White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

The human habenula is responsive to changes in luminance and circadian rhythm.

The habenula is a pivotal structure in the neural network that implements various forms of cognitive and motivational functions and behaviors. Moreover, it has been suggested to be part of the brain's circadian system, not at least because habenular neurons are responsive to retinal illumination and exhibit circadian modulations of their firing patterns in animal research. However, no study has directly investigated the human habenula in this regard. We developed a paradigm in which alternating phases of high and low luminance are used to study human habenular functioning. In two experiments with independent samples, fMRI data of 24 healthy participants were acquired at a field strength of 7T, and of 21 healthy participants at 3T. Region of interest analyses revealed that the human habenula is responsive to light as well, resulting in a decrease in activation when a change in luminance occurs. Although this pattern is not predicted by animal research, we were able to replicate this finding in a second independent data set. Furthermore, we demonstrate that the strength of decrease in activation is modulated in a circadian fashion, being more strongly deactivated in morning than in afternoon sessions. Taken together, these findings provide strong evidence that changes in illumination elicit changes in habenular activation and that these changes appear to be more pronounced in the morning than in the afternoon.

Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

BACKGROUND: Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. METHODS: Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. RESULTS: During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. CONCLUSIONS: Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

Error-related brain activity as a transdiagnostic endophenotype for obsessive-compulsive disorder, anxiety and substance use disorder.

BACKGROUND: Increased neural error-signals have been observed in obsessive-compulsive disorder (OCD), anxiety disorders, and inconsistently in depression. Reduced neural error-signals have been observed in substance use disorders (SUD). Thus, alterations in error-monitoring are proposed as a transdiagnostic endophenotype. To strengthen this notion, data from unaffected individuals with a family history for the respective disorders are needed. METHODS: The error-related negativity (ERN) as a neural indicator of error-monitoring was measured during a flanker task from 117 OCD patients, 50 unaffected first-degree relatives of OCD patients, and 130 healthy comparison participants. Family history information indicated, that 76 healthy controls were free of a family history for psychopathology, whereas the remaining had first-degree relatives with depression (n = 28), anxiety (n = 27), and/or SUD (n = 27). RESULTS: Increased ERN amplitudes were found in OCD patients and unaffected first-degree relatives of OCD patients. In addition, unaffected first-degree relatives of individuals with anxiety disorders were also characterized by increased ERN amplitudes, whereas relatives of individuals with SUD showed reduced amplitudes. CONCLUSIONS: Alterations in neural error-signals in unaffected first-degree relatives with a family history of OCD, anxiety, or SUD support the utility of the ERN as a transdiagnostic endophenotype. Reduced neural error-signals may indicate vulnerability for under-controlled behavior and risk for substance use, whereas a harm- or error-avoidant response style and vulnerability for OCD and anxiety appears to be associated with increased ERN. This adds to findings suggesting a common neurobiological substrate across psychiatric disorders involving the anterior cingulate cortex and deficits in cognitive control.

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Investigation of the potassium fluoride post deposition treatment on the CIGSe/CdS interface using hard X-ray photoemission spectroscopy - a comparative study.

The impact of the potassium fluoride post deposition treatment on CIGSe chalcopyrite absorbers is investigated by means of depth resolved hard X-ray photoemission spectroscopy of the near surface region. Two similar, slightly Cu-poor CIGSe absorbers were used with one being treated by potassium fluoride prior to the chemical bath deposition of an ultrathin CdS layer. The thickness of the CdS layer was chosen to be in the range of about 10 nm in order to allow the investigation of the CIGSe/CdS interface by the application of hard X-rays, increasing the information depth up to 30 nm. Besides strong intermixing on both samples, an increased Cu depletion of the KF treated absorber was observed in combination with an increased accumulation of Cd and S. In addition, a general shift of about 0.15 eV to higher binding energies of the CIGSe valence band at the absorber surface as well as the CIGSe and CdS related core levels was measured on the KF treated sample. This phenomenon is attributed to the impact of additional cadmium which acts as donor and releases further electrons into the conduction band of the absorber. Finally, the electrons accumulate at the CdS surface after having passed the interface region. This additional surface charge leads to a pronounced shift in the photoemission spectra as observed on the KF treated CIGSe absorber compared to the non-treated absorber.

