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.

One Year of Outpatient Dialectical Behavioral Therapy and Its Impact on Neuronal Correlates of Attachment Representation in Patients with Borderline Personality Disorder Using a Personalized fMRI Task.

(1) Background: BPD is characterized by affect dysregulation, interpersonal problems, and disturbances in attachment, but neuroimaging studies investigating attachment representations in BPD are rare. No study has examined longitudinal neural changes associated with interventions targeting these impairments. (2) Methods: We aimed to address this gap by performing a longitudinal neuroimaging study on n = 26 patients with BPD treated with Dialectic Behavioral Therapy (DBT) and n = 26 matched healthy controls (HCs; post intervention point: n = 18 BPD and n = 23 HCs). For functional imaging, we applied an attachment paradigm presenting attachment related scenes represented in drawings paired with related neutral or personalized sentences from one's own attachment narratives. In a prior cross-sectional investigation, we identified increased fMRI-activation in the human attachment network, in areas related to fear response and the conflict monitoring network in BPD patients. These were especially evident for scenes from the context of loneliness (monadic pictures paired with individual narrative sentences). Here, we tested whether these correlates of attachment representation show a near-to-normal development over one year of DBT intervention. In addition, we were interested in possible associations between fMRI-activation in these regions-of-interest (ROI) and clinical scores. (3) Results: Patients improved clinically, showing decreased symptoms of borderline personality organization (BPI) and increased self-directedness (Temperament and Character Inventory, TCI) over treatment. fMRI-activation was increased in the anterior medial cingulate cortex (aMCC) and left amygdala in BPD patients at baseline which was absent after intervention. When investigating associations between scores (BPI, TCI) and functional activation, we found significant effects in the bilateral amygdala. In contrast, aMCC activation at baseline was negatively associated with treatment outcome, indicating less effective treatment effects for those with higher aMCC activation at baseline. (4) Conclusions: Monadic attachment scenes with personalized sentences presented in an fMRI setup are capable of identifying increased activation magnitude in BPD. After successful DBT treatment, these increased activations tend to normalize which could be interpreted as signs of a better capability to regulate intensive emotions in the context of "social pain" towards a more organized/secure attachment representation. Amygdala activation, however, indicates high correlations with pre-treatment scores; activation in the aMCC is predictive for treatment gain. Functional activation of the amygdala and the aMCC as a response to attachment scenes representing loneness at baseline might be relevant influencing factors for DBT-intervention outcomes.

White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

Structural integrity of the insula and emotional facial recognition performance following stroke.

The role of the human insula in facial emotion recognition is controversially discussed, especially in relation to lesion-location-dependent impairment following stroke. In addition, structural connectivity quantification of important white-matter tracts that link the insula to impairments in facial emotion recognition has not been investigated. In a case-control study, we investigated a group of 29 stroke patients in the chronic stage and 14 healthy age- and gender-matched controls. Lesion location of stroke patients was analysed with voxel-based lesion-symptom mapping. In addition, structural white-matter integrity for tracts between insula regions and their primarily known interconnected brain structures was quantified by tractography-based fractional anisotropy. Our behavioural analyses showed that stroke patients were impaired in the recognition of fearful, angry and happy but not disgusted expressions. Voxel-based lesion mapping revealed that especially lesions centred around the left anterior insula were associated with impaired recognition of emotional facial expressions. The structural integrity of insular white-matter connectivity was decreased for the left hemisphere and impaired recognition accuracy for angry and fearful expressions was associated with specific left-sided insular tracts. Taken together, these findings suggest that a multimodal investigation of structural alterations has the potential to deepen our understanding of emotion recognition impairments after stroke.

Chronic pain is associated with less grey matter volume in the anterior cingulum, anterior and posterior insula and hippocampus across three different chronic pain conditions.

