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Abstract Presurgical evaluation is still challenging for MRI‐negative epilepsy patients. As non‐invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non‐invasive methods in MRI‐negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post‐processing was performed using a Morphometric Analysis Program (MAP) on T1‐weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non‐invasive methods. Eighty‐six patients were included in this study. Complete resection of the MAP‐positive regions or the MEG‐positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co‐localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure‐free outcome. Plain Language Summary Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI‐negative epilepsy patients can be difficult. In this study, we intended to use non‐invasive examinations to explore the potential epileptic lesions in MRI‐negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non‐invasive examinations and neuroimaging post‐processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Abstract Introduction The efficiency of The International Classification of Headache Disorders (ICHD-3) in reflecting patients’ disability has recently been questioned. This prompts consideration that clinical features beyond pain may more accurately indicate the extent of underlying brain impairment than the mere frequency of headache days. Important cognitive dysfunctions and psychological impairment have been reported in burdensome cases of migraine, and the presence of these alterations has been associated with biological changes in the nervous system. This study aimed to compare migraine-related disability within a specific patient group, classified using ICHD-3 criteria or classified based on findings from a neuropsychological evaluation using machine learning. Additionally, a complementary voxel-based morphometry (VBM) comparison was conducted to explore potential neuroanatomical differences between the resulting groups. Patients and methods The study included episodic and chronic migraine patients seeking consultation at a specialized headache department. A neuropsychological evaluation protocol, encompassing validated standardized tests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) and disability (MIDAS), was administered. Results from this evaluation were input into an automated K-means clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxel-based Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts between the two distinct grouping configurations. Results The study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine. Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Cluster two exhibited significantly higher levels of depression, anxiety, and perceived stress, and performed worse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores between episodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs 62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients in cluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS (68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significant differences in grey matter volume between the two clusters were noted, particularly involving the precuneus, while differences between chronic and episodic migraine patients did not withstand correction for multiple comparisons. Conclusions The classification of migraine patients based on neuropsychological characteristics demonstrates a more effective separation of groups in terms of disability compared to categorizing them based on the chronic or episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explain differences in treatment responses among apparently similar patients.

Background: The loss of an only child, known as Shidu in China, is a profoundly distressing experience, often leading to Prolonged Grief Disorder (PGD). Despite its impact, the structural brain alterations associated with PGD, potentially influencing cognitive impairments in Shidu parents, remain understudied.Objective: This study aims to identify brain structural abnormalities related to prolonged grief and their relation with cognitive inhibition in Shidu parents.Methods: The study included 40 Shidu parents and 42 non-bereaved participants. Prolonged grief was evaluated using the Prolonged Grief Questionnaire (PG-13). We employed voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to assess brain structural alterations and their correlation with cognitive inhibition, as measured by Stroop interference scores.Results: Findings suggest that greater prolonged grief intensity correlates with reduced grey matter volume in the right amygdala and the left supramarginal gyrus (SMG). Additionally, enhanced amygdala-to-whole-brain structural connectivity showed a marginal association with prolonged grief, particularly with emotional-related symptoms. Furthermore, a decrease in SMG volume was found to mediate the relation between prolonged grief and Stroop Time Inference (TI) score, indicating an indirect effect of prolonged grief on cognitive inhibition.Conclusions: The study provides insight into the neural correlates of prolonged grief in Shidu parents, highlighting the SMG’s role in cognitive inhibition. These findings emphasise the need for comprehensive grief interventions to address the complex cognitive and emotional challenges faced by this unique bereaved population.

Introduction: The cause of Developmental Coordination Disorder (DCD) is unknown, but neuroimaging evidence suggests that DCD may be related to altered brain development. Children with DCD show less structural and functional connectivity compared to typically developing (TD) children, but few studies have examined cortical volume in children with DCD. The purpose of this study was to investigate cortical grey matter volume using voxel-based morphometry (VBM) in children with DCD compared to TD children. Methods: This cross-sectional study was part of a larger randomized-controlled trial (ClinicalTrials.gov ID: NCT02597751) that involved various MRI scans of children with/without DCD. This paper focuses on the anatomical scans, performing VBM of cortical grey matter volume in 30 children with DCD and 12 TD children. Preprocessing and VBM data analysis were conducted using the Computational Anatomy Tool Box-12 and a study-specific brain template. Differences between DCD and TD groups were assessed using a one-way ANOVA, controlling for total intracranial volume. Regression analyses examined if motor and/or attentional difficulties predicted grey matter volume. We used threshold-free cluster enhancement (5,000 permutations) and set an alpha level of 0.05. Due to the small sample size, we did not correct for multiple comparisons. Results: Compared to the TD group, children with DCD had significantly greater grey matter in the left superior frontal gyrus. Lower motor scores (meaning greater impairment) were related to greater grey matter volume in left superior frontal gyrus, frontal pole, and right middle frontal gyrus. Greater grey matter volume was also significantly correlated with higher scores on the Conners 3 ADHD Index in the left superior frontal gyrus, superior parietal lobe, and precuneus. These results indicate that greater grey matter volume in these regions is associated with poorer motor and attentional skills. Discussion: Greater grey matter volume in the left superior frontal gyrus in children with DCD may be a result of delayed or absent healthy cortical thinning, potentially due to altered synaptic pruning as seen in other neurodevelopmental disorders. These findings provide further support for the hypothesis that DCD is related to altered brain development. [ABSTRACT FROM AUTHOR]

Most of mammalian physiology is under the control of biological rhythms, including the endocrine system with time-varying hormone secretion. Precision neuroimaging studies provide unique insights into how the endocrine system dynamically regulates aspects of the human brain. Recently, we established estrogen's ability to drive widespread patterns of connectivity and enhance the global efficiency of large-scale brain networks in a woman sampled every 24 h across 30 consecutive days, capturing a complete menstrual cycle. Steroid hormone production also follows a pronounced sinusoidal pattern, with a peak in testosterone between 6 and 7 A.M. and nadir between 7 and 8 P.M. To capture the brain's response to diurnal changes in hormone production, we carried out a companion precision imaging study of a healthy adult man who completed MRI and venipuncture every 12-24 h across 30 consecutive days. Results confirmed robust diurnal fluctuations in testosterone, 17ß-estradiol--the primary form of estrogen--and cortisol. Standardized regression analyses revealed widespread associations between testosterone, estradiol, and cortisol concentrations and whole-brain patterns of coherence. In particular, functional connectivity in the Dorsal Attention Network was coupled with diurnally fluctuating hormones. Further, comparing dense-sampling datasets between a man and a naturally cycling woman revealed that fluctuations in sex hormones are tied to patterns of whole-brain coherence in both sexes and to a heightened degree in the male. Together, these findings enhance our understanding of steroid hormones as rapid neuromodulators and provide evidence that diurnal changes in steroid hormones are associated with patterns of whole-brain functional connectivity. [ABSTRACT FROM AUTHOR]

Objective: Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level. Methods: This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy. Results: We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome. Significance: Our research highlights the role of hippo-thalamic-basalcortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy. [ABSTRACT FROM AUTHOR]