Performance monitoring in obsessive-compulsive undergraduates: Effects of task difficulty.

Both obsessive-compulsive disorder and subclinical obsessive-compulsive (OC) symptoms seem to be associated with hyperactive error-related brain activity. The current study examined performance monitoring in subjects with subclinical OC symptoms using a new task with different levels of difficulty. Nineteen subjects with high and 18 subjects with low OC characteristics performed a random dot cinematogram (RDC) task with three levels of difficulty. The high and low OC groups did not differ in error-related negativity (ERN), correct-related negativity (CRN) and performance irrespective of task difficulty. The amplitude of the ERN decreased with increasing difficulty whereas the magnitude of CRN did not vary. ERN and CRN approached in size and topography with increasing difficulty, which suggests that errors and correct responses are processed more similarly. These results add to a growing number of studies that fail to replicate hyperactive performance monitoring in individuals with OC symptoms in task with higher difficulty or requiring learning. Together with these findings our results suggest that the relationship between OC symptoms and performance monitoring may be sensitive to type of task and task characteristics and cannot be observed in a RDC that differs from typically used tasks in difficulty and the amount of response-conflict.

Default mode network subsystem alterations in obsessive-compulsive disorder.

BACKGROUND: Although neurobiological models of obsessive-compulsive disorder (OCD) traditionally emphasise the central role of corticostriatal brain regions, studies of default mode network integrity have garnered increasing interest, but have produced conflicting results. AIMS: To resolve these discrepant findings by examining the integrity of default mode network subsystems in OCD. METHOD: Comparison of seed-based resting-state functional connectivity of 11 default mode network components between 46 patients with OCD and 46 controls using functional magnetic resonance imaging. RESULTS: Significantly reduced connectivity within the dorsal medial prefrontal cortex self subsystem was identified in the OCD group, and remained significant after controlling for medication status and life-time history of affective disorders. Further, greater connectivity between the self subsystem and salience and attention networks was observed. CONCLUSIONS: Results indicate that people with OCD show abnormalities in a neural system previously associated with self-referential processing in healthy individuals, and suggest the need for examination of dynamic interactions between this default mode network subsystem and other large-scale networks in this disorder.

Distribution and genetic structure of Aedes japonicus japonicus populations (Diptera: Culicidae) in Germany.

In recent years, the number of imported cases of arthropod-borne diseases in Europe, such as dengue fever, has increased steadily, as did the emergence and distribution of invasive insect vectors. Consequently, the risk of disease spreading into previously unaffected regions through invasive mosquitoes is also increasing. One example of an invasive mosquito is Aedes japonicus japonicus (A. j. japonicus), which spread from its original habitat in Japan to North America and Europe. This species has been shown to act as a vector for Japanese encephalitis and West Nile viruses. In Europe, A. j. japonicus has been detected in Switzerland, Belgium, Slovenia, and Germany, where it has become a resident species. Here, we describe the recent spread and genetic structure of A. j. japonicus populations in Germany. By monitoring the species in Baden-Württemberg in 2011 and 2012, we observed a considerable enlargement of the infested area from 54 municipalities in 2011 to 124 municipalities in 2012. To elucidate the colonization of Europe by A. j. japonicus, seven microsatellite loci were studied in 106 individuals sampled in Germany and Switzerland in 2012. The same markers were genotyped in 31 North American and 26 Japanese specimens. Population genetic analyses indicated that A. j. japonicus in Baden-Württemberg and North Rhine-Westphalia represented two genetically distinct populations with FST-values of 0.073-0.152, suggesting that they originated from two independent introduction events in the past. These results are of particular interest in light of vectorial variability for the transmission of viruses and other pathogens in Europe.

A late-life neurogenetic signature of exposure to combat stress - A monozygotic discordant twin study.

