Cortical Brain Structures Research Articles

Genetically predicted brain cortical structure mediates the causality between insulin resistance and cognitive impairment

BackgroundInsulin resistance is tightly related to cognition; however, the causal association between them remains a matter of debate. Our investigation aims to establish the causal relationship and direction between insulin resistance and cognition, while also quantifying the mediating role of brain cortical structure in this association.MethodsThe publicly available data sources for insulin resistance (fasting insulin, homeostasis model assessment beta-cell function and homeostasis model assessment insulin resistance, proinsulin), brain cortical structure, and cognitive phenotypes (visual memory, reaction time) were obtained from the MAGIC, ENIGMA, and UK Biobank datasets, respectively. We first conducted a bidirectional two-sample Mendelian randomization (MR) analysis to examine the susceptibility of insulin resistance on cognitive phenotypes. Additionally, we applied a two-step MR to assess the mediating role of cortical surficial area and thickness in the pathway from insulin resistance to cognitive impairment. The primary Inverse-variance weighted, accompanied by robust sensitivity analysis, was implemented to explore and verify our findings. The reverse MR analysis was also performed to evaluate the causal effect of cognition on insulin resistance and brain cortical structure.ResultsThis study identified genetically determined elevated level of proinsulin increased reaction time (beta=0.03, 95% confidence interval [95%CI]=0.01 to 0.05, p=0.005), while decreasing the surface area of rostral middle frontal (beta=-49.28, 95%CI=-86.30 to -12.27, p=0.009). The surface area of the rostral middle frontal mediated 20.97% (95%CI=1.44% to 40.49%) of the total effect of proinsulin on reaction time. No evidence of heterogeneity, pleiotropy, or reverse causality was observed.ConclusionsBriefly, our study noticed that elevated level of insulin resistance adversely affected cognition, with a partial mediation effect through alterations in brain cortical structure.

Association of the Volumes of Limbic Brain Structures with the Development of Psychoneurological Disorders in Patients with Ischemic Stroke

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0 =10.9; β = –4.27; p = 0.04) and in-creased salivary α-amylase activity (β0 = –3.55; β = 2.68e–05; p = 0.02). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0 = 3.41; β = –0.99; p = 0.047), smaller temporal pole volume (β0 = 3.41; β = –3.12; p = 0.06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0 = 3.41; β = –0.05; p = 0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

Educational attainment, brain cortical structure, and sarcopenia: a Mendelian randomization study.

Previous observational studies have suggested associations between high-level educational attainment (EA) and a lower risk of sarcopenia. However, the causality inferred from those studies was subjected to residual confounding and reverse causation. The protective effect of EA on sarcopenia may be mediated via changes in brain cortical structure. The aim of this study was to use a two-step Mendelian randomization (MR) analysis to illustrate the causal relationship between EA, brain cortical structure, and sarcopenia. Instrumental variables at the genome-wide significance level were obtained from publicly available datasets, and inverse variance weighted as the primary method was used for MR analysis. We perform several sensitivity analyses, including Cochran Q test, MR-Egger intercept test, leave-one-out analyses, and MR Pleiotropy Residual Sum and Outlier to evaluate the reliability of the results. EA was causally associated with increased appendicular lean mass (β = 0.25, 95% confidence interval (CI): 0.19 to 0.31, p = 2.25 × 10-15), hand grip strength (left: β = 0.042, 95% CI: 0.013 to 0.071, p = 4.77 × 10-3 and right: β = 0.050, 95% CI: 0.022 to 0.079, p = 5.17 × 10-4), and usual walking pace (β = 0.20, 95% CI: 0.18 to 0.22, p = 6.16 × 10-83). In addition, EA was associated with increased brain cortical surface area (β = 4082.36, 95% CI: 2513.35 to 5681.38, p = 3.40 × 10-7) and cortical thickness (TH) (β = 0.014, 95% CI: 0.0045 to 0.023, p = 3.45 × 10-3). Regarding the causal effect of EA on usual walking pace, the mediatory effect of TH was 0.0069 and the proportion of mediation by TH was 3.43%. The study will have revealed the protective causal effect of EA on sarcopenia, which provides a reference for the prevention of sarcopenia at the public health level. We also will have found EA could affect the brain cortical structure, and the brain cortical structure could mediate the protective effect of EA against sarcopenia risk.