A growing body of evidence indicates intra- and inter-regional heterogeneity of astrocytes in the brain. However, because of a lack of an efficient method for isolating astrocytes from the spinal cord, little is known about how much spinal cord astrocytes are heterogeneous in adult mice. In this study, we developed a new method for isolating spinal astrocytes from adult mice using a cold-active protease from Bacillus licheniformis with an astrocyte cell surface antigen-2 (ACSA-2) antibody. Using fluorescence-activated cell sorting, isolated spinal ACSA-2+ cells were divided into two distinct populations, ACSA-2high and ACSA-2low. By analyzing the expression of cell-type marker genes, the ACSA-2high and ACSA-2low populations were identified as astrocytes and ependymal cells, respectively. Furthermore, ACSA-2high cells had mRNAs encoding genes that were abundantly expressed in the gray matter (GM) but not white matter astrocytes. By optimizing enzymatic isolation procedures, the yield of GM astrocytes also increased. Therefore, our newly established method enabled the selective and efficient isolation of GM astrocytes from the spinal cord of adult mice and may be useful for bulk- or single-cell RNA-sequencing under physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186 diffusion-weighted MRIs from participants between 2 weeks to 100 years of age. Age-related changes in gray matter and WM partial volumes and microstructural WM properties, both brain-wide and on 29 reconstructed tracts, were investigated as a function of biological sex and hemisphere, when appropriate. We investigated the curve fit that would best explain age-related differences by fitting linear, cubic, quadratic, and exponential models to macro and microstructural WM properties. Following the first steep increase in WM volume during infancy and childhood, the rate of development slows down in adulthood and decreases with aging. Similarly, microstructural properties of WM, particularly fractional anisotropy (FA) and mean diffusivity (MD), follow independent rates of change across the lifespan. The overall increase in FA and decrease in MD are modulated by demographic factors, such as the participant's age, and show different hemispheric asymmetries in some association tracts reconstructed via probabilistic tractography. All changes in WM macro and microstructure seem to follow nonlinear trajectories, which also differ based on the considered metric. Exponential changes occurred for the WM volume and FA and MD values in the first five years of life. Collectively, these results provide novel insight into how changes in different metrics of WM occur when a lifespan approach is considered. [ABSTRACT FROM AUTHOR]

• Brain activation assessed during action anticipation in table tennis experts vs. novices. • MVPA distinguished experts from novices with 90.48% accuracy during action anticipation. • Regions involved in conflict monitoring or motor cognition distinguished expert/novice. • Findings suggest roles for all these brain regions in action anticipation in experts. An exceptional ability to accurately anticipate an opponent's action is paramount for competitive athletes and highlights their experiential mastery. Despite conventional associations of action observation with specific brain regions, neuroimaging discrepancies persist. To explore the brain regions and neural mechanisms undergirding action anticipation, we compared distinct brain activation patterns involved in table tennis serve anticipation of expert table tennis athletes vs. non-experts by using both univariate analysis and multivoxel pattern analysis (MVPA). We collected functional magnetic resonance imaging data from 29 table tennis experts and 34 non-experts as they pressed a button to predict the trajectory of a ball in a table tennis serve video truncated at the moment of racket-ball contact vs. pressing any button while viewing a static image of the first video frame. MVPA was applied to assess whether it could accurately differentiate experts from non-experts. MVPA results indicated moderate accuracy (90.48%) for differentiating experts from non-experts. Brain regions contributing most to the differentiation included the left cerebellum, the vermis, the right middle temporal pole, the inferior parietal cortex, the bilateral paracentral lobule, and the left supplementary motor area. The findings suggest that brain regions associated with cognitive conflict monitoring and motor cognition contribute to the action anticipation ability of expert table tennis players. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have revealed alterations in habenular (Hb) structure and functional connectivity (FC) in psychiatric conditions. The Hb plays a particularly critical role in regulating negative emotions, which trigger excessive food intake and obesity. However, obesity and weight loss intervention (i.e., laparoscopic sleeve gastrectomy [LSG])–associated changes in Hb structure and FC have not been studied. We used voxel-based morphometry analysis to measure changes in gray matter volume (GMV) in the Hb in 56 patients with obesity at pre-LSG and 12 months post-LSG and in 78 normal-weight (NW) control participants. Then, we conducted Hb seed-based resting-state FC (RSFC) to examine obesity-related and LSG-induced alterations in RSFC. Finally, we used mediation analysis to characterize the interrelationships among Hb GMV, RSFC, and behaviors. Compared with NW participants, Hb GMV was smaller in patients at pre-LSG and increased at 12 months post-LSG to levels equivalent to that of NW; in addition, increases in Hb GMV were correlated with reduced body mass index (BMI). Compared with NW participants, pre-LSG patients showed greater RSFCs of the Hb–insula, Hb–precentral gyrus, and Hb–rolandic operculum and weaker RSFCs of the Hb–thalamus, Hb–hypothalamus, and Hb–caudate; LSG normalized these RSFCs. Decreased RSFC of the Hb-insula was correlated with reduced BMI, Yale Food Addiction Scale rating, and emotional eating; reduced hunger levels were correlated with increased RSFCs of the Hb–thalamus and Hb–hypothalamus; and reduced BMI and Yale Food Addiction Scale ratings were correlated with increased RSFCs of the Hb–thalamus and Hb–hypothalamus, respectively. The bidirectional relationships between Hb GMV and RSFC of the Hb–insula contributed to reduced BMI. These findings indicate that LSG increased Hb GMV and that its related improvement in RSFC of the Hb–insula may mediate long-term benefits of LSG for eating behaviors and weight loss. [ABSTRACT FROM AUTHOR]

Introduction: The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the causal impact of GM on LC and identify potential immune cell mediators. Methods: The utilized data for the Genome-Wide Association Studies (GWAS) were summarized as follows: gut microbiota data from the Dutch Microbiome Project (DMP) (N = 7,738), lung cancer data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and International Lung Cancer Consortium (ILCCO) (Ncase = 29,266, Ncontrol = 56,450) included four types of cancer: NSCLC, LUAD, LUSC, and SCLC, and immune cell data from European populations (N = 3,757). We employed bi-directional two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis to assess the causal relationship between GM and LC and potential immune cell mediators. Results: Bi-directional UVMR analysis revealed that 24 gut microbiota species can affect LC, while LC can affect the abundance of 17 gut microbiota species. Mediation analysis demonstrated that six immune cells mediated the causal relationships of seven gut microbiota species on LC: "CCR7 on naive CD8+ T cell" mediated the causal relationship between s_Alistipes_putredinis and LUAD, with a mediation proportion of 9.5% and P = 0.018; "IgD-CD27-B cell %lymphocyte" mediated the causal relationships between g_Gordonibacter and s_Gordonibacter_pamelaeae with LUSC, with mediation proportions of 11.8% and 11.9%, respectively and P = 0.029; "CD20-CD38-B cell %lymphocyte" mediated the causal relationship between s_Bacteroides_clarus and SCLC, with a mediation proportion of 13.8% and P = 0.005; "CD20 on IgD+ CD38- unswitched memory B cell" mediated the causal relationship between s_Streptococcus_thermophilus and SCLC, with a mediation proportion of 14.1% and P = 0.023; "HLA DR on CD14- CD16+ monocyte" mediated the causal relationship between s_Bifidobacterium_bifidum and SCLC, with a mediation proportion of 8.7% and P = 0.012; "CD45 on Granulocytic Myeloid-Derived Suppressor Cells" mediated the causal relationship between f_Lactobacillaceae and SCLC, with a mediation proportion of 4.0% and P = 0.021. Conclusion: This Mendelian randomization study identified several specific gut microbiotas that exhibit causal relationships with lung cancer and potentially mediate immune cells. [ABSTRACT FROM AUTHOR]

Background: Tight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes. Methods: Retrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated. Results: Among 161 patients included (median age 76.8 years, range 60.8–93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj β coeff: -0.217, 95%CI: [-0.416 to -0.018], p =.033), the precentral gyri (adj βcoeff:-0.277, 95%CI: [-0.482 to -0.073], p =.009), the superior frontal gyri (adj βcoeff: -0.244, 95%CI: [-0.458 to -0.030], p =.026), the calcarine cortex (adj βcoeff:-0.193, 95%CI: [-0.386 to -0.001], p =.049), the superior occipital gyri (adj βcoeff: -0.291, 95%CI: [-0.521 to -0.061], p =.014) and the inferior occipital gyri (adj βcoeff: -0.236, 95%CI: [-0.456 to – 0.015], p =.036). Conclusion: A significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample. [ABSTRACT FROM AUTHOR]