Animal models suggest that experiencing high-stress levels induces changes in amygdalar circuitry and gene expression. In humans, combat exposure has been shown to alter amygdalar responsivity and connectivity, but abnormalities have been indicated to normalize at least partially upon the termination of stress exposure. In contrast, other evidence suggests that combat exposure continues to exert influence on exposed individuals well beyond deployment and homecoming, as indicated by longitudinal psychosocial evidence from veterans, and observation of greater health decline in veterans late in life. Accordingly, the experience of combat stress early in life may affect amygdalar responsivity late in life, a possibility requiring careful consideration of the confounding effects of aging, genetic factors, and symptoms of post-traumatic stress disorder. Here, we investigated amygdalar responsivity in a unique sample of 16 male monozygotic (MZ) twin pairs in their sixties, where one but not the other sibling had been exposed to combat stress in early adulthood. Forty years after combat experience, a generally blunted amygdalar response was observed in combat-exposed veterans compared to their non-exposed twin siblings. Spatial associations between these phenotypical changes and patterns of gene expression in the brain were found for genes involved in the synaptic organization and chromatin structure. Protein-protein interactions among the set of identified genes pointed to histone modification mechanisms. We conclude that exposure to combat stress early in life continues to impact brain function beyond the termination of acute stress and appears to exert prolonged effects on amygdalar function later in life via neurogenetic mechanisms.

Heart rate and heart rate variability in obsessive-compulsive disorder: Evidence from patients and unaffected first-degree relatives.

Altered heart rate (HR) and heart rate variability (HRV) are common observations in psychiatric disorders. Yet, few studies have examined these cardiac measures in obsessive-compulsive disorder (OCD). The current study aimed to investigate HR and HRV, indexed by the root mean square of successive differences (RMSSD) and further time domain indices, as putative biological characteristics of OCD. Electrocardiogram was recorded during a five-minute resting state. Group differences between patients with OCD (n = 96), healthy participants (n = 112), and unaffected first-degree relatives of patients with OCD (n = 47) were analyzed. As potential moderators of group differences, we examined the influence of age and medication, respectively. As results indicated, patients with OCD showed higher HR and lower HRV compared to healthy participants. These group differences were not moderated by age. Importantly, subgroup analyses showed that only medicated patients displayed lower HRV compared to healthy individuals, while HR alterations were evident in unmedicated patients. Regarding unaffected first-degree relatives, group differences in HRV remained at trend level. Further, an age-moderated group differentiation showed that higher HRV distinguished relatives from healthy individuals in young adulthood, whereas at higher age lower HRV was indicative of relatives. Both the role of familial risk and medication in HRV alterations need further elucidation. Pending future studies, alterations in HR and potentially HRV might serve as useful indices to characterize the pathophysiology of OCD.

Cue reactivity and its inhibition in pathological computer game players.

Despite a rising social relevance of pathological computer game playing, it remains unclear whether the neurobiological basis of this addiction-like behavioral disorder and substance-related addiction are comparable. In substance-related addiction, attentional bias and cue reactivity are often observed. We conducted a functional magnetic resonance study using a dot probe paradigm with short-presentation (attentional bias) and long-presentation (cue reactivity) trials in eight male pathological computer game players (PCGPs) and nine healthy controls (HCs). Computer game-related and neutral computer-generated pictures, as well as pictures from the International Affective Picture System with positive and neutral valence, served as stimuli. PCGPs showed an attentional bias toward both game-related and affective stimuli with positive valence. In contrast, HCs showed no attentional bias effect at all. PCGPs showed stronger brain responses in short-presentation trials compared with HCs in medial prefrontal cortex (MPFC) and anterior cingulate gyrus and in long-presentation trials in lingual gyrus. In an exploratory post hoc functional connectivity analyses, for long-presentation trials, connectivity strength was higher between right inferior frontal gyrus, which was associated with inhibition processing in previous studies, and cue reactivity-related regions (left orbitofrontal cortex and ventral striatum) in PCGPs. We observed behavioral and neural effects in PCGPs, which are comparable with those found in substance-related addiction. However, cue-related brain responses were depending on duration of cue presentation. Together with the connectivity result, these findings suggest that top-down inhibitory processes might suppress the cue reactivity-related neural activity in long-presentation trials.