How Late Nights Influence Brain Cortical Structures: Distinct Neuroanatomical Measures Associated With Late Chronotype in Young Adults.

Chronotype is an inherent physiological trait reflecting an individual's subjective preference for their sleep awakening time, exerting a substantial influence on both physical and mental well-being. While existing research has established a close relationship between chronotype and individual brain structure, prior studies have predominantly focused on individual measurements of brain structural scales, thereby limiting the exploration of the underlying mechanisms of structural changes. This study seeks to validate previous research findings and enhance our understanding of the correlation between circadian rhythm preference and diverse cortical indicators in healthy young individuals. Magnetic resonance imaging (MRI) scans and chronotype assessments were conducted once for all participants, comprising 49 late chronotype (LC) young adults and 49 matched early chronotype young adults. The Chronotype Questionnaire was utilized to assess morningness and eveningness preferences. Surface-based analysis of structural MRI data revealed that LC young adults exhibited thinner cortical thickness of left pars orbitalis and lower cortical mean curve of right paracentral gyrus. Overall, this study represents a significant advancement in elucidating the connection between brain structure and function within the context of chronotypes.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease

IntroductionThe bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. MethodsThis study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. ResultsA total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. ConclusionThe detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Cerebrale ischemie als oorzaak van verminderd bewustzijn: het Percheron-infarct

Artery of Percheron infarction as an unusual cause of a reduced level of consciousness An acute onset of hemiparesis, aphasia or hemianopsia will promptly lead to the diagnosis of a stroke. However, a thalamic infarction does not always manifest with these classical symptoms due to its crucial role as a relay station between cortical brain structures, subcortical areas and the brainstem. The case of an 87-year-old woman with an altered state of consciousness due to bilateral thalamic ischemia as a result of an artery of Percheron infarction is reported. This case illustrates the clinical and diagnostic challenges in patients with an altered consciousness. The differential diagnosis is broad. One has to exclude a bilateral thalamic infarction since an early diagnosis of an ischemic stroke is crucial to initiate a proper treatment and thereby prevent morbidity and mortality.

COPD, PRISm and lung function reduction affect the brain cortical structure: a Mendelian randomization study

Chronic obstructive pulmonary disease (COPD) has been associated with alterations in the brain cortical structure. Nonetheless, the causality between COPD and brain cortical structure has not been determined. In the present study, we used Mendelian randomization (MR) analysis to explore the causal effects of genetic predicated COPD on brain cortical structure, namely cortical surface area (SA) and cortical thickness (TH). Genetic association summary data for COPD were obtained from the FinnGen consortium (N = 358,369; Ncase = 20,066). PRISm summary genetic data were retrieved from a case–control GWAS conducted in the UK Biobank (N = 296,282). Lung function indices, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were extracted from a meta-analysis of the UK Biobank and SpiroMeta consortium (N = 400,102). Brain cortical structure data were obtained from the ENIGMA consortium (N = 51,665). Inverse-variance weighted (IVW) method was used as the primary analysis, and a series of sensitivity tests were exploited to evaluate the heterogeneity and pleiotropy of our results. The results identified potential causal effects of COPD on several brain cortical specifications, including pars orbitalis, cuneus and inferior parietal gyrus. Furthermore, genetic predicated lung function index (FEV1, FVC and FEV1/FVC), as well as PRISm, also has causal effects on brain cortical structure. According to our results, a total of 15 functional specifications were influenced by lung function index and PRISm. These findings contribute to understanding the causal effects of COPD and lung function to brain cortical structure.

Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6 J).