Procrastination is universally acknowledged as a problematic behavior with wide-ranging consequences impacting various facets of individuals' lives, including academic achievement, social accomplishments, and mental health. Although previous research has indicated that future self-continuity is robustly negatively correlated with procrastination, it remains unknown about the neural mechanisms underlying the impact of future self-continuity on procrastination. To address this issue, we employed a free construction approach to collect individuals' episodic future thinking (EFT) thoughts regarding specific procrastination tasks. Next, we conducted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to explore the neural substrates underlying future self-continuity. Behavior results revealed that future self-continuity was significantly negatively correlated with procrastination, and positively correlated with anticipated positive outcome. The VBM analysis showed a positive association between future self-continuity and gray matter volumes in the right ventromedial prefrontal cortex (vmPFC). Furthermore, the RSFC results indicated that the functional connectivity between the right vmPFC and the left inferior parietal lobule (IPL) was positively correlated with future self-continuity. More importantly, the mediation analysis demonstrated that anticipated positive outcome can completely mediate the relationship between the vmPFC-IPL functional connectivity and procrastination. These findings suggested that vmPFC-IPL functional connectivity might prompt anticipated positive outcome about the task and thereby reduce procrastination, which provides a new perspective to understand the relationship between future self-continuity and procrastination. [ABSTRACT FROM AUTHOR]

Connectome studies have shown how Alzheimer's disease (AD) disrupts functional and structural connectivity among brain regions. But the molecular basis of such disruptions is less studied, with most genomic/transcriptomic studies performing within-brain-region analyses. To inspect how AD rewires the correlation structure among genes in different brain regions, we performed an Inter-brain-region Differential Correlation (Inter-DC) analysis of RNA-seq data from Mount Sinai Brain Bank on four brain regions (frontal pole, superior temporal gyrus, parahippocampal gyrus and inferior frontal gyrus, comprising 264 AD and 372 control human post-mortem samples). An Inter-DC network was assembled from all pairs of genes across two brain regions that gained (or lost) correlation strength in the AD group relative to controls at FDR 1%. The differentially correlated (DC) genes in this network complemented known differentially expressed genes in AD, and likely reflects cell-intrinsic changes since we adjusted for cell compositional effects. Each brain region used a distinctive set of DC genes when coupling with other regions, with parahippocampal gyrus showing the most rewiring, consistent with its known vulnerability to AD. The Inter-DC network revealed master dysregulation hubs in AD (at genes ZKSCAN1, SLC5A3, RCC1, IL17RB, PLK4, etc.), inter-region gene modules enriched for known AD pathways (synaptic signaling, endocytosis, etc.), and candidate signaling molecules that could mediate region-region communication. The Inter-DC network generated in this study is a valuable resource of gene pairs, pathways and signaling molecules whose inter-brain-region functional coupling is disrupted in AD, thereby offering a new perspective of AD etiology. [ABSTRACT FROM AUTHOR]

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions. Personalized brain activity models in Alzheimer's disease detect synergistic amyloid-β and tau impacts on neuronal excitability values, which significantly predict brain atrophy, p-tau217 plasma concentrations, and cognitive deterioration. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a complex autoimmune disease of central nervous system (CNS) characterized by the myelin sheath destruction and compromised nerve signal transmission. Understanding molecular mechanisms driving MS development is critical due to its early onset, chronic course, and therapeutic approaches based only on symptomatic treatment. Cytokines are known to play a pivotal role in the MS pathogenesis with interleukin-6 (IL-6) being one of the key mediators. This study investigates contribution of IL-6 produced by microglia and dendritic cells to the development of experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of MS. Mice with conditional inactivation of IL-6 in the CX3CR1+ cells, including microglia, or CD11c+ dendritic cells, displayed less severe symptoms as compared to their wild-type counterparts. Mice with microglial IL-6 deletion exhibited an elevated proportion of regulatory T cells and reduced percentage of pathogenic IFNγ-producing CD4+ T cells, accompanied by the decrease in pro-inflammatory monocytes in the CNS at the peak of EAE. At the same time, deletion of IL-6 from microglia resulted in the increase of CCR6+ T cells and GM-CSF-producing T cells. Conversely, mice with IL-6 deficiency in the dendritic cells showed not only the previously described increase in the proportion of regulatory T cells and decrease in the proportion of TH17 cells, but also reduction in the production of GM-CSF and IFNγ in the secondary lymphoid organs. In summary, IL-6 functions during EAE depend on both the source and localization of immune response: the microglial IL-6 exerts both pathogenic and protective functions specifically in the CNS, whereas the dendritic cell-derived IL-6, in addition to being critically involved in the balance of regulatory T cells and TH17 cells, may stimulate production of cytokines associated with pathogenic functions of T cells. [ABSTRACT FROM AUTHOR]

Introduction: The prefrontal–cingulate–thalamic areas are associated with ejaculation control. Functional abnormalities of these areas and decreased grey matter volume (GMV) in the subcortical areas have been confirmed in premature ejaculation (PE) patients. However, no study has explored the corresponding GMV changes in the prefrontal–cingulate–thalamic areas, which are considered as the important basis for functional abnormalities. This study aimed to investigated whether PE patients exhibited impaired GMV in the brain, especially the prefrontal–cingulate–thalamic areas, and whether these structural deficits were associated with declined ejaculatory control. Methods: T1‐weighted structural magnetic resonance imaging (MRI) data were acquired from 50 lifelong PE patients and 50 age‐, and education‐matched healthy controls (HCs). The PE diagnostic tool (PEDT) was applied to assess the subjective symptoms of PE. Based on the method of voxel‐based morphometry (VBM), GMV were measured and compared between groups. In addition, the correlations between GMV of brain regions showed differences between groups and PEDT scores were evaluated in the patient group. Results: PE patients showed decreased GMV in the right dorsolateral superior frontal gyrus (clusters = 13, peak T‐values = −4.30) and left thalamus (clusters = 47, T = −4.33), and increased GMV in the left middle cingulate gyrus (clusters = 12, T = 4.02) when compared with HCs. In the patient group, GMV of the left thalamus were negatively associated with PEDT scores (r = −0.35; P = 0.01). Receiver operating characteristic (ROC) analysis showed that GMV of the right dorsolateral superior frontal gyrus (AUC = 0.71, P < 0.01, sensitivity = 60%, specificity = 78%), left thalamus (AUC = 0.72, P < 0.01, sensitivity = 92%, specificity = 46%) and middle cingulate gyrus (AUC = 0.69, P < 0.01, sensitivity = 50%, specificity = 90%), and the combined model (AUC = 0.84, P < 0.01, sensitivity = 78%, specificity = 80%) all had the ability to distinguish PE patients from HCs. Conclusion: Disturbances in GMV were revealed in the prefrontal–cingulate–thalamic areas of PE patients. The findings implied that decreased GMV in the dorsolateral prefrontal cortex and thalamus might be associated with the central pathological neural mechanism underlying the declined ejaculatory control while increased GMV in the middle cingulate gyrus might be the compensatory mechanism underlying PE. [ABSTRACT FROM AUTHOR]

