann B, Billebaut B, Bauer J et al. Practical Aspects of novel MRI Techniques in Neuroradiology: Part 1-3D Acquisitions, Dixon Techniques and Artefact Reduction. Fortschr Röntgenstr 2022; 194: 1100 - 1108.

An uncertainty-aware, shareable, and transparent neural network architecture for brain-age modeling.

The deviation between chronological age and age predicted from neuroimaging data has been identified as a sensitive risk marker of cross-disorder brain changes, growing into a cornerstone of biological age research. However, machine learning models underlying the field do not consider uncertainty, thereby confounding results with training data density and variability. Also, existing models are commonly based on homogeneous training sets, often not independently validated, and cannot be shared because of data protection issues. Here, we introduce an uncertainty-aware, shareable, and transparent Monte Carlo dropout composite quantile regression (MCCQR) Neural Network trained on N = 10,691 datasets from the German National Cohort. The MCCQR model provides robust, distribution-free uncertainty quantification in high-dimensional neuroimaging data, achieving lower error rates compared with existing models. In two examples, we demonstrate that it prevents spurious associations and increases power to detect deviant brain aging. We make the pretrained model and code publicly available.

Acute soft tissue injury to the temporomandibular joint and posttraumatic assessment after mandibular condyle fractures: a longitudinal prospective MRI study.

OBJECTIVE: Evaluation of acute soft tissue injury of the temporomandibular joint (TMJ) with type I-VI fractures immediately after trauma and investigation of the longitudinal evolution including response to conservative treatment using MRI. METHODS: The joints of 24 patients with 33 condylar fractures (15 unilateral, nine bilateral) were imaged on a 1 Tesla MR system within the first 24 h post-trauma. 12 of these patients with 16 condylar fractures (eight unilateral, four bilateral) were clinically re-evaluated using MRI after 3 months of closed treatment. The position, morphology, and signal intensities of the disc, capsule, retrodiscal tissue, and osseous structures were documented. RESULTS: In the acute phase, disc displacements (DDs) were diagnosed in 8 out of 33 joints with fracture, including posterior DDs in two joints and tears of the inferior retrodiscal lamina in 11 joints. The follow-up MRI in 12 patients revealed new DD in four joints on the fractured side (FS) including a posterior DD and an increased degree of displacement, and new DDs in two joints in the non-fractured side (NFS). CONCLUSION: Preexisting and traumatic DD and soft tissue injuries are frequent findings in patients with condylar fracture. Independent of the degree of trauma, condylar fractures may determine the subsequent development of DD on both FS and NFS. Early MR imaging may help initiate well-directed specific measures for better outcomes in the acutely injured TMJ.

Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Social support and hippocampal volume are negatively associated in adults with previous experience of childhood maltreatment.

Background: Childhood maltreatment has been associated with reduced hippocampal volume in healthy individuals, whereas social support, a protective factor, has been positively associated with hippocampal volumes. In this study, we investigated how social support is associated with hippocampal volume in healthy people with previous experience of childhood maltreatment. Methods: We separated a sample of 446 healthy participants into 2 groups using the Childhood Trauma Questionnaire: 265 people without maltreatment and 181 people with maltreatment. We measured perceived social support using a short version of the Social Support Questionnaire. We examined hippocampal volume using automated segmentation (Freesurfer). We conducted a social support × group analysis of covariance on hippocampal volumes controlling for age, sex, total intracranial volume, site and verbal intelligence. Results: Our analysis revealed significantly lower left hippocampal volume in people with maltreatment (left F1,432 = 5.686, p = 0.018; right F1,433 = 3.371, p = 0.07), but no main effect of social support emerged. However, we did find a significant social support × group interaction for left hippocampal volume (left F1,432 = 5.712, p = 0.017; right F1,433 = 3.480, p = 0.06). In people without maltreatment, we observed a trend toward a positive association between social support and hippocampal volume. In contrast, social support was negatively associated with hippocampal volume in people with maltreatment. Limitations: Because of the correlative nature of our study, we could not infer causal relationships between social support, maltreatment and hippocampal volume. Conclusion: Our results point to a complex dynamic between environmental risk, protective factors and brain structure - in line with previous evidence - suggesting a detrimental effect of maltreatment on hippocampal development.

Novelty seeking is associated with increased body weight and orbitofrontal grey matter volume reduction.