BACKGROUND: Chronic pain of different aetiologies and localization has been associated with less grey matter volume (GMV) in several cortical and subcortical brain areas. Recent meta-analyses reported low reproducibility of GMV alterations between studies and pain syndromes. METHODS: To investigate GMV in common chronic pain conditions defined by body location (chronic back pain, n = 174; migraine, n = 92; craniomandibular disorder, n = 39) compared to controls (n = 296), we conducted voxel-based morphometry and determined GMV from high-resolution cranial MRIs obtained in an epidemiologic survey. Mediation analyses were performed between the presence of chronic pain and GMV testing the mediators stress and mild depression. The predictability of chronic pain was investigated with binomial logistic regression. RESULTS: Whole-brain analyses yielded reduced GMV within the left anterior insula and the anterior cingulate cortex, for a ROI approach additionally the left posterior insula and left hippocampus showing less GMV across all patients with chronic pain. The relationship of pain with GMV in the left hippocampus was mediated by self-reported stressors in the last 12 months. Binomial logistic regression revealed a predictive effect for GMV in the left hippocampus and left anterior insula/temporal pole for the presence of chronic pain. CONCLUSIONS: Chronic pain across three different pain conditions was characterized by less GMV in brain regions consistently described for different chronic pain conditions before. Less GMV in the left hippocampus mediated by experienced stress during the last year might be related to altered pain learning mechanisms in chronic pain patients. SIGNIFICANCE: Grey matter reorganization could serve as a diagnostic biomarker for chronic pain. In a large cohort, we here replicated findings of less grey matter volume across three pain conditions in the left anterior and posterior insula, anterior cingulate and left hippocampus. Less hippocampal grey matter was mediated by experienced stress.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Performance in information processing speed is associated with parietal white matter tract integrity in multiple sclerosis.

Background: The Symbol Digit Modalities Test (SDMT) is most frequently used to test processing speed in patients with multiple sclerosis (MS). Functional imaging studies emphasize the importance of frontal and parietal areas for task performance, but the influence of frontoparietal tracts has not been thoroughly studied. We were interested in tract-specific characteristics and their association with processing speed in MS patients. Methods: Diffusion tensor imaging was obtained in 100 MS patients and 24 healthy matched controls to compare seed-based tract characteristics descending from the superior parietal lobule [Brodman area 7A (BA7A)], atlas-based tract characteristics from the superior longitudinal fasciculus (SLF), and control tract characteristics from the corticospinal tract (CST) and their respective association with ability on the SDMT. Results: Patients had decreased performance on the SDMT and decreased white matter volume (each p < 0.05). The mean fractional anisotropy (FA) for the BA7A tract and CST (p < 0.05), but not the SLF, differed between MS patients and controls. Furthermore, only the FA of the SLF was positively associated with SDMT performance even after exclusion of the lesions within the tract (r = 0.25, p < 0.05). However, only disease disability and total white matter volume were associated with information processing speed in a linear regression model. Conclusions: Processing speed in MS is associated with the structural integrity of frontoparietal white matter tracts.

Functional MRI in Radiology-A Personal Review.

We, here, provide a personal review article on the development of a functional MRI in the radiology departments of two German university medicine units. Although the international community for human brain mapping has met since 1995, the researchers fascinated by human brain function are still young and innovative. However, the impact of functional magnetic resonance imaging (fMRI) on prognosis and treatment decisions is restricted, even though standardized methods have been developed. The tradeoff between the groundbreaking studies on brain function and the attempt to provide reliable biomarkers for clinical decisions is large. By describing some historical developments in the field of fMRI, from a personal view, the rise of this method in clinical neuroscience during the last 25 years might be understandable. We aim to provide some background for (a) the historical developments of fMRI, (b) the establishment of two research units for fMRI in the departments of radiology in Germany, and (c) a description of some contributions within the selected fields of systems neuroscience, clinical neurology, and behavioral psychology.

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression.

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.

A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms.

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires neuroanatomical expertise. We previously released an open-source dataset of stroke T1w MRIs and manually-segmented lesion masks (ATLAS v1.2, N = 304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the field. Here we present ATLAS v2.0 (N = 1271), a larger dataset of T1w MRIs and manually segmented lesion masks that includes training (n = 655), test (hidden masks, n = 300), and generalizability (hidden MRIs and masks, n = 316) datasets. Algorithm development using this larger sample should lead to more robust solutions; the hidden datasets allow for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke research.

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy.

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Neural Correlates of Attachment Representation in Patients With Borderline Personality Disorder Using a Personalized Functional Magnet Resonance Imaging Task.