Anopheles plumbeus (Diptera: Culicidae) in Europe: a mere nuisance mosquito or potential malaria vector?

BACKGROUND: Anopheles plumbeus has been recognized as a minor vector for human malaria in Europe since the beginning of the 20th century. In recent years this tree hole breeding mosquito species appears to have exploited novel breeding sites, including large and organically rich man-made containers, with consequently larger mosquito populations in close vicinity to humans. This lead to investigate whether current populations of An. plumbeus would be able to efficiently transmit Plasmodium falciparum, the parasite responsible for the most deadly form of malaria. METHODS: Anopheles plumbeus immatures were collected from a liquid manure pit in Switzerland and transferred as adults to the CEPIA (Institut Pasteur, France) where they were fed on P. falciparum gametocytes produced in vitro. Anopheles gambiae mosquitoes served as controls. Development of P. falciparum in both mosquito species was followed by microscopical detection of oocysts on mosquito midguts and by sporozoite detection in the head/thorax by PCR and microscopy. RESULTS: A total of 293 wild An. plumbeus females from four independent collections successfully fed through a membrane on blood containing P. falciparum gametocytes. Oocysts were observed in mosquito midguts and P. falciparum DNA was detected in head-thorax samples in all four experiments, demonstrating, on a large mosquito sample, that An. plumbeus is indeed receptive to P. falciparum NF54 and able to produce sporozoites. Importantly, the proportion of sporozoites-infected An. plumbeus was almost similar to that of An. gambiae (31 to 88% An. plumbeus versus 67 to 97% An. gambiae). However, the number of sporozoites produced was significantly lower in infected An. plumbeus. CONCLUSION: The results show that a sample of field-caught An. plumbeus has a moderate to high receptivity towards P. falciparum. Considering the increased mobility of humans between Europe and malaria endemic countries and changes in environment and climate, these data strongly suggest that An. plumbeus could act as a vector for malaria and thus significantly contribute to increasing the malaria transmission risk in Central-Western Europe. In locations showing high vulnerability to the presence of gametocyte carriers, the risk of transmission of malaria by An. plumbeus should be considered.

Identification of field-caught Culicoides biting midges using matrix-assisted laser desorption/ionization time of flight mass spectrometry.

Culicoides biting midges are of great importance as vectors of pathogens and elicitors of allergy. As an alternative for the identification of these tiny insects, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was evaluated. Protein mass fingerprints were determined for 4-5 field-caught reference (genetically confirmed) individuals of 12 Culicoides species from Switzerland, C. imicola from France, laboratory-reared C. nubeculosus and a non-biting midge. Reproducibility and accuracy of the database was tested in a validation study by analysing 108 mostly field-caught target Culicoides midges and 3 specimens from a non-target species. A reference database of biomarker mass sets containing between 24 and 38 masses for the different species could be established. Automated database-based identification was achieved for 101 of the 108 specimens. The remaining 7 midges required manual full comparison with the reference spectra yielding correct identification for 6 specimens and an ambiguous result for the seventh individual. Specimens of the non-target species did not yield identification. Protein profiling by MALDI-TOF, which is compatible with morphological and genetic identification of specimens, can be used as an alternative, quick and inexpensive tool to accurately identify Culicoides biting midges collected in the field.

Error-Related Brain Activity in Patients With Obsessive-Compulsive Disorder and Unaffected First-Degree Relatives: Evidence for Protective Patterns.