Analysis of the mechanisms underlying autism spectrum disorder (ASD) is an urgent task due to the ever-increasing prevalence of this condition. The study of critical periods of neuroontogenesis is of interest, since the manifestation of ASD is often associated with prenatal disorders of the brain development. One of the currently promising hypotheses postulates a connection between the pathogenesis of ASD and the dysfunction of neurotransmitters and neurotrophins. In this study, we investigated the expression of key dopamine receptors (Drd1, Drd2), brain-derived neurotrophic factor (Bdnf), its receptors (Ntrkb2, Ngfr) and the transcription factor Creb1 that mediates BDNF action, as well as cerebral dopamine neurotrophic factor (Cdnf) during the critical periods of embryogenesis (e14 and e18) and postnatal development (p14, p28, p60) in the hippocampus and frontal cortex of BTBR mice with autism-like behavior compared to the neurotypical C57BL/6 J strain. In BTBR embryos, on the 14th day of prenatal development, an increase in the expression of the Ngfr gene encoding the p75NTR receptor, which may lead to the activation of apoptosis, was found in the hippocampus and frontal cortex. A decrease in the expression of Cdnf, Bdnf and its receptor Ntrkb2, as well as dopamine receptors (Drd1, Drd2) was detected in BTBR mice in the postnatal period of ontogenesis mainly in the frontal cortex, while in the hippocampus of mature mice (p60), only a decrease in the Drd2 mRNA level was revealed. The obtained results suggest that the decrease in the expression levels of CDNF, BDNF-TrkB and dopamine receptors in the frontal cortex in the postnatal period can lead to significant changes in both the morphology of neurons and dopamine neurotransmission in cortical brain structures. At the same time, the increase in p75NTR receptor gene expression observed on the 14th day of embryogenesis, crucial for hippocampus and frontal cortex development, may have direct relevance to the manifestation of early autism.

Brain age as a biomarker for pathological versus healthy ageing – a REMEMBER study

ObjectivesThis study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions.MethodsThe REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject.ResultsMCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p < .001) and BPAD (r = -0.26,p < .001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p = .014) and moderate (p = .040) drinkers.ConclusionsBrain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health.

Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow-up study.

Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long-lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8-9 years. This follow-up study aimed to examine whether these findings persisted into adolescence. Prospective observational follow-up study involving twenty-one 14- to 15-year-old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty-five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention-deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus-pituitary-adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference -2.0, 95% confidence interval [CI]: -7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress-induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency-adjusted means: 16.0 Hz vs 17.8 Hz, mean difference -1.83 Hz, 95% CI: -3.21 to -0.45, p = 0.01). In 14- to 15-year-old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow-up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.

NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1’s activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder’s clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation.

Elucidating the association of obstructive sleep apnea with brain structure and cognitive performance

BackgroundObstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined.MethodsWe conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits.ResultsOur MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW β (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume.ConclusionsOverall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance.

Causal association of depression, anxiety, cognitive performance, the brain cortical structure with pulmonary arterial hypertension: A Mendelian randomization study

BackgroundPatients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. MethodsPAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. ResultsPAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. LimitationsThe enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. ConclusionCausal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms.

The causal relationship between physical activity, sedentary behavior and brain cortical structure: a Mendelian randomization study.

Physical activity and sedentary behavior, both distinct lifestyle behaviors associated with brain health, have an unclear potential relationship with brain cortical structure. This study aimed to determine the causal link between physical activity, sedentary behavior, and brain cortical structure (cortical surface area and thickness) through Mendelian randomization analysis. The inverse-variance weighted method was primarily utilized, accompanied by sensitivity analyses, to confirm the results' robustness and accuracy. Analysis revealed nominally significant findings, indicating a potential positive influence of physical activity on cortical thickness in the bankssts (β = 0.002mm, P = 0.043) and the fusiform (β = 0.002mm, P = 0.018), and a potential negative association of sedentary behavior with cortical surface area in the caudal middle frontal (β = -34.181mm2, P = 0.038) and the pars opercularis (β = -33.069mm2, P = 0.002), alongside a nominally positive correlation with the cortical surface area of the inferior parietal (β = 58.332mm2, P = 0.035). Additionally, a nominally significant negative correlation was observed between sedentary behavior and cortical thickness in the paracentral (β = -0.014mm, P = 0.042). These findings offer insights into how lifestyle behaviors may influence brain cortical structures, advancing our understanding of their interaction with brain health.

Aerobic Exercise and Endocannabinoids: A Narrative Review of Stress Regulation and Brain Reward Systems.

