Aberrant brain dynamics in individuals with clinical high risk of psychosis.

Background: Resting-state network (RSN) functional connectivity analyses have profoundly influenced our understanding of the pathophysiology of psychoses and their clinical high risk (CHR) states. However, conventional RSN analyses address the static nature of large-scale brain networks. In contrast, novel methodological approaches aim to assess the momentum state and temporal dynamics of brain network interactions. Methods: Fifty CHR individuals and 33 healthy controls (HC) completed a resting-state functional MRI scan. We performed an Energy Landscape analysis, a data-driven method using the pairwise maximum entropy model, to describe large-scale brain network dynamics such as duration and frequency of, and transition between, different brain states. We compared those measures between CHR and HC, and examined the association between neuropsychological measures and neural dynamics in CHR. Results: Our main finding is a significantly increased duration, frequency, and higher transition rates to an infrequent brain state with coactivation of the salience, limbic, default mode and somatomotor RSNs in CHR as compared to HC. Transition of brain dynamics from this brain state was significantly correlated with processing speed in CHR. Conclusion: In CHR, temporal brain dynamics are attracted to an infrequent brain state, reflecting more frequent and longer occurrence of aberrant interactions of default mode, salience, and limbic networks. Concurrently, more frequent and longer occurrence of the brain state is associated with core cognitive dysfunctions, predictors of future onset of full-blown psychosis.

Sex differences in multiple sclerosis relapse presentation and outcome: a retrospective, monocentric study of 134 relapse events.

Background: Reporting of sex-specific analyses in multiple sclerosis (MS) is sparse. Disability accrual results from relapses (relapse-associated worsening) and independent thereof (progression independent of relapses). Objectives: A population of MS patients during relapse treated per standard of care was analyzed for sex differences and short-term relapse outcome (3-6 months) as measured by Expanded Disability Status Scale (EDSS) change. Design: Single-center retrospective study. Methods: We analyzed 134 MS relapses between March 2016 and August 2020. All events required relapse treatment (steroids and/or plasma exchange). Demographic, disease, and paraclinical characteristics [cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI)] were displayed separated by sex. Multivariable linear regression was run to identify factors associated with short-term EDSS change. Results: Mean age at relapse was 38.4 years (95% confidence interval: 36.3-40.4) with a proportion of 71.6% women in our cohort. Smoking was more than twice as prevalent in men (65.8%) than women (32.3%). In- and after-relapse EDSSs were higher in men [men: 3.3 (2.8-3.9), women: 2.7 (2.4-3.0); men: 3.0 (1.3-3.6); women: 1.8 (1.5-2.1)] despite similar relapse intervention. Paraclinical parameters revealed no sex differences. Our primary model identified female sex, younger age, and higher EDSS at relapse to be associated with EDSS improvement. A higher immunoglobulin G (IgG) quotient (CSF/serum) was associated with poorer short-term outcome [mean days between first relapse treatment and last EDSS assessment 130.2 (79.3-181.0)]. Conclusion: Sex and gender differences are important in outcome analyses of MS relapses. Effective treatment regimens need to respect putative markers for a worse outcome to modify long-term prognosis such as clinical and demographic variables, complemented by intrathecal IgG synthesis. Prospective trials should be designed to address these differences and confirm our results.

An analysis of 134 acute relapses of multiple sclerosis reveal sex differences influencing recovery from relapse Sex-specific analyses are important in medicine, but more knowledge is still needed. Multiple sclerosis (MS) as an inflammatory disease of the brain and spinal cord mainly affects younger people who are at risk for development of disability. Disability may result from acute relapses of the disease that insufficiently recover. Our analysis aimed to assess sex differences with a special focus on the acute relapse and 3 to 6 months later on average. We collected existing data from our center and identified 134 relapse events with sufficient data for further analysis. All relapses were treated with medical (high-dose steroids) and/or interventional treatment (plasma exchange). We analyzed the influence of sex, age, smoking, relapse severity, relapse treatment and other treatment (immunotherapy) for MS. In a second analysis, cerebrospinal fluid (CSF) and imaging (MRI) parameters were included. Our cohort consisted of 72% women. The mean age was 38 years. Smoking was twice as common in men (66%) than in women (32%). Men also experienced more severe disability in and after the relapse. Several other factors were similar between men and women. Female sex and younger age were associated with lower disability after a relapse. Paradoxically, also higher disability in the relapse was associated with lower disability later on. This might be a statistical phenomenon and partly explained by overall low disability levels in our analysis. It might therefore not be true for more advanced disease stages with higher disability. The presence of a certain CSF marker (intrathecal IgG synthesis) was associated with higher disability after the relapse. Our analysis thus identified markers associated with different relapse recovery, male vs. female sex being one of them.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

Taking appreciation to heart: appreciation at work and cardiovascular risk in male employees.