Background: Indicators of increased error monitoring are associated with obsessive-compulsive disorder (OCD), as shown in electroencephalography and functional magnetic resonance imaging studies. As most studies used strictly controlled samples (excluding comorbidity and medication), it remains open whether these findings extend to naturalistic settings. Thus, we assessed error-related brain activity in a large, naturalistic OCD sample. We also explored which activity patterns might qualify as vulnerability endophenotypes or protective factors for the disorder. To this aim, a sample of unaffected first-degree relatives of patients with OCD was also included. Methods: Participants (84 patients with OCD, 99 healthy control participants, and 37 unaffected first-degree relatives of patients with OCD) completed a flanker task while blood oxygen level-dependent responses were measured with functional magnetic resonance imaging. Aberrant error-related brain activity in patients and relatives was identified. Results: Patients with OCD showed increased error-related activity in the supplementary motor area and within the default mode network, specifically in the precuneus and postcentral gyrus. Unaffected first-degree relatives showed increased error-related activity in the bilateral inferior frontal gyrus. Conclusions: Increased supplementary motor area and default mode network activity in patients with OCD replicates previous studies and might indicate excessive error signals and increased self-referential error processing. Increased activity of the inferior frontal gyrus in relatives may reflect increased inhibition. Impaired response inhibition in OCD has been demonstrated in several studies and might contribute to impairments in suppressing compulsive actions. Thus, increased inferior frontal gyrus activity in the unaffected relatives of patients with OCD may have contributed to protection from symptom development.

Error-related activity of the sensorimotor network contributes to the prediction of response to cognitive-behavioral therapy in obsessive-compulsive disorder.

BACKGROUND: Although cognitive behavioral therapy is a highly effective treatment for obsessive-compulsive disorder (OCD), yielding large symptom reductions on the group level, individual treatment response varies considerably. Identification of treatment response predictors may provide important information for maximizing individual treatment response and thus achieving efficient treatment resource allocation. Here, we investigated the predictive value of previously identified biomarkers of OCD, namely the error-related activity of the supplementary motor area (SMA) and the sensorimotor network (SMN, postcentral gyrus/precuneus). METHODS: Seventy-two participants with a primary diagnosis of OCD underwent functional magnetic resonance imaging (fMRI) scanning while performing a flanker task prior to receiving routine-care CBT. RESULTS: Error-related BOLD response of the SMN significantly contributed to the prediction of treatment response beyond the variance accounted for by clinical and sociodemographic variables. Stronger error-related SMN activity at baseline was associated with a higher likelihood of treatment response. CONCLUSIONS: The present results illustrate that the inclusion of error-related SMN activity can significantly increase treatment response prediction quality in OCD. Stronger error-related activity of the SMN may reflect the ability to activate symptom-relevant processing networks and may thus facilitate response to exposure-based CBT interventions.

Surface Passivation and Detrimental Heat-Induced Diffusion Effects in RbF-Treated Cu(In,Ga)Se2 Solar Cell Absorbers.

Alkali postdeposition treatments of Cu(In,Ga)Se2 absorbers with KF, RbF, and CsF have led to remarkable efficiency improvements for chalcopyrite thin film solar cells. However, the effect of such treatments on the electronic properties and defect physics of the chalcopyrite absorber surfaces are not yet fully understood. In this work, we use scanning tunneling spectroscopy and X-ray photoelectron spectroscopy to compare the surface defect electronic properties and chemical composition of RbF-treated and nontreated absorbers. We find that the RbF treatment is effective in passivating electronic defect levels at the surface by preventing surface oxidation. Our X-ray photoelectron spectroscopy (XPS) data points to the presence of chemisorbed Rb on the surface with a bonding configuration similar to that of a RbInSe2 bulk compound. Yet, a quantitative analysis indicates Rb coverage in the submonolayer regime, which is likely causing the surface passivation. Furthermore, ab initio calculations confirm that RbF-treated surfaces are less prone to oxidation (in the form of Ga, In, and Se oxides) than bare chalcopyrite surfaces. In addition, elemental diffusion of Rb along with Na, Cu, and Ga is found to occur when the samples are annealed under ultrahigh vacuum conditions. Magnetic sector secondary ion mass spectrometry measurements indicate that there is a homogeneous spatial distribution of Rb on the surface both before and after annealing, albeit with an increased concentration at the surface after heat treatment. Depth-resolved magnetic sector secondary ion mass spectrometry measurements show that Rb diffusion within the bulk occurs predominantly along grain boundaries. Scanning tunneling and XPS measurements after subsequent annealing steps demonstrate that the Rb accumulation at the surface leads to the formation of metallic Rb phases, involving a significant increase of electronic defect levels and/or surface dipole formation. These results strongly suggest a deterioration of the absorber-window interface because of increased recombination losses after the heat-induced diffusion of Rb toward the interface.

The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.