Background: Fear of abandonment and aloneness play a key role in the clinical understanding interpersonal and attachment-specific problems in patients with borderline personality disorder (BPD) and has been investigated in previous functional Magnet Resonance Imaging (fMRI) studies. The aim of the present study was to examine how different aspects of attachment representations are processed in BPD, by using for the first time an fMRI attachment paradigm including personalized core sentences from the participants' own attachment stories. We hypothesized that BPD patients would show increased functional involvement of limbic brain regions associated with fear and pain (e.g., the amygdala and the anterior cingulate cortex) when presented personalized attachment relevant stimuli representing loneliness compared to healthy controls (HC). Methods: We examined the attachment classifications of 26 female BPD patients and 26 female HC using the Adult Attachment Projective Picture System (AAP). We used an fMRI-adapted attachment paradigm to investigate the neural correlates of attachment. All participants were presented three personalized (vs. neutral) sentences extracted from their AAP attachment narrative, combined with standardized AAP pictures representing being alone (monadic) or in interactive (dyadic) attachment situations. Results: As expected, the classification of unresolved attachment was significantly greater in BPD compared to HC. BPD patients showed increased fMRI-activation in brain areas associated with fear, pain, and hyperarousal than HC when presented with personalized attachment-relevant alone stimuli. In particular, pictures with monadic attachment situations induced greater anterior medial cingulate cortex, anterior insula, amygdala, thalamus and superior temporal gyrus activation in the patient group. Conclusion: The results point to increased fMRI-activation in areas processing emotional distress and painful experiences in BPD patients. In particular, the emotional cascade reflecting attachment distress was evoked by combining monadic pictures, representing abandonment and aloneness, with the patients' personalized narrative material. Our results confirmed and replicated previous results that illustrate once again the high relevance of aloneness and feelings of abandonment for BPD in the context of attachment trauma. Moreover, our results support the hypothesis of hypermentalization in response to attachment distress as a core feature of social-cognitive impairment in BPD associated with common treatment implications across different therapeutic orientations.

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Reasons for Non-Attendance in the German National Mammography Screening Program: Which Barriers Can Be Overcome Using Telephone Counseling?-A Randomized Controlled Trial.

INTRODUCTION: Germany has established a national mammography screening program (MSP). Despite extensive awareness campaigns, the participation rate is only 54%, which is considerably below the European guidelines' recommendation of at least 70%. Several reasons why women do not participate are already known. Telephone consultations along with invitation letters have improved the participation rate. Here, we analyzed the reasons for non-participation and offered barrier-specific counseling to examine which impediments can be overcome to improve participation. STUDY DESIGN: In a randomized controlled trial, women who had not attended their proposed screening appointment in the MSP after a written invitation were contacted by telephone and asked why they did not attend. Barrier-specific counseling via telephone was then offered. Participation in the MSP was rechecked 3 months after counseling. SETTING: 1772 women, aged 50-69 years, who had not scheduled a mammography screening after a written invitation were contacted by telephone and asked for their reasons for non-participation. INTERVENTION: The reasons were recorded by the calling consultant and categorized either during the call or later based on their recorded statements. Afterward, the women received counseling specific to their statements and were given general information about the MSP. MAIN OUTCOME MEASURES: We categorized the reasons given, calculated their frequency, and analyzed the probabilities to which they could be successfully addressed in individual counseling. Participation rates were determined post-consultation according to the reason(s) indicated. RESULTS: The data were analyzed in 2022. After exclusions, 1494 records were analyzed. Allowing for multiple reasons to be stated by every individual 3280 reasons for not attending were abstracted. The most frequent reason was participation in "gray screening" (51.5%), which included various breast cancer prevention measures outside the national MSP. Time problems (26.6%) and health reasons (17.3%) were also important. Counseling was most effective when women had not participated for scheduling reasons. CONCLUSION: Several reasons prevented women from participating in the MSP. Some reasons, such as time-related issues, could be overcome by telephone counseling, but others, like barriers resulting from fear of the examination procedure or its result, could not.

Complex Regional Pain Syndrome: Thalamic GMV Atrophy and Associations of Lower GMV With Clinical and Sensorimotor Performance Data.