Aerobic exercise is a widely adopted practice, not solely for enhancing fitness and reducing the risk of various diseases but also for its ability to uplift mood and aid in addressing depression and anxiety disorders. Within the scope of this narrative review, we seek to consolidate current insights into the endocannabinoid-mediated regulation of stress and the brain's reward mechanism resulting from engaging in aerobic exercise. A comprehensive search was conducted across Medline, SPORTDiscus, Pubmed, and Scopus, encompassing data available until November 30, 2023. This review indicates that a bout of aerobic exercise, particularly of moderate intensity, markedly augments circulating levels of endocannabinoids-N-arachidonoyl-ethanolamine (AEA) and 2-acylglycerol (2-AG), that significantly contributes to mood elevation and reducing stress in healthy individuals. The current understanding of how aerobic exercise impacts mental health and mood improvement is still unclear. Moderate and high-intensity aerobic exercise modulatesstress through a negative feedback mechanism targeting both the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system, thereby facilitating stress regulation crucial role in endocannabinoid synthesis, ultimately culminating in the orchestration of negative feedback across multiple tiers of the HPA axis, coupled with its influence over cortical and subcortical brain structures. The endocannabinoid has been observed to govern the release of neurotransmitters from diverse neuronal populations, implying a universal mechanism that fine-tunes neuronal activity and consequently modulates both emotional and stress-related responses. Endocannabinoids further assume a pivotal function within brain reward mechanisms, primarily mediated by CB1 receptors distributed across diverse cerebral centers. Notably, these endocannabinoids partake in natural reward processes, as exemplified in aerobic exercise, by synergizing with the dopaminergic reward system. The genesis of this reward pathway can be traced to the ventral tegmental area, with dopamine neurons predominantly projecting to the nucleus accumbens, thereby inciting dopamine release in response to rewarding stimuli.

Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.

Chemotherapy-induced cognitive impairment in breast cancer survivors: A systematic review of studies from 2000 to 2021.

Studies have indicated that apart from enhancing patient survival, chemotherapy has adverse side effects on the psychological, social, and cognitive functions of breast cancer survivors. This study was conducted to understand chemotherapy's impact on breast cancer survivors' cognitive functions. Our study is a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched English databases, including PubMed/MEDLINE, PsycINFO, and Web of Science, and Persian databases, such as Irandoc and Elmnet, using Persian keywords of cancer, breast cancer, chemotherapy, cognitive functions, executive functions, and neuropsychological functions. Two reviewers independently evaluated the full text of the articles according to predefined criteria. Among the 937 available studies, 26 were selected based on the inclusion and exclusion criteria, of which 17 (65%) were longitudinal and 9 (35%) were cross-sectional. The findings indicated a significant relationship between the use of chemotherapy and cognitive impairments, most notably attention, working and short-term memory, and executive functions. However, the studies differed in their findings regarding the long-term persistence of cancer-related cognitive impairment (CRCI), which could be due to the wide range of tools used, different methods to measure cognitive functions, and the difference in the sample size of the studies. Chemotherapy, affecting cortical and subcortical brain structures, causes a set of cognitive impairments that can lead to impairments in social responsibility acceptance, daily functioning, and quality of life of women. Therefore, rigorous and extensive research design is required to understand the causes and consequences of CRCI using standardized and sensitive measures of cognitive functions. Specifically, studies comparing the effects of different chemotherapy regimens on cognition and potential mechanisms and/or moderators of CRCI would be instrumental in designing more effective therapy regimens and evaluating the efficacy and cost-effectiveness of cognitive rehabilitation and supportive care programs.

Retinal Microvasculature Causally Affects the Brain Cortical Structure: A Mendelian Randomization Study