Background: Whereas clinical experience in dementia indicates high risk for financial mismanagement, there has been little formal study of real world financial errors in dementia. Objective: We aimed to compare caregiver-reported financial mistakes among people with Alzheimer's disease, behavioral variant frontotemporal dementia (bvFTD), and primary progressive aphasia (PPA). Methods: Caregivers reported whether participants with dementia had made financial mistakes within the last year; and if so, categorized these as resulting from: (a) being too trusting or gullible, (b) being wasteful or careless with money, or (c) trouble with memory. In a pre-registered analysis ), we examined the hypotheses that (1) financial mistakes due to impaired socioemotional function and diminished sensitivity to negative outcomes are more prevalent in bvFTD than in Alzheimer's disease, and (2) financial mistakes due to memory are more prevalent in Alzheimer's disease than in bvFTD. Exploratory analyses addressed vulnerability in PPA and brain-behavior relationships using voxel-based morphometry. Results: Concordant with our first hypothesis, bvFTD was more strongly associated than Alzheimer's disease with mistakes due to being too trusting/gullible or wasteful/careless; contrary to our second hypothesis, both groups were similarly likely to make mistakes due to memory. No differences were found between Alzheimer's disease and PPA. Exploratory analyses indicated associations between financial errors and atrophy in right prefrontal and insular cortex. Conclusions: Our findings cohere with documented socioemotional and valuation impairments in bvFTD, and with research indicating comparable memory impairment between bvFTD and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. Objective: This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. Methods: We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. Results: Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. Conclusion: We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015). [ABSTRACT FROM AUTHOR]

Imaging studies of subthreshold depression (StD) have reported structural and functional abnormalities in a variety of spatially diverse brain regions. However, there is no consensus among different studies. In the present study, we applied a multimodal meta‐analytic approach, the Activation Likelihood Estimation (ALE), to test the hypothesis that StD exhibits spatially convergent structural and functional brain abnormalities compared to healthy controls. A total of 31 articles with 25 experiments were included, collectively representing 1001 subjects with StD. We found consistent differences between StD and healthy controls mainly in the left insula across studies with various neuroimaging methods. Further exploratory analyses found structural atrophy and decreased functional activities in the right pallidum and thalamus in StD, and abnormal spontaneous activity converged to the middle frontal gyrus. Coordinate‐based meta‐analysis found spatially convergent structural and functional impairments in StD. These findings provide novel insights for understanding the neural underpinnings of subthreshold depression and enlighten the potential targets for its early screening and therapeutic interventions in the future. [ABSTRACT FROM AUTHOR]

Objective: In temporal lobe epilepsy (TLE), a taxonomy classifying patients into 3 cognitive phenotypes has been adopted: minimally, focally, or multidomain cognitively impaired (CI). We examined gray matter (GM) thickness patterns of cognitive phenotypes in drug‐resistant TLE and assessed potential use for predicting postsurgical cognitive outcomes. Methods: TLE patients undergoing presurgical evaluation were categorized into cognitive phenotypes. Network edge weights and distances were calculated using type III analysis of variance F‐statistics from comparisons of GM regions within each TLE cognitive phenotype and age‐ and sex‐matched healthy participants. In resected patients, logistic regression models (LRMs) based on network analysis results were used for prediction of postsurgical cognitive outcome. Results: A total of 124 patients (63 females, mean age ± standard deviation [SD] = 36.0 ± 12.0 years) and 117 healthy controls (63 females, mean age ± SD = 36.1 ± 12.0 years) were analyzed. In the multidomain CI group (n = 66, 53.2%), 28 GM regions were significantly thinner compared to healthy controls. Focally impaired patients (n = 37, 29.8%) showed 13 regions, whereas minimally impaired patients (n = 21, 16.9%) had 2 significantly thinner GM regions. Regions affected in both multidomain and focally impaired patients included the anterior cingulate cortex, medial prefrontal cortex, medial temporal, and lateral temporal regions. In 69 (35 females, mean age ± SD = 33.6 ± 18.0 years) patients who underwent surgery, LRMs based on network‐identified GM regions predicted postsurgical verbal memory worsening with a receiver operating curve area under the curve of 0.70 ± 0.15. Interpretation: A differential pattern of GM thickness can be found across different cognitive phenotypes in TLE. Including magnetic resonance imaging with clinical measures associated with cognitive profiles has potential in predicting postsurgical cognitive outcomes in drug‐resistant TLE. ANN NEUROL 2024;95:984–997 [ABSTRACT FROM AUTHOR]

Previous studies have reported sex differences in altered brain function in patients with chronic insomnia (CI). However, sex-related alterations in brain morphology have rarely been investigated. This study aimed to investigate sex-specific grey matter (GM) alterations in patients with CI and to examine the relationship between GM alterations and neuropsychological assessments. Ninety-three (65 females and 28 males) patients and 78 healthy (50 females and 28 males) controls were recruited. Structural magnetic resonance imaging data were analysed using voxel-based morphometry to test for interactions between sex and diagnosis. Spearman's correlation was used to assess the associations among structure, disease duration, and sleep-, mood-, and cognition-related assessments. Males with CI showed reduced GM volume in the left inferior parietal lobe, left middle cingulate cortex, and right supramarginal gyrus. Females with CI showed increased GM volume in the right Rolandic operculum. Moreover, mood-related assessments were negatively correlated with GM volumes in the right supramarginal gyrus and left inferior parietal lobe in the male patients, and cognitive-related assessments were positively correlated with GM volumes in the Rolandic operculum in the female patients. Our findings indicate sex-specific alterations in brain morphology in CI, thereby broadening our understanding of sex differences in CI and potentially providing complementary evidence for the development of more effective therapies and individual treatments. [ABSTRACT FROM AUTHOR]

Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients. [ABSTRACT FROM AUTHOR]

Summary: This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non‐snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral‐based regions of interest were identified using the Desikan‐Killiany atlas. Student's t‐tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes. [ABSTRACT FROM AUTHOR]

Hemifacial spasm (HFS) is a syndrome characterized by involuntary contractions of the facial muscles innervated by the ipsilateral facial nerve. Currently, microvascular decompression (MVD) is an effective treatment for HFS. Diffusion weighted imaging (DWI) is a non-invasive advanced magnetic resonance technique that allows us to reconstruct white matter (WM) virtually based on water diffusion direction. This enables us to model the human brain as a complex network using graph theory. In our study, we recruited 32 patients with HFS and 32 healthy controls to analyze and compare the topological organization of whole-brain white matter networks between the groups. We also explored the potential relationships between altered topological properties and clinical outcomes. Compared to the HC group, the white matter network was disrupted in both preoperative and postoperative groups of HFS patients, mainly located in the somatomotor network, limbic network, and default network (All P < 0.05, FDR corrected). There was no significant difference between the preoperative and postoperative groups (P > 0.05, FDR corrected). There was a correlation between the altered topological properties and clinical outcomes in the postoperative group of patients (All P < 0.05, FDR corrected). Our findings indicate that in HFS, the white matter structural network was disrupted before and after MVD, and that these alterations in the postoperative group were correlated with the clinical outcomes. White matter alteration here described may subserve as potential biomarkers for HFS and may help us identify patients with HFS who can benefit from MVD and thus can help us make a proper surgical patient selection. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) is related to aberrant aggregation of immune cells in the plaques. This study focused on identification of abnormal T cell subtypes and inflammatory factors in CHD patients. To this end, the subtypes of T cells in peripheral blood of CHD patients (n=141) and healthy controls (n=46) were analyzed by flow cytometry. Plasma concentrations of cytokines were analyzed by multiplex assay. It was shown that the number of T helper cells producing granulocyte-macrophage CSF (GM-CSF) was higher in CHD patients in comparison with healthy controls. In addition, the fractions of Th1 and Th17 cells as well as the levels of IL-4, IL-5, IL-6, and IL-10 in CHD patients also surpassed the control values (p<0.05). However, the level of GM-CSF was insignificantly lower in CHD patients. Thus, we revealed a relationship between the number of T cells producing GM-CSF and the severity of CHD. Our results can be used to develop new potential biomarkers for CHD detection. [ABSTRACT FROM AUTHOR]

Purpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress. Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups. Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1. Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Mild cognitive impairment (MCI) is a common symptom observed in individuals with Parkinson's disease (PD) and a main risk factor for progressing to dementia. Our objective was to identify early anatomical brain changes that precede the transition from healthy cognition to MCI in PD. Methods: Structural T1-weighted magnetic resonance imaging data of PD patients with healthy cognition at baseline were downloaded from the Parkinson's Progression Markers Initiative database. Patients were divided into two groups based on the annual cognitive assessments over a 5-year time span: (i) PD patients with unstable healthy cognition who developed MCI over a 5-year follow-up (PD-UHC, n = 52), and (ii) PD patients who maintained stable healthy cognitive function over the same period (PD-SHC, n = 52). These 52 PD-SHC were selected among 192 PD-SHC patients using propensity score matching method to have similar demographic and clinical characteristics with PD-UHC at baseline. Seventy-five percent of these were used to train a support vector machine (SVM) algorithm to distinguish between the PD-UHC and PD-SHC groups, and tested on the remaining 25% of individuals. Shapley Additive Explanations (SHAP) feature analysis was utilized to identify the most informative brain regions in SVM classifier. Results: The average accuracy of classifying PD-UHC vs. PD-SHC was 80.76%, with 82.05% sensitivity and 79.48% specificity using 10-fold cross-validation. The performance was similar in the hold-out test sets with all accuracy, sensitivity, and specificity at 76.92%. SHAP analysis showed that the most influential brain regions in the prediction model were located in the frontal, occipital, and cerebellar regions as well as midbrain. Discussion: Our machine learning-based analysis yielded promising results in identifying PD individuals who are at risk of cognitive decline from the earliest disease stage and revealed the brain regions which may be linked to the prospective cognitive decline in PD before clinical symptoms emerge. [ABSTRACT FROM AUTHOR]

Aim of the study. To assess whether the middle temporal gyrus (MTG) approach to mesial temporal lobe (MTL) tumours is an effective procedure for the treatment of epilepsy in children. Clinical rationale for the study. MTL tumours are a common cause of drug-resistant epilepsy in children. There is as yet no consensus regarding their treatment. One possibility is resection via a MTG approach. Material and methods. We assessed the medical records of patients treated at the Department of Neurosurgery, Children's Memorial Health Institute, Warsaw, Poland between 2002 and 2020. A prospectively maintained database including clinical, laboratory, and radiographic presentation, as well as pre- and post-operative course, was analysed. Patients with at least a one-year follow-up were included. Results. There were 14 patients aged 4-18 years who underwent a MTG approach for a MTL tumour. All presented with epileptic seizure, and none had neurological deficit on admission to hospital. Median follow-up was 2.5 years. Neuronavigation was used to adjust the approach, localise the temporal horn, and achieve radical resection of the tumour and the hippocampus. Gross total resection was performed in all cases. In most patients, histopathological examination revealed ganglioglioma. One patient had transient aphasia. Two patients developed hemiparesis after surgery, which later improved. One of them also experienced visual disturbances. Acute complications were more frequent in younger patients (p = 0.024). In all cases, MRI confirmed complete resection and there was no tumour recurrence during the follow-up period. 13/14 patients remained seizure-free (Engel class I). Conclusions and clinical implications. The MTG approach to MTL tumours is an effective procedure for the treatment of epilepsy in children. It avoids removal of the lateral temporal lobe and poses only a minor risk of permanent neurological complications. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread adoption of combination antiretroviral therapy (cART) in managing HIV, the virus’s impact on the brain structure of patients remains significant. This study aims to longitudinally explore the persistent effects of HIV on brain structure, focusing on changes in gray matter volume (GMV) and structural covariance network (SCN) among patients at the Asymptomatic Neurocognitive Impairment (ANI) stage. Methods: This research involved 45 HIV patients diagnosed with ANI and 45 demographically matched healthy controls (HCs). The participants were observed over a 1.5-year period. Differences in GMV between groups were analyzed using voxel-based morphometry (VBM), while the graph theory model facilitated the establishment of topological metrics for assessing network indices. These differences were evaluated using two-sample t-tests and pairedsample t-tests, applying the network-based statistics method. Additionally, the study examined correlations between GMV and cognitive performance, as well as clinical variables. Results: Compared with HCs, HIV patients demonstrated reduced GMV in the right middle temporal gyrus and left middle frontal gyrus (FWE, p  <  0.05), along with decreased betweenness centrality (BC) in the left anterior cingulate and paracingulate cortex. Conversely, an increase in the clustering coefficient (Cp) was observed (FDR, p  <  0.05). During the follow-up period, a decline in GMV in the right fusiform gyrus (FWE, p  <  0.05) and a reduction in node efficiency (Ne) in the triangular part of the inferior frontal gyrus were noted compared with baseline measurements (FDR, p  <  0.05). The SCN of HIV patients exhibited small-world properties across most sparsity levels (Sigma >1), and area under the curve (AUC) analysis revealed no significant statistical differences between groups. Conclusion: The findings suggest that despite the administration of combination antiretroviral therapy (cART), HIV continues to exert slow and sustained damage on brain structures. However, when compared to HCs, the small-world properties of the patients’ SCNs did not significantly differ, and the clustering coefficient, indicative of the overall information-processing capacity of the brain network, was slightly elevated in HIV patients. This elevation may relate to compensatory effects of brain area functions, the impact of cART, functional reorganization, or inflammatory responses. [ABSTRACT FROM AUTHOR]

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience's neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition. [ABSTRACT FROM AUTHOR]

Some individuals show a discrepancy between cognition and the amount of neuropathological changes characteristic for Alzheimer's disease (AD). This phenomenon has been referred to as 'resilience'. The molecular and cellular underpinnings of resilience remain poorly understood. To obtain an unbiased understanding of the molecular changes underlying resilience, we investigated global changes in gene expression in the superior frontal gyrus of a cohort of cognitively and pathologically well-defined AD patients, resilient individuals and age-matched controls (n = 11–12 per group). 897 genes were significantly altered between AD and control, 1121 between resilient and control and 6 between resilient and AD. Gene set enrichment analysis (GSEA) revealed that the expression of metallothionein (MT) and of genes related to mitochondrial processes was higher in the resilient donors. Weighted gene co-expression network analysis (WGCNA) identified gene modules related to the unfolded protein response, mitochondrial processes and synaptic signaling to be differentially associated with resilience or dementia. As changes in MT, mitochondria, heat shock proteins and the unfolded protein response (UPR) were the most pronounced changes in the GSEA and/or WGCNA, immunohistochemistry was used to further validate these processes. MT was significantly increased in astrocytes in resilient individuals. A higher proportion of the mitochondrial gene MT-CO1 was detected outside the cell body versus inside the cell body in the resilient compared to the control group and there were higher levels of heat shock protein 70 (HSP70) and X-box-binding protein 1 spliced (XBP1s), two proteins related to heat shock proteins and the UPR, in the AD donors. Finally, we show evidence for putative sex-specific alterations in resilience, including gene expression differences related to autophagy in females compared to males. Taken together, these results show possible mechanisms involving MTs, mitochondrial processes and the UPR by which individuals might maintain cognition despite the presence of AD pathology. [ABSTRACT FROM AUTHOR]