Introduction: While perceived appreciation at work has been associated with self-reported health and wellbeing, studies considering biological health markers are lacking. In this study, we investigated whether appreciation at work would relate to coronary heart disease (CHD) risk as well as the specificity of this proposed association. Methods: Our study comprised a total of 103 male participants, including apparently healthy, medication-free, non-smoking men in the normotensive to hypertensive range (n = 70) as well as medicated hypertensive and CHD patients (n = 33). CHD risk was assessed by blood pressure [mean arterial pressure (MAP)], the diabetes marker glycated hemoglobin A1c (HbA1c), blood lipids [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio], coagulation activity (D-dimer and fibrinogen), and inflammation [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)]. Perceived appreciation at work, as well as potentially confounding psychological factors (social support, self-esteem, and work strain due to a lack of appreciation), were measured by self-report questionnaires. Results: We found higher appreciation at work to relate to lower overall composite CHD risk (p's ≤ 0.011) and, in particular, to lower MAP (p's ≤ 0.007) and lower blood lipids (p's ≤ 0.031) in medication-free participants as well as all participants. This overall association was independent of confounding factors, including related psychological factors (p's ≤ 0.049). Discussion: Our findings indicate that appreciation at work might be an independent health-promoting resource in terms of CHD risk. Implications include that encouraging appreciation at work may help reduce the development and progression of CHD.

The analysis of association between single features of small vessel disease and stroke outcome shows the independent impact of the number of microbleeds and presence of lacunes.

The impact of small vessel disease (SVD) on stroke outcome was investigated either separately for its single features in isolation or for SVD sum score measuring a qualitative (binary) assessment of SVD-lesions. We aimed to investigate which SVD feature independently impacts the most on stroke outcome and to compare the continuous versus binary SVD assessment that reflects pronouncement and presence correspondingly. Patients with a first-ever anterior circulation ischemic stroke were retrospectively investigated. We performed an ordered logistic regression analysis to predict stroke outcome (mRS 3 months, 0-6) using age, stroke severity, and pre-stroke disability as baseline input variables and adding SVD-features (lacunes, microbleeds, enlarged perivascular spaces, white matter hyperintensities) assessed either continuously (model 1) or binary (model 2). The data of 873 patients (age 67.9 ± 15.4, NIHSS 24 h 4.1 ± 4.8) was analyzed. In model 1 with continuous SVD-features, the number of microbleeds was the only independent predictor of stroke outcome in addition to clinical parameters (OR 1.21; 95% CI 1.07-1.37). In model 2 with the binary SVD assessment, only the presence of lacunes independently improved the prediction of stroke outcome (OR 1.48, 1.1-1.99). In a post hoc analysis, both the continuous number of microbleeds and the presence of lacunes were independent significant predictors. Thus, the number of microbleeds evaluated continuously and the presence of lacunes are associated with stroke outcome independent from age, stroke severity, pre-stroke disability and other SVD-features. Whereas the presence of lacunes is adequately represented in SVD sum score, the microbleeds assessment might require another cutoff and/or gradual scoring, when prediction of stroke outcome is needed.

Triggered Seizures for Ictal SPECT Imaging: A Case Series and Feasibility Study.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

TopCoW: Benchmarking Topology-Aware Anatomical Segmentation of the Circle of Willis (CoW) for CTA and MRA.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.

Adaptation of the Concept of Brain Reserve for the Prediction of Stroke Outcome: Proxies, Neural Mechanisms, and Significance for Research.

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies-quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging.

Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T.

GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml. Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively. Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus). Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1--inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio. Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012). Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18-27 min (GABA+) and 9-18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

Growing importance of brain morphometry analysis in the clinical routine: The hidden impact of MR sequence parameters.

Volumetric assessment based on structural MRI is increasingly recognized as an auxiliary tool to visual reading, also in examinations acquired in the clinical routine. However, MRI acquisition parameters can significantly influence these measures, which must be considered when interpreting the results on an individual patient level. This Technical Note shall demonstrate the problem. Using data from a dedicated experiment, we show the influence of two crucial sequence parameters on the GM/WM contrast and their impact on the measured volumes. A simulated contrast derived from acquisition parameters TI/TR may serve as surrogate and is highly correlated (r=0.96) with the measured contrast.

Diagnosis of Small Unruptured Intracranial Aneurysms : Comparison of 7 T versus 3 T MRI.