Novelty seeking (NS) has previously been identified as a personality trait that is associated with elevated body mass index (BMI) and obesity. Of note, both obesity and reduced impulse control - a core feature of NS - have previously been associated with grey matter volume (GMV) reductions in the orbitofrontal cortex (OFC). Yet, it remains unknown, if body weight-related grey matter decline in the OFC might be explained by higher levels of NS. To address this question, we studied associations between NS, BMI and brain structure in 355 healthy subjects. Brain images were pre-processed using voxel-based morphometry (VBM). BMI was calculated from self-reported height and weight. The Tridimensional Personality Questionnaire (TPQ) was used to assess NS. NS and BMI were associated positively (r = .137, p = .01) with NS being a significant predictor of BMI (B = 0.172; SE B = 0.05; ß = 0.184; p = 0.001). Significant associations between BMI and GMV specifically in the OFC (x = -44, y = 56, z = -2, t(350) = 4.34, k = 5, pFWE = 0.011) did not uphold when correcting for NS in the model. In turn, a significant negative association between NS and OFC GMV was found independent of BMI (x = -2, y = 48, z = -10, t(349) = 4.42, k = 88, pFWE = 0.008). Body mass-related grey matter decrease outside the OFC could not be attributed to NS. Our results suggest that body-weight-related orbitofrontal grey matter reduction can at least partly be linked to higher levels of NS. Given the pivotal role of the OFC in overweight as well as cognitive domains such as impulse inhibition, executive control and reward processing, its association with NS seems to provide a tenable neurobiological correlate for future research.

Alexithymia and automatic processing of facial emotions: behavioral and neural findings.

BACKGROUND: Alexithymia is a personality trait characterized by difficulties identifying and describing feelings, an externally oriented style of thinking, and a reduced inclination to imagination. Previous research has shown deficits in the recognition of emotional facial expressions in alexithymia and reductions of brain responsivity to emotional stimuli. Using an affective priming paradigm, we investigated automatic perception of facial emotions as a function of alexithymia at the behavioral and neural level. In addition to self-report scales, we applied an interview to assess alexithymic tendencies. RESULTS: During 3 T fMRI scanning, 49 healthy individuals judged valence of neutral faces preceded by briefly shown happy, angry, fearful, and neutral facial expressions. Alexithymia was assessed using the 20-Item Toronto Alexithymia Scale (TAS-20), the Bermond-Vorst Alexithymia Questionnaire (BVAQ) and the Toronto Structured Interview for Alexithymia (TSIA). As expected, only negative correlations were found between alexithymic features and affective priming. The global level of self-reported alexithymia (as assessed by the TAS-20 and the BVAQ) was found to be related to less affective priming owing to angry faces. At the facet level, difficulties identifying feelings, difficulties analyzing feelings, and impoverished fantasy (as measured by the BVAQ) were correlated with reduced affective priming due to angry faces. Difficulties identifying feelings (BVAQ) correlated also with reduced affective priming due to fearful faces and reduced imagination (TSIA) was related to decreased affective priming due to happy faces. There was only one significant correlation between alexithymia dimensions and automatic brain response to masked facial emotions: TAS-20 alexithymia correlated with heightened brain response to masked happy faces in superior and medial frontal areas. CONCLUSIONS: Our behavioral results provide evidence that alexithymic features are related in particular to less sensitivity for covert facial expressions of anger. The perceptual alterations could reflect impaired automatic recognition or integration of social anger signals into judgemental processes and might contribute to the problems in interpersonal relationships associated with alexithymia. Our findings suggest that self-report measures of alexithymia may have an advantage over interview-based tests as research tools in the field of emotion perception at least in samples of healthy individuals characterized by rather low levels of alexithymia.

Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning.

Exact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48 h after production. The mean, maximum, and minimum HU values for the axial and coronal reconstructions were recorded. Each thrombus underwent a corresponding histological analysis, together with a laboratory analysis of water and iron contents. Decision trees, a type of supervised machine learning, were used to select the primary variable altering attenuation and the best parameter for predicting histology. The decision trees selected red blood cells (RBCs) for correlation with all attenuation parameters (p < 0.001). Conversely, maximum attenuation on axial CT offered the greatest accuracy for discriminating up to four groups of clot histology (p < 0.001). Similar RBC-rich thrombi displayed variable imaging associated with different iron (p = 0.023) and white blood cell contents (p = 0.019). Water content varied among the different histologies but did not in itself account for the differences in attenuation. Independent factors determining clot attenuation were the RBCs (ß = 0.33, CI = 0.219-0.441, p < 0.001) followed by the iron content (ß = 0.005, CI = 0.0002-0.009, p = 0.042). Our findings suggest that it is possible to extract more and valuable information from NCCT that can be extrapolated to provide insights into clot histological and chemical composition.

Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort.

BACKGROUND: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age. METHODS: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer. RESULTS: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions. CONCLUSIONS: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Influence of electroconvulsive therapy on white matter structure in a diffusion tensor imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time. METHODS: Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response. RESULTS: Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology. CONCLUSION: Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood-brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.