Non-fatal opioid overdoses are associated with significant morbidity. Hypoxic brain injury caused by opioid-induced respiratory depression is a key mechanism of such morbidity. For example, reports describe an amnestic syndrome in opioid users associated with acute injury to the hippocampus, a brain region that is highly susceptible to hypoxic injury. In our recent study we investigated the effects of non-fatal opioid overdose on the hippocampal volume in a well-characterized sample of opioid use disorder (OUD) patients with a history of overdose (OD) compared to those with no prior overdose (NOD). Using structural magnetic resonance imaging (MRI) and voxel-based morphometry, we observed lower hippocampal volume in patients with a history OD than in the NOD group. These findings support an association between non-fatal opioid overdose and hippocampal injury, which we hypothesize contributes to recently reported cases of OUD related amnestic syndrome. Here we review our study findings and the potential pathophysiological mechanisms underlying the acute and delayed hippocampal injury in nonfatal opioid overdose. We also discuss the implications for the risk of overdose and brain injury with the increased prevalence of fentanyl and xylazine contamination of the illicit opioid supply. Lastly, we highlight considerations for clinical management of the underappreciated neurological injury and cognitive dysfunction in OUD patients. [ABSTRACT FROM AUTHOR]

While research has unveiled and quantified brain markers of abnormal neurodevelopment, clinicians still work with qualitative metrics for MRI brain investigation. The purpose of the current article is to bridge the knowledge gap between case-control cohort studies and individual patient care. Here, we provide a unique dataset of seventy-three 3-to-17 years-old healthy subjects acquired with a 6-minute MRI protocol encompassing T1 and T2 relaxation quantitative sequence that can be readily implemented in the clinical setting; MP2RAGE for T1 mapping and the prototype sequence GRAPPATINI for T2 mapping. White matter and grey matter volumes were automatically quantified. We further provide normative developmental curves based on these two imaging sequences; T1, T2 and volume normative ranges with respect to age were computed, for each ROI of a pediatric brain atlas. This open-source dataset provides normative values allowing to position individual patients acquired with the same protocol on the brain maturation curve and as such provides potentially useful quantitative biomarkers facilitating precise and personalized care. [ABSTRACT FROM AUTHOR]

Background: Violence in schizophrenia (SCZ) is a phenomenon associated with neurobiological factors. However, the neural mechanisms of violence in patients with SCZ are not yet sufficiently understood. Thus, this study aimed to explore the structural changes associated with the high risk of violence and its association with impulsiveness in patients with SCZ to reveal the possible neurobiological basis. Method: The voxel-based morphometry approach and whole-brain analyses were used to measure the alteration of gray matter volume (GMV) for 45 schizophrenia patients with violence (VSC), 45 schizophrenia patients without violence (NSC), and 53 healthy controls (HC). Correlation analyses were used to examine the association of impulsiveness and brain regions associated with violence. Results: The results demonstrated reduced GMV in the right insula within the VSC group compared with the NSC group, and decreased GMV in the right temporal pole and left orbital part of superior frontal gyrus only in the VSC group compared to the HC group. Spearman correlation analyses further revealed a positive correlation between impulsiveness and GMV of the left superior temporal gyrus, bilateral insula and left medial orbital part of the superior frontal gyrus in the VSC group. Conclusion: Our findings have provided further evidence for structural alterations in patients with SCZ who had engaged in severe violence, as well as the relationship between the specific brain alterations and impulsiveness. This work provides neural biomarkers and improves our insight into the neural underpinnings of violence in patients with SCZ. [ABSTRACT FROM AUTHOR]

Background: Myelin and iron are major contributors to the cortical MR signal. The aim of this study was to investigate 1. Can MP2RAGE-derived contrasts at 7T in combination with k-means clustering be used to distinguish between heavily and sparsely myelinated layers in cortical gray matter (GM)? 2. Does this approach provide meaningful biological information? Methods: The following contrasts were generated from the 7T MP2RAGE images from 45 healthy controls (age: 19–75, f/m = 23/22) from the ATAG data repository: 1. T1 weighted image (UNI). 2. T1 relaxation image (T1map). 3. INVC/T1map ratio (RATIO). K-means clustering identified 6 clusters/tissue maps (csf, csf/gm-transition, wm, wm/gm transition, heavily myelinated cortical GM (dGM), sparsely myelinated cortical GM (sGM)). These tissue maps were then processed with SPM/DARTEL (volume-based analyses) and Freesurfer (surface-based analyses) and dGM and sGM volume/thickness of young adults (n = 27, 19–27 years) compared to those of older adults (n = 18, 42–75 years) at p<0.001 uncorrected. Results: The resulting maps showed good agreement with histological maps in the literature. Volume- and surface analyses found age-related dGM loss/thinning in the mid-posterior cingulate and parahippocampal/entorhinal gyrus and age-related sGM losses in lateral, mesial and orbitofrontal frontal, insular cortex and superior temporal gyrus. Conclusion: The MP2RAGE derived UNI, T1map and RATIO contrasts can be used to identify dGM and sGM. Considering the close relationship between cortical myelo- and cytoarchitecture, the findings reported here indicate that this new technique might provide new insights into the nature of cortical GM loss in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Case-control studies in major depression have established numerous regional grey and white matter effects in fronto-limbic brain regions. Yet, brain structural studies of dimensional depressive psychopathology within the subclinical spectrum are still limited, in particular for multi-modal imaging approaches. Using voxel-based and surface-based morphometry (cortical thickness) in combination with diffusion tensor imaging (DTI) in a large non-clinical sample (N = 300), we correlated grey and white matter structural variation with subclinical depressive symptoms assessed with Beck's Depression inventory (BDI). We found a significant decrease of axial diffusivity associated with higher BDI scores in the left hippocampal part of the cingulum bundle (p < 0.05, threshold free cluster enhanced [TFCE] p -value) and some grey matter trend results e.g., a non-linear negative correlation of cortical thickness with depressive symptom load in the right pre/postcentral cortex (pFWE = 0.054, family wise error [FWE] peak level corrected) and a trend in grey matter volume decrease in women in the inferior frontal gyrus (pFWE = 0.054). Since all grey matter effects disappear after FWE correction, we assume more stable effects in a larger, less homogenous sample enriched by help-seeking subjects covering a wider range of subclinical psychopathology. Our study adds correlations between single depressive symptoms and brain structure to a growing literature. Since subclinical depression is increasingly recognised to be relevant in our understanding of manifest depression, early detection and identification of potential brain correlates of minor depressive symptoms has the potential to expand and reveal possible biomarkers and early psychological treatment. • Subclinical depressive symptoms cause structural grey (trend effect) and white matter changes in healthy subjects. • Limbic/hippocampal brain regions are affected by singe depressive symptoms. • Brain structural changes might be relevant in risk states of depression. [ABSTRACT FROM AUTHOR]

To gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from the UK Biobank (n = 380,379), the FinnGen Program (n = 290,361), and the Million Veteran Program (n = 175,163) together with UK Biobank genome-wide data (n = 33,224) related to 3935 brain imaging–derived phenotypes (IDPs). A genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX–brain associations, a 2-sample Mendelian randomization was performed considering multiple methods and sensitivity analyses. A subsequent multivariable Mendelian randomization was conducted to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms. After false discovery rate correction (q <.05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UK Biobank, FinnGen, and Million Veteran Program). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent multivariable Mendelian randomization analysis, reduced area of the right posterior middle cingulate gyrus (β = −0.09, p = 8.01 × 10−4) and reduced gray matter volume of the right anterior superior temporal gyrus (β = −0.09, p = 1.55 × 10−3) had direct effects on ANX. In the ANX symptom-level analysis, the right posterior middle cingulate gyrus was negatively associated with "tense, sore, or aching muscles during the worst period of anxiety" (β = −0.13, p = 8.26 × 10−6). This study identified genetically inferred effects that are generalizable across large cohorts, thereby contributing to our understanding of how changes in brain structure and function can lead to ANX. [ABSTRACT FROM AUTHOR]