PURPOSE: Differentiating normal anatomical variants such as an infundibulum or a vascular loop from true intracranial aneurysms is crucial for patient management. We hypothesize that high-resolution 7 T magnetic resonance imaging (MRI) improves the detection and characterization of normal anatomical variants that may otherwise be misdiagnosed as small unruptured aneurysms. METHODS: This is a retrospective, single-center study. All patients were scanned on a clinically approved 7 T MRI scanner and on a 3 T scanner. Image analysis was performed independently by three neuroradiologists blinded to clinical information. The presence of an unruptured intracranial aneurysm (UIA) and level of diagnostic certainty were assessed and the interrater agreement was calculated. If an aneurysm was present, the anatomic location and shape were recorded and compared. RESULTS: In total, 53 patients with equivocal cerebrovascular findings on 1.5 T or 3 T MRI referred for a 7T MRI examination were included. Aneurysms were suspected in 42 patients examined at 3 T and in 23 patients at 7 T (rate difference 36%, 95% confidence interval, CI, 19-53%, p-value < 0.001). Major disagreement between the field strengths was observed in the A1 segment of anterior cerebral artery/anterior communicating artery (A1/ACOM) complex. The interrater agreement among the readers on the presence of an aneurysm on 7 T MRI was higher than that for 3 T MRI (0.925, 95% CI 0.866-0.983 vs. 0.786, 95% CI 0.700-0.873). CONCLUSION: Our analysis demonstrates a significantly higher interrater agreement and improved diagnostic certainty when small intracranial aneurysms are visualized on 7 T MRI compared to 3 T. In a selected patient cohort, clinical implementation of 7 T MRI may help to establish the definitive diagnosis and thus have a beneficial impact on patient management.

Higher striatal glutamate in male youth with internet gaming disorder.

Internet gaming disorder (IGD) was included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a research diagnosis, but little is known about its pathophysiology. Alterations in frontostriatal circuits appear to play a critical role in the development of addiction. Glutamate is considered an essential excitatory neurotransmitter in addictive disorders. This study's aim was to investigate striatal glutamate in youth with IGD compared to healthy controls (HC). Using a cross-sectional design, 25 adolescent male subjects fulfilling DSM-5 criteria for IGD and 26 HC, matched in age, education, handedness and smoking, were included in the analysis. A structural MPRAGE T1 sequence followed by a single-voxel magnetic resonance spectroscopy MEGA-PRESS sequence (TR = 1500 ms, TE = 68 ms, 208 averages) with a voxel size of 20 mm3 were recorded on 3 T Siemens Magnetom Prisma scanner. The voxel was placed in the left striatum. Group comparison of the relative glutamate and glutamine (Glx) was calculated using regression analysis. IGD subjects met an average of 6.5 of 9 DSM-5 IGD criteria and reported an average of 29 h of weekly gaming. Regression analysis showed a significant group effect for Glx, with higher Glx levels in IGD as compared to HC (coef. = .086, t (50) = 2.17, p = .035). Our study is the first to show higher levels of Glx in the striatum in youth with IGD. The elevation of Glx in the striatum may indicate hyperactivation of the reward system in IGD. Thus, results confirm that neurochemical alterations can be identified in early stages of behavioral addictions.

No-reflow phenomenon in stroke patients: A systematic literature review and meta-analysis of clinical data.

BACKGROUND: The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. AIM: The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke. METHODS: A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model. RESULTS: Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21-37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15-0.31). CONCLUSION: The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.

Associations of resting-state perfusion and auditory verbal hallucinations with and without emotional content in schizophrenia.

Auditory Verbal Hallucinations (AVH) are highly prevalent in patients with schizophrenia. AVH with high emotional content lead to particularly poor functional outcome. Increasing evidence shows that AVH are associated with alterations in structure and function in language and memory related brain regions. However, neural correlates of AVH with emotional content remain unclear. In our study (n = 91), we related resting-state cerebral perfusion to AVH and emotional content, comparing four groups: patients with AVH with emotional content (n = 13), without emotional content (n = 14), without hallucinations (n = 20) and healthy controls (n = 44). Patients with AVH and emotional content presented with increased perfusion within the amygdala and the ventromedial and dorsomedial prefrontal cortex (vmPFC/ dmPFC) compared to patients with AVH without emotional content. In addition, patients with any AVH showed hyperperfusion within the anterior cingulate gyrus, the vmPFC/dmPFC, the right hippocampus, and the left pre- and postcentral gyrus compared to patients without AVH. Our results indicate metabolic alterations in brain areas critical for the processing of emotions as key for the pathophysiology of AVH with emotional content. Particularly, hyperperfusion of the amygdala may reflect and even trigger emotional content of AVH, while hyperperfusion of the vmPFC/dmPFC cluster may indicate insufficient top-down amygdala regulation in patients with schizophrenia.