Results on gray matter alterations in complex regional pain syndrome (CRPS) showed heterogeneous findings. Since CRPS is a rare disease, most studies included only small and heterogeneous samples resulting in a low reliability of findings between studies. We investigated 24 CRPS patients with right upper limb affection in the chronic stage of disease using structural MRI and clinical testing. We focused on gray matter volume (GMV) alterations of the brain in comparison to 33 age matched healthy controls, their association to clinical characteristics (duration of pain syndrome and pain intensity ratings) and sensorimotor performance (finger dexterity and spatiotactile resolution). When applying an explorative whole brain analysis CRPS patients showed lower GMV in the bilateral medial thalamus. No other areas showed a relevant GMV difference for the group comparisons. When applying a region of interest driven approach using anatomical masks of the thalamus, ACC/mPFC, putamen, and insula we found relevant associations of clinical and behavioral data in ACC and insula. Whereas, the GMV in ACC showed negative associations with pain intensity and CRPS duration, the GMV of the left posterior insula was negatively associated with sensorimotor performance of the affected hand side. Overall, our results are in accordance to results of others describing a thalamic reduction of GMV in patients with neuropathic pain and are also in accordance with associations of pain intensity and duration with reduced ACC in general in patients with chronic pain syndromes. Sensorimotor performance seems to be related to posterior insula GMV reduction, which has not been described yet for other patient groups.

Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study.

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.

Do Belonging and Social Exclusion at School Affect Structural Brain Development During Adolescence?

Students' sense of belonging presents an essential resource for academic and health outcomes, whereas social exclusion at school negatively impacts students' well-being and academic performance. Aiming to understand how feelings of school-related belonging and exclusion shape the structural brain development, this study applied longitudinal questionnaire-based data and MRI data from 71 adolescent students (37 females, Mage at t1 = 15.0; t2 = 16.1 years). All were white participants from Germany. Voxel-based morphometry revealed only an association of social exclusion (and not of belonging) and gray matter volume in the left anterior insula: From t1 to t2, there was less gray matter decrease, the more social exclusion students perceived. School-related social exclusion and disturbed neurodevelopment are thus significantly associated.

Influence of cardiovascular risk-factors on morphological changes of cerebral arteries in healthy adults across the life span.

Cerebral artery morphological alterations have been associated with several cerebrovascular and neurological diseases, whereas these structures are known to be highly variable among healthy individuals. To date, the knowledge about the influence of cardiovascular risk factors on the morphology of cerebral arteries is rather limited. The aim of this work was to investigate the impact of cardiovascular risk factors on the regional cerebroarterial radius and density. Time-of-Flight magnetic resonance angiography from 1722 healthy adults (21-82 years) were used to extract region-specific measurements describing the main cerebral artery morphology. Multivariate statistical analysis was conducted to quantify the impact of cardiovascular risk factors, including clinical and life behavioural factors, on each region-specific artery measurement. Increased age, blood pressure, and markers of obesity were significantly associated with decreased artery radius and density in most regions, with aging having the greatest impact. Additionally, females showed significantly higher artery density while males showed higher artery radius. Smoking and alcohol consumption did not show any significant association with the artery morphology. The results of this study improve the understanding of the impact of aging, clinical factors, and life behavioural factors on cerebrovascular morphology and can help to identify potential risk factors for cerebrovascular and neurological diseases.

Gray Matter Brain Alterations in Temporomandibular Disorder Tested in a Population Cohort and Three Clinical Samples.

Temporomandibular pain (TMD) is a frequent symptom comprising pain around the mandibular jaw with a high dependence on stressors. Chronic pain has been associated with changes of the brains gray matter volume (GMV), but previous studies on GMV alterations associated with TMD have yielded contradictory results. This might be caused by divergent samples and study methods. We here tested GMV alterations using voxel based morphometry in three clinical samples (summing up to 47 TMD patients) and a population sample with 57 participants who indicated facial pain for the last 6 months. The GMV of pain patients was compared against age-matched and gender-matched participants without chronic pain (60 for the clinical sample comparison and 381 for the cohort sample comparison) who underwent the same assessments as the patient group (MRI measurements and data evaluation using CAT12). In a region of interest analysis, only the clinical samples showed an effect of decreased GMV in the anterior medial cingulate cortex reaching into the medial prefrontal cortex, known to be especially vulnerable for chronic pain gray matter volume reduction. The analysis of the population-based sample did not reveal relevant GMV differences. Overall, an important question remains as to whether most inconsistent results from voxel based morphometry-studies in chronic pain are related to chance results facilitated by small sample size and selection of patient samples. PERSPECTIVE: Using voxel based morphometry 2 samples with chronic temperomandibular pain were compared to controls investigating the brains GMV. Only the clinical sample showed a decrease in anterior cingulate GMV. Contradicting results on GMV loss in temperomandibular pain might be based on small samples in prior studies.