Background: For nonmoyamoya patients with anterior cerebral artery (ACA) stenosis or occlusion, whether direct revascularization of the ACA territory can prevent stroke is still unclear. The objective of this study was to investigate the efficacy and safety of a parietal branch of superficial temporal artery-interposed superficial temporal artery-to-ACA bypass (PISAB) for preventing stroke in patients with symptomatic atherosclerotic ACA stenosis or occlusion (SAASO). Methods: We retrospectively analyzed the data from patients with SAASO who had undergone PISAB in our center between April 2016 and November 2021. The rates of patency, satisfaction (revascularization grades A and B) of bypass, perioperative complications, recurrence of ischemic stroke, changes in bypass flow, and improvements in cerebral blood perfusion were analyzed. Results: A total of 19 SAASO patients were involved in this study. Sixteen out of 19 (84.2%) patients were free from any cerebral ischemic events after surgery. Only 3 patients (15.8%) had recurrent stroke postoperatively. Two (10.5%) surgery- related complications occurred, including hyperperfusion syndrome and minor stroke. No skin ischemic complications occurred. The average follow-up period was 50.6 ± 18.3 months. The flow rate of the bypass was significantly increased half a year after surgery (56.2 ± 8.0 mL/min vs. 44.3 ± 5.3 mL/min, p < 0.001). The ratio of ipsilateral/contralateral mean transit time in the superior frontal gyrus was decreased significantly after bypass (1.08 ± 0.07 vs. 1.23 ± 0.05, p < 0.001) and continued to decrease 6 months after surgery (1.05 ± 0.04 vs. 1.08 ± 0.07, p = 0.002). The patency rate of PISAB was 94.7% (18/19) 2 years after surgery. The satisfaction rate of bypass was 89.5% (17/19). Conclusion: The results of this study indicate that PISAB, as a safe superficial bypass, can effectively reduce the risk of stroke in SAASO patients. More precise conclusions will require randomized control studies. [ABSTRACT FROM AUTHOR]

Music is a universal human attribute. The study of amusia, a neurologic music processing deficit, has increasingly elaborated our view on the neural organization of the musical brain. However, lesions causing amusia occur in multiple brain locations and often also cause aphasia, leaving the distinct neural networks for amusia unclear. Here, we utilized lesion network mapping to identify these networks. A systematic literature search was carried out to identify all published case reports of lesion-induced amusia. The reproducibility and specificity of the identified amusia network were then tested in an independent prospective cohort of 97 stroke patients (46 female and 51 male) with repeated structural brain imaging, specifically assessed for both music perception and language abilities. Lesion locations in the case reports were heterogeneous but connected to common brain regions, including bilateral temporoparietal and insular cortices, precentral gyrus, and cingulum. In the prospective cohort, lesions causing amusia mapped to a common brain network, centering on the right superior temporal cortex and clearly distinct from the network causally associated with aphasia. Lesion-induced longitudinal structural effects in the amusia circuit were confirmed as reduction of both gray and white matter volume, which correlated with the severity of amusia. We demonstrate that despite the heterogeneity of lesion locations disrupting music processing, there is a common brain network that is distinct from the language network. These results provide evidence for the distinct neural substrate of music processing, differentiating music-related functions from language, providing a testable target for noninvasive brain stimulation to treat amusia. [ABSTRACT FROM AUTHOR]

Background: Portable low-field-strength magnetic resonance imaging (MRI) systems represent a promising alternative to traditional high-field-strength systems with the potential to make MR technology available at scale in lowresource settings. However, lower image quality and resolution may limit the research and clinical potential of these devices. We tested two super-resolution methods to enhance image quality in a low-field MR system and compared their correspondence with images acquired from a high-field system in a sample of young people. Methods: T1- and T2-weighted structural MR images were obtained from a low- field (64mT) Hyperfine and high-field (3T) Siemens system in N = 70 individuals (mean age = 20.39 years, range 9--26 years). We tested two super-resolution approaches to improve image correspondence between images acquired at high- and low-field: (1) processing via a convolutional neural network ('SynthSR'), and (2) multi-orientation image averaging. We extracted brain region volumes, cortical thickness, and cortical surface area estimates. We used Pearson correlations to test the correspondence between these measures, and Steiger Z tests to compare the difference in correspondence between standard imaging and super-resolution approaches. Results: Single pairs of T1- and T2-weighted images acquired at low field showed high correspondence to high-field-strength images for estimates of total intracranial volume, surface area cortical volume, subcortical volume, and total brain volume (r range = 0.60--0.88). Correspondence was lower for cerebral white matter volume (r = 0.32, p = 0.007, q = 0.009) and non-significant for mean cortical thickness (r = -0.05, p = 0.664, q = 0.664). Processing images with SynthSR yielded significant improvements in correspondence for total brain volume, white matter volume, total surface area, subcortical volume, cortical volume, and total intracranial volume (r range = 0.85--0.97), with the exception of global mean cortical thickness (r = 0.14). An alternative multi-orientation image averaging approach improved correspondence for cerebral white matter and total brain volume. Processing with SynthSR also significantly improved correspondence across widespread regions for estimates of cortical volume, surface area and subcortical volume, as well as within isolated prefrontal and temporal regions for estimates of cortical thickness. Conclusion: Applying super-resolution approaches to low-field imaging improves regional brain volume and surface area accuracy in young people. Finer-scale brain measurements, such as cortical thickness, remain challenging with the limited resolution of low-field systems. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). Methods: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. Results: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. Conclusions: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD. [ABSTRACT FROM AUTHOR]

Introduction: Differential diagnosis among subjects with Primary Progressive Aphasia (PPA) can be challenging. Structural MRI can support the clinical profile. Visual rating scales are a simple and reliable tool to assess brain atrophy in the clinical setting. The aims of the study were to establish to what extent the visual rating scales could be useful in the differential diagnosis of PPA, to compare the clinical diagnostic impressions derived from routine MRI interpretations with those obtained using the visual rating scale and to correlate results of the scales in a voxel-based morphometry (VBM) analysis. Method: Patients diagnosed with primary progressive aphasia (PPA) according to current criteria from two centers—Ospedale Maggiore Policlinico of Milan and Hospital Clínic de Barcelona—were included in the study. Two blinded clinicians evaluated the subjects MRIs for cortical atrophy and white matter hyperintensities using two protocols: routine readings and the visual rating scale. The diagnostic accuracy between patients and controls and within PPA subgroups were compared between the two protocols. Results: One hundred fifty Subjects were studied. All the scales showed a good to excellent intra and inter-rater agreement. The left anterior temporal scale could differentiate between semantic PPA and all other variants. The rater impression after the protocol can increase the accuracy just for the logopenic PPA. In the VBM analysis, the scores of visual rating scales correlate with the corresponding area of brain atrophy. Conclusion: The Left anterior temporal rating scale can distinguish semantic PPA from other variants. The rater impression after structured view improved the diagnostic accuracy of logopenic PPA compared to normal readings. The unstructured view of the MRI was reliable for identifying semantic PPA and controls. Neither the structured nor the unstructured view could identify the nonfluent and undetermined variants. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a debilitating neurological condition that often leads to central neuropathic pain (CNP). As the fundamental mechanism of CNP is not fully established, its management is one of the most challenging problems among people with SCI. To shed more light on CNP mechanisms, the aim of this cross-sectional study was to compare the brain structure between individuals with SCI and CNP and those without CNP by examining the gray matter (GM) volume and the white matter (WM) integrity. Fifty-two individuals with SCI—28 with CNP and 24 without CNP—underwent a magnetic resonance imaging (MRI) session, including a T1-weighted scan for voxel-based morphometry, and a diffusion-weighted imaging (DWI) scan for WM integrity analysis, as measured by fractional anisotropy (FA) and mean diffusivity (MD). We found significantly higher GM volume in individuals with CNP compared with pain-free individuals in the right superior (p < 0.0014) and middle temporal gyri (p < 0.0001). Moreover, individuals with CNP exhibited higher WM integrity in the splenium of the corpus callosum (p < 0.0001) and in the posterior cingulum (p < 0.0001), compared with pain-free individuals. The results suggest that the existence of CNP following SCI is associated with GM and WM structural abnormalities in regions involved in pain intensification and spread, and which may reflect maladaptive neural plasticity in CNP. [ABSTRACT FROM AUTHOR]