Evaluating automated longitudinal tumor measurements for glioblastoma response assessment.

Automated tumor segmentation tools for glioblastoma show promising performance. To apply these tools for automated response assessment, longitudinal segmentation, and tumor measurement, consistency is critical. This study aimed to determine whether BraTumIA and HD-GLIO are suited for this task. We evaluated two segmentation tools with respect to automated response assessment on the single-center retrospective LUMIERE dataset with 80 patients and a total of 502 post-operative time points. Volumetry and automated bi-dimensional measurements were compared with expert measurements following the Response Assessment in Neuro-Oncology (RANO) guidelines. The longitudinal trend agreement between the expert and methods was evaluated, and the RANO progression thresholds were tested against the expert-derived time-to-progression (TTP). The TTP and overall survival (OS) correlation was used to check the progression thresholds. We evaluated the automated detection and influence of non-measurable lesions. The tumor volume trend agreement calculated between segmentation volumes and the expert bi-dimensional measurements was high (HD-GLIO: 81.1%, BraTumIA: 79.7%). BraTumIA achieved the closest match to the expert TTP using the recommended RANO progression threshold. HD-GLIO-derived tumor volumes reached the highest correlation between TTP and OS (0.55). Both tools failed at an accurate lesion count across time. Manual false-positive removal and restricting to a maximum number of measurable lesions had no beneficial effect. Expert supervision and manual corrections are still necessary when applying the tested automated segmentation tools for automated response assessment. The longitudinal consistency of current segmentation tools needs further improvement. Validation of volumetric and bi-dimensional progression thresholds with multi-center studies is required to move toward volumetry-based response assessment.

Added value of advanced workup after the first seizure: A 7-year cohort study.

OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.

Resting-state perfusion in motor and fronto-limbic areas is linked to diminished expression of emotion and speech in schizophrenia.

Negative symptoms (NS) are a core component of schizophrenia affecting community functioning and quality of life. We tested neural correlates of NS considering NS factors and consensus subdomains. We assessed NS using the Clinical Assessment Interview for Negative Symptoms and the Scale for Assessment of Negative Symptoms. Arterial spin labeling was applied to measure resting-state cerebral blood flow (rCBF) in 47 schizophrenia patients and 44 healthy controls. Multiple regression analyses calculated the relationship between rCBF and NS severity. We found an association between diminished expression (DE) and brain perfusion within the cerebellar anterior lobe and vermis, and the pre-, and supplementary motor area. Blunted affect was linked to fusiform gyrus and alogia to fronto-striatal rCBF. In contrast, motivation and pleasure was not associated with rCBF. These results highlight the key role of motor areas for DE. Considering NS factors and consensus subdomains may help identifying specific pathophysiological pathways of NS.

Case report: Psychosis and catatonia in an adolescent patient with adipsic hypernatremia and autoantibodies against the subfornical organ.

This is the first description of a patient in which adipsic hypernatremia, a rare autoimmune encephalitis, presented in combination with complex psychiatric symptomatology, including psychosis and catatonia. Adipsic hypernatremia is characterized by autoantibodies against the thirst center of the brain. These autoantibodies cause inflammation and apoptosis in key regions of water homeostasis, leading to lack of thirst and highly increased serum sodium. To date, the symptoms of weakness, fatigue and drowsiness have been associated with adipsic hypernatremia, but no psychiatric symptomatology. Here, we showcase the first description of an adolescent patient, in which severe and complex psychiatric symptoms presented along with adipsic hypernatremia. The patient experienced delusion, hallucinations, restlessness and pronounced depression. Further, he showed ritualized, aggressive, disinhibited and sexualized behavior, as well as self-harm and psychomotor symptoms. Due to his severe condition, he was hospitalized on the emergency unit of the child and adolescent psychiatry for 8 months. Key symptoms of the presented clinical picture are: childhood-onset complex and treatment-resistant psychosis/catatonia, pronounced behavioral problems, fatigue, absent thirst perception, hypernatremia and elevated prolactin levels. This case report renders first evidence speaking for a causal link between the autoimmune adipsic hypernatremia and the psychotic disorder. Moreover, it sheds light on a new form of autoimmune psychosis.

The Brain Tumor Segmentation (BraTS) Challenge 2023: Brain MR Image Synthesis for Tumor Segmentation (BraSyn).

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.