PurposeTo reveal the causality between retinal vascular density (VD), fractal dimension (FD) and brain cortex structure using Mendelian randomization (MR). DesignCross-sectional study. ParticipantsGenome-wide association studies of VD and FD involving 54,813 participants from the UK Biobank were used. The brain cortical features, including the cortical thickness (TH) and surficial area (SA), were extracted from 51,665 patients across 60 cohorts. SA and TH were measured globally and in 34 functional regions using magnetic resonance imaging. MethodsBidirectional univariable MR (UVMR) was used to detect the causality between FD, VD and brain cortex structure. Multivariable MR (MVMR) was used to adjust for confounding factors, including body mass index and blood pressure. Main Outcome MeasuresThe global and regional measurements of brain cortical surface area and cortical thickness. ResultsAt the global level, higher VD is related to decreased TH (β =-0.0140 mm, 95% CI: -0.0269 mm to -0.0011 mm, P = 0.0339). At the functional level, retinal FD is related to the TH of banks of the superior temporal sulcus and transverse temporal region without global weighted, as well as the SA of the posterior cingulate after adjustment. VD is correlated with the SA of subregions of the frontal lobe and temporal lobe, in addition to the TH of the inferior temporal, entorhinal and pars opercularis regions in both UVMR and MVMR. Bidirectional MR studies showed a causation between the SA of the parahippocampal and cauda middle frontal gyrus and retinal VD. No pleiotropy was detected. ConclusionsFD and VD causally influence the cortical structure and vice versa, indicating that the retinal microvasculature may serve as a biomarker for cortex structural changes. Our study provides insights into utilizing noninvasive fundus images to predict cortical structural deteriorations and neuropsychiatric disorders.

From teeth to brain: dental caries causally affects the cortical thickness of the banks of the superior temporal sulcus

ObjectivesDental caries is one of the most prevalent oral diseases and causes of tooth loss. Cross-sectional studies observed epidemiological associations between dental caries and brain degeneration disorders, while it is unknown whether dental caries causally affect the cerebral structures. This study tested whether genetically proxied DMFS (the sum of Decayed, Missing, and Filled tooth Surfaces) causally impacts the brain cortical structure using Mendelian randomization (MR).MethodsThe summary-level GWAS meta-analysis data from the GLIDE consortium were used for DMFS, including 26,792 participants. ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) consortium GWAS summary data of 51,665 patients were used for brain structure. This study estimated the causal effects of DMFS on the surface area (SA) and thickness (TH) of the global cortex and functional cortical regions accessed by magnetic resonance imaging (MRI). Inverse-variance weighted (IVW) was used as the primary estimate, the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy.ResultsGenetically proxied DMFS decreases the TH of the banks of the superior temporal sulcus (BANSSTS) with or without global weighted (weighted, β = − 0.0277 mm, 95% CI: − 0.0470 mm to − 0.0085 mm, P = 0.0047; unweighted, β = − 0.0311 mm, 95% CI: − 0.0609 mm to − 0.0012 mm, P = 0.0412). The causal associations were robust in various sensitivity analyses.ConclusionsDental caries causally decrease the cerebral cortical thickness of the BANKSSTS, a cerebral cortical region crucial for language-related functions, and is the most affected brain region in Alzheimer’s disease. This investigation provides the first evidence that dental caries causally affects brain structure, proving the existence of teeth-brain axes. This study also suggested that clinicians should highlight the causal effects of dental caries on brain disorders during the diagnosis and treatments, the cortical thickness of BANKSSTS is a promising diagnostic measurement for dental caries-related brain degeneration.

Assessing brain integrity in patients with long-term and well-functioning metal-based hip implants.

Production of metal debris from implant wear and corrosion processes is now a well understood occurrence following hip arthroplasty. Evidence has shown that metal ions can enter the bloodstream and travel to distant organs including the brain, and in extreme cases, can induce sensorial and neurological diseases. Our objective was tosimultaneously analyze brain anatomy and physiology in patients with long-term and well-functioning implants. Included were subjects who had received total hip or hip resurfacing arthroplastywith an implantation time of a minimum of 7 years (n = 28) and age- and sex-matched controls (n = 32). Blood samples were obtained to measure ion concentrations of cobalt and chromium, and the Montreal Cognitive Assessment was performed. 3T MRI brain scans were completed with an MPRAGE sequence for ROI segmentation and multiecho gradient echo sequences to generate QSM and R2* maps. Mean QSM and R2* values were recorded for five deep brain and four middle and cortical brain structures on both hemispheres: pallidum, putamen, caudate, amygdala, hippocampus, anterior cingulate, inferior temporal, and cerebellum. No differences in QSM or R2* or cognition scores were found between both groups (p > 0.6654). No correlation was found between susceptibility and blood ion levels for cobalt or chromium in any region of the brain. No correlation was found between blood ion levels and cognition scores.Clinical significance: Results suggest that metal ions released by long-term and well-functioning implants do not affect brain integrity.