Numerous studies utilizing voxel-based morphometry (VBM) have documented gray matter (GM) alterations in patients with chronic low back pain (CLBP) compared to healthy controls. However, the inconsistency in GM abnormalities observed across different studies has hindered their potential application as objective neuroimaging biomarkers or therapeutic targets. To address this issue, we conducted a comprehensive meta-analysis of VBM studies to identify robust GM differences between CLBP patients and healthy controls. The databases including PubMed, Embase, and Web of Science were systematically searched from January 2000 to September 2022 to identify eligible neuroimaging studies. In this coordinate-based meta-analysis of VBM studies, the Seed-based d Mapping with Permutation of Subject Images method was used to quantitatively assess regional differences in GM between CLBP patients and healthy controls. Thirteen VBM studies, involving a total of 574 CLBP patients and 1239 healthy controls, were included in the meta-analysis. The findings revealed that CLBP patients exhibited increased GM in the left striatum and left postcentral gyrus and decreased GM in the left superior frontal gyrus, left cerebellum, right striatum, left insula, and right middle occipital gyrus compared to healthy controls. The jackknife sensitivity analysis confirmed the robustness of these neuroimaging findings. This study provides new insights into potential treatment strategies for CLBP and identifies neuroimaging biomarkers for pain chronification. These findings highlight the importance of considering regional GM abnormalities in the development of clinical interventions for CLBP. [ABSTRACT FROM AUTHOR]

Infantile epileptic spasms syndrome (IESS) would accompany with severe neurological impairment. Our study aimed to explore the potential mechanism by employing voxel-based and surface-based morphometry to detect brain microwould accompany with severe neurological impairment. Our study aimed to explore the potential mechanism by employing voxel-based and surface-based morphometry to detect brain microanatomic structure alteration. The IESS group had 21 males and 13 females (mean age: 17.7 ± 15.6 months), whereas the healthy controls group had 22 males and 10 females (mean age: 29.4 ± 18.7 months). High-resolution 3D T1WI was performed. Computational Anatomy Toolbox implemented in Statistical Parametric Mapping 12 was used to measure the gray matter and white matter volume, and the cortical thickness separately. Independent sample t test was used to assess between-group differences. IESS group was assessed using the Bayley Scales of Infant Development. The IESS group showed a significantly decreased volume of gray matter in right middle temporal gyrus, inferior temporal gyrus, superior temporal gyrus, right fusiform, and bilateral precuneus (P < 0.001). There were no significant between-group differences with respect to white matter volume or cortical thickness (P > 0.001). The results of Bayley Scales of Infant Development showed that the Mental Development Index (MDI) and Psychomotor Development Index scores of children with IESS were almost concentrated in the range of <70. MDI score showed a positive correlation with gray matter reduction area in IESS group. Children with IESS had impaired cognitive and delayed motor development. And the decreased gray matter in the right temporal lobe, fusiform, and bilateral precuneus could be the potential anatomic basis for impaired function, such as hearing, visual, and language. [ABSTRACT FROM AUTHOR]

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms. [ABSTRACT FROM AUTHOR]

Background: In juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE. Methods: A total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE). Results: Patients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2–3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0–1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity. Conclusions: j-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI. [ABSTRACT FROM AUTHOR]

Facial emotion recognition (FER), including sadness, is altered in bipolar disorder (BD). However, the relationship between this impairment and the brain structure in BD is relatively unexplored. Furthermore, its association with clinical variables and with the subtypes of BD remains to be clarified. Twenty euthymic patients with BD type I (BD-I), 28 BD type II (BD-II), and 45 healthy controls completed a FER test and a 3D-T1-weighted magnetic resonance imaging. Gray matter volume (GMV) of the cortico-limbic regions implicated in emotional processing was estimated and their relationship with FER performance was investigated using network analysis. Patients with BD-I had worse total and sadness-related FER performance relative to the other groups. Total FER performance was significantly negatively associated with illness duration and positively associated with global functioning in patients with BD-I. Sadness-related FER performance was also significantly negatively associated with the number of previous manic episodes. Network analysis showed a reduced association of the GMV of the frontal–insular–occipital areas in patients with BD-I, with a greater edge strength between sadness-related FER performance and amygdala GMV relative to controls. Our results suggest that FER performance, particularly for facial sadness, may be distinctively impaired in patients with BD-I. The pattern of reduced interrelationship in the frontal–insular–occipital regions and a stronger positive relationship between facial sadness recognition and the amygdala GMV in BD may reflect altered cortical modulation of limbic structures that ultimately predisposes to emotional dysregulation. Future longitudinal studies investigating the effect of mood state on FER performance in BD are warranted. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling illnesses that profoundly restricts psychosocial functions and impairs quality of life. However, the treatment rate of MDD is surprisingly low because the availability and acceptability of appropriate treatments are limited. Therefore, identifying whether and how treatment delay affects the brain and the initial time point of the alterations is imperative, but these changes have not been thoroughly explored. We investigated the functional and structural alterations of MDD for different durations of untreated illness (DUI) using regional homogeneity (ReHo) and voxel-based morphometry (VBM) with a sample of 125 treatment-naïve MDD patients and 100 healthy controls (HCs). The MDD patients were subgrouped based on the DUI, namely, DUI ≤ 1 M, 1 < DUI ≤ 6 M, 6 < DUI ≤ 12 M, and 12 < DUI ≤ 48 M. Subgroup comparison (MDD with different DUIs) was applied to compare ReHo and grey matter volume (GMV) extracted from clusters of regions with significant differences (the pooled MDD patients relative to HCs). Correlations and mediation effects were analysed to estimate the relationships between the functional and structural neuroimaging changes and clinical characteristics. MDD patients exhibited decreased ReHo in the left postcentral gyrus and precentral gyrus and reduced GMV in the left middle frontal gyrus and superior frontal gyrus relative to HCs. The initial functional abnormalities were detected after being untreated for 1 month, whereas this duration was 3 months for GMV reduction. Nevertheless, a transient increase in ReHo was observed after being untreated for 3 months. No significant differences were discovered between HCs and MDD patients with a DUI less than 1 month or among MDD patients with different DUIs in either ReHo or GMV. Longer DUI was related to reduced ReHo with GMV as mediator in MDD patients. We identified disassociated functional and anatomical alterations in treatment-naïve MDD patients at different time points in distinct brain regions at the early stage of the disease. Additionally, we also discovered that GMV mediated the relationship between a longer DUI and diminished ReHo in MDD patients, disclosing the latent deleterious and neuro-progressive implications of DUI on both the structure and function of the brain and indicating the necessity of early treatment of MDD. [ABSTRACT FROM AUTHOR]